pediatrics - sppf.info

3132

TBILISI

ISS

N 2

66

7-9

84

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International Journal OF

P E D I A T R I C S

Editor-in-ChiefGEORGE CHAKHUNASHVILI

MD,PhD,DSc,Professor, Academician

(Georgia)

Editor-in-ChiefFUYONG JIAO

MD Prof and Head Children’sHospital of Shaanxi Provincial

People’s Hospital of Xi, an Jiaotong University, The Society

of Promotion Children’s Healthof Shaanxi Province. Executive

Councillor of ISPCAN (China)

THE SOCIAL PEDIATRIC PROTECTION FUNDDate of Foundation: 30.09.1998Date and Number Of Registration: #147 9.10. 1998wAddress:Tbilisi, Ljubljana 21, 0154 Tel.: 995 593337154E-mail: [email protected]; [email protected] Contact: Prof.George Chakhunashvili Job of Contact: Chairman of The Board Branches of Fund:Mtskheta; Kutaisi; Gori.; Abasha.; Batumi.; Sagarejo; Gurjaani; Telavi; Tchiatura;

Zugdidi; Territory of Operation:Georgia (eu) Aim Social Pediatric Protection Fund is to execute programs of social

pediatric development and maintain rights and healthcare of Children, Mothers andAdolescents. Fund has great organizational experience, technical equipment and skilledmembers.Most of the members are Professors at TSMU, who have clinical and educational

experience of 15-20 years and were one of the first, Before the independence, to readlectures about congenital infections, sexually transmitted diseases and prevention ofHIV. Fund is also cooperating with physicians, psychologists, Lawyer (who operate infield of social assistance) and Public figures. By the joint forces of all the people abovesaid SPPF is able to hold free medical examinations, juridicial consultations, charityevents, informational lectures about healthy way of life, congenital infection, HIV,Social subjects and etc.Since 1997 more than 93.000 Children and Hundreds of older people have been

medically for free in the framework of charity events. Before Independence, The activemembers of SPPF and their consortium in 1980-1990 examined above 124 000Children, all over Georgia.

1. Shaanxi International Medical Exchange Promotion Association (SIMEA)Date of establishment: June 1994Registration number: 51610000520157511DAddress: No. 22, Huancheng East Road, Xincheng District, Xi'an City, Shaanxi

ProvinceE-mail: [email protected]: Fuyong JiaoSIMEA was established in 1994 with the approval of the Shaanxi Provincial

Department of Civil Affairs. It is a first-level social organization under the charge ofthe Shaanxi Provincial Health and Family Planning Commission. The concept of"seeking well-being" will give full play to the advantages and characteristics of thegathering of experts, a wide range of disciplines, and a sound network, aiming to builda platform for international medical exchanges and mutual learning.

2. Children's Hospital of Shaanxi Provincial People's HospitalDate of establishment: 1950Address: No. 256, Youyi West Road, Beilin District, Shaanxi ProvinceContact: Fuyong JiaoSince its establishment in 1950, the Children's Hospital of Shaanxi Provincial

People's Hospital has experienced more than 70 years of development. It is now theChildren's Hospital of the Third Affiliated Hospital of Xi'an Jiaotong University. It is achildren's hospital integrating medical treatment, teaching, and scientific research.Shaanxi Province Kawasaki Disease Diagnosis and Treatment Center, Shaanxi ProvincePediatrics Clinical Medicine Research Center, National Drug Research Institute(Children Neuromedicine Specialty), Shanghai Cooperation Organization HospitalCooperative Alliance International Exchange Center, and China Kawasaki DiseaseWebsite (ww.chinakd.org) have been established. ), European Center for TraditionalChinese Medicine (Prague). Insist on innovating the "send out and invite in"communication methods for academic exchanges and scientific research cooperation.

3.The Institution of Shaanxi Province Clinical Medicine Demonstration Inter-national Science and Technology CooperationEstablished time: 2020Address: No. 256, Youyi West Road, Beilin District, Xi'an City, Shaanxi ProvinceContact: Fuyong JiaoE-mail: [email protected] Shaanxi Provincial Clinical Medicine Demonstration International Science and

Technology Cooperation Base was established in 2020. It is an organization approvedby the Shaanxi Provincial Department of Science and Technology to promoteinternational cooperation and exchanges in clinical medicine and guide the province tocarry out international cooperation and exchanges in clinical medicine. The cooperationbase is set up in Shaanxi Provincial People's Hospital. Actively expand foreign medicalresources, and provide a lasting communication channel for domestic medical andhealth institutions and public health service units to learn international advanced man-agement experience and strengthen the training of talent teams.

THE SOCIAL PEDIATRIC PROTECTION FUND

Shaanxi International Medical Exchange Promotion Association (SIMEA)Children's Hospital of Shaanxi Provincial People's Hospital

Institution of Shaanxi Province Clinical Medicine Demonstration International Science and Technology Cooperation

International Journal OF

P E D I A T R I C S

2021

$2

2021

UDC (უაკ)-616-053.2 I - 69

Preface

Children is the hope of society, the future of world and mankind!Strong children make the world strong! In order to strengthen international medical academic exchanges and

improve the diagnostic and therapeutic skills of pediatricians, nurses and general practitioners around the world,the international Journal of Pediatrics was organized by the joint efforts of pediatricians and general practition-ers from China, Georgia, Poland, The Czech Republic, Turkmenistan and India et al . This journal is of great clin-ical significance and academic value to promote international communication among pediatric medical staff andimprove the diagnostic and treatment technology level of pediatric diseases. We hope that with our joint effortsand hard work, this journal will take root, sprout and grow in the world, bringing good news to the health of chil-dren around the world and benefiting children all over the world!

GEORGE CHAKHUNASHVILI (Georgia) and FUYONG JIAO (China)

2021

International Journal OF PEDIATRICS 3

INTERNATIONAL JOURNAL OF PEDIATRICS

Editor-in-ChiefGEORGE CHAKHUNASHVILI

MD, PhD, DSc, Professor, Academician (Georgia)

Editor-in-ChiefFUYONG JIAO

MD Prof and Head Children’s Hospital of Shaanxi Provincial People’s Hospital of Xi, an Jiaotong University, The Society of Promotion Children’s Health of Shaanxi Province. FORMER Executive Councillor of ISPCAN (China)

DEPUTY EDITOR / SUBEDITORS AND EDITORIAL BOARD MEMBERSOF INTERNATIONAL JOURNAL OF PEDIATRICS

SecretaryJIALE WNAG

Deputy editor / Subeditors

Editorial board members

Magazine layout - GeorgiaPrinted By: XX Publisher&Printing Co - China

Internet version - https://sppf.info/pdf/int-ped-journal-2021-1.pdf

E-mail: [email protected] (China)[email protected] (Georgia)

Tel.: office: 0086.029-85368194 (China)Mob.: 15398082028 //18966928051 (China)Mob.: (+995 593) 337154 (Georgia)

MD. Begench Annayev (Turkmenistan)MD. Karim Hamed Ali Ibrahim (Egypt)MD.Yulian Zhang (China)MD. Jacek Tabarkiewicz (Poland)MD.Yanni Chen (China)MD. Sergiusz Jozwiak (Poland)MD. Berényi Marianne (Huangary)MD. Vesna Stojanovic (Serbia)Omar Mohamud Hassan (Kenya)MD.Muhammad Yousuf (Bangladesh)MD.Abu Taiub M Mohiuddin Chowdhury (Bangladesh)MD. Zhaoling Shi (China)MD.Aziz Koleilat (Lebanon)MD. Giuseppe Marraro (Italy)Xianglong Duan (Xi’an, China)

MD. Bilal Haider Shamsi (Pakistan)MD. Carlo Catassi (Italy)MD. Dr Senthil Arun Kumar Dr (India)MD. Tudor Lucian POP (Romania)MD. Dávid Horváth (Huangary)MD. Helena Maltezou (Greece)MD. Tungalag Osgonbaatar (Mongolia)MD. Kai-Sheng Hsieh (China)K. Chakhunashvili MD. Ph.D. (Georgia)MD. Chang-Keun Kim (S. Korea)MD.Alhaji Adam Abubakari (Ghana)MD. Hui Wen (China)MD. Jianying Feng (China)MD.Wenyan Jiao (China)

Wang Xia (China)Haotian Xu (China)Liu Juan (China)li Huirong (China)Gao Chunyan (China)

D. Chakhunashvili MD. Ph.D. (Georgia)Mu Zhilong (China)Zhang Yuxian (China)Qiao Yanmei (China)Yan Xiaohua (China)Taomin Bai (China)Li Wei (China)

Ali Raza (Pakistan)P. Kervalishvili Prof. (Georgia)Zhang Hong (China)Yan xianpeng (China)D. Tskomelidze Prof. (Georgia)Gao ying (China)Xu Haotian (China)

International Journal OF PEDIATRICS

2021

4

adVanced artIcle

securItY scIence In PedIatrIcs ....................... 5George chakhunashvili

orIGInal artIcles and scIentIfIc actIVItIes In PedIatrIcs

effectIVe treatMent and recoVerY of sars-coV-2 Infected Infant/cHIldren In a faMIlY cluster outbreaK ....................... 9Zhou chongchen (M.d.), luo shuying (M.sc), fiaz ahmad (Ph.d.), Zhou Yibo (M.sc), cheng Yibing(M.d.), Jiao fuyong (M.d.)

coronaVIrus dIsease (coVId-19) sItuatIon In MonGolIa ........................................ 14tungalag osgonbaatar

clInIcal ManaGeMent of cHIldren wItHKawasaKI dIsease durInG tHe sItuatIon of PreVentIon and control of coVId-19 .......... 15fuyong Jiao, sheng Zhang, Ji Ma, Jing ni, Juyan wang, Xiaohong lI, Zhilong Mu, wei Han, Gaitao He, lei Ma, fuyong Jiao

studIes of VIbratIonal ProPertIes of PatHoGenIc nanobIosYsteMs bY sPectroscoPIc MetHods of InVestIGatIon ... 19P. Kervalishvili, t. berberashvili, t. bzhalava, l. chakhvashvili, a. Kekelidze

InVestIGatIons of VIbratIonal ProPertIes of VIruses and VIrus-lIKe PartIcles bY coMPutInG MetHods ............... 29tamar berberashvili, tamar bzhalava, lali chakhvashvili, anna Kekelidze, salome Karseladze,lasha basadze, tohid talebifar, alexandre soselia, Paata Kervalishvili

researcH ProGress of KawasaKI dIsease In sHocK sYndroMe ........................... 40fuyong Jiao, tungala osgonbaatar, wen Hie, abudumutailipu Maihemuti

clInIcal analYsIs of 3 neonatal wItH PneuMotHoraX ............................................. 44Zhongming Yun, Yanmei Qiao, Yonglin liu, lifang li, Yanling li, Zhaoyu Yang, fuyong Jiao

KaleIdoscoPe of InterestInG worKs

MIMIcrY In HuMans ................................................ 48davit tskhomelidze, Medea tskhomelidze

about soMe PeculIarItIes of twIns ........... 49d. tskhomelidze, n. chiladze

coVId-19 sItuatIon In GHana-brIef analYsIs ........................................................................ 50alhaji adam abubakari, solomon Gumanga, Hawawu Hussein

ProGress In tHe ePIGenetIcs of KawasaKI dIsease ............................................ 52wang chenyue, Jiao fuyong, feng Jianying

clInIcal analYsIs of 5 cases of cHIldren wItH sars-coV-2 InfectIon In faMIlY cluster outbreaK ........................... 58Zhou chongchen, luo shuying, Ma lei, Xiao Qi, Zhou Yibo, Zhen Xinggang, feng Yingjun, li Min, Jiao fuyong

new ProGress In nursInG researcH of KawasaKI dIsease ............................................. 62Zhang Hong, liu Hongmei, deng feidan, Zhang Xibin, niu Qian, Ma Ji

dIfferent

PHYsIcal GrowtH and Pubertal deVeloPMent of scHool-aGed cHIldren In ulaanbaatar ................................. 66tungalag osgonbaatar, erdenetuya Ganbaaatar

a case rePort of faMIlY cluster carbonMonoXIde PoIsonInG wItH delaYed encePHaloPatHY and lIterature reVIew ....... 69Xianpeng Yan, Xuan wan, Xiaohua Yan, Jianying feng,Jiemin wang, fuyong Jiao

researcH ProGress of breastfeedInG In cHIna ......................................................................... 72Jiale wang, Haotian Xu, Yunyi liang, fuyong Jiao

PractIcInG PHYsIcIans

„coVId-19 PneuMonIa: tHe first case of successful treatMent of a crItIcal Ill newborn after cesarean sectIon“ .......... 75fuyong Jiao, chongchen Zhou, Yibo cheng, shuying luo, lei Ma, Xinggang Zhen, Yingjun feng, Min li, stefan bittmann

MultIcenter clInIcal studY of 156 cHIldren wItH KawasaKI dIsease durInG coVId-19 ........................................................ 77lin-na wang, fu-Yong Jiao, Yu wei, Ying-Jun feng,Jing-li Zhang, Zhao-Xia Zhang, shu-bin tang, Ya-li li, Peng-Jiang Kang, Ya-le Zhang, Hui-rong li

cHInese PedIatrIc eXPert consensuson tHe use of IntraVenous IMMunoGlobulIn In KawasaKI dIsease ...... 83

InforMatIon

“tHe role of tHe socIal PedIatrIcs ProtectIon fund In GeorGIan PedIatrIcs - 1998-2021“ ............................................ 84G. chakhunashvili

CONTENTS

Secondly, science and security mustbe determined together with social-eco-nomic and ecological environment. To-gether with each of these two factors sci-ence may have both positive and nega-tive sides. Thus, in my opinion, scienceof the XXI century should serve themankind at high level of urbanization,safety of each citizen of this country andcarry on preventive measurementsagainst possible negative influence. In-troduction of high technologies in inves-tigations, existence of precise medicalstatistical database, creation of moderncomputer programs and their usage(prog-nosis of disease course, establishment ofrisk factors and groups, etc) – that is allon the basis of which it will be possibleto solve many problems existing in theXXI century.

Proceeding from the above-said, de-velopment of sciences and monitoring onthem appear to be a main task, whichtakes into account creation of safe envi-ronment for human health, improvementof life conditions. At the same time it isnecessary to carry out possible eco-pathological preventive measures, whichshould be considered as a principalstrategy of the XXI century.

At present it is doubtful that devel-opment of science is approaching its topheights. Particularly usage of gene en-gineering makes it possible to create anew human being. Today there exists amethod for artificial fertilization and thenewborns are already in evidence. In theXX century we became witnesses of hu-man being’s stepping out of the rocketinto the space and even visiting otherplanets.

However it does not mean that sci-ence is developing in such a way, thatevery one can equally understand its de-velopment in different branches.

Let me explain how I personally in-terpret science and security.

First of all development of scienceshould be based on the maintenance ofbioethical standards.

Secondly, science and security mustbe determined together with social-economic and ecological environ-ment. Together with each of thesetwo factors science may have both pos-itive and negative sides. Thus, in myopinion, science of the XXI centuryshould serve the mankind at high lev-el of urbanization, safety of each cit-izen of this country and carry on pre-

ventive measurements against possiblenegative influence.

Proceeding from the above-said ourintention was to discuss several impor-tant topics regarding health care in or-der to carry on necessary preventivemeasurements.

A necessary condition for carrying onpreventive measurements is a fundamen-tal knowledge of the problem and striv-ing for meaningful strategic directions,which of course is based on: a) precisemedical statistics; b) higher medicaltechnologies; c) modern computer treat-ed analysis (on prognosis and new pro-grams), which underlie our conclu-sions.

Each region of the world is charac-terized by peculiar situation-state in thesphere of public health care. In order toestimate this it is necessary to discuss:

general situation in the regionexpected life span and death-rateexpected span of healthy lifeclasses of diseases, such as:

a) infectious diseases – tuberculosispassing through sexual way (includingHIV/AIDS), malaria, diseases whichmight be prevented by means of vaccineprophylaxis (diphtheria, hepatitis, po-liomyelitis)

b) non-infectious diseases (cardiovas-cular diseases, tumors, obesity, dia-betes mellitus)

c) psychic healthd) accidents and traumasAnd the most important thing today

is Covid infections and fighting them.For estimation of situation in public

health in the region it is necessary to an-alyze data of separate groups of popula-tion: the I group comprises data aboutchildren’s health. In this group death-rateof newborns and children aged 5 yearsare important. Neonatal mortality, espe-cially at earlier stage, determines a gen-eral level of newborns’ mortality. It is

2021


ADVANCED ARTICLE

securItY scIence In PedIatrIcsGeorGe cHaKHunasHVIlI

MD.PHD.Dsc. Professor, Academician (Tbilisi, Georgia)

abstract:In the XXI century a great attention should be devoted to the problems

of global heating, resulting in natural calamities and spread of different dis-eases. therefore, measures against expected epidemic should be taken.

science and security must be determined together with social-economicand ecological environment. together with each of these two factors sciencemay have both positive and negative sides. thus, in my opinion, science ofthe XXI century should serve the mankind at high level of urbanization, safe-ty of each citizen of this country and carry on preventive measurements againstpossible negative influence. Introduction of high technologies in investiga-tions, existence of precise medical statistical database, creation of modern com-puter programs and their usage(prognosis of disease course, establishmentof risk factors and groups, etc) – that is all on the basis of which it will be pos-sible to solve many problems existing in the XXI century.

Kevword: Pediatrics, Security, Disease, Preventive measurements Children’s rights.


2021

clear, that in those countries, wheremortality of newborns is high, its decreasemay be achieved by reduction of mortal-ity level in newborns, while decrease ofmortality in newborns is achieved by at-tenuating of neonatal mortality level.While estimating children’s health it isnecessary to consider children’s nutrition,including nursing during the first year oflife and deficit of microelements in chil-dren’s feeding; children’s diseases (theircourse). All above mentioned indices de-pend on amount of the needed bed-placesfor children in hospitals, which should beconsidered together with social-eco-nomic and ecological conditions of theregion.

At the same time, mortality rate inmothers, children immunization, carry-ing out preventive measures against tu-berculosis and HIV/AIDS stipulatestate of infant health.

Currently our research group con-ducts the project "Role of viralpathogens among infants with systemicinfections" supported by the GeorgianResearch and Development Foundation(GRDF). Our US partner is the re-search group at the Department of Mi-crobiology, Virology, Immunology andMolecular Diagnostics of the School ofMedicine, University of Pittsburgh atMagee-Women's Hospital.

Political events of the last ten yearsadversely affected child health in Geor-gia. Currently the infant mortality ratein the country is very high and variesfrom 15 to 25 deaths per 1000 livebirths. In Georgia one of the most im-portant causes of the infant death is thedevelopment of generalized infections.In the majority of such cases thecausative agents are not being identified.As a rule, all newborns with a general-ized infection with wide range of non-specific symptoms; including hyperther-mia or hypothermia, jaundice, bleedingwith associated coagulopathy, respira-tory insufficiency, vascular instability,hepatomegalia, splenomegaly; are diag-nosed as "neonatal sepsis" (withoutidentification of etiology) and treatedwith broad-spectrum antibiotics. Despitethis “empiric” treatment, the mortalityrate for neonates with generalized infec-tions of unknown origin is high, estimat-ed to be over 65%. In addition, the"neonatal sepsis" is frequently associ-ated with infections of central nervoussystem - meningitis and encephalitis,which makes prognosis even poorer.

Until now testing for viral infectionsin pediatric patients was ultimatelyrare, and included only serological test-ing, leaving physicians to treat patientswith limited clinical information. Yet,some patients with generalized infectionare likely to have a viral infection, a sub-set of whom has a treatable viral infec-tion. Early identification of preventableor treatable viral infections is a key toreducing the low survival rate seen inthis high-risk population.

Among the viral pathogens, membersof the herpes viruses and enterovirusesplay the most important role in the de-velopment of generalized infections innewborns.

Through our project we have estimat-ed the prevalence of herpes viruses andenteroviruses among neonates withgeneralized infections, described clin-ical and immunological status of the in-fants by infection type; estimated sur-vival, by infection type and clinical/im-munological status; piloted the rapid andsimple PCR based methods for screen-ing and typing of viruses in neonates,which are based on the ultramodern mo-lecular diagnostic methodology.

In parallel we are implementing thediagnostic and preventive measures forsuch an important infection as one in-duced by Human ImmunodeficiencyVirus (HIV). Until now in Georgia thisinfection was not seriously consideredin paediatric clinical practice. Our ac-tivities in this field give us opportuni-ty to perform the early diagnostics of thisinfection and through this contribute tothe prevention of the HIV epidemic inour country.

Thus, all above mentioned is close-ly connected with social, economicand ecological factors, which will be dis-cussed below. At the same time we can’tavoid the problem of defence of chil-dren’s rights, although all above men-tioned indices concern this problem.

Since coming into force of conven-tion of children’s rights up today therehas been some progress in the defenceof children’s rights. Some important stepshave been made. A new legislation wasdeveloped with more refined internation-al standards, such as additional proceed-ings of the convention of children rightsabout trade with children, children pros-titution and pornography, use of children

6

Table 1

Indices of sick rate and morbidity degree among forced displaced persons from Abkhazia

Source: Data of Health Care Ministry of Abkhazian Autonomic Republic

58232232048

933

105659211041814132556445222319921

11

3584924

54955

293563706

339

170195518355662130413621066340

3

2474790

18645

14178-

946

1242

1131346318

19688299512191914208

23

12172523

44905

8432-

604

592

354239

98251186505 99580

3

8042374

23303

total

total

new cases total

Including 14 yearsold children

new casesInfectious and parasitic diseases tumorsdiseases of endocrine system, nutrition disor-ders and metabolism blood and hemopoietic diseases, separate dis-orders involving immune mechanism Psychical and behavioral disordersdiseases of nervous systemdiseases of blood circulation systemdiseases of respiratory organsdiseases of digestive organsdiseases of genitourinary systemskin and subcutaneous cellular tissue diseasesdiseases of osteomuscular system and con-junctive tissues congenital anomalies, deformations andchromosomal diseasessome states induced in perinatal period symptoms, signs and divergence from the norm traumas, intoxications In all

in armed conflicts. Highly important arethe rights of children in conflict zonesand I can’t help dealing with it on the ex-ample of Georgia.

Demolition of the USSR and regain-ing of independence of Georgia havebrought to its population political disor-ders, civil war and disorganization of eco-nomics. As a result of conflicts and sep-arative movements in South Osetia andAbkhazia there took place fierce strugglesand processes of forced migration. At pres-ent, as is known, Abkhazia and South Os-etia are governed by de facto separativegovernments, which are not recognized bythe International Commonwealth.

While considering data given in Table1, it is clear that in 2002 as compared to2001, sick rate among forced displacedpersons decreased by 5,8%, and morbid-ity degree - by 33,6%. In spite of such areduction among forced displaced per-sons sick rate is 1,93-fold greater, whiledegree of morbidity – 1,6-fold greater. In2006 these indices were the same.

Especially high indices of sick rate andmorbidity degree are observed accordingto the main following classes: in case ofinfectious and parasitic diseases sick rateis 3,6 fold and morbidity degree - 2,9 foldgreater as compared to analogous medi-um indices of the country; blood and he-mopoietic diseases – correspondingly2,5 and 1,9 fold greater; diseases of nerv-ous system and sense organs – correspond-ingly 2,4 and 2 fold greater; diseases of res-piratory organs – correspondingly 2,4 and1,3 fold greater; diseases of digestive or-gans – correspondingly 2,5 and 1,6 foldgreater; diseases of genitourinary system– correspondingly 3,4 and 2,4 fold greater;skin and subcutaneous cellular tissuediseases - correspondingly 3,7 and 2,7 foldgreater; traumas and intoxications - cor-respondingly 1,2 and 1,2 fold greater.

As regard the children, in 2002 sickrate of forced displaced children was 1,4fold and morbidity degree 1,1 foldgreater than those of analogous indicesin the country, among them: infectiousand parasitic diseases – corresponding-ly was 3,9 and 3,3 fold greater; bloodand hemopoietic diseases – correspond-ingly 1,5 and 1,3 fold greater; diseasesof nervous system and sense organs –correspondingly 2,6 and 3,7 fold greater;diseases of respiratory organs – corre-spondingly 1,4 fold greater; diseases ofdigestive organs – correspondingly 1,9and 1,2 fold greater; skin and subcuta-

neous cellular tissue diseases - corre-spondingly 19 and 1,3 fold greater.

It is important that problems con-cerned with health, nutrition, education,as well as to defence and developmentof children are more acute in the zonesof conflicts than in other regions ofGeorgia. The International Common-wealth had better expand its own role inthese zones for solving the problems ofdefence of children’s rights.

And indeed “Child has the right to bedefended since embryo”.

Let me come back to the following:Several important International Meet-

ings were held, such as: YokohamaWorld Congress held in 2001, which wasdirected against sexual exploitation ofchildren for commercial reasons and aspecial session of General Assembly ofUNO held in 2002 devoted to children.Obligations of governments and civilcommunities of different countries con-cerning defence of children’s rights werecorroborated at these meetings and meas-ures for their fulfillment were taken.

Let me finish the above said by thewords of Anders Johns (Secretary gen-eral, Interparliament Union) and CarolBelam (Executive director, ChildrenFund of UNO):

“In spite of the mentioned obligationsand promises, children still suffer fromviolence, cruel treatment and exploita-tion. It is clear that our efforts are as nec-essary today as fifteen years ago. Wewill be able to create a suitable world forchildren in case if each child is protect-ed from exploitation, violence, crueltreatment and ignorance.

Besides the above discussed problemof children’s state, in order to estimatesituation in the regions it is necessary tocharacterize groups of adults, women’shealth and aging, as well as groups ofhealthy persons.

While considering science and secu-rity, main determinants of health, par-ticularly social-economical, should benoted. Health and development of thecountry, poverty, psycho-social fac-tors, employment of population, educa-tion, general factors – these are the top-ics, which in cumulation creates one ofthe basic social-economic determinantof regions and separate states.

One of the main determinants ofhealth is also a way of life, which consistsof feeding, physical activity, smoking, al-coholism, drug addiction-toxemia.

With the support of UNICEF wehave fulfilled a project “Social-psycho-logical, medical-prophylactic and reha-bilitation measures of children andadults in Penitentiary Institutions”, oneof the main goals of which was the studyof drug addiction and toxemia problemsin above mentioned contingent.

Data of clinical-laboratory and instru-mental investigation in 417 children andadults have been analyzed. Questionnairefor Darvy and Bass aggression investiga-tion, Shind test, Loosher colour test wereused which permit to create a perfect “psy-chological portrait” of under age criminalswith recommendations having properpractical significance. In future the latterwill be a basis for creation of behavioralprophylactic model having a harmful in-fluence on the society and on themselves.

Results of investigations carried out wereanalyzed by means of modern computerprograms, involving psychological test-questionnaires and drawings in crayons.

Analysis of data obtained has shown that:1. In children and adults of such cat-

egory we deal with yet unformed per-son, subjected to definite changes.

2. While considering obtained resultsthe I, II and III necessary stages wereoutlined, where:

The I stage stipulates pretrial period.The II stage stipulates measures to be

taken during trial.The III stage – after being sentenced.Most children formally refuse the fact

of smoking, hashish and glue tasting, butit is not true. The majority of them be-fore the arrest used different toxic sub-stances (glue, petroleum), which needa great attention at the I-II-III stages.

Thus, investigations carried out haveshown that there is a necessity of takingprophylactic measures against toxemiaand drug addiction in children and adultsin order to avoid formation of groups ofpersons committing a criminal offence.

An important determinant of healthis physical environment, hygienic planof action at present must be a strategicdirection for all regions and countries.During last years quite new approachesand principles in health defence spherewere formulated in the documents andprograms of WHO, including Euro-pean Conferences on environment andhealth defence - Frankfurt (1989),Helsinki (1994) and London (1999).

According to these principles, sectorsof environment and health defence were

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imposed responsibility for elaborationand fulfillment of such mechanisms inhuman health and environment defencepolicy and spheres of its management,which in respect of ecology should pro-vide a stable development, effectiveprevention of harmful environmental fac-tors on human health and control on it.

Taking into account the fact, that theway and conditions of life, environmen-tal and genetic factors have a great ef-fect on human health, while share ofhealth defence is only 12-14%, a greatattention of WHO to the problems of en-vironmental and health defence be-comes more comprehensible.

Taking into account the fact that inevery state above mentioned principlesand initiatives must be recognized, thelaws “About environmental defence” and“About health defence” should determinecompetencies of corresponding min-istries in the sphere of provision ofsafe environment for human health.

At present considering current de-mands in many countries elaboration ofsanitary-hygienic norms and rules deter-mining safe environment has begun andmain standard documents have alreadybeen prepared, including norms of radi-ation safety, hygienic standards of electro-magnetic irradiation influence, hygienicstandards determining safety of drinkingand recreation water, atmospheric air, soiland food-stuffs, hygienic standards of pes-ticide content in environmental objects, hy-gienic requirements for labor conditionsand safety, etc. By fulfillment of de-mands of these documents it will be pos-sible to prevent an influence of harmfulfactors on health of country population.

At the same time, to create a safe en-vironment for human health appears tobe an important task for the economicsof all countries, especially for countrieswith transitional economics. To solve thisproblem is possible only by joint effortsof different ministries and organiza-tions, as well as by self-governmental in-stitutions and board of administration.

That’s why their goal must be theelaboration and fulfillment a nationalproject for environmental hygiene,study and estimation of problems exist-ing in the spheres of health-care and en-vironmental defence, as well as deter-mination of priority directions and ac-tions in order to solve them.

It should be considered a completeaspect of environment and health de-

fence taking into account: policy in thesphere of environment and health de-fence, management of environment im-provement, quality of water and air,quality and safety of food-stuffs, stableresidues and soil contamination, ioniz-ing and non-ionizing irradiation, natu-ral calamities, industrial accidents, etc.

While considering each of thesequestions one should take into accountsocial-economic, climate-geographi-cal, demographic and other factors of thecountry, particularly: estimation andanalysis of health risk connected withenvironmental harmful factors; determi-nation of priority problems to improveenvironmental defence; formulationand accomplishment of concrete meas-ures for prevention of harmful environ-mental factors affecting human healthand sanitary and epidemic situation.

All above-said follows from theconception of interconnections betweenhuman activities of different kinds, itsaction on biosphere, as well as environ-mental influence on human health.

Besides, there must be elaborated andaccomplished such a policy in thesphere of environmental and healthdefence, which, in regard to ecology,provides a stable development, effectiveprophylaxis of environmental factorshaving a harmful effect on humanhealth and its control, as well as creationof available safe environment based onprinciples of justice.

The following indices should bestudied which will elucidate:

a) effect of environmental factors onindices of human health state; b) revealterritories and regions, which are distin-guished by a high level of pollution andharmful influence on human health.

It is necessary to consider and esti-mate the following:

a) systems of management of envi-ronment hygiene;

b) resources for accomplishment ofpolicy of environmental and health de-fence

c) besides, concrete priority factorsof the environment, particularly:

water. Problems of improvement ofwater-supply of populated places as wellas questions of sanitary state and meas-ures for prevention from pollution of sea-side regions and other recreation objects.

air. Degree of atmospheric air pol-lution of populated places and sanitarydefence measurements.

stable debriss and soil contamina-tion. Questions of chemical safety anddefence of the environment (soil, air, wa-ter) of inhabited places from domesticagricultural and industrial toxic debris.

food-stuffs. Measures for reducing riskof influence on health; state conception ofsafe feeding of population is presented.

Ionizing and non-ionizing irradiation.Radiation background. Sources of ioniz-ing and non-ionizing irradiation existingin the country. Measures to be taken.

natural calamities and industrialaccidents. Topics of readiness for ex-pected natural calamities and industri-al accidents as well as readiness for pro-phylaxis and their liquidation.

Industrial and domestic environ-ment. Labor conditions of employedpopulation, prophylactic measures forprofessional diseases, traumatism andpoisoning; Creation of physical, socialand psychological environment desirablefor health in inhabited places.

towns and large populated places.Hygienic-ecological problems createdin big towns, ecopathology with preven-tive measures.

Temperature of the environment - Inthe XXI century a great attention shouldbe devoted to the problems of globalheating, resulting in natural calamitiesand spread of different diseases. There-fore, measures against expected epidem-ic should be taken.

Accomplishment of above said maybe possible only on the strength of co-operation and intersector cooperation ofrelevant ministries, departments, insti-tutions, self-governmental institutionsand boards of administration and non-governmental organizations with abroad participation of population. A spe-cial role must be played by self-govern-mental institutions and boards of admin-istration, which according to recommen-dations of WHO must elaborate and ac-complish plans for regions and towns,separate projects for improvement theenvironment and public health. In orderto realize concrete priority measures inmost countries (especially, in the post so-viet space) taking into account a com-plicated social-economic situation, it willbe necessary to search different sourcesfor financing, including assistance of in-ternational organizations, funds anddonor countries. As to our region, it isnecessary to have close contacts withSouth Caucasus and the Black Sea

8

Basin countries, first of all to solve suchproblems as water and health, contam-ination of the Black Sea, problems of theMtkvari river basin, etc.

Introduction of high technologiesin investigations, existence of precisemedical statistical database, creation ofmodern computer programs and their us-age(prognosis of disease course, estab-lishment of risk factors and groups, etc)– that is all on the basis of which it willbe possible to solve many problems ex-isting in the XXI century.

Proceeding from the above-said, de-velopment of sciences and monitoring onthem appear to be a main task, whichtakes into account creation of safe envi-

ronment for human health, improvementof life conditions. At the same time it isnecessary to carry out possible eco-pathological preventive measures, whichshould be considered as a principalstrategy of the XXI century.

Let me finish my report by the wordsof Catholicos-Patriarch of All Georgia,His holiness and Beatitude, Ilia II:

“Life of human-being is an examina-tion. It is suffering and we must endureit with dignity. Every human beingcreated by the God is an image (icon)of Him, but we must remember that hu-man being is always followed by a sin

committed by Adam and Eve. A humanbeing is helpless and he needs thegrace of holy spirit; he needs help ofchurch as it is the strongest ecclesiasti-cal force; church is the abode where ahuman being gets grace of holy spirit.That’s why our ancestors blessed eachother so “Rejoice on earth and in heav-en“. The only condition of this appearsto be closeness to the Lord, fulfillmentof His supreme will. We must hasten todo good, as nobody knows about thatwonderful and secret day when a manwill appear before the Lord, kindnessdone by us goes to the Lord”.

conflict of Interest: authors de-clare that they have no conflict of in-terest.

*corresPondInG autHor:Dr. fIaZ aHMad (Ph.D.)State Key Laboratory of Marine

Resource Utilization in South ChinaSea, College of Oceanology, HainanUniversity, Haikou, Hainan 570228,China

E-mail: [email protected]: +861 3227829157

Co-authors details: Email ID andcontact number

ZHou cHonGcHen (M.D.):E-mail: [email protected] Number: +86 13939000588

luo sHuYInG (M.Sc):E-mail: [email protected] Number: +86 13526559369

ZHou YIbo (M.Sc):E-mail: [email protected] Number: +86 13523710237

cHenG YIbInG (M.D.)E-mail: [email protected] Number: +86 15516181980

JIao fuYonG (M.D.):E-mail: [email protected] Number: +86 15398082028

lIu Yalun (ungraduated):E-mail: [email protected] Number: +86 17795820506

2021


”cHIldren’s rIGHts Must be defended sInce eMbrYo”

effectIVe treatMentand recoVerY of

sars-coV-2 Infected Infant/cHIldren

In a faMIlY clusteroutbreaK

sHort tItle: treatMent of sars-coV-2 InfectIon In faMIlY cluster outbreaK

ORIGINAL ARTICLES AND SCIENTIFIC ACTIVITIES IN PEDIATRICS

ZHou cHonGcHen (M.d.), luo sHuYInG (M.sc),Henan Provincial Children’s Hospital (Children'sHospital Affiliated to Zhengzhou University),Zhengzhou, Henan 450018, China

fIaZ aHMad (Ph.d.),State Key Laboratory of Marine Resource Utiliza-tion in South China Sea, College of Oceanology,Hainan University, Haikou, Hainan 570228, China

ZHou YIbo (M.sc), cHenG YIbInG (M.d.), Henan Provincial Children’s Hospital (Children'sHospital Affiliated to Zhengzhou University),Zhengzhou, Henan 450018, China

JIao fuYonG (M.d.)Children’s Hospital, Shaanxi Provincial People’sHospital, Xi’an, Shaanxi 710068, China


2021

10

IntroductIonThe data on epidemiological and

clinical characteristics in pediatric pa-tients are limited. The cluster infectionof COVID-19 in a family of five includ-ing 10-year children was reported fromWuhan in late January[1].

Compared to adults, the clinicalmanifestations and lung CT abnormal-ities of patchy opacities are more mod-est in children[2]. In China, as of 7 Feb-ruary 2020, this new form of COVID-19 pneumonia was reported in 285children, including 10 newborns[3, 4].

The new coronavirus (SARS-CoV-2) has caused huge losses to human lifeand the economy. The number of con-firmed COVID-19 cases and deaths hasbeen increasing in the many countriesof the world, but data on the epidemi-ological and clinical characteristics ofpediatric patients are limited. Chil-dren have become susceptible to SARS-CoV-2 infection due to immature im-mune function. As of 24: 00 on Febru-ary 7,2020,285 children with new-type coronavirus pneumonia were re-ported nationwide, including 10 new-

borns. Epidemiological investigationssuggest that the population is general-ly susceptible to the new coronavirus,and some children have a clear familygathering history [3, 4].

National Health Commission of thePeople's Republic of China, ‘Notice onIssuing a COVID-19 Infected Pneumo-nia Diagnosis and Treatment Plan (Tri-al Version 7)’on 3 March 2020, men-tions that children, infants, and neonatesare also susceptible to the new coron-avirus. They may present with atypicalsymptoms of malaise, shortness ofbreath, and the gastrointestinal manifes-tation of vomiting and diarrhea. Yet,most of the affected children presentedwith mild disease with low fever and fa-tigue without clinical features of pneu-monia[5].

In this paper, we aim to share our ex-perience of clinical course and manage-ment of COVID-19 in newborn and chil-dren treated at the specialized referralchildren hospital in Henan, China.

MetHodsSubject Retrospective case summaryFive children who were diagnosed

with SARS-CoV-2 new coronavirusinfection through nucleic acid testingand other treatment in Henan ProvincialChildren's Hospital (Children's Hospi-tal Affiliated to Zhengzhou University)from January to February 2020 were en-rolled as research subjects. Five patientsincluding 2 males and 3 females agingbetween 5 days to 8.6 years were treat-ed. Among them, one was asympto-matic, three were mild, and one was ofcritical illness. This study was ap-

abstractPurpose: this study aimed to diagnose coronavirus infection in children

based on clinical, laboratory, imaging features and its treatment. Methods:design: diagnosis and treatment. setting: Henan Provincial children’s Hos-pital, Henan Zhengzhou 450018, china. Subjects: five patients including 2males and 3 females aging between 5 days to 8.6 years. Intervention: all pa-tients underwent throat swabs and blood nucleic acid tests, chest radiogra-phy and computed thermography (ct) examinations. the patients were treat-ed with interferon nebulization, oral chinese medicine, ribavirin andlopinavir/ritonavir orally (1.5ml, 2 times / d×5d). Main outcome measure: weconsidered gender, age, and epidemiology and laboratory examinationdata. Results: Patient 1 showed reduction in hemoglobin and erythrocytes with22 time increased dose of d2-polymer compared with other four patients. theblood cell sedimentation rate in patient 1 was 40 while in others it was nor-mal. the c-reactive protein, calcitonin and influenza-a, b virus were nor-mal, while sars-coV-2 nucleic acid by throat swab and blood tests were pos-itive in all patients. three of the chest radiographs showed rough lung tex-ture, but ct case 1 showed small patchy shadows in multiple sites, cases 2and 3 showed patchy shadows of the right lung, and cases 4 and 5 were nor-mal. all five patients cured, discharged, and followed up were normal. con-clusions: other than critical case, the symptomatic treatment was given witha good prognosis. attention should be paid to avoid transmission among fam-ily members, and timely monitoring and evaluation of the pediatric statusof infected families for early detection and diagnosis.

Kevword: Children, Novel coronavirus, Infection, Diagnosis

Table 1

Clinical profile of Children with COVID-19 treated at Henan Children’s Hospital, China, during January to March 2020.

no.= case number, adm= admission date, family +ve= family members tested positive for coVId-19, expo to diag= exposure to diagnosis days,Vom/diarr= vomiting and diarrhea, fevr=fever persisting for days, stay=hospital stay in days, Y=yes, n=no.

*case 1. the parents lived in wuhan, Hubei and returned to Xinyang, Henan on 22 January 2020. same day in afternoon of returning, moth-er felt cold and lethargic but took it at exertion from travel. she had cesarean delivery on 31 January, G1P1, 38+5 weeks. she had positive nu-cleic acid test for coVId-19 on 1st february.

** were siblings

1*234**5**

MfMff

5d6M

7Y6M6Y7M8Y6M

2/230/119/22/22/2

criticalMildMild MildMild

53255

YYYYY

542089

3838.1

normal38.637.4

nnnnn

YYnnn

nnnnn

185n22

2916161515

no. Gender age adm. clinicalcategory

epidemiology

fami-ly +ve

wuhanrelated

exp. todiag. (d)

fever (0C) sneeze cough Vomiting/diarrhea

fever(d)

Main clinical Manifestations Hospital-ized (d)

proved by the Ethics Committee ofZhengzhou Children's Hospital and in-formed consent was obtained from thechildren's families.

MetHod1. Diagnostic criteria. (1) Both throat

swabs and blood nucleic acid testswere positive. (2) The diagnostic crite-ria were conducted following the firstedition of the Chinese Journal of Pedi-atrics "Children's 2019 New Coron-avirus Infection Diagnosis and Pre-vention Suggestions" on a trial basis.

2. According to the ICD-10 number,query and retrieve clinical data throughelectronic medical records.

The gender, age, epidemiology, lab-oratory examination, and imaging data(chest X-ray and CT) of the childrenwere collected and analyzed.

3. Clinical types according to the in-fection status of children and the clin-ical characteristics of a confirmed diag-nosis, they are divided into five types[5,6]: asymptomatic infection, mild,common, severe, critical.

Statistical methodsDescriptive analysis, measurement

data are expressed as M (range).

resultsGeneral InformationThere were five children from four

families, 3 girls and 2 boys, age mini-mum of 5 days (case 1) to a maximumof 8 years and six months (case 5). Case4 and 5 were siblings both female,Table 1. Epidemiological findings re-vealed cluster infection in families in-volving 20 members in total, includinggrandparents, parents, and sisters of theinfected child who presented to the hos-pital. Fever was seen in four children(except case 3), with a maximum of 38.6°C. None had runny nose, vomiting, ordiarrhea. The median hospital stay was16 days, highest of 29 days (case 1) andlowest 15 days (case 4 and 5), Table1.The minimum age is 5 days after birth.The parents lived in Wuhan until thechild was born. Department G1P1,born 38 +5 weeks after cesarean section,A's score, and other unknown. Beforeadmission, the parents of the child re-turned to Xinyang, Henan from Wuhanon January 22, and the mother of thechild felt cold and lethargic in the after-noon. A cesarean section was per-formed on January 31, and a new coro-

navirus infection was confirmed onFebruary 1 with a positive nucleic acidtest, indicating that the mother had a newcoronavirus infection during childbirth.

Although the new coronavirus infec-tion occurred only five days after birth,it suggested that it was not caused byvertical infection of mothers and infants.Because the mother was infected withthe new coronavirus before cesarean sec-tion.

Table 1.Clinical Manifestations and Labora-

tory TestsLaboratory data are shown in Table

2 & 3, WBC was highest 12.41×109/L(case 1) and lowest 4.79 (case 2). Thelymphocyte percentage was high incase 1 and 2, and low in the other threecases ranging from 24.7-31.9%.

Hemoglobin was lowest at 10.1g/Land red blood cells 3.07 ×1012/L in case1. Platelet was >440×109/L (in two cas-es: case 2 and 3). Alanine aminotrans-ferase(ALT), aspartate aminotrans-ferase(AST), lactate dehydro gena -se(LDH), and creatine kinase isoen-zymes(CK-MB) were normal or not re-quested in all five cases. The D-dimer(D-2 polymer) was high at 22.48 ug/Lin case 1 more than 50 times than oth-ers (lowest 0.2 in case 3).

Chest x-ray showed increased lungmarkings in case 1, 2, and 3. Chest CTshowed multiple small patches in bothlungs in case 1, Figure 1. In case 2 and3, patches were seen in the right lungson chest CT. The siblings, case 4 and 5had normal CT and chest x-ray findings,Table 4.

treatMentThe treatment, heart failure was

seen in the 5-day age neonate, case 1,requiring ICU care with mechanical ven-

tilation and immunoglobulin. Remain-ing 4 cases were mild and managed ina high dependency unit without ICU orventilation. Supportive care withnebulization containing interferon α-2bwas given to all five children. Oral Chi-nese medicine was used in all. Ribavirinwas used in four children. Case 1 and 2received lopinavir /ritonavir oral 1.5ml,2 times/d for 5d. Glucocorticoid and os-eltamivir were not used in any children,Table 5.

The outcome was the full recovery inall five children. Before discharge, alltested negative for the COVID-19 nu-cleic acid test, Table 6. The family wasadvised to continue to separate thechild and observe at home for twoweeks after the discharge. At two weeksregular follow all were doing well.

dIscussIonFamilial cluster infection 5 children

from four family epidemiology suggesta family cluster infection, of which 20family members were involved in the in-fection. Including grandparents, grand-ma, father, mother, and sister. Amongthem, the neonates were critically illonly 5 days after birth. Before birth, hisparents were in Wuhan. After the moth-er became infected with the new coro-navirus pneumonia, she had a fever andthen had a cesarean section. A positivecheckup confirmed the diagnosis.

Clinically, fever is the main manifes-tation. Four children (80%) had a feverranging from cough, asthma, vomiting,and diarrhea. This shows that fever is themost common manifestation of neona-tal coronavirus infection in children. It'salso a signal and a clue. It is the first per-formance that should be taken serious-ly. Italian studies report that fever is themost common manifestation of 83% -98%, while cough and shortness of

2021


Table 2Laboratory examination of 5 children COVID-19 treated at Henan Children's

Hospital, China, during January to March 2020

12345

wbc (×109/l)12.954.799.024.825.02

n (%)0.505%0.175%0.613%0.427%0.388%

l (%)0.4950.7720.3190.2470.271

rbc (×1012/l)3.075.055.234.524.60

HGb (g/l)101 g/l127 g/l148 g/l126 g/l135 g/l

Plt (×109/l)356451447283261

№ blood tests

no.= case number, wbc= white blood cells, n= lymphocytes, l= neutrophils rbc= red bloodcells, Plt= Platelets


2021

breath account for 31% - 55%. None ofthe 5 children had congenital, genetic,and metabolic diseases[ 6, 7, 8, 9].

According to its symptoms and clin-ical manifestations, it is divided into anasymptomatic infection, mild, com-mon, severe, and critical. Studies sug-gest that children with a new type ofcoronavirus infection have five clinicalcharacteristics. First, the number of in-fections is smaller than that of adults.Second, symptoms and clinical manifes-tations are lighter than those of adults.Third, there are fewer complicationsthan adults. Fourth, recovery is fasterthan that of adults, and fifth have a bet-ter prognosis. This may be related to lessexposure of children than adults, pedi-atric immune function is not yet fully de-veloped, pediatric infections are mildand inaccurate, and therefore, the diag-nosis cannot be found in time and is eas-ily missed.

Five cases had family members witha history of infection. Fever is the mainsymptom of most children. Except forExample 3, fever is low to moderate, witha maximum body temperature of 38.6.The clinical and immunological charac-teristics of children need attention, andfurther research and discussion are need-ed. One patient in this group had no clin-ical manifestations despite a nucleicacid test and a family member who was

diagnosed with a new coronavirus infec-tion. It should be noted that children withasymptomatic infection should be vigi-lant because those with no symptoms ormild symptoms are likely to become ahidden source of infection that should bepaid attention to. It has been reported thatmost of the early lymphocytes were re-duced in adults and lower in 4 cases.Leukocytes in children under 5 years ofage have two crosses. Lymphocytes arenormally higher than neutrophils. So ifthe lymphocytes decrease, it may be re-lated to viral infection.

Increased D-dimer is an indicator ofserious infection. The D-dimer in thisgroup of cases was as high as 22.248.It was 22 times higher than in other cas-es, but there was no significant differ-ence between C-reactive protein(CRP),procalcitonin(PCT) in mild and criticalillness. In adult patients, AST, ALT,LDH, isoenzymes, etc. increased, but nosignificant increase in children in thisgroup. A positive nucleic acid test is animportant basis for the diagnosis of newcrown infection. In this group of 5children, throat swabs, blood nucleicacid tests were positive twice, and nonegative children. The patient was dis-charged from the hospital with a nega-tive secondary test and continued to beseparated and observed at home for twoweeks after discharge [3, 7].

It has been reported that the nucleicacid test may be negative in the earlystage, so the chest radiograph and CT ofepidemiological history and symptomssuggest that children with new crownsshould be repeatedly tested for nucleicacid to avoid missed diagnosis. Nega-tive throat swabs but positive analswabs have been reported to indicate along period of exclusion of the virusfrom the intestinal tract. Chest radi-ographs of 3 patients in this groupshowed rough lung texture, but CTexamination showed patchy consolida-tion shadows in multiple parts of bothlungs and right lung.

It shows that chest CT is earlier andmore diagnostic value than chest radi-ograph. Given the low sensitivity ofnucleic acid detection, to preventmissed diagnosis, epidemiologicaland clinical manifestations should becombined, and combined diagnosis ofnucleic acid examination and chest CTshould be used to reduce missed diag-nosis [8].

In terms of treatment. Because chil-dren with neo-crown infections are lessill and have a better prognosis, they aremainly family-gathered. For ordinary,asymptomatic, mild cases, a specialmedication is not emphasized. Exceptfor case 1 who was treated in the ICUin the group, the remaining 4 cases wereclosely observed after hospitalization,and they were cured after being support-ed by symptomatic treatment. No spe-cial changes were observed after twoweeks of follow-up. Example 1, the pa-tient recovered and was dischargedfrom the hospital despite the onset ofdisease on 5 days after birth and treat-ment with mechanical ventilation. Theapplication of antiviral drugs such as rib-avirin in children with new crown infec-

12

Table 3

Laboratory examination of 5 children COVID-19 treated at Henan Children's Hospital, China, during January to March 2020.

no.= case number, crP= c-reactive Protein, Pct= Procalcitonin, esr= erythrocyte sedimentation rate, alt= alanine aminotransferase, ast= as-partate aminotransferase, ldH= lactate dehydrogenase, cK-Mb: creatine kinase- myocardial band, d-2= d-dimer (d-2 polymer), na= not applicable.

№

12345

crP(mg/l)<0.50.5

<0.5nana

Pct(ng/dl)0.0920.11

0.039nana

esr(mm/h)

401112nana

flu virusa/bna

--

nana

alt(u/l)46.721.848.4nana

ast(u/l)37.855.332.8nana

ldH(u/l)nana

261.3nana

cK Mb(u/l)48.3na14.7nana

d-2polymer

22.480.40.2nana

chest radiograph

rough lung texturerough lung texturerough lung texture

normalnormal

chest ct

Multiple small patchesMultiple small patches

Patchy shadow of right lungnormalnormal

Table 4

Imaging (chest X-ray, chest CT) of 5 children with COVID-19 treated at HenanChildren's Hospital, China, during January to March 2020

№1234*5*

sexMfMff

age5d6m

7y6m6y7m8y6m

chest x-ray increased lung markingYYY

normalnormal

chest ct multiple small patches Y both lungsY right lungY right lung

normalnormal

no.= case number, M= male, f= female, Y= yes, * were sibling

tion suggests that further studies on ef-ficacy, safety, and toxic side effects areneeded. Patients 1 and 2 orally took lo -pi navir/ritonavir orally (1.5ml, 2 times/ -d×5d)antiviral treatment. None of the 5patients received oseltamivir phosphate[4, 6, 8, 10, 11].

Except for neonates in this group, theremaining four cases were not treatedwith antibiotics, and emphasis wasplaced on avoiding blind or incorrect useof antibacterial drugs. Reasonable selec-tion of antibiotics should be based onbacterial infection and bacterial cultureand drug sensitivity tests. For critical-ly ill patients, a short course of smalldoses of gamma ball and glucocorticoidcan be given. The application of tradi-tional Chinese medicine should betreated with individualized syndromesaccording to the age, physique, and con-dition of the child. It is recommendedto take traditional Chinese medicine in-stead of injecting traditional Chinesemedicine preparations.

α-2b interferon nebulization, as amedication for respiratory diseases, iscurrently widely used, but the clinicalefficacy of novel coronavirus infectionis still lacking theoretical and clinical ev-idence of rigorous scientific researchsuch as randomized double-blind place-bo control. Therefore, further clinicalrigorous scientific research is needed toprovide scientific theoretical and exper-imental evidence for clinical applica-tions. Moreover, atomization may in-crease the risk of aerosol infection,which deserves further discussion anddiscussion.

conclusIonConclusions: Other than critical case,

the symptomatic treatment was givenwith a good prognosis. Attention shouldbe paid to avoid transmission amongfamily members, and timely monitoring

and evaluation of the pediatric status ofinfected families for early detection anddiagnosis.

acKnowleGMentDeclaration of Interest:NoneFunding:None

references1. Weblink Wuhan Municipal Health

Committee. Wuhan Municipal HealthCommittee on current pneumonia in ourcity Situation report of the epidemic[EB/OL]. (2019- 12- 31) [2020-02-01]. http: //wjw.wuhan.gov.cn/ front/ -web/ showDetail/ 2019123108989.

2. Weblink World Health Organiza-tion. Home care for patients with sus-pected novel coronavirus (nCoV) infec-tion presenting with mild symptoms andmanagement of contacts [EB/OL](2020-01-20) [2020-02-03].https://www.who.int/ publications�detail/.

3. Weblink National Health Commit-tee of the People's Republic of China.As of 20: 00 on February 10, the latestsituation of epidemic situation of newcoronavirus pneumonia [EB/OL].(2020-02-11) [2020-02-11]. http://www.gov.cn/xinwen/2020- 02/11/con-tent_5477103.htm.

4. Weblink National Health Commis-sion of the People's Republic of China.Notice on prevention and control ofpneumonia in children and pregnantwomen with new coronavirus infection[EB/OL]. (2020-02-02) [2020-02-02].http: //www.nhc.gov.cn /fys/s7902/ 202 -002/de2d62a5711c41ef9b2c4b6f4d1f2136.shtml.

5. Weblink National Health Com-mission of the People's Republic ofChina. Notice on Issuing a COVID-19Infected Pneumonia Diagnosis andTreatment Plan (Trial Version 5)

[EB/OL] (2020-02-05) [2020-02-05].http: //www.nhc. gov. cn /yzygj/s7653p/ -2 0 2 0 0 2 / 3 b 0 9 b 8 9 4 a c 9 b 4 2 0 4 a -79db5b8912d4440.shtml.

6. Standard journal article Cai JH,Wang XS, Ge YL, Xia AM, Chang HL,Tian H, et al. [First case of 2019 novelcoronavirus infection in children inShanghai]. Zhonghua er ke za zhi = Chi-nese journal of pediatrics. 2020; 58:E002.

7. Standard journal article Cao B,Wang Y, Wen D, Liu W, Wang J, Fan G,et al. A Trial of Lopinavir–Ritonavir inAdults Hospitalized with Severe Covid-19. New England Journal of Medicine.2020; 382: 1787-99.

8. Standard journal article ChughtaiAA, Seale H, Islam MS, Owais M, Mac-intyre CR. Policies on the use of respi-ratory protection for hospital healthworkers to protect from coronavirus dis-ease (COVID-19). Int J Nurs Stud.2020; 105: 103567-67.

9. Standard journal article Bordi L,Nicastri E, Scorzolini L, Di Caro A,Capobianchi MR, Castilletti C, et al. Dif-ferential diagnosis of illness in patientsunder investigation for the novel coro-navirus (SARS-CoV-2), Italy, February2020. Eurosurveillance. 2020; 25:2000170.

10. Standard journal article Chan JF-W, Yuan S, Kok K-H, To KK-W, Chu H,Yang J, et al. A familial cluster of pne -u monia associated with the 2019 nov-el coronavirus indicating person-to-person transmission: a study of a fam-ily cluster. The Lancet. 2020; 395: 514-23.

11. Standard journal article Chen Z-M, Fu J-F, Shu Q, Chen Y-H, Hua C-Z,Li F-B, et al. Diagnosis and treatmentrecommendations for pediatric respira-tory infection caused by the 2019 nov-el coronavirus. World journal of pedi-atrics. 2020: 1-7.

2021


Table 5

Treatment of 5 children with COVID-19 treated at Henan Children's Hospital, China, during January to March 2020

no.= case number, Icu= intensive care unit, Y=yes, n=no

№

12345

Heartfailure

nnnnn

Icu

Ynnnn

Mechanicalventilation

Ynnnn

supportiveoxygen therapy

Ynnnn

nebulized inhaledinterferon alpha-2b

YYYYY

rib-avirin

YnYYY

lopinavir/ ritonavir

YYnnn

oselta -mivir

nnnnn

cefop-erazone

Ynnnn

Gluco-corticoid

nnnnn

Immunoglob-ulin (IVIG)

YYnnn

chinese her -bal medicine

YYYYY


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14

OVERVIEWMongolia is located between Russia

to the north and China to the south,where it neighbors the Inner MongoliaAutonomous Region. Total populationin Mongolia is about 3.3 million andnearly half of the people live in the cap-ital, Ulaanbaatar, and in other provincialcenters. About two-thirds of the totalpopulation is under age 30,36% ofwhom are under 141.

It is imperative for Mongolia totake COVID-19 seriously because ofits vulnerability. The rate of infectionof COVID-19 pose a great threat toMongolia medically, economically,and socially. The first case of COVID-19 in Mongolia confirmed on March10, was a French company employeewho traveled into Mongolia fromRussia.

As of May 18, 2020, there have beenno confirmed cases of communitytransmission and there are 1623 peo-ple in quarantine2; however, the num-bers are expected to grow as Mongo-lians are expected to return home fromabroad.

SITUATION OF COVID-19

TOTAL CASES: 140 (March, 10-May, 18)

RECOVERED: 24DEATH: 0IMPORTED CASES: 140NO LOCAL CASES REPORTED.

Majority of cases (about 80%) areuniversity students who returnedfrom overseas. They are oftenhealthy and with no other comorbidi-ties. 5 children (aged 8-16) and 2pregnant women are confirmed forCOVID-19.

About 28% of cases are mild or withno symptoms, 50% are moderate, and21% of cases are severe2.

Government strategies for combat-ing COVID-19:

Closed all schools and kinder-gartens starting from January 25. Theclosures were originally intended to lasta month but were later extended to May31. All classes are now conducted viaTV and the internet.

All public events including confer-ences, sports, and festivals have beencanceled across the country, while all ed-

ucational institutes are to remain closeduntil 31 May.

All sport clubs, night clubs,karaoke are closed and only restaurants,stores close at 22: 00 pm.

Stores and public places don’tserve if a person didn’t wear amask.

The government closed the borderwith China and all air traffic wasstopped. All passengers who arrived toMongolia on special chartered flightsfrom other countries were screenedand stay into a 21-day quarantine.

Canceled the national holidayTsagaan Sar, the Mongolian lunar newyear.

Readiness for COVID-19 transmis-sion, all stages of hospitals preparing formedicine, medical staffs and other sup-plies.

For health emergency preparedness,organized 2 days of simulation exercise.

REFERENCE1. National statistical office of Mon-

golia, 2020.2. Daily news of Mongolian health

ministry. May 18, 2020.

SUMMARYAs a developing country, the government takes various actions to combat

COVID-19 successfully. All imported cases are under control. But becauseof the expectation of more people returning from overseas, it’s still a greatthreat to our population. And the economic situation is getting worse becauseof all kinds of lockdown.

TUNGALAG OSGONBAATARMongolian National University of Medical Sciences

Email: [email protected]

CORONAVIRUS DISEASE (COVID-19)SITUATION IN MONGOLIA

CONFIRMED CASES60

50

40

30

20

10

010.03 17.03 24.03 31.03 7.04 14.04 21.04 28.04 5.05 12.05

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1. oVerVIew:In December 2019, an outbreak of new

coronavirus pneumonia (COVID-19)broke out in Wuhan, Hubei Province, Chi-na, and quickly spread to all parts of thecountry. The "Diagnosis and TreatmentPlan for New Coronavirus Infected Pneu-monia (Trial Version 4)" issued by the Na-tional Health Commission For the firsttime, children were included in the sus-ceptible population, and it was mentionedthat the symptoms of children's cases wererelatively mild. Chinese Journal of Pedi-atrics also published "Diagnosis andPrevention of Children's 2019 New Typeof Filling Virus Infection/Pneumonia(Trial First Edition)". With the increasein the number of infection cases, reportsof children's illnesses have gradually in-creased, and the prevention and controlsituation for children groups is still grim.It has been reported that 10% of COVID-19 patients are accompanied by Kawasa-ki disease and even the formation of coro-nary aneurysms.

Since April this year, there havebeen cases of multi-system inflamma-

tory syndrome (also known as "MIS-C")similar to Kawasaki disease in childrenin the United Kingdom, Italy, the Unit-ed States, and South Korea.

Italy’s Bergamo is a severely affect-ed area with severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2) epidemic. In the past month, there hasbeen a concentrated outbreak ofKawasaki disease in this area. Recent-ly, researchers have evaluated SARS-CoV- 2 The incidence and characteris-tics of Kawasaki-like diseases during theepidemic. Studies suggest that during theepidemic of New Coronary Pneumonia,the incidence of Kawasaki disease inBergamo, Italy increased by 30 times,and that during the epidemic, the chil-dren were older, had a higher rate of car-diac involvement and were characterizedby macrophage activation syndrome.

2. tHe dIscoVerY and deVeloPMent of KawasaKI dIseaseKawasaki Tosaku (Tomisaku Kawa -

saki) reported KD in Japan for the first

time in 1967 through descriptive statis-tics on the clinical manifestations of 50children, but the etiology and pathogen-esis of KD are still unclear. Accordingto reports, children of almost all ethnic-ities have KD, and it has increased yearby year in recent years. In the long run,undiagnosed and untreated KD in child-hood may affect health care delivery sys-tems in developing countries [1]. Coro-nary artery injury is the most seriouscomplication of KD. The incidence ofcoronary artery injury in children withuntreated or untreated KD is as high as20% to 25% [2]. In developed countries,KD has replaced rheumatic fever as themain cause of acquired heart disease inchildren. This study retrospectively an-alyzed the clinical data of childrenwith KD combined with coronaryaneurysms and summarized their clin-ical features to improve clinicians' un-derstanding of KD in coronaryaneurysms.

3. brIef IntroductIon of KawasaKI dIsease1) concept and clinical performanceKawasaki disease (KD), also known

as mucosal skin lymph node syndrome,is an acute febrile rash disease charac-terized by systemic vasculitis, whichmainly occurs in children under 5years of age. The diagnostic criteriamainly include fever lasting more than5 days, and have 4 or more of the fol-lowing 5 main clinical manifestations:1. Abnormal lips or oral mucosa, includ-ing lip congestion and chapped, diffusemucosa of the oral mucosa, protrudingtongue, hyperemia Strawberry tongue".2. Bilateral conjunctival hyperemiaoccurs within 3-4 days after the onset

suMMarYIn december 2019, a new coronavirus (2019-ncoV) infection outbreak

in wuhan, Hubei Province, china has spread to all parts of the country.epidemiology shows that the population is generally susceptible to the virus,and patients with basic diseases are severe, High-risk groups of criticallyill patients, and the number of children and adolescent infection cases is in-creasing. children with Kawasaki disease have poor basic conditions. af-ter 2019-ncoV infection, they will bring serious challenges to the diagno-sis and treatment of these children. combining the clinical characteristicsof children with 2019-ncoV infection and the diagnosis and treatment ofchildren with Kawasaki disease, the clinical management recommendationsfor children with Kawasaki disease 2019-ncoV infection are presented herefor clinical reference.

Keyword: Kawasaki disease; new coronavirus pneumonia; children

clInIcal ManaGeMentof cHIldren wItHKawasaKI dIsease

durInG tHe sItuatIon of PreVentIon and

control of coVId-19

fuYonG JIao, sHenG ZHanG, JI Ma, JInG nI, JuYan wanG, XIaoHonG lI, ZHIlonG Mu, weI Han, GaItao He, leI Ma,fuYonG JIao

(Correspond Author E-mai: [email protected])


2021

of the disease. The purulent dischargeis dissipated after heat remission. 3. Cer-vical lymph nodes are swollen, whichcan be unilateral or bilateral, greaterthan 1.5cm, hard and tender, but the sur-face is not red and there is no suppura-tion. It appears at the beginning of thedisease and dissipates when the feversubsides. 4. Abnormal limbs, acuteedema and palmar-plantar erythema inthe hands and feet during the acutephase, membranous peeling occurs atthe junction of the finger, toe, andskin at the recovery stage, and there isa transverse groove in the finger andtoenails. In severe cases, the finger andtoenails can also fall off. 5. Abnormalskin. Polymorphic skin spots and scar-let fever-like rashes often appear in thefirst week, and redness and peeling ofthe perianal skin may also occur [16]

2) review of Kawasaki disease:Kawasaki disease generally occurs

in all seasons. It is necessary to masterand learn the relevant professionalknowledge about the disease, and maketimely preventive and nursing measuresto reduce the troubles and injuriescaused by the disease to children. So,should Kawasaki disease be reviewedforever? Kawasaki disease is a manifes-tation of vasculitis, the most commonacute multi-system inflammatory dis-ease affecting infants and young chil-dren. The disease may be characterizedby high fever, red rash on the mouth andthroat, inflammation of the mucousmembranes, and swelling of the lymphnodes (lymph nodes). In addition, indi-viduals with Kawasaki disease may de-velop arteries that carry blood to the af-fected coronary arteries, heart muscle(myocarditis), the inflammatory wall ofthe heart muscle (coronary arteritis), andassociated widening or bulging(aneurysm) Inflammation [12], and/orother symptoms and findings.

3) Kawasaki disease review schedule:Review of no coronary artery diseaseChildren with normal coronary arter-

ies in the acute phase of Kawasaki dis-ease undergo a comprehensive exami-nation (including physical examina-tion, electrocardiogram, and echocardio-graphy, etc.) at 1, 3, 6 months, and 1 to2 years after discharge.

In the first three months of Kawasa-ki disease, you need to review whetherthe erythrocyte sedimentation rate, C-reactive protein, and myocardial en-

zymes are normal. At the same time, youneed to check the head and other heman-giomas for physical examination.

Review of coronary aneurysm le-sions

Coronary aneurysms occur in 15% to25% of children with Kawasaki diseasewho have not been effectively treated.Long-term follow-up should be followedclosely, once every 6 to 12 months,monthly review, and coronary angiog-raphy if necessary.

Coronary aneurysm disappears spon-taneously more than 2 years after the dis-ease, but often has abnormalities suchas thickening of the wall and weaken-ing of the elasticity.

Large aneurysms are often not easyto completely disappear, often causingthrombosis or stenosis.

4) after recovery from Kawasakidisease

After the recovery of Kawasaki dis-ease, the heart problems must be re-viewed regularly within two to sevenmonths [5]. It is necessary to check theelectrocardiogram and electrocardio-gram. This is necessary because manyKawasaki diseases are caused by incom-plete treatment. Late complications [14].

In particular, cardiovascular compli-cations: coronary artery dilation, severeaneurysm prolongation for severalyears. After recovery, it is normal threetimes in a row, and it is checked againin 3 to 5 years to check whether thereare sequelae.

4. brIef IntroductIon of new coronaVIrusAt the end of 2019, since the emer-

gence of a new coronavirus (SARS-CoV-2, previously known as 2019-nCoV) in-fection in China, the development of theepidemic has attracted worldwide atten-tion. The World Health Organization(WHO) has paid close attention to it, andmany expert meetings have finally con-cluded that the epidemic is an "emer-gency public health event of internation-al concern." Since the epidemic situationwas determined, the whole country hasmade prevention and control of the epi-demic situation and protection of the peo-ple's lives the top priority of the entireparty and the country. China has takenserious and responsible positive meas-ures, even at all costs, to strictly preventand control, and to control the spread ofthe epidemic to the smallest extent.

The latest World Health Organizationepidemic report focuses its technologyon the zoonotic component of the newcoronavirus. There is increasing evidencethat the 2019 new coronavirus is asso-ciated with other known coronavirusescirculating in bats, proving that it is as-sociated with the bat subspecies Phinolo-phus bat. The International Committeeon Taxonomy of Viruses (ICTV) statedthat the new coronavirus was named"SARS-CoV-2" (Severe Acute Respira-tory Syndrome Coronavirus 2). Thezoonotic transmission of SARS-CoV andSARS-CoV-2 and the clinical manifes-tations of human infection with SARS-CoV-2 have yet to be confirmed, high-lighting the need to study the entire virusgroup. [3].

1) epidemiological characteristicsof new coronary pneumonia:

Source of infection: The source of in-fection seen so far is mainly patients in-fected with new coronavirus. Invisibleinfections and asymptomatic infectionsmay also become the source of infection.

Transmission route: droplets andcontact transmission through the respi-ratory tract are the main transmissionroutes. In many places, new coronavirus-es have been detected in the stool of di-agnosed patients, and there is a risk offecal-oral transmission. Aerosol trans-mission refers to the nucleus composedof the protein and pathogens left by thewater droplets lost in the air suspensionprocess, forming the nucleus of theaerosol, which can float to a distancethrough the form of an aerosol, causinglong-distance transmission. There iscurrently no evidence that the newcoronavirus is transmitted by aerosol.Mother-to-infant transmission has re-ported that the mother is a patient diag-nosed with new coronavirus pneumonia,and the throat swab virus nucleic acidis positive in the newborn 30 hours af-ter birth, suggesting that the new coro-navirus may cause neonatal Gan Ruo-nan through mother-to-child transmis-sion. Of course, more are needed. Sci-entific research confirmed. The trans-mission routes such as the digestive tracthave yet to be clarified. [11]

Susceptible crowd: The crowd isgenerally susceptible. The elderly andthose with underlying diseases such asasthma, diabetes, and heart diseasemay be at increased risk of contractingthe virus.

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5. ProtectIon, dIaGnosIsand treatMent of cHIldren wItH Kd durInG tHe ePIdeMIc:1) Protective measures for children Hand hygiene should be done

first, the key is to wash hands frequent-ly and wash hands correctly. Older chil-dren and adolescents can wash theirhands independently, but under parentalsupervision; young children need towash their hands with parental assis-tance. Parents should wash their handsfirst, and after helping children washtheir hands, they should clean theirhands again. Avoid touching your eyesand nose with dirty hands. Wash yourhands before eating, after defecation,after contact with secretions, beforewearing a mask, and after taking off amask. Wash your hands according to theseven-step hand washing method. Final-ly, dry your hands with a disposable drytissue, and then use it to turn off thefaucet. (2) Wear the mask correctly [14].Children's masks are children's N95masks, children's surgical masks, chil-dren's medical masks, disposable chil-dren's masks and cotton masks in orderof protection level. Children over theage of 1 need to wear a mask when go-ing out. It is recommended to wear aN95 mask or a disposable surgicalmask for children in high-risk areas.Disposable masks can be worn in non-high-risk areas. The mask should com-pletely cover the mouth and nose, andshould not be exposed to the nasal cav-ity. Do not touch the outside of the maskwhile wearing the mask or when remov-ing the mask to avoid infection. Parentsshould pay attention to children's breath-ing when wearing masks to avoid suf-focation. Parents also need to wearmasks correctly and wear masks them-selves before wearing masks for chil-dren [9]. (3) Pay attention to personalhygiene. Take frequent showers, man-icures, change clothes frequently, andkeep them clean and tidy. Children andadolescents should be informed in de-tail to avoid direct contact with humansecretions, especially oral or respirato-ry secretions, urine and feces. Educatechildren and adolescents not to coverthem directly with their hands whensneezing or coughing. Instead, usecorrect arm bends to cover them. Try tocover the nose and mouth with paper

towels or towels. Pay attention to foodhygiene, ensure adequate sleep, keepwarm and prevent cold. (4) Avoidgathering activities and minimize therisk of exposure to the source of infec-tion. When you have to go out, youshould wear a mask, try not to take pub-lic transportation, and go out to mini-mize the exposure of the elevator. [7]

2) Protection guidance for familymembers

Minimize outing activities, do notvisit patients with suspected or con-firmed COVID-19; if you must go out,you need to wear a mask; and wash yourhands first after going out home. Personswho go out to contact with COVID-19suspected or diagnosed patients must bestrictly isolated for at least 14 days,while avoiding contact with children. Itis recommended that families try not toaccept visitors. Children and all fami-ly members should observe fever,cough, chest tightness, shortness ofbreath, vomiting, diarrhea, fatigue andother symptoms; if the above symptomsshould be treated in time, and should notbe observed at home. Maintain regularventilation and cleanliness of homewindows. Surfaces of objects with highfrequency contact, such as elevatorbuttons, door handles, light switches, TVremote controls, mobile phones, etc.,should be cleaned and disinfected if nec-essary. [8]

3) Protection and monitoring ofchildren with suspected or confirmedcoVId-19 cases of Kd

The similarity between KD and chil-dren's COVID-19 poses new challengesto the diagnosis and treatment of chil-dren with KD during the epidemic.Since the outbreak of new coronaviruspneumonia (COVID-19) in Wuhan inmid-December 2019, we have diag-nosed and treated 156 children with KD,including 95 boys and 61 girls, mainlychildren from 1 month to 17 years old,Of which more are 1-year-old chil-dren, less are 8-year-old, 10-year-old and17-year-old children;

During COVID-19, we jointly inves-tigated the diagnosis and treatment ofchildren with KD in six centers, includ-ing Zhengzhou, Xi'an, Baoji, Hebei, Xi-anyang, Shenzhen, and Yulin. Accord-ing to the following standards [4]:

Expansion: diameter ≥2.5SD;Small aneurysm: localized dilation

shows an inner diameter ≤4 mm (5-year-

old children: the inner diameter of onesegment is 1.5 times the adjacentsegment) Z score ≥2.5 to <5;

Moderate aneurysm: aneurysm innerdiameter >4 mm and <8 mm (children≥5 years: the inner diameter of the seg-ment is 1.5 to 4 times that of theadjacent segment) z score ≥5t<10;

Giant aneurysm: an aneurysm withan inner diameter of 8 mm (children ≥5years old: the inner diameter of one seg-ment is more than 4 times the adjacentsegment) z score ≥10.

In this special case, children withfever need to undergo layer-by-layerscreening to exclude COVID-19. The di-agnosis and treatment of children withfever in China is divided into three steps:

(1) Sub-inspection: All children needto be sub-inspected by professionalnurses. After the sub-inspection, they aredivided into 2 major categories. Thosewithout fever can go to ordinary outpa-tient clinics; those with fever should goto hot clinics;

(2) Children's fever clinic: . First,the nucleic acid test needs to beimproved to exclude COVID-19; .Children with cough symptoms need toimprove chest CT examination if nec-essary;

(3) Re-examination patients: Be-cause children with KD need to regular-ly review cardiac ultrasound, but thehospital takes preventive and controlmeasures during the epidemic, so thesepatients who need to be re-examinedshould adopt:

. Online appointment;. Treat in the nearest local hospital;. Video remote consultation;. Online outpatient appointments;. Inpatient diagnosis and treat-

ment in non-scheduled hospitals [13];According to the above-mentioned

triage methods, KD patients who werenewly diagnosed and re-diagnosed werepromptly diagnosed and treated, and thecure rate was greatly improved, andthere was no delay in the treatment ofKD patients due to the epidemic. There-fore, during the epidemic, we shouldalso formulate a reasonable plan for thetreatment of non-COVID-19 children,so as not to delay the optimal treatmenttime [13].

4) continued medication duringKawasaki disease:

Kawasaki disease (KD) is vasculitisin children associated with severe coro-

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nary artery disease. It is the most com-mon cause of pediatric acquired heartdisease in developed countries, andmany rapidly industrializing developingcountries have reported this situationmore and more. The incidence variesgreatly between countries and is thehighest in Northeast Asia. In Japan, near-ly 100 children under five years of agesuffer from the disease, while sub-Sa-haran Africa has the lowest incidence.The cause of KD is still uncertain.Suppose there is an interaction be-tween genetic susceptibility and sever-al environmental and immune factors.Several susceptibility genes have beenidentified to be associated with the de-velopment of KD and increased risk ofcoronary artery disease. Gene-gene as-sociation and changes in DNA methy-lation have also been found to play a keyrole in the pathogenesis and prognosisof KD.

During the epidemic, the first diag-nosis of Kawasaki disease should be in-travenously infused with large doses ofgamma globulin (IVIG), 2g/(kg•time),oral aspirin 50~80mg/(kg•d), dipyri-damole 3~5mg/(kg • D); Vitamin D800u/time, once/day; after the conditionis stable, can be discharged from hometo continue oral medication, 3 days af-ter fever or the disappearance of acutesymptoms, aspirin reduction, 3 ~5mg/(kg•d), Lasts from February toMarch [6, 16].

6. SUMMARYAt this particular moment of the

outbreak, the management of differentpopulations, especially the proper man-agement of basic diseases, will signif-icantly affect the outcome and progno-sis of the disease. KD is a common ba-sic disease of children and adolescents.This disease is mucosal skin lymph nodesyndrome. It is necessary to grasp theprinciples of its comprehensive preven-tion and control and individual treat-ment, to block the deterioration of thedisease as early as possible, and to avoidthe occurrence of severe COVID-19. Toachieve a better prognosis. Up to now,the disease caused by 2019-nCoV infec-tion is still in the stage of continuousrecognition. Therefore, this managementrecommendation will be continuouslyimproved based on the deepening of themedical workers' knowledge of thedisease.

REFERENCES:1. Singh S, Sharma A, Jiao FY.

Kawasaki Disease: Issues in Diagnosisand Treatment--A Developing CountryPerspective. Indian J Pediatr. 2016;83(2): 140-5.

2. Burns JC, Glode MP. Kawasakisyndrome. Lancet. 2004; 364(9433):533-44.

3. Liu Changxiao, Yi Xiulin, WangYuli, Yan Fengying; understanding thenew coronavirus (SARS-CoV-2) anddiscussing the strategy for the develop-ment of antiviral drugs; 2020, 43(03),361-371 DOI: 10.7501/j.issn.1674-6376.2020.03.001

4. Cooperative Group of Respirato-ry Intgection, the Subspecialty Group ofRespiratory, the Society of Pediatrics,Chinese Medical Association; The Ed-itorial Board of Chinese Journal ofPractical Pediatriatrics.Association onthe collection, transfer and detection ofmicrobiological testing soecimen inchildren with respiratory infection(fo-cusing on virus) [J] .Chin J Pract pEDI-ATR, 2019, 34 (8) : 657-660.DOI: 10. -19538/j .ek2019090601.

5. Alessandra Marchesi, IsabellaTarissi de Jacobis, Donato Rigante, et al,Kawasaki disease: guidelines of the Ital-ian Society of Pediatrics, part I - defi-nition, epidemiology, etiopathogene-sis, clinical expression and managementof the acute phase, Italian Journal of Pe-diatrics2018; 44: 102.

6. Sheng Tongtong. Application val-ue of echocardiography in coronary ar-tery damage of Kawasaki disease[J].World's Latest Medical InformationAbstracts, 2019, 19(62): 25-26.

7. Li Xiaoling, Feng Ziwei, Gao Yan.20 cases of Kawasaki disease [J]. Prac-tical Journal of Pediatrics, 2003, 18(2):107-107-107, 146. DOI: 10.3969/j.issn. -1003-515X.2003.02.040

8. Zhang Lei, Cao Qing, Wang Ying,et al. Questions and answers and expertadvice for rapid screening and preven-tion of new coronavirus pneumonia inchildren [J/OL]. Chinese Journal ofPractical Pediatrics, 2020, 35 (2020-02-21).http: //rs.yiigle.com/yufabiao/11825 -98. htm. DOI: 10.3760/cma.j.issn.2095-428X.2020.02.005.

9.Recommendations for preventionand management of new coronavirusdisease in children with neuromusculardisease during outbreak [J/OL]. ChineseJournal of Practical Pediatrics, 2020, 35

(2020-02-25).http: //rs.yiigle.com/yu-fabiao /1182681.htm. DOI: 10.3760/ -cma. j.issn.2095-428X.2020.02.008.

10. ZhouW. A handbook of 2019-nCoV pneumonia control and preven-tion[M]. Wuhan: Hubei Science andTechnology Press, 2020

11. "New Coronary Pneumonia Di-agnosis and Treatment Program" (Tri-al Version 7) http: //www.cohf.cn -/acs/670.

12. Zhao Chunna, Du Zhongdong,Gao Lingling. Analysis of risk factorsfor coronary artery disease in childrenwith Kawasaki disease[J]. ChineseJournal of Practical Pediatrics, 2016,31(9): 659-661. DOI: 10.3760 /cma. -j.issn.2095- 428X.2016.09.005

13. Zhang Guocheng, Cheng Xi-aoning, Ding Hui, et al. ManagementGuidelines for Strengthening Children’sFever Examination Process during NewCoronavirus Pneumonia Outbreak (FirstEdition) [J/OL]. Chinese Journal ofPractical Pediatrics, 2020, 35 (2020-02-20).http: //rs.yiigle.com/yufabiao/118 -2322. htm. DOI: 10.3760/cma.j.i ssn. -2095-428X.2020.02.004.[Pre-publishedonline].

14. Zhang Xiaolin, Du Zhongdong,Jin Lanzhong, et al. Follow-up andclinical retrospective analysis of 35 pa-tients with Kawasaki disease complicat-ed with coronary artery thrombo sis[J].Chinese Journal of Practical Pediatrics,2017, 32(21): 1653-1656. DOI: 10.3760/cma.j.issn.2095-428X.2017. 21.013

15. Practical Preventive Medicine2020 Issue 04 ISSN: 1006-3110.

16. Rheumatism, Endocarditis andKawasaki Disease Committee, Ameri-can College of Cardiology and Ameri-can Academy of Pediatrics Guidelinesfor the diagnosis, treatment and long-term follow-up of Journal of AppliedClinical Pediatrics. 2012, Issue 13.ISSN: 1003-515X.

17. Does COVID-19 Uses ACE-2-Receptors of the Epidermis As Entryinto the Body? Research in Pediatrics &Neonatology, RPN.000590. 4(3).2020.

18. Bittmann S: Covid-19-The Roleof Children and Search for EffectiveTreatment Options with Promising viewto Angiotensin II Inhibitors AmericanJournal of Biomedical Science and Re-search 2020 - 8(4). (MS.ID.001273.DOI: 10.34297/AJBSR.2020.08. 001273).

19. Stefan Bittmann, ElisabethLuchter, Elena Moschüring-Alieva,

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Gloria Villalon, Anne Weissenstein:COVID 19: Camostat and The Role ofSerine Protease Entry Inhibitor TM-PRSS2 Journal of Regenerative Biolo-gy and Medicine, 2020; 2(2): 1-2.

20. Fuyong Jiao, Stefan Bittmann:A new classifification of clinical fifind-ings and treatment options of SARS-CoV-2 infection in children from Chi-na Advances of Pediatric Research2020, 7: 37. dot: 10.35248/2385-4529.20.7.37

21. Stefan Bittmann, Elisabeth Lu -chter, Gloria Villalon, Elena Moschüri -ng-Alieva, Anne Weissenstein Clin-iBittmann S:

22. COVID-19 in Adults and Chil-dren: The Clock is Ticking. Journal ofRegenerative Biology and Medicine,2020; 2(2): 1-2. l Landmarks of COVID-19 in Newborn, Children and TeenagersJournal of Pediatric Health and Nutrition.

23. Bittmann S*, Luchter E and Vil-lalon G: COVID-19: The Importance ofMouth Mask and Good Virostatic MouthHygiene to Prevent Infection PaediatrNeonatal Med 2(1): 112, 2020

24. Stefan Bittmann*, ElisabethLuchter, Anne Weissenstein, GloriaVillalon SARS-CoV-2-Infection in Chil-dren and Newborn: Less Severe Than inAdults?

25. American Journal of BiomedicalScience and Research 2020 - 8(3).(MS.ID.001269. DOI: 10.34297/AJB-SR.2020.08.001269).

26. Stefan Bittmann, Anne Weis-senstein, Gloria Villalon, Elena Moschü -ring-Alieva, Lara Bittmann, ElisabethLuchter: Treatment Options in COVID-19: The Role of Bioavailable AntiviralRibonucleoside Analogon NHC in vit-ro Journal of Regenerative Biologyand Medicine, 2020; 2(2): 1-2.024

27. Stefan Bittmann, Elisabeth Luchter,Gloria Villalon: COVID-19-fatality Analy-sis 3 Months after Outbreak in ChildrenClinical Surgery Journals, Vol 4 Iss 2.

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1. INTRODUCTIONMedical disasters prediction, manage-

ment and control are one of the mainparts medical planning and preparation.The term “disaster medicine” first ap-peared in the medical lexicon in the post- World War II era [1]. The term “dis-aster medicine” would continue to ap-pear sporadically in both the medical andpopular press until the 1980s when thefirst concerted effort to organize a med-ical response corps for disasters becomes

the part of the National Disaster Med-ical System.

Viruses are assembled in the infect-ed host cells of human, animals, orplants. Because of viral breeding the,host cell dies. There are especiallyviruses which are breeding in the cell ofthe bacteria. Viruses spread in many dif-ferent ways. Just as many viruses arevery specific as to which host species ortissue they attack, each species of virusrelies on a particular propagation way.

The interdisciplinary collaboration(Biomedicine and Biophysics, PhysicalResearch, Information Technologiesand Systems) is an engine of strength-en the abilities of researchers in devel-opment of new biophysical and biomed-ical methods and tools. Those workswhich are based on novel achieve-ments in optical spectrometry, laserand molecular physics as well as infor-mation technologies and systems arecritically important for study of commonproperties of nano-scale virus-like par-ticles, and elaboration of basic conceptsand new revolutionary method for es-timation unique vibration/oscillationproperties, determine the unique “finger-prints” of pathogenic micro-organisms,especially viruses.

Farther development of new methodsof pathogens treatment is greatly facil-itated by an improved understanding ofthe pathophysiology of epidemic dis-eases. There is therefore a need to ad-

ABSTRACTDiseases caused by viral infections are one of the biggest problems for glob-

al health, and as methods involved in diagnostics are getting faster and moreefficient, methods of their therapy are still need to be stronger. This retro-spective study aimed to explore nano biospectroscopy research and technol-ogy in the field of virology in order to provide a theoretical and computer mod-eling and experimental support for the techniques used, and to suggest theapplying tools that have not been used previously.

Keywords: virology, spectroscopy, computer modeling, radiation resonancetherapy

STUDIES OF VIBRATIONALPROPERTIES

OF PATHOGENICNANOBIOSYSTEMS BY

SPECTROSCOPIC METHODS

OF INVESTIGATIONP. KERVALISHVILI, T. BERBERASHVILI, T. BZHALAVA, L. CHAKHVASHVILI, A. KEKELIDZEGeorgian Technical University


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dress the current knowledge gaps in dis-ease aetiology in order to support inno-vation in evidence-based therapy. In thiscontext, a better understanding of themechanisms that are common to sever-al diseases, in particular of those lead-ing to co-morbidities, constitutes an im-portant challenge. The special attentionmust be focused on the integration ofpre-clinical and clinical studies for theidentification of mechanisms commonto several diseases. Performing activi-ties should assess and validate the rel-evance of these common mechanismsand of their biomarkers (where relevant)on the development of disease-specif-ic pathophysiology, as well as their rolein the development of co-morbidities inboth males and females. The expectedimpact should provide: A better under-standing of disease pathways and / ormechanisms common to a number ofdiseases; new directions for clinical re-search for better disease prevention,health promotion, therapy develop-ment, and the management of co-mor-bidities. In this direction the multidis-ciplinary development of ability to de-tect rapidly, directly and selectivelyindividual virus particles has the poten-tial to significantly impact healthcare,since it could enable diagnosis at the ear-liest stages of replication within ahost‟s system. Simultaneous acquisitionof the vibrational and electronic finger-prints of molecular systems of biolog-ical interest, at the interface between liq-uid media, or at the air/solid, air/liquidinterfaces is difficult to achieve withconventional linear optical spectroscopydue to their rather poor sensitivity to thelow number of molecules or their mal-adjustment to water environment (in-frared absorption). It relies on inelasticscattering of monochromatic light, usu-

ally from a laser in the visible, near in-frared, or near ultraviolet range. Thelaser light interacts with molecular vi-brations, phonons or other excitations inthe system, resulting in the energy of thelaser photons being shifted up or down.The shift in energy gives informationabout the vibrational modes in the sys-tem. Infrared spectroscopy yields sim-ilar, but complementary, information.Spontaneous scattering is typically veryweak, and as a result the main difficul-ty of this kind of spectroscopy is sepa-rating the weak non-elastically scatteredlight from the intense Rayleigh scatteredlaser light.

Current paper presents some informa-tion about studies carried out in the lastdecade using spectroscopic methods asa research tool in the field of virology.Spectroscopic analyses are sensitiveto variations in the biochemical compo-sition of the sample, are non-destructive,fast and require the least sample prepa-ration, making spectroscopic techniquestools of great interest in biologicalstudies. Herein important chemometricalgorithms that have been used in viro-logical studies are also evidenced as agood alternative for analyzing the spec-tra, discrimination and classification ofsamples. Techniques that have not yetbeen used in the field of virology arealso suggested. This methodologyemerges as a new and promising fieldof research, and may be used in the nearfuture as diagnosis tools for detectingdiseases caused by viruses.

2. THEORETICAL AND EXPERIMENTAL STUDIESWith the advancement of technolo-

gy and consequently advanced spec-troscopy, the interest of researchers inspectroscopic techniques in biologicalstudies has grown. This field of scienceis known as biospectroscopy, and meansthe use of spectroscopy to analyze bi-ological objects. Several studies havebeen conducted involving identificationof bacteria [3,4], viruses [5,6],cancer di-agnosis [7], and even in the field offorensic entomotoxicology [8], demon-strating that spectroscopic techniques arecapable of detecting biochemicalchanges in biological matrices.

Viruses are submicroscopic infectiousagents and obligate intracellular para-sites. They are totally dependent on a

host cell because they are not able togenerate energy to conduct all biolog-ical processes (fig.1). Virus particles(virions) come in a variety of sizes andshapes.

However, approximately sphericalshapes with diameters in the range be-tween 50nm and 100nm are especiallycommon. Many nearly spherical virus-es are revealed by X-ray crystallographyto have icosahedral symmetry. A typi-cal virus particle contains genetic ma-terial, RNA or DNA, surrounded by aprotein coat (capsid). Such an objectshould have reasonably distinct vibra-tional frequencies, the study of whichmay be of interest. Excitation of thesevibrations could have applications in ei-ther the diagnosis or treatment of viraldiseases. The sole discussion of these vi-brational modes conjectured that ultra-sound in the GHz range could be reso-nantly absorbed by HIV virus particles,leading to their destruction [9]. The twomethods most commonly used in clin-ical diagnoses of viruses are enzyme-linked immunosorbent assay, with thebest known being the ELISA methodand real-time polymerase chain reaction(PCR). These methods have broughtbenefits such as high levels of repeata-bility and reproducibility, ease in han-dling and robustness [10]. However,they have also some negative points. Asexample, both methodsrequires highquality reagents; in some situationsthey are not suitable for identifying spe-cific viral species/strains and they arealso destructive to the samples. Thus,there is a need for techniques that are asadvantageous as ELISA and PCR tech-niques, and which have fewer disadvan-tages.

The potential of spectroscopic tech-niques in the detection and identifica-tion of virus-infected cells has been stud-ied using statistical methods as a sensi-tive, rapid and reliable methodology. Theability to discriminate between contam-inated and non-contaminated objects ina short time with high sensitivity whichcharacterized biospectroscopy deter-mine its high prospect for studyingviruses and similar pathogens [11,12].

An expected difficulty in the use ofbiospectroscopy in virology is related tothe fact that humans have a great diver-sity of virus circulating in their organ-ism, and each human has a unique mi-crobiome. Because of it, obtaining a fin-

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Fig. 1 Corona virus. https://www. goo gle. -com /url?sa=i&url= https%3A%2F% 2Fthe -co nversation.com%2F4-unusual-things-weve-learned-about-the-coronavirus-since-the-start-of-the-pandemic

gerprint would be more difficult inview of the specificity of each organism.The solution to this problem seems tobe the use of a broad and well-traineddatabase, and changes obtained by mul-tivariate statistical analysis, differenti-ating these alterations [13,14].

The main spectroscopic techniquesthat have been used in virological stud-ies are nuclear magnetic resonancespectroscopy (NMR) [15], Raman spec-troscopy [16], infrared spectroscopy(IR) [17] and molecular fluorescencespectroscopy [18]. These techniques areknown to provide rapid responses andreliable data, as well as having power-ful structural elucidation capability.

Such advantages highlight the pos-sibility of identifying and classifying dif-ferent types of virus using spectro-scopic techniques. In this paper, studiesusing biospectroscopy coupled to statis-tical methods of classification in viro-logical investigations are emphasized.First, we will discuss the most common-ly used spectroscopic techniques, andthen we will discuss the computation-al processes used to extract useful infor-mation from the obtained spectra (spec-tral preprocessing, multivariate classi-fication algorithms, performance eval-uation).

3. conVersatIonIn order to understand the possible

pathway of biospectroscopy develop-ment it is necessary to use the new sci-ence and technology tool calls bionan-otechnology. The main objective ofthis modern discipline is cellular uptakeof nanosize molecules functioning with-in the cell. If the size of molecules is big-ger than 10nm are taken by the celltrough a clathrin-assisted mode of en-docytosis called pinocytosis, while par-ticles of size greater than 200 nm in di-ameter are usually phagocytosed by themacrophages.

In comparison with cellular mole-cules (nano-ensembles) the size ofviruses varies from 20 to 300 nanome-ters. Practically all viruses by the sizesare smaller, than bacteria. Viruses aremasterpieces of nanoengineering witha basic common architecture that con-sists of the capsid – a protein shell madeup of repeating protein subunits- whichpacks within it the viral genome. Nano-sized biological agents and pathogenssuch as viruses are known to be respon-

sible for a wide variety of diseases suchas flu, AIDS and herpes, and havebeen used as bioreagents [19,20]. For to-day there are experimentally certifieddata that Viral nanoparticles are emptiedvirus cells that can carry drugs direct-ly to cancer cells to kill them [21]. Sci-entists have engineered viral nanopar-ticles from plant viruses, insect viruses,and animal viruses [22]. Viral nanopar-ticles could revolutionize cancer treat-ment, acting not only as a safer, morespecific form of cancer treatment, butalso as a new imaging tool. The nanopar-ticles could create a type of drug deliv-ery that is extremely tumor specific withgreatly reduced side effects. The viralnanoparticles would be more soluble andhave higher drug efficacy than currenttreatments [23,24].

Oscillations are generated by bio-chemical oscillators that incorporate theperiodic variation in a parameter overtime to generate an oscillatory output.Spatial oscillators incorporate the peri-odic variation in the localization of aprotein to define subcellular positionssuch as the site of cell division and thelocalization of DNA. There are somedata which are focuses on the mecha-nisms of oscillators and the designprinciples of temporal and spatial oscil-latory systems [25].

Current optical detection methodswhich are well developed for single mi-crometer size particles, cannot be ap-plied to nanoparticles due to a strong sig-nal dependence on particle size. Typi-cally, such sensors consist of a lightsource which illuminates a sample vol-ume of an aerosol or a liquid flow con-taining the particles of interest. An off-axis detector measures power of scat-tered light. The latter is a function of par-ticle properties such as size, concentra-tion, and optical density. In the tens ofnanometers size regime particles act asdipoles, therefore the power of scatteredlight is proportional to the sixth powerof particles size. Lowering the detectionsize limits for the existing detectorsplaces an impossible requirement onnoise optimization. Therefore, a signalwhich has weaker particle size depend-ence can allow access to smaller parti-cles [26]. There are several virus quan-tification techniques available to virol-ogists, such as the quantitative PCR(polymerase chain reaction) method[27], the plaque titer method [28] and the

image enhanced microscopy (IEM)technique [29]. However, a problemcommon to most of these techniques isthat the analysis of a sample involvesseveral tedious steps, which can takeseveral hours to multi plays to complete.The fast detection and characterizationof nanoparticles, such as viruses orenvironmental pollutants, are importantin fields ranging from biosensing toquality control. However, most existingtechniques have practical throughputlimitations, which significantly limittheir applicability to low concentrationanalysis.

A wide range of potential applicationscan be foreseen, including real-timeanalysis of clinically relevant virussamples and contamination control ofprocessing fluids used in the semicon-ductor industry [30].For nanoparticlestructures identification a rather inter-esting method is Vibrational Spec-troscopy (VS), which provides the mostdefinitive means of identifying the sur-face species generated upon molecularadsorption and the species generated bysurface [31, 32].

The experimental results are com-pared with theoretical calculations basedon an elastic continuum model and ap-propriate Raman selection rules de-rived from a bond Polaris ability mod-el. The observed Raman mode is shownto belong to one of the Raman-active ax-ial modes of the M13 phage protein coat.It is expected that the detection and char-acterization of this low-frequency vibra-tional mode can be used for applicationsin biomedical nanotechnology such asfor monitoring the process of virusfunctionalization and self-assembly.Recently, a technique which departs rad-ically from conventional approaches hasbeen proposed. This novel technique uti-lizes biological objects such as virusesas nano-templates for the fabrication ofnanostructure elements. Low wavenumber (<or= 20 cm-1) acoustic vibra-tions of the M13 phage have beenstudied using Raman spectroscopy [33].

The experimental results are com-pared with theoretical calculations basedon an elastic continuum model and ap-propriate Raman selection rules de-rived from a bond polarizability mod-el. Aside from serving as a protectivelayer, capsids are involved with variousother aspects of their respective virus lifecycles including timely viral genome en-

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capsulation (self-4assembly and genomepackaging), cell-to-cell virus transport,entry into host-cell (e.g., via cell recep-tor binding), genome release into hostcell, etc.

The utility of the class system is notentirely lost, however; specific angle pat-terns within the capsid ensures the ex-istence of distinct hexamer shapes (eachshape is colored distinctly in. Evidenceindicates that capsid formation is nucle-ated, often starting with a single

capsomer species (e.g., pentamers;for the purposes of this paper, a cap-somer is a generally symmetric clusterof either five or six subunits), which thenproceeds to completion by the additionof small subunit clusters (or singlesubunits). In T~1 capsid, where subunitsare in identical/equivalent environ-ments, nucleated assembly will be pos-sible with no additional machinery.However, the formation of two or morecapsomers from a single interaction sitewill require the employment of addition-al machinery to ensure high yields of thenative state. For example, quasi-equiv-alent switches are required for the prop-er assembly of capsids containing twodistinct capsomers: a pentamer andone type of hexamer. The addition of asecond hexamer shape necessitates therequirement of a second mechanismsuch as auxiliary proteins for proper as-sembly. For spherical virus capsids re-quiring more distinct hexamer shapes.Additional mechanisms to stabilizethose new shapes at exactly the right po-sitions within the forming capsid arelikely to be also needed dominantlyform.

Because capsids from different class-es display markedly different geome-tries, they are bound to display differ-ent physical properties. The periodic na-ture of capsid hexamer contents also use-ful in understanding „„T-switching‟‟: aprocess that permits canonical capsidsubunits to more easily sample capsidscontaining similar hexamer shapes.This allows for a segue to understand-ing currently intractable and deadlypleomorphic viruses like Ebola andarenaviruses. For example, from theabove T-switching rule, the available di-versity of an arena virus may only be ex-plained if we assume that the biologi-cally relevant form of the arenavirus isthe T~12 capsid. Non-icosahedral cap-sids. Although the framework presented

doesn‟t appear to readily explain non-icosahedral capsids (some are just„slightly‟ non-icosahedral, such as thenatively prolate phi29 capsids, whileothers are wildly different in form,such as Ebola with its natively filamen-tous shape), those capsids, like theiricosahedral counterparts, also displaycapsomer sub-structures.

In light of this, the geometric con-straints analogous to endo angles that af-fect capsomer shape may be useful inobtaining insights into non-icosahe-dral capsid morphology, behavior, andclassification. It will be exciting to seewhether incorporating the non-icosahe-dral capsids into an expanded capsid pe-riodic table will be possible. All canon-ical capsids (made up of trapezoidal sub-units) may be built from a single typeof pentamer and a repertoire of distincthexamer shapes (colored distinctly onlyonce in each capsid. The hexamer shapeis described by the number of endo an-gles it displays.

Yet, the ability to detect rapidly, di-rectly, and selectively individual virusparticles has the potential to significant-ly impact healthcare, since it could en-able diagnosis at the earliest stages ofreplication within a host‟s system. Onepromising approach for the direct elec-trical detection of biological macromol-ecules uses semi-conducting nano-wiresor carbon nano-tubes configured asfield-effect transistors, which changeconductance upon binding of chargedmacro-molecules to receptors linked tothe device surfaces. One of the simplestmedical nanomaterials is a surface per-forated with holes, or nanopores. Thesepores are large enough to allow smallmolecules to pass but are small enoughto impede the passage of much largervirus particles. The next step was cylin-drical gold nano-tubules with inside di-ameters as small as 1.6 nm. Whentubules were positively charged, posi-tive ions were excluded and only neg-ative ions were transported throughthe membrane. With a negative voltage,only positive ions could pass. The com-bining voltage gating with pore size,shape, and charge constraints allowsachieving precise control of ion trans-port with significant molecularspecificity. Lieber‟s group has report-ed direct, real-time electrical detectionof single virus particles with high selec-tivity using nano-wire field- effect tran-

sistors to measure discrete conduc-tance changes characteristic of bindingand unbinding on nano-wire arraysmodified with viral anti-bodies [34].

The integrity of such devices allowsincreasing the number of the detectionviruses. The analysis of the manifold lit-erature shows, that task of the detectionpathogenic micro-organisms is timely.Therefore, our available method wouldbe one brick in the solution of theproblems like that. Simultaneous acqui-sition of the vibrational and electronicfingerprints of molecular systems of bi-ological interest, at the interface betweenliquid media, or at the air/solid, air/liq-uid interfaces in conditions similar tothose encountered in nature or in mod-el environments requires the use of sen-sitive and specific spectroscopic probes.One of the promising solutions of thisproblem is the use of the nonlinear Two-Color Sum-Frequency Generation Spec-troscopy (2C-SFG) that meets the de-sired spectroscopic requirements.

The goal of this approach is to probemembrane models of various formsand in various environments: (i) lipidmonolayers and bilayers; (ii) depositedon substrates, floating on water asLangmuir layers and at a liquid-liquidinterface; (iii) alone and in interactionwith molecules, including peptides andproteins; (iv) submitted to controlledstress(chemical, pH, electrochemicalpotential).The increasing amount ofavailable data of protein three-dimen-sional atomic structures, determinedmostly by X-ray crystallography (relat-ed to the fast expansion of that fieldaround third generation synchrotronstorage rings) and NMR, has givenmuch information about role of manyproteins in biological processes. How-ever, it has been pointed out that know-ing the structure does not directly leadto the knowledge of the function, andthat the protein alone, without its envi-ronment or its partners of interaction, isnot totally informative. Additionally,some proteins cannot be satisfactorilycrystallized and thus cannot be ac-cessed by X-ray crystallographic meth-ods. Among them, membrane proteinsneed their membrane partners to fullyplay their role and are often not able tocrystallize. In situ studies, and their ac-cording investigation techniques, aretherefore favored for such objects. In thefollowing, in situ should not be under-

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stood as in vivo, but imply rather that theobjects are designed and studied in anenvironment mimicking what they ex-perience in vivo.

Specific in situ techniques allow di-rect investigation of key functional be-haviors of synthetic membrane models(lipid mono and bilayers in an aqueousenvironment interacting either with se-lected proteins, ions or organic molecules)[35-36]. The strong absorption of the wa-ter vapor and the poor detection proper-ties of conventional FTIR spectroscopyled to the discarding of this technique forthe study of such interfacial systems. Thisevidence for the limited range of infraredspectroscopic tools dedicated to thestudy of such fragile objects in their spe-cific environment was written only aboutten years ago. From that time, there hasbeen a lot of progress from the spectro-scopic point of view.

In addition to IR absorption spec-troscopy (conventional or attenuated to-tal reflection (ATR) configuration),three other IR-based spectroscopieshave been able to address the issue ofa molecular layer on water with a sig-nal-to-noise ratio sufficient to extract sci-entific information from experimentaldata. Raman spectroscopy is often usedon biological environment, although thelow count rate on monolayers requireslong acquisition times. It has been re-cently reported the detection of virus-es by acoustic oscillations [37,38].

However, the process of “ruptureevent scanning”, which was report, in-volves the separation of a virus particlefrom antibodies by ultrasound. This isdistinct from the excitation of the vibra-tional modes of the virus particle itself,and occurs at much lower frequencies.There have also been some experi-mental studies of ultrasonic absorptionby empty viral capsids [39, 40]. Theseexperiments reveal an enhanced absorp-tion in the MHz range as proteins re-assemble into a capsid, but do not finda resonant peak in this frequency range.At the same time, it was emphasized thatthese and other results show that viralcapsids are flexible and change size orshape in response to vibrations or tochanges in temperature or pH [41].

One the most promising methods ofbiospectroscopy is SFG. These ultrashortpulsed lasers based optical measurementmethod is unique for investigation of vi-brational modes of different viruses

and other pathogenic microorganisms aswell as study of nature of their oscilla-tion processes and parameters of oscil-lation. Non-linear optics and its reso-nance technologies is possible directionof organization of treatment of patho-genic microorganisms in their differentliving media. Contrary to the previousones, this second order nonlinear processis intrinsically specific to an interface,and involves no contribution from mol-ecules in a centrosymmetric bulk, i.e.,in solution or in gas phase. It has beenextensively applied to solid interfaces invacuum, controlled atmosphere andelectrochemical conditions.

For a few years, technological devel-opment of picosecond and femtosecondtunable laser sources have led both to anincrease of the number of SFG experi-mental setups around the world and toa progressive application to fragile orburied interfaces. In addition to uniqueSFG setup is research based on usage ofthe CLIO Free Electron laser [42,43].This latter allows probing specific vibra-tions located in the near and far infrared,which is again unique

to date. Although molecular fluores-cence spectroscopy has been little usedin studies in the field of virology, it isalso an interesting approach with greatpotential in this perspective. This tech-nique analyzes the fluorescence ca-pacity of a sample [44], where a beamof high energy light (usually in the ul-traviolet region) is irradiated on the sam-ple to be excited into a higher electron-ic energy level; then the fluorophoremolecule will rapidly lose energy to thisenvironment through non-radiative

modes (called internal conversion) andwill return to the lowest vibrational lev-el of the lowest electronic excited state.The molecule persists at this vibroniclevel for a period of time known as thefluorescence lifetime, and then returnsto the fundamental electronic state byemitting a photon with energy lowerthan the irradiated one [45].

The excitation and emission spectrumare recorded by the instrument and isgenerally used to build excitation-emis-sion (EEM) fluorescence matrices.An-other commonly-employed form of flu-orescence technique is fluorescencecorrelation spectroscopy (FCS), whichis used for temporal and spatial analy-sis of molecular interactions of biomol-ecules present in solution at extremelylow concentrations. This technique isbased on the principle that a fluo-rophore molecule has a specific free dif-fusion rate that is directly related to itssize. This basic principle, for example,can be used to study protein interactions.As with other spectroscopic techniques,molecular fluorescence spectroscopyprovides rapid results with high sensi-tivity and specificity, and is non-destruc-tive, making this technique a tool of in-terest in the field of virology.

Spectroscopically interrogating bio-logical samples analyze definitely needsto use computational tools which facil-itate the information collection and ex-traction. For this, it is necessary to ad-dress the different computational meth-ods and tools and among them there areemployed the methods:

Preprocessing and multivariateanalysis techniques, which consists the

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Fig.2. Visual effect of different pre-processing on a set spectrum. Source: Bak-er M.J., Trevisan J., Bassan P., et all. Using Fourier transform IR spectroscopyto analyze biological materials. Nat. Protoc. 2014; 9:1771–1791.

raw atr-ftIr spectra

normalization to the amide I Peak normalization to the amide II Peak Vector normalization Vector normalization

1.800 1.600 1.400 1.200 1.000

1.800 1.600 1.400 1.200 1.000

1.800 1.600 1.400 1.200 1.000 1.800 1.600 1.400 1.200 1.000 1.800 1.600 1.400 1.200 1.000 1.800 1.600 1.400 1.200 1.000

1.800 1.600 1.400 1.200 1.000 1.800 1.600 1.400 1.200 1.000

wavenumber (cm-1)

second differentationrubber band baseline correction first differentation


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correction and improvement of the sig-nal-to-noise ratio of the spectrum, com-monly employed before data analysis.[fig.2].

Spectral cut and Baseline correc-tion, which include determination of ex-act region of interest and diminish of thewavenumbers which are not absorbedand light scattering occurs due to the non- homogenous particle size [46].

Spectral normalization techniquesare used when it is necessary to removespectral changes responsible for thethickness or concentration of the sam-ple, making the normalized spectra be-come comparable to each other. [47].

Multivariate analysis techniquesare employed to analyze multivariatedata, meaning data having two or morevariables per object. Examples are first-order data (such as IR, Raman spectrum)and second-order data (such as fluores-cence).

Principal component analysis(PCA)is an unsupervised multivariateanalysis technique widely used in bio-logical studies. This technique is usedto reduce the dimensionality of thesample's data and generate a new visu-alization.

Cluster analysis (CA) techniquesare unsupervised methods of pattern

recognition that aim to group thespectra into groups when there is noinformation about the classes. [48].

Partial least squares (PLS) is a mul-tivariate calibration technique that findsfactors (latent variables, LVs) in thespectra set that explain the maximumvariance in the reference variables set,using the simultaneous decompositionof the two.

Linear discriminant analysis (LDA)is a supervised technique widely usedfor class discrimination..

Successive projections algorithm(SPA) is a progressive variable selectiontechnique. This means that it startswith a variable (wavelength orwavenumber, for example) and addsnew variables in each interaction untilan optimal number is selected.

The genetic algorithm is a techniquethat mimics Darwin's theory of evolution,where evolution occurs by natural selec-tion in which the more adapted organ-isms have a greater chance of survival.In the case of GA, the variable selectionprocess begins with a randomly formedpopulation of variables [49].

Sensitivity (SENS) can be definedas the confidence that a positive resultfor a sample of the labeled class is ob-tained [50].

Diagnostic virology continues toevolve rapidly. Viral testing is now es-sential for the care of a number of pa-tient groups, including hospitalizedpatients with acute respiratory infec-tions; transplant recipients and other im-munocompromised patients; patients in-fected with human immunodeficiencyvirus (HIV), hepatitis C virus (HCV),and hepatitis B virus (HBV); and infantswith possible congenital infection.Multiple test methods continue to beused, but molecular tests are emergingas the dominant technology. A varietyof commercial molecular assays havebeen or are in the process of being ap-proved or cleared as in vitro diagnos-tic tests by the Food and Drug Admin-istration (FDA) [51].

During the last years in response ofglobal spraying the new structuraltypes of corona viruses the method ofestimation unique vibration/oscilla-tion properties, determine the unique“fingerprints” of pathogenic micro-or-ganisms, especially viruses. The maintask of the works done by internation-al group including Georgian, French,German British and Greek researcher-swas elaboration of optical resonancespectrometry method of detection andtreatment of pathogenic nanobiostruc-

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Fig. 3. Viral Capsids and their forms

Viral capsid

cell-spcificaptamer

up to 180 molecules installed inside cell targeting

delivery vehicle

au/PeG

1

(a)

(c)

(e)

(b)

(d)

+

(f)

2

-Mg2- pH 4.5

n

cP

removal ofnucleic acid

nanomaterial-encapsulatedViral capsid

orencapsulation

templatesynthesis

tures including corona type viruses[52-53].

Viruses and their genomes are most-ly enclosed and protected by sphericalcapsids - symmetric coats or shellscomposed primarily of multiple copiesof protein subunits (Fig.3). Aside fromserving as a protective layer, capsids areinvolved with various other aspects oftheir respective virus life cycles includ-ing timely viral genome encapsulation(self - assembly and genome packaging),cell-to-cell virus transport, entry intohost-cell (e.g., via cell receptor binding),genome release into host cell, etc. De-spite their central importance to the lifecycle, the various evolutionary pressuresacting on spherical capsids are not wellknown. Half a century of empirical datahas uncovered a large array of capsidssizes that range from tens to manythousands in subunit composition.Spherical capsids of all observed sizesmay be obtained from a grouping oftwelve pentamers (symmetric clusters offive subunits) separated by a variablenumber of hexamers (clusters of six sub-units). For spherical virus capsids requir-ing more distincthexamer shapes. Ad-ditional mechanisms to stabilize thosenew shapes at exactly the right positionswithin the forming capsid are likely tobe also needed dominantly form.

Because capsids from different class-es display markedly different geome-tries, they are bound to display differ-ent physical properties. The periodic na-ture of capsid hexamer contents also use-ful in understanding „T-switching‟: aprocess that permits canonical capsidsubunits to more easily sample capsidscontaining similar hexamer shapes.This allows for a segue to understand-ing currently intractable and deadlypleomorphic viruses like Ebola andarenaviruses. All canonical capsids(made up of trapezoidal subunits) maybe built from a single type of pentamerand a repertoire of distinct hexamershapes (colored distinctly only once ineach capsid. The hexamer shape is de-scribed by the number of endo angles itdisplays. It is necessary to underline thateffect of destroy of enveloped viruses isbased on the highly symmetric structure(e.g. icosahedral and others) of manyviruses, which leads to a well-definedresonant frequency which may bespecifically absorbed by these structuresand may subsequently lead to their ir-

reversible damage. Modeling and Sim-ulation of oscillation effects in differentviruses including corona like ones isbased on studies of biostructure’s phys-ical characteristics, scattering and ab-sorption properties. Estimation of elec-tromagnetic (EM) spectrum and reso-nance wave length ranges is importantfor characterization of nano-micro-scaled particles and determination ofbiostructures unique spectral signa-tures, essential in bio-agents detectingand identification systems, and becom-ing as a great challenge in real systemsinvestigations. Method of estimation ofspectral response on EM field & parti-cle interaction is based on solutions ofelectrodynamics two (2D) or three (3D)dimensional boundary tasks. Analyticalexpressions of EM fields are derivedfrom rigorous solutions of Maxwell’sand Helmholtz’s equations and definedthrough the dimensionless parameters,diameters over an excitation wave-length. It makes possible to apply theclassical well-known approach to sub-micro particles characterization. One ofthe ways for estimation of resonance fre-quencies range is the method determin-ing the eigenvalues and correspondingeigenvectors obtained by algebraic sys-tem of functional equations which couldbe written based on the solution of elec-trodynamic task considering EM wave-VL particle scattering [54]. Algebraicsystem has more complicated formwhen VL particle is of core-shellbiostructure with different electric pa-rameters. Resonant wavelength range ispredicted theoretically in the vicinity ofvalues corresponding the maximums ofintensity of particular scattered partialwaves. Estimation of resonant wave-length range based on determination offar-field characteristics such as scatter-ing or absorption cross sections, the in-tensity of energy, wholly representingthe response on wave-particle interac-tion is considered as the reasonable anddecisive solution preferable for study-ing the spectroscopic properties and de-termination of possible spectral signa-tures of bioparticles, viruses. Method ofstudying spectroscopic characteristicsbased on elaborated physical models ofviruses represents the new possibility forestimation of spectroscopic propertiesand resonance wavelength range of vi-ral nanoparticles, virions. Thus, twomain mediums of different structures

and properties constitute the virion:capsid of protein capsomeres and nucle-ic acids into the capsid. Type, numberand arrangement of capsomers andlength of nucleic acid are essential indefining the size of capsid designedmostly in near-symmetrical geometry,having the unique self-assemble mech-anism. A simple calculation shows,that the ratio of inner (core) and outerspherical volumes of icosahedral capsidof bacteriophage T7 (of diameters inner1 d = 42.6 nm and outer 2 d =56.6 nm)is approximately0.426 [55], so quite alarge portion (0.57) of volume in viri-on is occupied by the capsid proteins.Capsid’s size is large enough than the„discrete‟ nature of protein subunits,therefore the influence of that on cap-sid whole geometry could probably beless significant. This fact allows virionto be modelled as a spherical core-shellparticle of smooth inner or outer sur-faces. Core-shell VLP model of spher-ical geometry could be used as the firstapproximation of shape-structure oficosahedral unenveloped virion. Thestructure and geometry of capsids aswell as processes happening inside a lay-er probably dominate in determinationof physical, spectroscopic properties ofnano-sized particles, virions.

Theoretical approach of studyingspectroscopic properties of VLPs isbased on classical Maxwell's EM the-ory, separation of variables method forsolving Helmholtz's (wave) equation.Solution of Helmholtz’s equation leadsto the Bessel’s and/or Legendre’s equa-tions [56]. EM fields in different areasof VLP are written as the sums of mul-tipole-waves with unknown multipolecoefficients. Application of boundaryconditions to EM field components oncore-shell surfaces and labor consum-ing mathematical transformations leadsto rigorous theoretical solution of EMscattering problem on single VL parti-cle. Analysis of EM field expressionsshow that arguments of functions deter-mining the multipole coefficients andscattered fields depend only on relativevalues of particles diameters over wave-length. Therefore, it makes possible toexpand the research area, and the find-ings of well-established Mie theory[57] considering the light scattering ona homogeneous sphere be applied tonanoparticles of core-shell morphologyand particles of biological origin as well.

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Spectral response on EM wave-VLPinteraction is determined by estimationof far-field (r‹‹2d/λ) characteristics rep-resenting the angular distribution of scat-tered (absorbed) energy. Scatteringproperties are characterized via ex-pressions such as: the total scatteringcross section.

Proposed theoretical solution, analyt-ical expressions of EM fields make pos-sible to estimate the fields in the areasof core, shell and surrounding areas ofVLPs. based on machine learning andmodeling techniques have been used forgenerating a simulated spectrum ofnanoparticle of given size and availableliterature optical constants. Computersimulation (based on MatLabR2013bsoftware) was carried out for TMVparticles characterization. Parameters ofTMV particle are obtained from scien-tific publications based on differentmeasuring technics. Length of TMVvirion is 280-300 nm, outer (d2) and in-ner (d1) diameters of capsid are 18 nmand 4 nm, correspondingly. Two mod-els - homogeneous cylindrical (of diam-eter) and homogeneous of core-shellstructure (of diameters - outer and inner),are used for simulation study of TMVvirion. Computer simulation shows,that expected resonant spectral responseis observable on far-field characteristics,resonant vibrational frequencies ofwhole TMV particle may be associatedto scattering cross-section maximums.Values and locations of maximumsstrongly depend on dielectric and mag-netic parameters, distance between theneighbor maximums increases thelonger wave lengths range is.

Cylindrical model of TMV virion: di-ameter =18 nm, dielectric permittivity

of particle and surrounding medium,magnetic permeabilities of particle andsurrounding medium. Near-field distri-bution presented in a form of isolines ofEM field amplitudes (Fig. 4), indicatesthe locations of energy maximums in-side and outside of particle. Investiga-tion of EM field distribution makes pos-sible to have insight vision ofnanobioparticles [59-61].

Proposed computing model is usefulfor investigation of spectroscopic prop-erties of nanobioparticles and appreci-ation of possible resonant wave lengthranges correlating with scattering/ab-sorbing efficiency of VLP.

Experimental data obtained by apply-ing exquisite techniques and outcomesof theoretical or simulation modelsshould complement each other and ver-ify factors such as possible anisotropyofcore-shell areas of virion, surfaceroughness and inhomogeneity unfore-seen in simplified approaches.

4. conclusIonsSpectroscopic methods have the

characteristic of providing fast resultsand reliable information related to thecomposition of the samples. The stud-ies presented here have shown promis-ing results in a field of science that needsto be better explored. It has been shownthat multivariate analysis techniques areof great importance to analyze spectro-scopic data, providing the potential toidentify and classify biological samples.We do hope that with advancement inthis field of study, spectroscopic meth-ods and tools will be used in bio med-icine in the near future. Methods of lighttherapy of different diseases based on es-timation of EM field characteristics

and resonant wave ranges based on com-puter simulation of nanobioparticlescharacterization will be widely imple-mented, and possibility of determinationof resonant (own) frequencies of entiresystem of molecules including virionswill be a key point for that.

It is a well-known fact that the yogisof ancient times practiced meditation-al techniques to get rid of diseases andstay healthy. Meditations induce the pos-itive vibrations which are known to killmany of the harmful microorganismswhich get into our body. Recent frontiersin technology are exploring the possi-bility of using external excitations to vi-brate a virus to its death.

The genetic material of virus isDNA/RNA enclosed within the protec-tive protein shell (Capsid). Every cell inhuman body has a natural tendency tovibrate at frequency known as the nat-ural frequency, and so the virus. Natu-ral frequency values of these vibrationsare very high compared to healthycells, and depend on the molecularstructure and differ from virus to virus.

acKnowledGMentAuthors are very grateful to the

CARYS-19-297 project “Spectrovir1”of Shota Rustaveli National ScienceFoundation of Georgia for support inperforming the necessary investiga-tions.

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Figure 4. 3 Isolines of EM field amplitudes for cylindrical model of TMVvirion, in the range of (-,+ ). Diameter of cylinder: =18 nm; dielectric permit-tivity: of cylindrical particle - (a), 12 (b), surrounding medium -, excitation wavelength = 23.5 nm, (X,Y) plane is perpendicular to the axis of cylinder.

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1. IntroductIonViruses are assembled in the infect-

ed host cells of human, animals, orplants. Because of viral breeding the,host cell dies. There are especiallyviruses which are breeding in the cell ofthe bacteria. Viruses spread in many dif-ferent ways. Just as many viruses arevery specific as to which host species ortissue they attack, each species of virusrelies on a particular propagation way.

The interdisciplinary collaboration(Biomedicine and Biophysics, PhysicalResearch, Information Technologiesand Systems) is an engine of strength-en the abilities of researchers in devel-opment of new biophysical and biomed-ical methods and tools. Those workswhich are based on novel achieve-ments in optical spectrometry, laserand molecular physics as well as infor-mation technologies and systems arecritically important for study of commonproperties of nano-scale virus-like par-ticles, and elaboration of basic conceptsand new revolutionary method for es-timation unique vibration/oscillationproperties, determine the unique “finger-prints” of pathogenic micro-organisms,especially viruses.Farther developmentof new methods of pathogens treatmentis greatly facilitated by an improved un-derstanding of the pathophysiology ofepidemic diseases. There is therefore a

need to address the current knowledgegaps in order to support innovation inevidence-based therapy. In this context,a better understanding of the mecha-nisms that are common to several dis-eases, in particular of those leading toco-morbidities, constitutes an importantchallenge. The special attention must befocused on the integration of pre-clin-ical and clinical studies for the identi-fication of mechanisms common toseveral diseases. Performing activitiesshould assess and validate the relevanceof these common mechanisms and oftheir biomarkers (where relevant) on thedevelopment of disease-specific patho-physiology, as well as their role in thedevelopment of co-morbidities in bothmales and females. The expected impactshould provide: A better understandingof disease pathways and / or mecha-nisms common to a number of diseases;new directions for clinical research forbetter disease prevention, health promo-tion, therapy development, and themanagement of co-morbidities. In thisdirection the multidisciplinary develop-ment of ability to detect rapidly, direct-ly and selectively individual virus par-ticles has the potential to significantlyimpact healthcare, since it could enablediagnosis at the earliest stages of repli-cation within a host’s system. Simulta-neous acquisition of the vibrational

and electronic fingerprints of molecu-lar systems of biological interest, at theinterface between liquid media, or at theair/solid, air/liquid interfaces is difficultto achieve with conventional linear op-tical spectroscopy due to their ratherpoor sensitivity to the low number ofmolecules or their maladjustment to wa-ter environment (infrared absorption).It relies on inelastic scattering of mono-chromatic light, usually from a laser inthe visible, near infrared, or near ultra-violet range. The laser light interactswith molecular vibrations, phonons orother excitations in the system, result-ing in the energy of the laser photons be-ing shifted up or down. The shift in en-ergy gives information about the vibra-tional modes in the system. Infraredspectroscopy yields similar, but comple-mentary, information. Spontaneous scat-tering is typically very weak, and as aresult the main difficulty of this kind ofspectroscopy is separating the weak non-elastically scattered light from the in-tense Rayleigh scattered laser light.

Current paper presents some informa-tion about studies carried out in the lastdecade using spectroscopic methods asa research tool in the field of virology.Spectroscopic analyses are sensitiveto variations in the biochemical compo-sition of the sample, are non-destructive,fast and require the least sample prepa-ration, making spectroscopic techniquestools of great interest in biologicalstudies. Herein important chemometricalgorithms that have been used in viro-logical studies are also evidenced as agood alternative for analyzing the spec-tra, discrimination and classification ofsamples. Techniques that have not yetbeen used in the field of virology are

diseases caused by viral infections are one of the biggest problems for global health,and as methods involved in diagnostics are getting faster and more efficient, methodsof their therapy are still need to be stronger. this retrospective study aimed to explorenano bio spectroscopy research and technology in the field of virology in order to pro-vide a theoretical and computer modeling support for the techniques used, and to sug-gest the applying tools that have not been used previously.

Keywords: virology, spectroscopy, computer modeling, radiation resonance therapy

InVestIGatIons of VIbratIonal ProPertIes

of VIruses and VIrus-lIKe PartIcles

bY coMPutInG MetHods

taMar berberasHVIlI, taMar bZHalaVa, lalI cHaKHVasHVIlI, anna KeKelIdZe,saloMe KarseladZe, lasHa basadZe, toHId talebIfar, aleXandre soselIa, Paata KerValIsHVIlIGeorgian Technical University


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also suggested. This methodologyemerges as a new and promising fieldof research, and may be used in the nearfuture as diagnosis tools for detectingdiseases caused by viruses.

tHeoretIcal andeXPerIMental studIesWith the advancement of technolo-

gy and consequently advanced spec-troscopy, the interest of researchers inspectroscopic techniques in biologicalstudies has grown. This field of scienceis known as biospectroscopy, and meansthe use of spectroscopy to analyze bi-ological objects. Several studies havebeen conducted involving identificationof bacteria [1,2], viruses [3,4], cancerdiagnosis [5], and even in the field offorensic entomotoxicology [6], demon-strating that spectroscopic techniques arecapable of detecting biochemicalchanges in biological matrices.

Viruses are submicroscopic infec-tious agents and obligate intracellularparasites. They are totally dependenton a host cell because they are not ableto generate energy to conduct all bio-logical processes. Virus particles (viri-ons) come in a variety of sizes andshapes.

However, approximately sphericalshapes with diameters in the range be-tween 50nm and 100nm are especially

common. Many nearly spherical virus-es are revealed by X-ray crystallographyto have icosahedral symmetry. A typi-cal virus particle contains genetic ma-terial, RNA or DNA, surrounded by aprotein coat (capsid). Such an objectshould have reasonably distinct vibra-tional frequencies, the study of whichmay be of interest. Excitation of thesevibrations could have applications in ei-ther the diagnosis or treatment of viraldiseases. The sole discussion of these vi-brational modes conjectured that ultra-sound in the GHz range could be reso-nantly absorbed by HIV virus particles,leading to their destruction [7].

The two methods most commonlyused in clinical diagnoses of viruses areenzyme-linked immunosorbent assay,with the best known being the ELISAmethod and real-time polymerase chainreaction (PCR). These methods havebrought benefits such as high levels ofrepeatability and reproducibility, ease inhandling and robustness [8]. However,they have also some negative points. Asexample, both methods requires highquality reagents; in some situationsthey are not suitable for identifying spe-cific viral species/strains and they arealso destructive to the samples. Thus,there is a need for techniques that are asadvantageous as ELISA and PCR tech-niques, and which have fewer disadvan-

tages. The potential of spectroscopictechniques in the detection and identi-fication of virus-infected cells has beenstudied using statistical methods as asensitive, rapid and reliable methodol-ogy. The ability to discriminate betweencontaminated and non-contaminatedobjects in a short time with high sensi-tivity which characterized biospec-troscopy determine its high prospect forstudying viruses and similar pathogens[9, 10].

An expected difficulty in the use ofbiospectroscopy in virology is related tothe fact that humans have a great diver-sity of virus circulating in their organ-ism, and each human has a unique mi-crobiome. Because of it, obtaining a fin-gerprint would be more difficult inview of the specificity of each organism.The solution to this problem seems tobe the use of a broad and well-traineddatabase, and changes obtained by mul-tivariate statistical analysis, differenti-ating these alterations [11, 12].

The main spectroscopic techniquesthat have been used in virologicalstudies are nuclear magnetic reso-nance spectroscopy (NMR) [13], Ra-man spectroscopy [14], infrared spec-troscopy (IR) [15] and molecular flu-orescence spectroscopy [16]. Thesetechniques are known to provide rap-id responses and reliable data, as wellas having powerful structural elucida-tion capability.

Such advantages highlight the pos-sibility of identifying and classifying dif-ferent types of virus using spectro-scopic techniques. In this paper, studiesusing biospectroscopy coupled to statis-tical methods of classification in viro-logical investigations are emphasized.First, we will discuss the most common-ly used spectroscopic techniques, andthen we will discuss the computation-al processes used to extract useful infor-mation from the obtained spectra (spec-tral preprocessing, multivariate classi-fication algorithms, performance eval-uation).

dIscussIon and analYZeIn order to understand the possible

pathway of biospectroscopy develop-ment it is necessary to use the new sci-ence and technology tool calls bionan-otechnology. The main objective ofthis modern discipline is cellular uptakeof nanosize molecules functioning with-

30

The two methods most commonly used inclinical diagnoses of viruses are enzyme-linkedimmunosorbent assay, with the best known be-ing the ELISA method and real-time polymerasechain reaction (PCR). These methods havebrought benefits such as high levels of repeata-bility and reproducibility, ease in handling androbustness [8]. However, they have also somenegative points. As example, both methods re-quires high quality reagents; in some situationsthey are not suitable for identifying specific vi-ral species/strains and they are also destructiveto the samples. Thus, there is a need for tech-niques that are as advantageous as ELISA andPCR techniques, and which have fewer disad-vantages. The potential of spectroscopic tech-niques in the detection and identification of virus-infected cells has been studied using statisticalmethods as a sensitive, rapid and reliablemethodology. The ability to discriminate be-tween contaminated and non-contaminatedobjects in a short time with high sensitivity whichcharacterized biospectroscopy determine itshigh prospect for studying viruses and similarpathogens [9,10].

An expected difficulty in the use of biospec-troscopy in virology is related to the fact that hu-mans have a great diversity of virus circulatingin their organism, and each human has a uniquemicrobiome. Because of it, obtaining a finger-print would be more difficult in view of thespecificity of each organism. The solution to thisproblem seems to be the use of a broad and well-trained database, and changes obtained bymultivariate statistical analysis, differentiat-ing these alterations [11,12].

The main spectroscopic techniques that havebeen used in virological studies are nuclear mag-netic resonance spectroscopy (NMR) [13], Ra-man spectroscopy [14], infrared spectroscopy (IR)[15] and molecular fluorescence spectroscopy[16]. These techniques are known to provide rap-id responses and reliable data, as well as havingpowerful structural elucidation capability.

Such advantages highlight the possibility ofidentifying and classifying different types of

virus using spectroscopic techniques. In this pa-per, studies using biospectroscopy coupled to sta-tistical methods of classification in virologicalinvestigations are emphasized. First, we will dis-cuss the most commonly used spectroscopictechniques, and then we will discuss the com-putational processes used to extract useful in-formation from the obtained spectra (spectralpreprocessing, multivariate classification algo-rithms, performance evaluation).

DISCUSSION AND ANALYZEIn order to understand the possible pathway

of biospectroscopy development it is necessaryto use the new science and technology tool callsbionanotechnology. The main objective of thismodern discipline is cellular uptake of nanosizemolecules functioning within the cell. If the sizeof molecules is bigger than 10nm are taken by thecell trough a clathrin-assisted mode of endocyto-sis called pinocytosis, while particles of size greaterthan 200 nm in diameter are usually phagocytosedby the macrophages. Phagocytosis occurs in spe-cialized cells called phagocytes, which includesmacrophages, neutrophils, and other white bloodcells, which destroys the molecular association.Invagination produces so called phagosomewhich usually fuses with one or more lysosomescontaining hydrolytic enzymes.

In comparison with cellular molecules(nano-ensembles) the size of viruses varies from20 to 300 nanometers. Practically all viruses bythe sizes are smaller, than bacteria. However, thelargest viruses, for example a virus of cow small-pox, have the same sizes, as well as the small-est bacteria (hlamidiya and rikketsiya) who tooare obligate parasites and breed only in livingcells. Therefore, as distinctive features of virus-es in comparison with other microscopiccausative agents of infections the sizes orobligatory parasitism, and features of a struc-ture and unique mechanisms of replication (re-production themselves) serve not. Viruses aremasterpieces of nanoengineering with a basiccommon architecture that consists of the cap-sid – a protein shell made up of repeating pro-

tein subunits- which packs within it the viralgenome.

Nano-sized biological agents and pathogenssuch as viruses are known to be responsible fora wide variety of diseases such as flu, AIDS andherpes, and have been used as bioreagents[17,18].

For today there are experimentally certifieddata that Viral nanoparticles are emptied viruscells that can carry drugs directly to cancer cellsto kill them [19]. Scientists have engineered vi-ral nanoparticles from plant viruses, insectviruses, and animal viruses [20]. Viral nanopar-ticles could revolutionize cancer treatment, act-ing not only as a safer, more specific form of can-cer treatment, but also as a new imaging tool. Thenanoparticles could create a type of drug deliv-ery that is extremely tumor specific with great-ly reduced side effects. The viral nanoparticleswould be more soluble and have higher drug ef-ficacy than current treatments [21,22].

Viruses and other biological species can becharacterized according to size, shape, and op-tical/spectroscopic properties. These propertiesallow them to be distinguished from other bi-ological species and from other particulates suchas dust particles.

In response to new tasks which face medicinedevelopment of a rapid and efficient diagnostictest is considered a high priority. In this directionthe decisive word belongs to development of nan-otechnologies which have a great potential for usein methods of detection, diagnosis and treatment.The gold nanorods (AuNR) are of particular in-terest, especially considering their optical prop-erties and chemistry of the surface, which allowseasy connection to organic molecules adapted tospecific needs. For research of mechanisms of ac-tion of viruses and pathogenic microorganismsthe study of their properties is very important in-cluding oscillations pervade biological systemsat all scales. In bacteria, oscillations control fun-damental processes, including gene expression,cell cycle progression, cell division, DNA seg-regation and cell polarity. Oscillations are gen-erated by biochemical oscillators that incorporatethe periodic variation in a parameter over timeto generate an oscillatory output. Spatial oscil-lators incorporate the periodic variation in the lo-calization of a protein to define subcellular po-sitions such as the site of cell division and the lo-calization of DNA. There are some data whichare focuses on the mechanisms of oscillators andthe design principles of temporal and spatial os-cillatory systems [23].

Current optical detection methods which arewell developed for single micrometer size par-ticles, cannot be applied to nanoparticles due toa strong signal dependence on particle size. Typ-ically, such sensors consist of a light sourcewhich illuminates a sample volume of anaerosol or a liquid flow containing the particlesof interest. An off-axis detector measures pow-er of scattered light. The latter is a function ofparticle properties such as size, concentration,and optical density. In the tens of nanometerssize regime particles act as dipoles, therefore thepower of scattered light is proportional to thesixth power of particles size. Lowering the de-

socialuri, ekologiurida klinikuri pediatria2626

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Fig.1. Example of Virion: Virus icosahedron A virus icosahedron (20-sided structure) shownin the (left) twofold, (centre) threefold, and (right) fivefold axes of symmetry. Edges of the upperand lower surfaces are drawn in solid and broken lines, respectively. Encyclopaedia Britannica'

Example of Virion: Virus icosahedron A virus icosahedron (20-sided structure) shownin the (left) twofold, (centre) threefold, and (right) fivefold axes of symmetry. Edges of theupper and lower surfaces are drawn in solid and broken lines, respectively. Encyclopae-dia Britannica'

twofold symmetry

IcosaHedron

fivefold symmetry

symmetryaxes symmetry

axes

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dna viral genome

threefold symmetry

in the cell. If the size of molecules is big-ger than 10nm are taken by the celltrough a clathrin-assisted mode of en-docytosis called pinocytosis, while par-ticles of size greater than 200 nm in di-ameter are usually phagocytosed by themacrophages. Phagocytosis occurs inspecialized cells called phagocytes,which includes macrophages, neu-trophils, and other white blood cells,which destroys the molecular associa-tion. Invagination produces so calledphagosome which usually fuses withone or more lysosomes containing hy-drolytic enzymes.

In comparison with cellular mole-cules (nano-ensembles) the size ofviruses varies from 20 to 300 nanome-ters. Practically all viruses by the sizesare smaller, than bacteria. However, thelargest viruses, for example a virus ofcow smallpox, have the same sizes, aswell as the smallest bacteria (hlamidiyaand rikketsiya) who too are obligateparasites and breed only in livingcells. Therefore, as distinctive fea-tures of viruses in comparison with oth-er microscopic causative agents of in-fections the sizes or obligatory para-sitism, and features of a structure andunique mechanisms of replication (re-production themselves) serve not.Viruses are masterpieces of nanoengi-neering with a basic common architec-ture that consists of the capsid – a pro-tein shell made up of repeating proteinsubunits- which packs within it the vi-ral genome.

Nano-sized biological agents andpathogens such as viruses are knownto be responsible for a wide variety ofdiseases such as flu, AIDS and herpes,and have been used as bioreagents[17, 18].

For today there are experimentallycertified data that Viral nanoparticles areemptied virus cells that can carry drugsdirectly to cancer cells to kill them [19].Scientists have engineered viralnanoparticles from plant viruses, insectviruses, and animal viruses [20]. Viralnanoparticles could revolutionize can-cer treatment, acting not only as asafer, more specific form of cancertreatment, but also as a new imagingtool. The nanoparticles could create atype of drug delivery that is extremelytumor specific with greatly reducedside effects. The viral nanoparticleswould be more soluble and have high-

er drug efficacy than current treat-ments [21,22].

Viruses and other biological speciescan be characterized according to size,shape, and optical/spectroscopic prop-erties. These properties allow them to bedistinguished from other biologicalspecies and from other particulatessuch as dust particles.

In response to new tasks which facemedicine development of a rapid and ef-ficient diagnostic test is considered ahigh priority. In this direction the deci-sive word belongs to development ofnanotechnologies which have a great po-tential for use in methods of detection,diagnosis and treatment. The goldnanorods (AuNR) are of particular in-terest, especially considering their op-tical properties and chemistry of the sur-face, which allows easy connection toorganic molecules adapted to specificneeds. For research of mechanisms ofaction of viruses and pathogenic mi-croorganisms the study of their proper-ties is very important including oscilla-tions pervade biological systems at allscales. In bacteria, oscillations controlfundamental processes, including geneexpression, cell cycle progression, celldivision, DNA segregation and cellpolarity. Oscillations are generated bybiochemical oscillators that incorporatethe periodic variation in a parameterover time to generate an oscillatory out-put. Spatial oscillators incorporate theperiodic variation in the localization ofa protein to define subcellular positionssuch as the site of cell division and thelocalization of DNA. There are somedata which are focuses on the mecha-nisms of oscillators and the designprinciples of temporal and spatial oscil-latory systems [23].

Current optical detection methodswhich are well developed for single mi-crometer size particles, cannot be ap-plied to nanoparticles due to a strongsignal dependence on particle size.Typically, such sensors consist of a lightsource which illuminates a sample vol-ume of an aerosol or a liquid flow con-taining the particles of interest. Anoff-axis detector measures power ofscattered light. The latter is a functionof particle properties such as size, con-centration, and optical density. In thetens of nanometers size regime particlesact as dipoles, therefore the power ofscattered light is proportional to the

sixth power of particles size. Loweringthe detection size limits for the existingdetectors places an impossible require-ment on noise optimization. There-fore, a signal which has weaker parti-cle size dependence can allow access tosmaller particles [24]. In the field of vi-rology, for example, it is critical to ac-curately quantify virus particles tostudy the effects of drug therapy in pa-tients; and also, to study viral fitness,replication, and inhibition. There areseveral virus quantification techniquesavailable to virologists, such as thequantitative PCR (polymerase chain re-action) method [25], the plaque titermethod [26] and the image enhancedmicroscopy (IEM) technique [27].However, a problem common to mostof these techniques is that the analysisof a sample involves several tedioussteps, which can take several hours tomulti plays to complete.

The fast detection and characteriza-tion of nanoparticles, such as virusesor environmental pollutants, are impor-tant in fields ranging from biosensingto quality control. However, most ex-isting techniques have practicalthroughput limitations, which signifi-cantly limit their applicability to lowconcentration analysis. There are someexperimental dates that an integratednanofluidic scheme for preconcentra-tion and subsequent detection ofnanoparticle samples within a contin-uous flow-through system. In These ex-periments using a Brownian ratchetmechanism increase the nanoparticleconcentration 27-fold. Single nanopar-ticles are subsequently detected andcharacterized by optical heterodyne in-terferometry. A wide range of potentialapplications can be foreseen, includingreal-time analysis of clinically relevantvirus samples and contamination con-trol of processing fluids used in thesemiconductor industry [28].

For nanoparticle structures identifi-cation a rather interesting method is Vi-brational Spectroscopy (VS), whichprovides the most definitive means ofidentifying the surface species generat-ed upon molecular adsorption and thespecies generated by surface. In princi-ple, any technique that can be used toobtain vibrational data from solid stateor gas phase samples (IR, Raman etc.)can be applied to the study of surfaces- in addition there are a number of tech-

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niques which have been specifically de-veloped to study the vibrations of mol-ecules at interfaces (EELS, SFG etc.)[29, 30].

There are, however, only two tech-niques that are routinely used for vibra-tional studies of molecules on surfaces- these are: IR Spectroscopy (of vari-ous forms, e.g. RAIRS, MIR) andElectron Energy Loss Spectroscopy(EELS). There are both advantages anddisadvantages in utilizing EELS, as op-posed to IR techniques, for the studyof surface species It offers the advan-tages of high sensitivity, variable selec-tion rules, spectral acquisition to below400 cm-1 but suffers from the limita-tions of use of low energy electrons.Raman spectroscopy is used to studylow-wave-number (≤20cm−1) acousticvibrations of the M13 phage. A well-defined Raman line is observed ataround 8.5cm−1. The experimentalresults are compared with theoreticalcalculations based on an elastic contin-uum model and appropriate Raman se-lection rules derived from a bond Po-laris ability model. The observed Ra-man mode is shown to belong to oneof the Raman-active axial modes of theM13 phage protein coat. It is expect-ed that the detection and characteriza-tion of this low-frequency vibrationalmode can be used for applications inbiomedical nanotechnology such as formonitoring the process of virus func-tionalization and self-assembly.

Recently, a technique which de-parts radically from conventional ap-proaches has been proposed. This nov-el technique utilizes biological objectssuch as viruses as nano-templates forthe fabrication of nanostructure ele-ments. For example, rod-shaped virus-es such as the M13 phage and tobaccomosaic virus have been successfullyused as biological templates for the syn-thesis of semiconductor and metallicnanowires. Low wave number (<or= 20cm-1) acoustic vibrations of the M13phage have been studied using Ramanspectroscopy [31]. The experimental re-sults are compared with theoreticalcalculations based on an elastic contin-uum model and appropriate Ramanselection rules derived from a bond po-larizability model. Aside from servingas a protective layer, capsids are in-volved with various other aspects oftheir respective virus life cycles includ-

ing timely viral genome encapsulation(self-4assembly and genome packag-ing), cell-to-cell virus transport, entryinto host-cell (e.g., via cell receptorbinding), genome release into hostcell, etc. Despite their central impor-tance to the life cycle, the variousevolutionary pressures acting on spher-ical capsids are not well known. Half acentury of empirical data has uncovereda large array of capsids sizes that rangefrom tens to many thousands in subunitcomposition. Spherical capsids of allobserved sizes may be obtained from agrouping of twelve pentamers (symmet-ric clusters of five subunits) separatedby a variable number of hexamers(clusters of six subunits). This is thecase for the T~7d papilloma viruseswhere all capsomers are made up of fivesubunits but they are in both hexavalentand pentavalent configuration, andlarger viruses whose ‘‘hexamers’’ areactually trimers of ‘‘fused’’ or covalent-ly bonded dimers. Capsid size may becharacterized by two integers, h and k,which describe the number of hexam-ers (hzk{1) one would have to ‘‘walkover’’ to get from one pentamer to anadjacent pentamer within a completedcapsid. The utility of the class systemis not entirely lost, however; specific an-gle patterns within the capsid ensuresthe existence of distinct hexamer shapes(each shape is colored distinctly in. Ev-idence indicates that capsid formationis nucleated, often starting with a sin-gle capsomer species (e.g., pentamers;for the purposes of this paper, a cap-somer is a generally symmetric clusterof either five or six subunits), whichthen proceeds to completion by the ad-dition of small subunit clusters (orsingle subunits). In T~1 capsid, wheresubunits are in identical/equivalent en-vironments, nucleated assembly will bepossible with no additional machinery.However, the formation of two or morecapsomers from a single interaction sitewill require the employment of addi-tional machinery to ensure high yieldsof the native state. For example, qua-si-equivalent switches are required forthe proper assembly of capsids contain-ing two distinct capsomers: a pen-tamer and one type of hexamer. The ad-dition of a second hexamer shape ne-cessitates the requirement of a secondmechanism such as auxiliary proteinsfor proper assembly. For spherical

virus capsids requiring more distincthexamer shapes. Additional mecha-nisms to stabilize those new shapes atexactly the right positions within theforming capsid are likely to be alsoneeded dominantly form.

Because capsids from different class-es display markedly different geome-tries, they are bound to display differ-ent physical properties. The periodic na-ture of capsid hexamer contents also use-ful in understanding ‘‘T-switching’’: aprocess that permits canonical capsidsubunits to more easily sample capsidscontaining similar hexamer shapes.This allows for a segue to understand-ing currently intractable and deadlypleomorphic viruses like Ebola andarenaviruses. For example, from theabove T-switching rule, the available di-versity of an arena virus may only be ex-plained if we assume that the biologi-cally relevant form of the arenavirus isthe T~12 capsid. Non-icosahedral cap-sids. Although the framework present-ed doesn’t appear to readily explain non-icosahedral capsids (some are just‘‘slightly’’ non-icosahedral, such as thenatively prolate phi29 capsids, whileothers are wildly different in form,such as Ebola with its natively filamen-tous shape), those capsids, like theiricosahedral counterparts, also displaycapsomer sub-structures. In light ofthis, the geometric constraints analogousto endo angles that affect capsomershape may be useful in obtaining in-sights into non-icosahedral capsid mor-phology, behavior, and classification. Itwill be exciting to see whether incorpo-rating the non-icosahedral capsids intoan expanded capsid periodic table willbe possible. All canonical capsids (madeup of trapezoidal subunits) may bebuilt from a single type of pentamer anda repertoire of distinct hexamer shapes(colored distinctly only once in eachcapsid. The hexamer shape is describedby the number of endo angles it displays.It is necessary to underline that effect ofdestroy of human immunodeficiencyvirus (HIV) and other enveloped virus-es is based on the highly symmetricstructure (e.g. icosahedral and others) ofmany viruses, which leads to a well-de-fined resonant frequency of ultrasoundin the GHz range and which may bespecifically absorbed by these structuresand may subsequently lead to their ir-reversible damage.

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In order to clarify the possible roleof nanoparticles in diseases recently as-sociated with them (such as Crohn’sdisease, neurodegenerative diseases,autoimmune diseases, and cancer),nanoscale characterization techniquesshould be used to a larger extent toidentify nanoparticles at disease sitesin affected organs or tissues, and to es-tablish pertinent interaction mecha-nisms. Rapid, selective, and sensitivedetection of viruses is central to imple-ment an effective response to viral in-fection, such as through medication orquarantine. Established methods for vi-ral analysis include plaque assays,immunological assays and transmissionelectron microscopy. These methodshave not achieved rapid detection at asingle virus level and often require arelatively high level of sample manip-ulation that is inconvenient for infec-tious materials. Yet, the ability to de-tect rapidly, directly, and selectively in-dividual virus particles has the poten-tial to significantly impact healthcare,since it could enable diagnosis at theearliest stages of replication within ahost’s system. One promising approachfor the direct electrical detection of bi-ological macromolecules uses semi-conducting nano-wires or carbon nano-tubes configured as field-effect transis-tors, which change conductance uponbinding of charged macro-molecules toreceptors linked to the device sur-faces. One of the simplest medicalnanomaterials is a surface perforatedwith holes, or nanopores. These poresare large enough to allow small mol-ecules to pass but are small enough toimpede the passage of much largervirus particles. The next step wascylindrical gold nano-tubules with in-side diameters as small as 1.6 nm.When tubules were positively charged,positive ions were excluded and onlynegative ions were transported throughthe membrane. With a negative voltage,only positive ions could pass. Thecombining voltage gating with poresize, shape, and charge constraints al-lows achieving precise control of iontransport with significant molecularspecificity. Lieber’s group has report-ed direct, real-time electrical detectionof single virus particles with high se-lectivity using nano-wire field- effecttransistors to measure discrete conduc-tance changes characteristic of binding

and unbinding on nano-wire arraysmodified with viral anti-bodies [32].

The integrity of such devices allowsincreasing the number of the detectionviruses. The analysis of the manifold lit-erature shows, that task of the detectionpathogenic micro-organisms is timely.Therefore, our available method wouldbe one brick in the solution of theproblems like that. Simultaneous acqui-sition of the vibrational and electronicfingerprints of molecular systems of bi-ological interest, at the interface betweenliquid media, or at the air/solid, air/liq-uid interfaces in conditions similar tothose encountered in nature or in mod-el environments requires the use of sen-sitive and specific spectroscopic probes.Such a characterization is difficult toachieve with conventional linear opti-cal spectroscopies due to their ratherpoor sensitivity to the low number ofmolecules (Raman) or their maladjust-ment to water environment (infrared ab-sorption), at the exception of PM-IR-RAS in specific work conditions. In ad-dition, these techniques are for most ofthem only partially surface specific. Oneof the promising solutions of this prob-lem is the use of the nonlinear Two-Col-or Sum-Frequency Generation Spec-troscopy (2C-SFG) that meets the de-sired spectroscopic requirements. Thegoal of this approach is to probe mem-brane models of various forms and invarious environments: (i) lipid monolay-ers and bilayers; (ii) deposited on sub-strates, floating on water as Langmuirlayers and at a liquid-liquid interface;(iii) alone and in interaction with mol-ecules, including peptides and pro-teins; (iv) submitted to controlled stress(chemical, pH, electrochemical poten-tial).

The increasing amount of availabledata of protein three-dimensional atom-ic structures, determined mostly byX-ray crystallography (related to the fastexpansion of that field around third gen-eration synchrotron storage rings) andNMR, has given much informationabout role of many proteins in biolog-ical processes. However, it has beenpointed out that knowing the structuredoes not directly lead to the knowledgeof the function, and that the proteinalone, without its environment or itspartners of interaction, is not totally in-formative. Additionally, some proteinscannot be satisfactorily crystallized

and thus cannot be accessed by X-raycrystallographic methods. Among them,membrane proteins need their mem-brane partners to fully play their roleand are often not able to crystallize. Insitu studies, and their according inves-tigation techniques, are therefore fa-vored for such objects. In the follow-ing, in situ should not be understood asin vivo, but imply rather that the objectsare designed and studied in an environ-ment mimicking what they experiencein vivo. On the other hand, due to theiressential role as the barrier between thecell cytoplasm and the extracellularmedium, membranes themselves alsoget a lot of attention regarding theirshape, stability, structure, composi-tion, modifications under stresses (pH,temperature, electric potential) and in-teraction with proteins, water andchemicals in solution. The electrical be-havior of bilayers makes them goodcandidates as membrane biosensorswhen attached to a conducting surface(semiconductor or metal). There are lotsof possibilities to get average informa-tion on a given parameter of a mem-brane and its evolution under a givenstress (e.g. diffusion of light, electro-chemical methods, microbalance meas-urements). Specific in situ techniquesallow direct investigation of key func-tional behaviors of synthetic mem-brane models (lipid mono and bilayersin an aqueous environment interactingeither with selected proteins, ions or or-ganic molecules) [33, 34].

The strong absorption of the watervapor and the poor detection propertiesof conventional FTIR spectroscopy ledto the discarding of this technique for thestudy of such interfacial systems. Thisevidence for the limited range of infraredspectroscopic tools dedicated to thestudy of such fragile objects in their spe-cific environment was written onlyabout ten years ago. From that time,there has been a lot of progress from thespectroscopic point of view. In additionto IR absorption spectroscopy (conven-tional or attenuated total reflection(ATR) configuration), three other IR-based spectroscopies have been able toaddress the issue of a molecular layer onwater with a signal-to-noise ratio suffi-cient to extract scientific informationfrom experimental data. PM-IRRAS, anIR absorption technique initially devel-oped to study the nanosurface of met-

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als, has been applied to that of liquids.Being less sensitive to IR radiation ab-sorption and easier to detect, Ramanspectroscopy is often used on biologi-cal environment, although the lowcount rate on monolayers requires longacquisition times. It has been recentlyreported the detection of viruses byacoustic oscillations [35, 36]. Howev-er, the process of “rupture event scan-ning”, which was report, involves theseparation of a virus particle from an-tibodies by ultrasound. This is distinctfrom the excitation of the vibrationalmodes of the virus particle itself, and oc-curs at much lower frequencies. Therehave also been some experimental stud-ies of ultrasonic absorption by empty vi-ral capsids [37, 38]. These experimentsreveal an enhanced absorption in theMHz range as proteins reassemble intoa capsid, but do not find a resonant peakin this frequency range. At the sametime, it was emphasized that these andother results show that viral capsids areflexible and change size or shape in re-sponse to vibrations or to changes intemperature or pH [39].

One the most promising methods ofbiospectroscopy is SFG. These ultra-short pulsed lasers based optical meas-urement method is unique for investi-gation of vibrational modes of differ-ent viruses and other pathogenic mi-croorganisms as well as study of natureof their oscillation processes and param-eters of oscillation. Non-linear opticsand its resonance technologies is pos-sible direction of organization of treat-ment of pathogenic microorganisms intheir different living media. Contrary tothe previous ones, this second ordernonlinear process is intrinsically specif-ic to an interface, and involves nocontribution from molecules in a cen-trosymmetric bulk, i.e., in solution orin gas phase. It has been extensively ap-plied to solid interfaces in vacuum, con-trolled atmosphere and electrochemicalconditions. For a few years, technolog-ical development of picosecond andfemtosecond tunable laser sources haveled both to an increase of the numberof SFG experimental setups around theworld and to a progressive applicationto fragile or buried interfaces. In addi-tion to unique SFG setup is researchbased on usage of the CLIO Free Elec-tron laser [40, 41]. This latter allowsprobing specific vibrations located in

the near and far infrared, which isagain unique to date.

Although molecular fluorescencespectroscopy has been little used instudies in the field of virology, it is alsoan interesting approach with great poten-tial in this perspective. This technique an-alyzes the fluorescence capacity of a sam-ple [42], where a beam of high energylight (usually in the ultraviolet region) isirradiated on the sample to be excited intoa higher electronic energy level; then thefluorophore molecule will rapidly lose en-ergy to this environment through non-ra-diative modes (called internal conversion)and will return to the lowest vibrationallevel of the lowest electronic excited state.The molecule persists at this vibronic lev-el for a period of time known as the flu-orescence lifetime, and then returns to thefundamental electronic state by emittinga photon with energy lower than the ir-radiated one [43]. The excitation andemission spectrum are recorded by the in-strument and is generally used to buildexcitation-emission (EEM) fluorescencematrices.

Another commonly-employed formof fluorescence technique is fluorescencecorrelation spectroscopy (FCS), whichis used for temporal and spatial analy-sis of molecular interactions of biomol-ecules present in solution at extremelylow concentrations. This technique isbased on the principle that a fluo-rophore molecule has a specific free dif-fusion rate that is directly related to itssize. This basic principle, for example,can be used to study protein interactions.As with other spectroscopic techniques,molecular fluorescence spectroscopyprovides rapid results with high sensi-tivity and specificity, and is non-destruc-tive, making this technique a tool of in-terest in the field of virology.

coMPutatIonal MetHodsof InVestIGatIonSpectroscopically interrogating bio-

logical samples analyze definitely needsto use computational tools which facil-itate the information collection and ex-traction. For this, it is necessary to ad-dress the different computational meth-ods and tools and among them there areemployed the methods:

Preprocessing and multivariateanalysis techniques, which consists

the correction and improvement ofthe signal-to-noise ratio of the spec-trum, commonly employed before dataanalysis.

Spectral cut and Baseline correc-tion, which include determination of ex-act region of interest and diminish of thewavenumbers which are not absorbedand light scattering occurs due to the non- homogenous particle size [44].

Spectral normalization techniquesare used when it is necessary to removespectral changes responsible for thethickness or concentration of the sam-ple, making the normalized spectra be-come comparable to each other. Amongthe possible normalizations, there is themin-max normalization, which can beapplied when there is a known peak thatis stable and consistent between thespecimens; or scaling methods to equal-ize the importance of each variable inmultivariate data. [45].

Multivariate analysis techniquesare employed to analyze multivariatedata, meaning data having two or morevariables per object. Examples are first-order data (such as IR, Raman spectrum)and second-order data (such as fluores-cence).

Principal component analysis(PCA) is an unsupervised multivariateanalysis technique widely used in bio-logical studies. This technique is usedto reduce the dimensionality of thesample's data and generate a new visu-alization. Dimensionality reduction oc-curs through a linear transformation ofthe original variables, generating orthog-onal variables called principal compo-nents (PC).

Cluster analysis (CA) techniquesare unsupervised methods of patternrecognition that aim to group thespectra into groups when there is no in-formation about the classes. Thesetechniques are exploratory thereforethey group the samples based on theirsimilarity between spectra. CA tech-niques include k-means clustering(KMC), fuzzy c-means cluster analy-sis (FCA) and hierarchical clusteranalysis (HCA) [46].

Partial least squares (PLS) is amultivariate calibration technique thatfinds factors (latent variables, LVs) inthe spectra set that explain the maxi-mum variance in the reference variablesset, using the simultaneous decompo-sition of the two. For this, PLS finds a

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set of new maximally correlated vari-ables orthogonal to each other, similarto PCA.

Linear discriminant analysis(LDA) is a supervised technique wide-ly used for class discrimination. It max-imizes the between-class variance overthe within-class variance in order to cre-ate a linear decision boundary betweenthem.

Successive projections algorithm(SPA) is a progressive variable selectiontechnique. This means that it startswith a variable (wavelength orwavenumber, for example) and addsnew variables in each interaction untilan optimal number is selected. This tech-nique uses multicollinearity minimiza-tion as a criterion for variable selection.

The genetic algorithm is a tech-nique that mimics Darwin's theory ofevolution, where evolution occurs bynatural selection in which the moreadapted organisms have a greater chanceof survival. In the case of GA, the vari-able selection process begins with a ran-domly formed population of variables[47]. Each chromosome is assigned anaptitude through a mathematical func-tion called fitness function, where chro-mosomes with the highest fitness val-ue are copied and the chromosomes withthe lowest fitness value are eliminatedin a step called the selection step. Afterthe selection step, genetic operatorsare probabilistically applied. The muta-tion operator makes a variable that is se-lected to be unselected or vice-versa, andthe crossover operator crosses the chro-mosomes.

Sensitivity (SENS) can be definedas the confidence that a positive resultfor a sample of the labeled class is ob-tained; specificity (SPEC) is the confi-dence that a negative result for a sam-ple of non-labeled classes is obtained;positive predictive value (PPV) meas-ures the proportion of positives that arecorrectly assigned; negative predictivevalue (NPV) measures the proportion ofnegatives that are correctly assigned;Youden's index (YOU) evaluates theclassifier's ability to avoid failure; pos-itive likelihood ratio (LR+) representsthe ratio between the probability of pre-dicting a sample as positive when it tru-ly is positive and the probability of pre-dicting a sample as positive when it isactually not positive; and the negativelikelihood ratio (LR−) represents the ra-

tio between the probability of predict-ing a sample as negative when it is ac-tually positive and the probability of pre-dicting a sample as negative when it istruly negative [48].

Diagnostic virology continues toevolve rapidly. Viral testing is now es-sential for the care of a number of pa-tient groups, including hospitalized pa-tients with acute respiratory infections;transplant recipients and other immuno-compromised patients; patients infect-ed with human immunodeficiency virus(HIV), hepatitis C virus (HCV), andhepatitis B virus (HBV); and infantswith possible congenital infection. Mul-tiple test methods continue to be used,but molecular tests are emerging as thedominant technology. A variety of com-mercial molecular assays have been orare in the process of being approved orcleared as in vitro diagnostic tests by theFood and Drug Administration (FDA)[49].

During the last years in response ofglobal spraying the new structural typesof corona viruses the method of estima-tion unique vibration/oscillation prop-erties, determine the unique “finger-prints” of pathogenic micro-organisms,especially viruses.

The main task of the works done byinternational group including Geor-gian, French, German British and Greekresearchers was elaboration of opticalresonance spectrometry method of de-tection and treatment of pathogenicnanobiostructures including corona typeviruses [50, 51].

Viruses and their genomes are most-ly enclosed and protected by sphericalcapsids - symmetric coats or shellscomposed primarily of multiple copiesof protein subunits. Aside from serv-ing as a protective layer, capsids are in-volved with various other aspects oftheir respective virus life cycles includ-ing timely viral genome encapsulation(self - assembly and genome packag-ing), cell-to-cell virus transport, entryinto host-cell (e.g., via cell receptorbinding), genome release into hostcell, etc. Despite their central impor-tance to the life cycle, the various evo-lutionary pressures acting on sphericalcapsids are not well known. Half a cen-tury of empirical data has uncovered alarge array of capsids sizes that rangefrom tens to many thousands in subunitcomposition. Spherical capsids of allobserved sizes may be obtained froma grouping of twelve pentamers (sym-metric clusters of five subunits) sepa-rated by a variable number of hexam-ers (clusters of six subunits). This is thecase for the T~7d papilloma viruseswhere all capsomers are made up offive subunits but they are in bothhexavalent and pentavalent configura-tion, and larger viruses whose ‘‘hexa-mers’’ are actually trimers of ‘‘fused’’or covalently bonded dimers.

Capsid size may be characterized bytwo integers, h and k, which describe thenumber of hexamers (hzk{1) one wouldhave to ‘‘walk over’’ to get from onepentamer to an adjacent pentamer with-in a completed capsid. The utility of the

2021


Operational scheme of the genetic algorithm (GA). In this scheme an initial popula-tion with 3 chromosomes is shown. A fitness value is assigned for each chromosome throughthe fitness function (F). Note that the chromosome with less fitness is discarded in the se-lection stage, while the larger one is doubly copied and the second largest fitness receivesa copy. It is observed that the chromosome is mutated through the mutation operator inthe second moment, and the other two chromosomes are crossed through the crossoveroperator.

010101001100111010

:

010101111010111010

:

110101011010110010

:

selectioncrossover

Mutation

Initial populationof the firstgeneration

Initial populationof the second

generation

fitness=0,4fitness=0,1fitness=0,8


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class system is not entirely lost, howev-er; specific angle patterns within the cap-sid ensures the existence of distincthexamer shapes (each shape is coloreddistinctly in. Evidence indicates that cap-sid formation is nucleated, often start-ing with a single capsomer species(e.g., pentamers; for the purposes of thispaper, a capsomer is a generally sym-metric cluster of either five or six sub-units), which then proceeds to comple-tion by the addition of small subunitclusters (or single subunits). In T~1 cap-sids, where subunits are in identical/eq -uivalent environments, nucleated assem-bly will be possible with no additionalmachinery. However, the formation oftwo or more capsomers from a single in-teraction site will require the employ-ment of additional machinery to ensurehigh yields of the native state. For ex-ample, quasi-equivalent switches are re-quired for the proper assembly of cap-sids containing two distinct capsomers:a pentamer and one type of hexamer.The addition of a second hexamershape necessitates the requirement of asecond mechanism such as auxiliaryproteins for proper assembly. For spher-ical virus capsids requiring more distincthexamer shapes. Additional mecha-nisms to stabilize those new shapes atexactly the right positions within theforming capsid are likely to be alsoneeded dominantly form.

Because capsids from different class-es display markedly different geome-tries, they are bound to display differ-ent physical properties. The periodic na-ture of capsid hexamer contents also use-ful in understanding ‘‘T-switching’’: aprocess that permits canonical capsidsubunits to more easily sample capsidscontaining similar hexamer shapes.This allows for a segue to understand-ing currently intractable and deadlypleomorphic viruses like Ebola andarenaviruses. For example, from theabove T-switching rule, the available di-versity of an arena virus may only be ex-plained if we assume that the biologi-cally relevant form of the arenavirus isthe T~12 capsid. Non-icosahedral cap-sids. Although the framework present-ed doesn’t appear to readily explain non-icosahedral capsids (some are just‘‘slightly’’ non-icosahedral, such as thenatively prolate phi29 capsids, whileothers are wildly different in form,such as Ebola with its natively filamen-

tous shape), those capsids, like theiricosahedral counterparts, also displaycapsomer sub-structures. In light ofthis, the geometric constraints analogousto endo angles that affect capsomershape may be useful in obtaining in-sights into non-icosahedral capsid mor-phology, behavior, and classification. Itwill be exciting to see whether incorpo-rating the non-icosahedral capsids intoan expanded capsid periodic table willbe possible.

All canonical capsids (made up oftrapezoidal subunits) may be built froma single type of pentamer and a reper-toire of distinct hexamer shapes (coloreddistinctly only once in each capsid. Thehexamer shape is described by thenumber of endo angles it displays. It isnecessary to underline that effect of de-stroy of enveloped viruses is based onthe highly symmetric structure (e.g.icosahedral and others) of many virus-es, which leads to a well-defined reso-nant frequency which may be specifi-cally absorbed by these structures andmay subsequently lead to their irre-versible damage.

Modeling and Simulation of oscilla-tion effects in different viruses includ-ing corona like ones is based on stud-ies of biostructure’s physical character-istics, scattering and absorption proper-ties. Estimation of electromagnetic(EM) spectrum and resonance wavelength ranges is important for character-ization of nano-micro-scaled particlesand determination of biostructuresunique spectral signatures, essential inbio-agents detecting and identificationsystems, and becoming as a great chal-lenge in real systems investigations.

Method of estimation of spectralresponse on EM field & particle inter-action is based on solutions of electro-dynamics two (2D) or three (3D) dimen-sional boundary tasks. Analytical expres-sions of EM fields are derived from rig-orous solutions of Maxwell’s andHelmholtz’s equations and definedthrough the dimensionless parameters,diameters over an excitation wave-length. It makes possible to apply theclassical well-known approach to sub-micro particles characterization.

One of the ways for estimation of res-onance frequencies range is the methoddetermining theeigenvalues and corre-sponding eigenvectors obtained by al-gebraic system of functional equations

which could be written based on the so-lution of electrodynamic task consider-ing EM wave-VL particle scattering[52]. Algebraic system has more com-plicated form when VL particle is ofcore-shell structure with different elec-tric parameters. Resonant wavelengthrange is predicted theoretically in thevicinity of values corresponding themaximums of intensity of particularscattered partial waves. Estimation ofresonant wavelength range based on de-termination of far-field characteristicssuch as scattering or absorption crosssections, the intensity of energy, whol-ly representing the response on wave-particle interaction is considered as thereasonable and decisive solution prefer-able for studying the spectroscopicproperties and determination of possi-ble spectral signatures of bioparticles,viruses.

Method of studying spectroscopiccharacteristics based on elaboratedphysical models of viruses represents thenew possibility for estimation of spec-troscopic properties and resonancewavelength range of viral nanoparticles,virions.

Thus, two main mediums of differ-ent structures and properties constitutethe virion: capsid of protein capsomeresand nucleic acids into the capsid. Type,number and arrangement of capsomersand length of nucleic acid are essentialin defining the size of capsid designedmostly in near-symmetrical geometry,having the unique self-assemble mech-anism. A simple calculation shows,that the ratio of inner (core) and outerspherical volumes of icosahedral capsidof bacteriophage T7 (of diameters inner1 d = 42.6 nm and outer 2 d =56.6 nm)is approximately 0.426 [53], so quite alarge portion (0.57) of volume in viri-on is occupied by the capsid proteins.Capsid’s size is large enough than the‘‘discrete’’ nature of protein subunits,therefore the influence of that on cap-sid whole geometry could probably beless significant. This fact allows virionto be modelled as a spherical core-shellparticle of smooth inner or outer sur-faces. Core-shell VLP model of spher-ical geometry could be used as the firstapproximation of shape-structure oficosahedral unenveloped virion. Thestructure and geometry of capsids aswell as processes happening inside a lay-er probably dominate in determination

36

of physical, spectroscopic properties ofnano-sized particles, virions.

Theoretical approach of studyingspectroscopic properties of VLPs isbased on classical Maxwell's EM the-ory, separation of variables method forsolving Helmholtz's (wave) equation.Solution of Helmholtz’s equation leadsto the Bessel’s and/or Legendre’s equa-tions [54]. EM fields in different areasof VLP are written as the sums of mul-tipole-waves with unknown multipolecoefficients. Application of boundaryconditions to EM field components oncore-shell surfaces and labour consum-ing mathematical transformations leadsto rigorous theoretical solution of EMscatteringproblem on single VL particle.Analysis of EM field expressions showthat arguments of functions determiningthe multipole coefficients and scat-tered fields depend only on relative val-ues of particles diameters over wave-length. Therefore, it makes possible toexpand the research area, and the find-ings of well-established Mie theory[55] considering the light scattering ona homogeneous sphere be applied tonanoparticles of core-shell morphologyand particles of biological origin as well.

Spectral response on EM wave-VLPinteraction is determined by estimationof far-field (r‹‹2d/λ) characteristics rep-resenting the angular distribution of scat-tered (absorbed) energy. Scatteringproperties are characterized via ex-pressions such as: the total scatteringcross section

Proposed theoretical solution, analyt-ical expressions of EM fields make pos-sible to estimate the fields in the areasof core, shell and surrounding areas ofVLPs. based on machine learning andmodeling techniques have been used forgenerating a simulated spectrum ofnanoparticle of given size and availableliterature optical constants.

Computer simulation (based on Mat-LabR2013b software) was carried outfor TMV particles characterization.Parameters of TMV particle are ob-tained from scientific publicationsbased on different measuring technics.Length of TMV virion is 280-300 nm,outer (d2) and inner (d1) diameters of

capsid are 18 nm and 4 nm, correspond-ingly. Two models - homogeneouscylindrical (of diameter) and homoge-neous of core-shell structure (of diam-eters - outer and inner), are used for sim-ulation study of TMV virion. Comput-er simulation shows, that expected res-onant spectral response is observable onfar-field characteristics, resonant vibra-tional frequencies of whole TMV par-ticle may be associated to scatteringcross-section maximums. Values and lo-cations of maximums strongly dependon dielectric and magnetic parameters,distance between the neighbor maxi-mums increases the longer wave lengthsrange is.

Near-field distribution presented ina form of isolines of EM field ampli-tudes), indicates the locations of en-ergy maximums inside and outside ofparticle. Investigation of EM fielddistribution makes possible to haveinsight vision of nanobioparticles[56-59].

Proposed computing model is usefulfor investigation of spectroscopic prop-erties of nanobioparticles and appreci-ation of possible resonant wave lengthranges correlating with scattering/ab-sorbing efficiency of VLP.

Experimental data obtained by apply-ing exquisite techniques and outcomesof theoretical or simulation modelsshould complement each other and ver-ify factors such as possible anisotropyof core-shell areas of virion, surfaceroughness and inhomogeneity unfore-seen in simplified approaches.

conclusIonsSpectroscopic methods have the

characteristic of providing fast resultsand reliable information related to thecomposition of the samples. The stud-ies presented here have shown prom-ising results in a field of science thatneeds to be better explored. It has beenshown that multivariate analysis tech-niques are of great importance to an-alyze spectroscopic data, providingthe potential to identify and classify bi-ological samples. We do hope thatwith advancement in this field ofstudy, spectroscopic methods and toolswill be used in bio medicine in the nearfuture. Methods of light therapy of dif-ferent diseases based on estimation ofEM field characteristics and resonantwave ranges based on computer sim-

ulation of nanobioparticles character-ization will be widely implemented,and possibility of determination ofresonant (own) frequencies of entiresystem of molecules including virionswill be a key point for that.

Author is very grateful to theCARYS�19�297 project “Spectro-vir1” of Shota Rustaveli National Sci-ence Foundation of Georgia for supportin performing the necessary investiga-tions.

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59. P.J. Kervalishvili, T.N. Bzhalava,Computer Simulation Study of Oscilla-tion Mechanisms and Physical Proper-ties of Nanosized Biostructures, Pub-lished in book: Innovative Smart Health-care and Bio-Medical Systems, CRCPress – Taylor and Francis, New York,2020, Chapter 6, 8 pages. DOIhttps://doi.org /10.1201/9781003044291.

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Fragment of the Algorithm for Releasing the Vibration Frequency Method for Viruses

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Kawasaki disease is a systemic vas-culitis that often involves medium-sizedarteries, especially coronary arteries [1].More children under the age of five areseen. Coronary artery abnormalities(CAAs) include coronary artery dilata-tion and aneurysm in 15 ~ 25% of un-treated children. In 2009, Kanegaye et al.[2] defined Kawasaki disease as Kawasa-ki disease shock syndrome (Kawasakidisease shock syndrome, KDSS).Kawasaki disease shock syndrome(KDSS) is a rare manifestation ofKawasaki disease (KD), but it can leadto serious sequelae and adverse results.The incidence of KDSS in KD patientswas 1.9% ~ 7.0% [3-6]. The incidence ofKDSS in China is lower than that in west-ern countries. In acute phase, about 5%of KD children developed hypotensionand shock. The main manifestations ofthis kind of children were tissue hypop-erfusion and hemodynamic instability, ac-companied by a clinical manifestationthat systolic blood pressure was contin-uously lower than the normal systolic de-pression value of 20% or more in chil-dren of the same age. Compared with KDchildren without shock symptoms, KDSSchildren have a higher risk of cardiovas-cular complications, such as mitral valveregurgitation and myocardial systolic dys-function, increased incidence of coronaryartery disease; resistance to immunoglob-ulin therapy; often complicated withmultiple organs

1. dIaGnosIs of KdssIn 2009, Kanegaye et al put forward

the diagnostic criteria of KDSS: persist-

ent blood pressure drop, systolic bloodpressure below 20% of the normalmean blood pressure in the correspon-ding age group or peripheral circulationperfusion disorder in children with KD.Systolic blood pressure < 70 mmHg inchildren aged 1 ~ 12 months or systolicblood pressure < [70 + 2x age (years)]mmHg in children aged 1 ~ 12 monthswas hypotension [7]. In addition, therewere KD manifestations of normal sys-tolic blood pressure and decreased di-astolic blood pressure in clinic. XueChaochao and others thought that it wasbetween KD and KDSS, which was thetransitional period of the course of dis-ease [8]. Foreign literature reportedthat KDSS accounted for 1.9% ~ 7% ofKD children [9]. About 1.78% ~ 1.90%of KD children in Taiwan had KDSS.Foreign statistics showed that KDSSwas more common in women than inmen [10] [11]. The error may be relat-ed to race, environment, sample num-ber and atypical early manifestation ofthe disease, which leads to lack ofclinical understanding and missed diag-nosis.

2. earlY recoGnItIon of KdssThe incidence of KDSS. There was

no significant gender difference be-tween men and women, although it wasreported that men were slightly morethan women [12]. Compared with non-shock KD, there was no significant dif-ference in the age of onset of KDSS

[13], which could occur in any agegroup, including adults. In contrast,KDSS was more likely to occur in in-fants under 6 months of age and childrenover 10 years of age. The overall medi-an age of onset was older than that ofKD, and it was more likely to occur inpatients with incomplete KD [14].

3. PossIble MecHanIsM of KdssThe mechanism of circulatory and

hemodynamic disorders of KD in acutephase is not clear. It is generally believedthat it is the result of multiple factors.The possible pathogenesis includescapillary leakage caused by vasculitis,myocardial systolic dysfunction andabnormal regulation of cytokines, whichmay affect each other to accelerate theoccurrence of circulatory disturbance.

3.1 capillaries leakageAlthough KD is characterized by

coronary artery damage, small andmedium vessels can be involved in thewhole body. Inflammatory factor storm,high expression of vascular endothelialgrowth factor and dysfunction of en-dothelial cells are the causes of vascu-lar endothelial injury, and then the in-crease of vascular permeability. Whenthe permeability of small blood vesselsand capillaries continues to increase, re-sulting in plasma exosmosis and loss ofsmall molecular proteins, followed bythe decrease of plasma colloid osmot-ic pressure, the significant decrease ofplasma albumin and the decrease of cir-culating blood volume [15]. The clini-cal manifestations were decreased blood

[key words] Kawasaki disease; Kawasaki disease shock syndrome;nursing;

fuYonG JIao,Children’s Hospital, shaanxi Provincial

people's Hospital. Xi’an, China

tunGala osGonbaatar,Association of Pediatric Researchers of Mongolia

wen HIe,Department of Pediatrics, Chang 'an Hospital, Xi’an China

abuduMutaIlIPu•MaIHeMutI, Class 1729, clinical medicine, Xi'an Medical College

researcHProGress of KawasaKI dIsease In sHocK sYndroMe

pressure, hypoperfusion of tissue, dif-fuse edema of the whole body and hy-drops in the third space, such as chestcavity and abdominal cavity.

3.2 Myocardial systolic dysfunctionIn patients with KD, in addition to

coronary artery damage, there are alsomyocardial cell damage and myocar-dial ischemia and myocardial infarctioncaused by coronary artery disease.Endocardial biopsies confirmed thatmyocardial fibrosis caused by dif-fused myocarditis injury is an impor-tant cause of left ventricular systolicdysfunction in patients with KD [16].The decrease of left ventricular ejectionfraction in KD is associated with theoccurrence of KDSS [17]. It should benoted that most patients with KD arein subclinical cardiac insufficiency,rather than an independent factor lead-ing to KDSS.

3.3 abnormal regulation of cytokines.Many scholars believe that KDSS

and septic shock have similar clinicalcharacteristics and immunologicalmechanism. Abnormal cytokine regula-tion and activation of intracellular sig-nal transduction pathway mediated bysuperantigen [18]. Continuous dilatationof microvessels leads to the decrease ofperipheral vascular resistance and cir-culation congestion.

4. nursInG care4. 1 nursing care of fever.Fever is a typical manifestation of

Kawasaki disease. Children withKawasaki disease shock syndrome haverepeated fever in the course of disease.The body temperature is between380Cand 390C, and the body temperatureis between 380C and 390C. Keep highfever and vital signs. Watch out forfebrile convulsion. Take positive cool-ing measures: when the body tempera-ture is not higher than 38.50C, try to takephysical cooling when the body temper-ature is not higher than 38.50C, such asusing antipyretic paste, warm waterwipe bath, drinking the right amount ofwarm water, etc., when the temperatureis more than 38.50C. At the same timeof physical cooling, antipyretic drugscan be used to cool down according to

the doctor's orders, and the body tem-perature can be measured every halfhour after taking cooling measures.Children often have the performance ofsweating when the heat recedes, wipedry in time and change the clothes intime to avoid cold and aggravate thecondition.

4.2 emergency careWhen KDSS occurs, nursing. The

child was immediately moved to the res-cue bed, the head raised 15 °, the low-er extremity raised 20 °, in order to in-crease the amount of blood in the heart.Heart rate, heart rate, pulse, blood pres-sure, transcutaneous pulse oxygen sat-uration, capillary filling time were ob-served and related nursing records weremade. Limb temperature-to a certain ex-tent, reflects the limb circulation and per-fusion, and can touch the limb to under-stand the shock during nursing. Main-tenance of effective ventilation, maskoxygen inhalation (5L/min) and timelyremoval of oral secretions and foreignbodies in children, if can not improveventilation, should be treated by me-chanical ventilation. Rapid venous vol-ume expansion can effectively increasethe volume of circulating blood, whichis the key to prevent shock deteriorationand make children turn to crisis. In nurs-ing care, two venous pathways suitablefor volume expansion can be quickly es-tablished within 5 minutes, and thethick proximal vein is selected, and thebest choice is for external jugular veinor external jugular vein. At the sametime, the Department of Anesthesiolo-gy was invited to carry out deep venouspuncture for the use of vasoactivedrugs.

4.3 Monitoring of blood pressureIf the child has shock symptoms of

hypotension on admission, it is impor-tant to correctly measure and record thechanges in blood pressure. According tothe age of the child, the cuff of differentwidth should be 2 ≤ 3 of the length ofthe upper arm. The normal average val-ue of blood pressure of different agescan be calculated by this formula, thatis, systolic blood pressure (mmHg) = 80+ (age x2), diastolic blood pressure 2 ≤3 of systolic blood pressure. Bloodpressure was measured once an hour

during the whole nursing process of thechild, and when dopamine or dobuta-mine was used, blood pressure wasmeasured every half hour if there wasa fluctuation of blood pressure in orderto adjust the dosage of the drug in atimely manner.

4.4 nursing care for the use of ex-panded drugs

The principle of both crystal fluidand colloidal fluid was adopted in theexpansion of shock. 20 ml of saline wasthe first choice in clinic, and the infu-sion was completed within 10 minutes.after rapid infusion of saline accordingto the doctor's orders, blood pressureand heart rate were monitored immedi-ately. The molecular weight of colloidalsolution is large, and the dilatation ef-fect is longer than that of crystal solu-tion, so normal saline continues to beinfused with colloidal body fluid afterexpansion. Albumin is the first choiceof colloidal fluid in clinical rescue. Thedose of 20ml/kg is completed within 30minutes. During volume expansion,attention should be paid to the wetsound of both lungs and the sudden en-largement of liver and spleen to avoidheart failure. After dilatation of lens andcolloid, blood pressure gradually re-turned to normal, consciousnesschanged, and no heart failure such aspulmonary edema, hepatosplenomegalyand so on.

4.5 nursing care of vasoactivedrugs

The combination of norepinephrineand dobutamine can play a synergisticrole in improving systemic hemodynam-ics. However, both of them are high-riskdrugs, the use process should be close-ly nursing and observation, first checkwhether the infusion pump is normal, inthe syringe and infusion tube. Paste thered mark on it. According to the normalblood pressure value of children inthis age group, the starting drug speedwas set according to the normal bloodpressure value, and the blood pressure,heart rate, blood oxygen saturation andother indexes were monitored every 30minutes according to the principle of lowconcentration to high concentration.When changing drugs, nursing actionshould be quick. When norepinephrine

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is used in peripheral veins, the local skincolor changes should be closely ob-served to prevent venous leakage. If ve-nous leakage occurs, infusion should bestopped immediately, and the infusionpathway should be changed in time tokeep blood pressure stable. At the sametime, phentolamine injection of 10mgshould be given local closure immedi-ately. The drug concentration should begradually reduced when stopping thedrug, and sudden withdrawal of the drugshould be strictly prohibited. If thechild appears blood pressure drop,drowsiness and even coma in the courseof withdrawal, the doctor should be re-ported immediately.

4.6 nursing care of gamma glob-ulin shock therapy

Gamma globulin is a blood product,before infusion, strict aseptic configu-ration operation should be carried out toevaluate the body temperature, if itreaches more than 38.50C, the doctorshould suspend the infusion. The chil-dren in this group were mentally soft anddifficult to take oral administration.Ibuprofen suppository or paracetamolwas given to embolize anus and an-tipyretic. The body temperature de-creased to less than 38.50C. Then con-figuration, first put gamma globulin atroom temperature for 15 minutes afterinput, before and after infusion of salineflushing tube, to avoid mixing with oth-er drugs to cause adverse reactions, atthe beginning of about 10ml/min, 15minutes later, if there is no adverse re-action, can speed up the infusion speed,but not more than 20ml/min [19]. In thecourse of medication, we should payclose attention to whether there are ad-verse reactions, once fever, rash and soon, immediately suspend infusion, no-tify doctors, and give antiallergic treat-ment.

4.7 corrective nursing care of hy-poalbuminemia and hyponatremia

Children with KDSS have differentdegrees of hypoalbuminemia and hy-ponatremia, which are significantlycorrelated with vascular inflammation[20]. It should be corrected slowly in thecourse of antishock therapy. The chil-dren in this group were treated with al-bumin on the first day, and the albumin

(1g/kg) was infused twice every otherday according to the doctor's orders. Af-ter 3 times, the albumin returned to thenormal range. Because it was a bloodproduct, the nursing should be infusedwithin 4 hours. Because hyponatremiacan cause nausea, vomiting, coma, con-vulsion and edema in children, sodiumshould be supplemented in time, usual-ly 24 ~ 48 hours, and blood sodium andother electrolytes should be closelymonitored in nursing.

4.8 aspirin careAspirin is a necessary drug for the

treatment of Kawasaki disease, and itis also the first choice. Aspirin has theeffect of anti-infection and anticoagu-lant. Early combined with immunoglob-ulin can effectively control the processof acute inflammation and reduce coro-nary artery disease. Every day on timeand according to the quantity to feed thechild, in order to reduce the stimulationof the drug to the gastric mucosa andform a drug-induced ulcer, the childrenare taking medicine after meals, takeproper amount of food before takingmedicine at night, do not take medicineon an empty stomach. If you havesymptoms of fever before and after tak-ing aspirin, be sure to interval at leastsix hours with Merrill Lynch or teno-lin, and ask the doctor in charge if youwant to adjust the duration of aspirinuse. During aspirin, attention should bepaid to the occurrence of bleeding,hematuria and black stool in the nose,skin, mucous membrane or gums, andthe liver function should be reviewedregularly. Tell the child not to pick hisnose with his hand; when brushing histeeth and gargling, use a soft toothbrushto gently move, if necessary, use an oralprotective bag to help the child clean hismouth; give the child a light and di-gestible diet to keep his stool unob-structed.

4.9 nursing of coronary arteryaneurysm

Children with coronary arteryaneurysm (KDSS) are prone to suddendeath caused by rupture. Nursing. Thechild was told to stay in bed and rest andreduce the work done by the heart.Closely observe whether the child hasuncomfortable symptoms, pay attention

to whether the heart rate is normal,whether the heart rate is uniform,whether the heart sound has murmurduring auscultation. For shock chil-dren, the action of turning over and pat-ting the back should be gentle, and whendefecation is difficult, the enema shouldbe given to Keselu to avoid the ruptureof coronary artery aneurysm. For chil-dren of different ages, personalitiesand psychological characteristics, taketargeted nursing measures: for older chil-dren to communicate more, to encour-age more language, to avoid increasingtheir psychological burden; for youngchildren, because of pain, fear and oth-er reasons often cry, can give toys, playcartoons to distract their attention, co-operate with treatment, if necessary togive drug sedation, in order to reduce theheart load.

4.10 nutrition careAfter the occurrence of KDSS, the

children should suspend eating, carry outtotal intravenous nutrition, and replen-ish the amount of 60 ~ 80ml/kg solutionevery day. Due to fever, rash, skin ero-sion and other reasons, children need tosupplement water-soluble vitaminsevery day to facilitate skin repair. Afterstable blood pressure and recovery ofconsciousness, the children were givena fluid or semi-fluid diet with high calo-rie, high protein and high vitamin con-tent to avoid eating raw, cold, hot,hard, sour, spicy and other foods, so asnot to affect the recovery process of thedisease.

4.11 skin and mucous membranenursing

Children with KD had conjunctivalcongestion in both eyes. When therewere more eye secretions, the eyeswere washed with saline 1 ~ 2 times aday, and erythromycin eye ointmentwas applied twice a day to avoidstrong light irradiation in the eyes.When the oral mucosa is chapped anderosive, gargle with sodium bicarbon-ate solution or saline every day, and ap-ply the mouth lip evenly after the vi-tamin E capsule is crushed every day.For finger end peeling, use disinfectionscissors to cut off, tell children not totear, avoid infection. Change sheets andclothes every day to avoid skin infec-

42

tion. Norepinephrine can cause strongcontraction of arterioles and venules ofthe whole body, and the contraction ofsuperficial vessels is more significant,resulting in dry and cold skin temper-ature, which can be covered with blan-kets, warm and dry towels applied tothe foot and other thermal insulationmeasures. There was no serious skin in-fection in all the children.

4.12 Psychological nursingThe child is relatively young, irrita-

ble and irritable during the acute peri-od, and gives more comfort and encour-agement. When in contact with thechild, there should be more limb con-tact, such as hugging, shaking hands andso on. Safe physical contact can increasethe child's sense of security. Childrencan also be prepared for favorite toys,books, or organize children and parentsto carry out some feasible and meaning-ful activities to enrich the child's lifeduring hospitalization and reduce themental stress of the child [8]. In addi-tion, try to concentrate on the operation,the action is gentle, reduce the stimu-lation to the child. Parents are worriedabout the prognosis because of thechild's condition, explain the disease,explain the disease knowledge, givepsychological support and spiritualcomfort, and establish confidence intreatment.

4.13 Health educationExplain the condition to the family

in time and give psychological support,do a good job of discharge guidance,including taking medicine as directedby the doctor, do not increase or de-crease the amount of medicine at willand observe whether there are digestivetract symptoms; give children easy todigest high vitamins, high protein foodsupplementary nutrition; regular outpa-tient review; pay attention to rest, donot exercise violently; need to be vig-ilant for coronary artery disease, 1month, 3 months, 6 months, 1 year af-ter discharge.

5. suMMarYIn a word, KDSS is a serious com-

plications of Kawasaki disease. Some ofthe early clinical symptoms of KDSS arenot typical and are easy to be missed or

misdiagnosed. Therefore, early identi-fication and timely and appropriatetreatment can quickly correct shock, re-duce coronary artery damage and mul-tiple organ injury and other seriouscomplications. It is also very importantto pay attention to the popularization ofnursing knowledge in hospitalized chil-dren. It will also improve the prognosisof children with KDSS.

reference[1] Mandal S, Pande A, Mandal D,

Sarkar A, Kahali D, Panja M. Variouscoronary artery complications ofKawasaki disease: series of 5 cases andreview of literature. [J]. Cardiovasc.Dis.Res. (2012) 3: 231e5.

[2] Kanegaye JT, Wilder MS, Molka-ra D, et al.Recognition of a kawasakidis-ease shock syndrome [J]. Pediatrics,2009123 (5): e783-e789.

[3] Qiu H, Li C, He Y, Weng F, ShiH, Pan L, et al.Association between leftventricular ejection fraction andKawasaki disease shock syndrome.Car-diol Young. [J] (2019) 29 / 178-84.

[4] Chen PS, Chi H, Huang FY,Peng CC, Chen MR, Chiu NC.Clinicalmanifestations of Kawasaki diseaseshock syndrome: a case-control study.JMicrobiol Immunol Infect. [J] (2015)48: 43-50.

al.Describing Kawasaki shock syn-drome: results from a retrospectivestudy and literature review.ClinRheumatol. [J] (2017)36: 223–8.

[6] Lin MT, Fu CM, Huang SK, WuMH.Population-based study ofKawasaki disease shock syndrome inTaiwan. Pediatr Infect Dis.[J] (2013)32:1384–6.

[7] Newburger, J.W., Takahashi, M.and Burns, J.C. Kawasaki Disease.Journal of the American College of Car-diology.(2015)67: 1738-1749.

[8] XUE Chaochao, PAN Guoquan,et al. Clinical characteristics of kawasa-ki disease in children with differentblood pressure types. Journal of Med-ical Research, 2017, 46(4): 78-82

[9] Kanegaye, J.T., Wilder, M.S.,Molkara, D., et al. (2009) Recognitionof a Kawasaki Disease Shock Syn-drome. Pediatrics, 123,783-789.

[10] Shan Mingfeng, Mei Xiaoli, etal. Clinical characteristics and relatedfactors of kawasaki disease shock syn-

drome in children. Chinese Journal ofPractical Clinical Pediatrics, 2018,33(9): 668-672.

[11] Lin, M.T., Fu, C.M., Huang,S.K., et al. (2013) Population BasedStudy of Kawasaki Disease Shock Syn-drome in Taiwan. The Pediatric Infec-tious Disease Journal, 32, 1384-1386.

[12] Gamez-Gonzalez LB, Moribe-Quintero I, Cisneros-Castolo M, et al.Kawasaki disease shock syndrome:unique and severe subtype of Kawasa-ki disease [J]. Pediatr Int, 2018, 60(9):781-790.

[13] Qi Y, Wu YH, Yang YL, et al.Clinical analysis of 16 cases of Kawasa-ki disease shock syndrome [J]. ChineseJournal of Pediatric Emergency Medi-cine, 2017, 24(12): 925-928.

[14] Taddio A, Rossi E, Monasta L,et al. Describing Kawasaki shock syn-drome: results from a retrospectivestudy and literature review [J]. ClinRheumatol, 2016, 36(1): 1-6.

[15] Chen Yuanmei, ZHANG Qi.Chinese journal of pediatric emergencymedicine, 2019, 26(6): 461-465. (in Chi-nese)

[16] Harada M, Yokouchi Y, Oharase-ki T, et al.Histopathological character-istics of myocarditis in acute-phaseKawasaki disease [J]. Histopathology,2012, 61 (6): 1156-1167.

[17] Qiu H, Li C, He Y, et al. Asso-ciation between left ventricular ejectionfraction and Kawasaki disease shocksyndrome[J].Cardiol Young, 2019,29(2): 178-184.

[18] Nagata S, Yamashiro Y, Ohtsu-ka Y, et al. Heat shock proteins and su-perantigenic properties of bacteria fromthe gastrointestinal tract of patientswith Kawasaki disease[J]. Immunology,2009, 128(4): 511-520.

[19] Shao Ying, XIE Chunhong,Wei Linlin, et al. Early observation andnursing of kawasaki disease complicat-ed with intestinal injury [J]. Nursing andrehabilitation, 2014, 13 (12): 1150.

[20] Chen PS, Chi H, Huang FY, etal. Clinical manifestations ofKawasakidisease shock syndrome: a case-controlstudy[J]. J MicrobiolImmunol Infect,2015, 48 (1) : 43.

[21] Pan Hong. Psychological char-acteristics and nursing strategies of pre-school patients [J]. Health Vision: Med-ical Edition, 2Ol4, 22(9): 703 704.

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Neonatal pneumothorax is a commonacute critical condition in neonatal NICU,accounting for between 1% and 2% of livebirths [1].In recent years, the incidence ofneonatal pneumothorax has been increas-ing due to the use of endotracheal intuba-tion, ventilator and continuous positivepressure ventilation in asphyxia resusci-tation.In order to reduce the incidence ofpneumothorax, the clinical data of 30neonatal pneumothorax children admittedto our hospital from January 2017 to De-cember 2020 were retrospectively ana-lyzed and summarized as follows.

1.1 data and methods: Pneumoth-orax was diagnosed according to ICD-10 disease code.30 cases of neonatalpneumothorax were treated from Janu-ary 2017 to December 2020, including20 males and 10 females.Gestational ageranged from 32 weeks to 41+2 weeks,including 6 cases of gestational age from32 weeks to 35+6 weeks, 3 cases ofgestational age from 36 weeks to ≤37

weeks, and 21 cases of gestational age> at 37 weeks.The birth weight rangedfrom 1700g to 4400g, including 4 cas-es with birth weight < 2500g and 26cases with birth weight ≥2500g.16 cas-es of normal delivery, 14 cases of cesare-an delivery; Apgar score < 7 in 22 cases,Apgar score ≥7 in 8 cases; There were9 cases of III degree amniotic fluid con-tamination and 21 cases of clear amni-otic fluid.There were 5 cases of prema-ture rupture of membranes and 25 cas-es without premature rupture.Therewere 7 cases of asphyxia resuscitation,5 cases of mechanical ventilation, 5 cas-es of neonatal hyaline membrane dis-ease, 9 cases of meconium inhalationsyndrome, 2 cases of neonatal pneumo-nia and 2 cases of spontaneous pneu-mothorax.Eighteen cases received en-dotracheal intubation and mechanicalventilation (HFOV), 8 cases receivedcontinuous positive pressure ventilation,and 4 cases received oxygen inhalationby headhood.Time of pneumothorax: 22

cases < 3 hours, 5 cases 3-6 hours, 3 cas-es > 6 hours after admission.

1.2 clinical manifestations: the chil-dren with mild symptoms were only mildshortness of breath, moaning, and no ob-vious pulmonary signs; Sever patientsshow varying degrees of dyspnea, de-creased percutaneous oxygen satura-tion, cyanosis, moaning, and restless-ness.During the course of non-invasiveand invasive assisted ventilation, the pa-tient's condition improved and then sud-denly experienced instability of oxygensaturation, moaning, worsening of dys-pnea, and changes in skin color (livid orpale).Physical examination: in severe cas-es, bilateral thoracic asymmetry andrespiratory movement asymmetry wereobserved. Percussion on the raised sideof the chest presented drum sound, andrespiratory sound on the affected side wasweakened on auscultation.Blood gasanalysis showed that PO2 decreasedless than 50mmHg in 23 cases (77%),PCO2 increased more than 45mmHg in15 cases (50%), SO2 decreased lessthan 90% in 21 cases (70%).Chest radi-ograph showed reduced lung volume,loss of lung texture and pneumothoraxline outside compressed lung.Severeheart, mediastinum to the healthy side dis-placement, low diaphragm; Partial dis-play of uneven lung transmittance.Forchest radiographs showing uneven trans-mittance and considering air leakage,chest CT examination was performed.

1.3 auxiliary examination(1) All children received emergency

bedside chest X-ray examination.ChestX-ray findings: some showed reducedlung volume on the affected side, lossof lung texture outside the compressedlung, and presence of pneumothoraxline. In severe cases, the heart was dis-placed from the mediastinum to thehealthy side, and the diaphragm waslow.Partial display of uneven lung

abstractobjective: to analyze the common causes, clinical features and treatment

measures of neonatal pneumothorax, and further reduce the incidence of pneu-mothorax.Methods: a total of 30 neonatal pneumothorax children admittedto our hospital from January 2017 to december 2020 were systematically re-viewed and analyzed.results: among the 30 cases of pneumothorax, patholog-ical pneumothorax was 16 (53.3%), iatrogenic pneumothorax was 12 (40.0%),spontaneous pneumothorax was 2 (6.7%).of the 12 cases with lung compressionratio ≤30%, 8 cases received conservative treatment, and 4 cases received con-servative gas absorption after thoracic ventilation.18 patients with lung com-pression ratio of >30%, 10 patients (55.6%) did not receive pleural aspirationand closed drainage under HfoV assisted breathing, and 8 patients (44.4%)received closed thoracic drainage.after treatment, 29 cases (96.7%) were curedand 1 case (3.3%) gave up treatment.conclusion: asphyxia recovery ヽmechan-ical ventilation, meconium inhaled syndrome, neonatal pulmonary hyaline mem-brane disease is the high risk factors of neonatal pneumothorax occurred, theprincipal means of treatment for mechanical ventilation (HfoV), pleural punc-ture extraction and chest closed drainage; strengthening the understanding andearly diagnosis of neonatal pneumothorax and taking the correct treatmentmeans can effectively improve the success rate of treatment.

Keywords: Pneumothorax Neonatal Etiology Treatment

ZHonGMInG Yun, YanMeI QIao, YonGlIn lIu, lIfanG lI, YanlInG lI,

Shenmu City Hospital Affiliated to Northwest University

ZHaoYu YanG,Class 02, Grade 2009, Postgraduate Office

of Xi 'an Medical College

fuYonG JIao,Children's Hospital of Shaanxi Provincial People's Hospital

corresponding author: fuyong Jiao e-mail: [email protected]

clInIcal analYsIs of 3 neonatalwItH PneuMotHoraX

transmittance.There were 6 cases of leftpneumothorax, 14 cases of right pneu-mothorax, and 10 cases of bilateralpneumothorax.Lung compression wasless than 30% in 12 cases, and ≥30% in18 cases.Some chest X-rays and CTscans are shown in Figure 1.

(2) Chest CT examination: in orderto further confirm the location, range anddegree of air leakage, 20 cases were ex-amined by chest CT examination.Among them, 10 cases were bilateralpneumothorax and 4 cases were com-bined with small volume of gas in me-diastinum.There were 10 cases of uni-lateral pneumothorax combined withsmall volume of mediastinal gas in 1case and medium volume of mediasti-nal gas in 1 case. CT showed severe ex-udation of both lungs in 18 cases.

(3) Blood gas analysis is shown inTable 1. Although blood gas analysis isnonspecific in the diagnosis of pneumoth-orax, pneumothorax is often characterizedby decreased blood oxygen partial pres-sure, increased carbon dioxide partial pres-sure, acidosis, and increased lactic acid.

1.4 treatment and outcome: All thechildren were treated with anti-infection,sedation and support for the primary pul-monary disease after admission.Theclinical symptoms and signs of 8 patientswith pneumothorax were relatively light.X-ray indicated that lung compressionwas about 10%, and oxygen chest wasabsorbed by headwear.X-ray and CTshowed lung compression of 10%~30%in 4 cases, and pneumothorax absorptionwas followed by chest puncture and ven-tilation with nasal obstruction and con-tinuous positive airway pressure.The re-maining 18 cases showed lung compres-sion > 30% by X-ray and CT, and all ofthem were treated with high frequencyoscillatory bypass (HFOV).All the 18children in this group received HFOVventilation after pneumothorax. TheHFOV machine is Draeger and Swiss

Fuping high-frequency ventilator. Theprinciple of selecting initial parametersis to improve the oxygenation and ven-tilation status of children with as low av-erage airway pressure as possible.Thepermissible partial pressure of oxygen islow, while the partial pressure of carbondioxide is high.Initial parameters: the av-erage airway pressure was 12 ~14cmH2O, the oscillation frequencywas 10 ~ 12Hz, the amplitude was 25 ~

35cmH2O, and the oscillation amplitudewas appropriate to the umbilical cord.Ini-tial parameters were selected accordingto child weight, gestational age andtranscutaneous oxygen saturation.Pa-rameter adjustment: All children weremonitored by a multifunctional monitorto maintain normal heart rate, blood pres-sure, body temperature and percuta-neous oxygen saturation between 90%and 95%.Regularly review the blood gasanalysis and adjust the parametersaccording to the results; Removalmethod: the child's vital signs were sta-ble, the transdermal oxygen saturationwas between 90% and 95%, the bloodgas analysis was normal, and the bedsideX-ray chest film showed that basicpneumothorax absorption and lung ven-tilation were significantly improved.Thechildren with closed thoracic drainagewere free of gas for 24h.According to thecondition of the original disease, it wasmaintained for 1 to 4 days, then the ven-tilator was changed to non-invasiveventilator, and the ventilator was re-moved.All the 17 cases recovered and

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Fig1 Partial chest radiograph and chest CT

Table1 blood gas analysis of 30 children

PH7.236.947.107.117.367.447.357.147.337.287.347.347.227.427.207.327.257.337.307.377.287.237.287.237.217.287.347.167.347.39

Po2 (mmHg)48.049.456.242.654.363.639.249.842.348.897.540.337.943.636.749.872.535.640.443.941.220.436.541.881.431.942.851.549.545.2

Pco2 (mmHg)51.042.568.367.840.527

42.152.639.745.834.938.253.531.452.139.344.538.840.027.147.547.847.751.250.449.142.352.438.539.9

lac (Mmol/l)3.83.55.25.13.33.15.15.23.14.63.33.75.32.32.81.44.12.12.53.52.66.22.53.11.63.52.15.35.02.0

so2 (%)88

72.897

74.794.396.484.184.088.587.999.083.877.090.673.690.995.081.082.990.582.336.780.079.597.368.685.485.987.488.9


2021

were discharged from hospital.One pa-tient gave up treatment.Of the 18 cases,10 did not receive thoracic ventilationand closed drainage, and 8 cases werecombined with closed thoracic drainage.

1.5 the resultsAmong the 30 patients with pneu-

mothorax, 16 cases (53.3%) were patho-logic pneumothorax, including 9 cases(56.3%) of mecium inhalation syndrome,5 cases (31.2%) of neonatal hyaluronicmembrane disease, and 2 cases (12.5%) ofneonatal pneumonia.There were 12 casesof iatrogenic pneumothorax (40.0%), 7 cas-es of parturient asphyxia resuscitation(58.3%), 5 cases of mechanical ventilation(41.7%).2 cases of spontaneous pneumoth-orax (6.7%).Lung compression ratio ≤30%in 12 cases, 8 cases of pneumothorax clin-ical symptoms and signs were light, X-rayindicated that lung compression was about10%, and oxygen was given to the headmask and pneumothorax absorption.X-rayand CT showed lung compression of10%~30% in 4 cases, and pneumothoraxabsorption was followed by chest punctureand ventilation with nasal obstructionand continuous positive airway pressure.In18 cases, lung compression ratio was30% >, 10 cases (55.5%) did not receivepleural ventilation and closed drainage af-ter HFOV, and 8 cases received closed tho-racic drainage (44.4%).After treatment, 29cases were cured 96.7%), 1 case gave uptreatment 3.3%).

2 dIscuss2.1 common causes of pneumothoraxThe incidence of pulmonary air leak-

age in live births is 1% ~ 2% [2], andthe incidence of air leakage in inpatientsin our hospital is 5.9‰. Alveolar pres-sure increase, alveolar hyperinflation andexpansion caused by any factor cancause alveolar rupture and air leakage,and more than half of them are pneu-mothorax.According to the causes andmechanisms of neonatal pneumothorax,the common types are pathologic, iatro-genic and spontaneous.Among the 30patients with pneumothorax, 16 werepathologic pneumothorax, 12 were ia-trogenic pneumothorax and 2 werespontaneous pneumothorax.

2.1.1 common causes of patholog-ical pneumothorax

2.1.1.1 Meconium Inhalation Syn-drome: In meconium Inhalation Syn-drome, meconium inhaled into the air-way can cause flap embolism, stimulatebronchial tubes, lead to bronchospasmand aggravate inflammation, airwayresistance is increased and lung compli-ance is inconsistent, gas is easy to en-

ter and not easy to exit, and alveolar rup-ture is easy to cause pneumothorax.Inthis group, there were 9 cases of meco-nium inhalation syndrome in pneu-mothorax, accounting for 56.3%, whichwas consistent with the reports in liter-ature [3,4]. All of them suddenly devel-oped dyspnea and cyanosis within 6hours after birth, chest X-ray and CTshowed that the lung tissue was com-pressed by 30% >, and improved afterthoracic closed drainage and mechani-cal ventilation (HFOV).

2.1.1.2 Neonatal hyaline membranedisease There were 5 cases of neonatalhyaline membrane disease, account-ing for 31.2%, all of which were prema-ture infants.The lack of surfactant in thelungs of premature infants leads to ex-tensive alveolar atrophy, decreasedalveolar stability, uneven alveolar pres-sure and different alveolar sizes, whichare prone to pneumothorax.In addi-tion, the use of CPAP and two-level as-sisted ventilation in premature infantscan also cause pneumothorax.

2.1.1.3 Neonatal pneumonia In thisgroup, there were 2 cases of neonatalpneumonia, accounting for 12.5%. Bothcases were caused by intrauterine infec-tion, which caused severe pneumonia,resulting in decreased pulmonary com-pliance and uneven lungs. Pneumotho-rax was easy to occur in the process ofrespiratory adjuvant therapy.

2.1.2 common causes of iatro-genic pneumothorax

2.1.2.1 Neonatal asphyxia resuscita-tion In this group, there were 7 cases ofneonatal asphyxia resuscitation, account-ing for 23.3%. As reported by Cui Yutao(5) et al., the incidence of neonatal as-phyxia complicated with pneumothoraxwas as high as 26.1%. Medical person-nel on the implementation of resuscita-tion of neonatal asphyxia when the airbag pressure to give oxygen when thepressure is too large or tracheal intuba-tion action is rough, the catheter is toodeep, also easy to cause pneumothorax.

2.1.2.2 Mechanical Ventilation Me-chanical ventilation and other diseases areconsidered risk factors for the develop-ment of pneumothorax and may affect theprognosis of pneumothorax. Studies [6]have shown that during mechanical ven-tilation, high positive end-inspiratorypressure (PIP) and positive end-expirato-ry pressure (PEEP) can cause the occur-rence of pneumothorax. In this group ofcases, mechanical ventilation compli-cated with pneumothorax in 5 cases, ac-counting for 41.7%. In newborns, espe-cially premature infants, lung immature,poor lung compliance, large airway resist-

ance, if the intubation position is too deep,mechanical ventilation parameters are notreasonable, such as high pressure, inhala-tion time is too long, sputum suction is notstandard caused by airway injury.In thecase of improved condition, alveolarrupture caused by unregulated pressurecan also cause iatrogenic pneumothorax[7]. In the course of treatment, the symp-toms include relief of dyspnea and sud-den aggravation of shortness of breath,persistent blueness, pale complexion,obvious trichovea of aspiration, thoracicasymmetry, thoracic eminence on the af-fected side, asymmetry of breathingsounds on auscultation, decreased percu-taneous oxygen saturation, urgent chestradiograph or chest CT examination,and urgent treatment of pneumothorax.

2.2 treatment of pneumothorax2.2.1 Conservative treatment: the

lung compression ratio of 12 cases inthis group was less than 30%, amongwhich 8 cases had mild clinical symp-toms and signs of pneumothorax. X-rayand CT indicated that lung compressionwas about 10%, and lung lesions weremild. Therefore, oxygen was given to thehead mask and pneumothorax absorp-tion was given.

2.2.2 Auxiliary ventilation after tho-racic puncture and ventilation: X-ray andCT showed lung compression of10%~30% in 4 cases. Due to the pres-ence of pulmonary inflammation andpoor pulmonary dilatation, patientswere treated with pneumothorax absorp-tion after nasal obstruction CPAP afterthoracic puncture and ventilation.

2.2.3 High frequency vibration ven-tilation or combined with closed thoracicdrainage: lung compression ratio of>30% in 18 cases, 9 cases (50%), althoughlung compression ratio of BBB>% butless than 50%, did not perform thoracicventilation and closed drainage pneu-mothorax absorption after HFOV, andclinical dyspnea improved quickly.Highfrequency concussion ventilation com-bined with closed thoracic drainage: 9cases (50%). High frequency oscillationventilation (HighFre - quencyOscillato-ryVentilation, HFOV) in our hospitalNICU utilization rate is higher thanChang Pin breathing machine, use effectis better Yulan Lin 's study showed thatPaCO2 decreased significantly after theapplication of HFOV, while PaO2 in-creased stably, both of which were sta-tistically significant compared with be-fore treatment [8]. HFOV has a tidal vol-ume less than or equal to the anatomicaldead space, a high frequency close to lungresonance, and a low mean airway pres-

46

sure.The alveolar pressure is alwaysconstant in the process of ventilation, andthe high-speed flow of gas increases thediffusion and convection effect. There-fore, effective gas exchange can be car-ried out under the condition of low in-haled oxygen concentration and airwaypressure, and lung baroinjury caused byhigh airway pressure can be avoided [9].It has a very good effect in the treatmentof air leakage.In addition to HFOV, 9 cas-es of pathological pneumothorax weretreated with closed thoracic drainage. Onepatient gave up treatment.The existingproblems of HFOV are as follows: (1)The severe effects of simultaneous pul-monary lesions in newborns with largebody weight may be worse than that ofregular mechanical ventilation.The useof preterm infants with gestational ageless than 32 weeks is limited due to im-mature brain development.In this study,a total of 18 cases of neonatal pneumoth-orax caused by various reasons weretreated with HFOV. Results: 17 caseswere cured, 1 case gave up, and no in-tracranial hemorrhage and other compli-cations were found. The application ofHFOV in the treatment of neonatalpneumothorax has good efficacy, and itis worthy of promotion in the treatmentof neonatal air leakage.

To sum up, pneumothorax sometimessymptoms are atypical, some dyspneais not obvious, but the color of the skinis pale, or pale gray, some of the per-formance of the heart rate increased, soneonates within 24 hours after birthshould pay attention to the observationof vital signs at the same time, pay at-tention to the abnormal color of the skin,the performance of dyspnea timelyconduct chest X-ray examination. ChestCT examination should be performed intime when air leakage is not confirmedby chest X - ray examination.However,for children with basic pulmonary le-sions, asphyxia resuscitation, CPAP,dual-level auxiliary ventilation and me-chanical ventilation, attention should bepaid to the changes of pulmonary signsand early bedside chest X-ray examina-tion can detect pneumothorax in timewhen the condition is not relieved or thecondition suddenly deteriorates aftercomprehensive treatment.In addition,children at high risk need continuousmonitoring of vital signs, and should bealert to pneumothorax when there areunexplained changes in vital signs.Correct endotracheal suction and the useof respiratory balloon, skilled endotra-cheal intubation, the application oflung protective ventilation strategy inmechanical ventilation, and the use of

alveolar surfactant in children withRDS can reduce the incidence of pneu-mothorax [10]. For children with lessthan 30% lung compression area andmild clinical symptoms, only conserva-tive treatment with oxygen inhalation isrequired, or even no oxygen inhalationis required. In children with spontaneousbreathing, non-tension pneumothoraxwith lung compression greater than30% May be cured by a single thorax as-piration.For children requiring CPAPand mechanical ventilation, airwaypressure should be as low as possible af-ter ventilation. For patients with persist-ent gas discharge after thorax puncture,closed thoracic drainage should be per-formed in time to reduce the adverse ef-fects on respiratory and circulatorysystems, and high frequency oscillato-ry ventilation (HFO) should be given.HFO can effectively improve oxygena-tion and increase gas exchange withoutincreasing ventilation pressure, andavoid recurrence of air leakage and re-lated lesions caused by prolonged andhigh oxygen concentration. In recentyears, pneumothorax, as one of the rou-tine applications of high-frequency os-cillatory ventilation, has been promot-ed clinically [11]. When there was nogas discharge in the drainage tube for24 hours, the respiratory sounds werenormal and symmetrical on auscultationof both lungs, and the chest X-raysuggested pneumothorax absorption, thedrainage tube could be pulled out afterthe withdrawal of the machine and theclamping tube were reexamined for 2days without pneumothorax.Patholog-ical pneumothorax frequently occurs innewborns. With the improvement ofmedical technology and the promotionof ventilator, more and more severelyill children have been treated, and theincidence of iatrogenic pneumothoraxhas also been increased [12]. Therefore,lower ventilation pressure should beused as far as possible in the treatmentof pulmonary substantial lesions.The in-cidence of pneumothorax can be re-duced by the combined treatment of lowtidal volume, permalable hypercapniaand alveolar surfactant, correct air-way management and rational use of re-suscitated airbag. For children with dys-pnea whose comprehensive treatmenteffect is poor and their condition sud-denly deteriorates, attention should bepaid to the pulmonary signs, and chestX-ray examination should be conduct-ed in time to detect pneumothorax assoon as possible.Reasonable treatmentafter the occurrence of pneumothoraxcan save the life of most children.

Thorax puncture and ventilation can re-duce the mortality rate when the respi-ration and circulation are seriously af-fected. Closed thoracic drainage com-bined with high frequency oscillationventilation is effective in the treat-ment of pneumothorax.

reference:[1]. Shao Xiaomei, Ye Hongmao, Qiu

Xiaoshan.Practical Neonatal (M). 5thEd. Beijing: People's Medical Publish-ing House. 2018: ISBN978-7-117-27403-6.

[2]. Shao Xiaomei, Ye Hongmao, QiuXiaoshan, et al. Neonatal air leak syn-drome. Applied Neonatology, 4th Edi-tion, 2010

[3]. Jin Hanzhen, Huang Demin,Guan Jixi. Practical neonatology [M].3rd Ed. Beijing: People's Medical Pub-lishing House, 2006: 451-454.

[4]. Qin Xiaofi, Fu Wanhai, YouChuming.Clinical analysis of 26 casesof neonatal pneumothorax [J]. ChineseJournal of Neonatology, 2010, 25(2):109-110. (in Chinese)

[5]. Cui Yutao, Li Kehua, Fan Xun-mei.Clinical study of neonatal pneu-mothorax caused by asphyxia. Journalof Pediatric Emergency Medicine,19952(1): 29

[6] . Apiliogullari B, Sunam GS, Cer-an S, et al. Evaluation of neonatalpneumothorax [J]. J Int Med Res, 2011,39 (6): 2436-2440.

[7]. Zhang Meijuan, Chen Lingling.Zhou Cailing, et al. Diagnosis and treat-ment of neonatal pneumothorax compli-cated by mechanical ventilation. ChineseJournal of Neonatology, 2011, 6 (4): 28.

[8]. Lin Lanyu.Efficacy of high fre-quency concussion ventilation in thetreatment of neonatal acute lung injury[J]. Chinese Journal of Misdiagnosis,2005, 5(18): 3455

[9]. Xiao ZH, LaCazet. High frequen-cy oscillating ventilation for severedyspnea in preterm infants: a report of32 cases [J]. Journal of Clinical Pedi-atrics, 2000, 18 (1): 34

[10]. Qin Xiaofi, Fu Wanhai, YouChuming.Clinical analysis of 26 casesof neonatal pneumothorax.Chinese Jour-nal of Neonatology, 2010, 25 (2): 116-117.

[11]. Wenliang Yu, Suyun Qian,Jianping Tao, Ed. Neonatal high fre-quency ventilation. Mechanical venti-lation in children, Shanghai Science andTechnology Press, 2011.

[12]. Ji Ling, Chen Dan, Li Zhirui.Risk factors of neonatal pneumothorax.Journal of Applied Medicine, 2012, 12(2): 213.

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48

It is well known that in the 21st cen-tury, modern medical-biological sci-ence is evolving so rapidly that some sci-entific terms and concepts are becomingobsolete, losing their original content andin need of renewal. Moreover, in paral-lel with new discoveries, more andmore new scientific terms are emerging,and these processes, in turn, contributeto the development of science too.

In one of our papers we tried to intro-duce a new scientific term in the Georgianscientific literature (1) and this term wasUprosi Mshoblebi (უფროსი მშობლ -ები), which due to the specificity of theGeorgian language corresponds to the word- senior parents and not Grandparents, how-ever, carry the same load in their meaning.In general, it should be noted that the Geor-gian language is rich in many scientificterms that exist in our native language (forexample, the English term - Siblings -fitsperfectly with the Georgian Dedma mi -shvili) and it can be said that in this regardwe are not so bad, but any language is aliving organism by nature looks like andrequires particularly careful handling.

The same applies to our Georgian lan-guage. At the same time in the name of sci-entists and linguists, it must be said that re-cently due to the rapid development of bi-ology and in particular molecular biologyand genetics and on the other hand thespread of new diseases (e.g. COVID-19widespread worldwide) occurred andmany important scientific terms havebeen established in the world scientific lit-erature. But lately our attention has beendrawn to the term molecular mimicry andthe amazing ability of parasites to use mo-lecular mimicry to significantly inhibit theaction of our immune system even in thebrain itself. It also seemed interesting so-called Müllerian mimicry - is a naturalphenomenon in which two or more well-defended species, often foul-tasting and thatshare common predators, have come tomimic each other's honest warning signals,to their mutual benefit.

At the same time mimicry - phenom-enon characterized by the superficial re-semblance of two or more organismsthat are not closely related taxonomical-ly. This resemblance confers an advan-

tage - such as protection from predation- upon one or both organisms by whichthe organisms deceive the animateagent of natural selection.

Mimicry is widespread particularlyamong butterflies and moths. It is alsofound in various birds and some mam-mals. But what about humans?

In ordinary life, people quite oftenimitate famous actors, singers, politi-cians, dancers, athletes, scientists andeven gangsters. Moreover, it can be saidthat they almost live their lives, dresslike them, talk like them, dance likethem, sometimes play football likethem and try and, if nothing else, at leastlook like their idols with their hairstyles.However, apart from this, there arepairs of people who carry completelydifferent genes and yet bear such astrong resemblance to other humans thatsometimes it is so difficult to distinguishthem from each other as identical twins.

To prove that humans also have the abil-ity to mimic, we decided to include in thispaper an excerpt from a book by the fa-mous American scientist David Eagleman;

tHe braInthe story of youEvery moment of our lives, our

brain circuitry decodes the emotions ofothers based on extremely subtle facialcues. To better understand how weread faces so rapidly and automatical-ly. American scientist David Eagle-man invited a group of people to his lab.Scientists placed two electrodes ontheir faces- one on the forehead and oneof the cheek-to measure small changesin their expressions. Then they hadthem look at photographs of faces.

When participants looked at a photothat showed, say, a smile, or a frown, sci-entists were able to measure short peri-ods of electrical activity that indicated par-ticipant`s own facial muscles were mov-ing, often very subtly. This is because ofsomething called mirroring: they were au-

suMMarYafter reading this paper, you may get the impression that the experiments

conducted by david eagleman were more about empathy than mimicry, butthere are so many genetic and epigenetic programs working in our body atthe same time that sometimes it is very difficult to say where mimicry beginsand ends. and in general, is it mimicry?!

Key words: genetic, epigenetic, mimicry, senior parents, Grandparents, genesexpression.

daVIt tsKHoMelIdZe, Department of molecular biology and parasitology (TSMU)

Medea tsKHoMelIdZe,Psychologist (Tbilisi,Georgia)

MIMIcrY In HuMans

KALEIDOSCOPE OF INTERESTING WORKS

(a) Cuckoo bee(b) Yellow jacket

tomatically using their own facial mus-cles to copy the expressions they were see-ing. A smile was reflected by a smile, evenif the movement of their muscles was tooslight to be visually obvious. Withoutmeaning to people ape one another.

At the same time this mirroringsheds light on a strange fact: coupleswho are married for a long time beginto resemble each other, and the longerthey have been married, the stronger theeffect. Researchers suggests this is notsimply because they adopt the sameclothes or hairstyles, but because they`vebeen mirroring each other`s faces for somany years that their patterns of wrin-kles start to look the same.

Why do we mirror? Does it serve a pur-pose? To find out, David Eagleman invit-ed a second group of people to the Lab-similar to the first group, except for one:this new group of people had been exposedto the most lethal toxin on the planet-thisis the Botulinum toxin, derived from a bac-terium, and it`s commonly marketed un-der the brand name Botox. When inject-ed into facial muscles, it paralyzes themand thereby reduces wrinkling.

However, beyond the cosmetic ben-efit, there`s a less known side effect of

Botox. Scientists showed Botox usersthe same set of photos. Their facial mus-cles showed less mirroring on ourelectromyogram. No surprise there-their muscles have been purposelyweakened. The surprise was some-thing else, originally reported in 2011by David Neal and Tanya Chartrand.Similar to their originally experiment,David Eagleman asked participantsfrom both groups (Botox and non-Botox, to look at expressive faces and

to choose which of four words best de-scribed the emotion shown.

On average, those with Botox wereworse at identifying the emotions in thepictures correctly. Why? One hypothe-sis suggests that the lack of feedback fromtheir facial muscles their ability to readother, we all know that the less mobilefaces of Botox users can make it hard totell what they are feeling; the surprise isthat those same frozen muscles canmake it hard for them to read others.

2021


references:1. Eagleman DavidThe brain the story of you-20172. Tskhomelidze Davit-About of some peculiarities of genes expression-2021

SOCIAL. ECOLOGICAL& CLINICAL PEDRIATRICS - 2021https://www.google.com/search?q=mimicry+meaning&rlzhttp://www.futura-sciences.us/dico/d/botany-mullerian-mimicry-50003947/

an adaptation where an animal protects itself by

looking like another animal

mimicryfake real coral snake king snake

Early observations on make-up twinsshowed that their birth was quite rare andunique, although the percentage of birthrates for both monozygotic and dizygot-ic twins has increased significantlyaround the world recently (1). This is dueto several factors, including the fact thata large proportion of women in the

world become pregnant between the agesof 30 and 40. In addition to excessiveconsumption of new means of fertiliza-tion, which can fertilize several egg (2).It is no coincidence that the birth of twinsis called an "experiment in nature" andallows us to study the influence of ge-netic, epigenetics and environmental

factors on an individual (3). Moreover,the twin research method helps scientiststo determine the role of genes and envi-ronmental factors in the development ofthe disease and to establish real symp-toms for example for COVID-19 (4).

The aim of our study was to determinehow the difference in the health of twins

suMMarYthe aim of our study was to determine how the difference in the health of

twins was affected by a seemingly insignificant factor such as fear of animals,particularly dogs. for this we interviewed the twins among which the attitudeto the dogs was different, one of the twins had a fear of dogs and the other hadsome pleasure in interacting with animals. specific questionnaire was used forthis. It was revealed that each twin who had a sense of fear for dogs was moreallergic comparing with its twin. It’s noteworthy that parasite invasion caseswere rare among them. the immunity of animal-loving twins was still foundto be more resistant to infectious diseases. It is obvious that relationship withanimals act as an environmental factor that may influences on various genet-ic programs both in monozygotic and dizygotic twins.

d. tsKHoMelIdZe, n. cHIladZeTbilisi State Medical University, Department of Medical Biology and Parasitology,Tbilisi, Georgia

about soMe PeculIarItIes

of twIns


2021

was affected by a seemingly insignificantfactor such as fear of animals, particular-ly dogs. For this we selected only casesof those twins where one of the twins hada fear of dogs and the other had somepleasure in interacting with dogs. We dis-tributed them questionnaires in which weasked the following questions:

1. Which twin was born first andwhich was born second?

2. At what time intervals did they dif-fer at the time of birth?

3. What was the difference betweenthem in terms of weight and height at thetime of birth and now?

4. Which twin was the leader amongthem?

5. Which was right-handed andwhich was left-handed and if they dif-fered from each other in this sign?

6. Were their fingerprints identical or not?7. Did they have a different calligra-

phy and signature?8. Whether they had their own spo-

ken language?9. Did they have moles or any differ-

ent marks on the body?10. Which twin was most bothered by

dental problems?11. Which foods did they prefer and

what was their favorite dish?12. Did they like to dress alike and

which twin was the leader in this regard?13. Did they always live in the same

environment or for some time theyhad to separate for different reasons?

14. Did their parents, relatives andfriends choose them from each other(question was only for monozygotictwins)?

15. Do strangers realize that they area dizygotic twins (question was only fornon-identical twins)?

16. Which twin was more suscepti-ble to infectious diseases and which wasmore severe?

17. Whether any of the twins hadcontracted an infectious or invasivedisease that did not affect any of them?

18. How did they react to the mosquitobite and how often did the insect bite them?

19. Which twin was afraid of dogsand which was not?

20. Were they bothered by allergies in gen-eral and allergies to dog fur in particular?

21. What is their hobby?Based on the answers to the question-

naires, we came to the conclusion thata survey of only 4 twins did not allowus to get comprehensive answers tosome of the questions related to thestudy of twins. However, on the otherhand, we found that each twin who hada sense of fear for dogs was more aller-gic comparing with the second. To oursurprise, sisters which were monozygot-ic twins and had the same fingerprintsrevealed different attitudes towardsdogs, i.e. fear of an animal was a com-mon occurrence for one of the twins, theother dreamed of having an animal in thefamily. As for infectious diseases, the ad-

vantages of animal-loving twin are notso obvious here. In only one case bothtwins suffered similarly from the sameinfectious disease. Also, the case of in-festation has been reported only once,and here the "scared" twin of dogswas more easily cured of parasitic dis-eases. As for the rest of the cases, the im-munity of animal-loving twins was stillfound to be more resistant not only toinfectious but also to other diseases.

In our opinion, the method of twins isa very important method in the study ofthe development of various diseases. Ofparticular interest in this regard is the dif-ferent "tolerance" of each twin in bothparasitic and infectious diseases. At thesame time of interest are allergic diseaseswith different currents in both monozy-gotic and dizygotic twins and the role ofthe environment in the dynamics of thedevelopment of this disease. It is no co-incidence that interactions with animalsplay a role in boosting immunity, al-though it should be noted that the num-ber of animal-borne parasitic diseases hasrisen sharply around the world recently,and adherence to rules such as "hand hy-giene" and other approaching of hygienewould help people to feel protectedfrom these kinds of diseases and to"make friends" with animals better.

50

references:1. national Vital statistics reports, Vol.68, №13, 20192. nessa carey, the epigenetics revolution, columbia university Press,

new York -2012, pp75-813. https: //covid.joinzoe.com/us-post/genetics-covid4. https: //www.medrxiv.org/content/10.1101/2020.04.22.20072124v25. https: //pubmed.ncbi.nlm.nih.gov /11733749/ lllll

oVerVIew of GHanaGhana is a Sub-Saharan African coun-

try in the West Africa and shares a bor-der with Togo to the East, Cote’ d'Ivoireto the West, Burkina Faso to the North andthe Atlantic Ocean at its southern coast.Ghana has the largest economy in West

alHaJI adaM abubaKarI,Henan University of Chinese Medicine, China

soloMon GuManGa,Tamale Teaching Hospital, Ghana

Hawawu HusseIn,Tamale Teaching Hospital, Ghana.

Tehran University of Medical Sciences, Iran

suMMarYthe Government and MoH have taken serious measures since the first

reported cases of coVId-19 in Ghana. despite a large number of recover-ies and low death rates the cumulative cases of coVId-19 would continueto rise since new infections are occurring. Most of the deaths were linked toexisting health problems or chronic cardiovascular and respiratory condi-tions, diabetes and malignant diseases.

coVId-19 sItuatIon InGHana-brIefanalYsIs

Africa and currently has 16 administra-tive regions. The estimated population is31,070,940 people as of the year 2020

Ghana recorded its first two cases ofCOVID-19 on the12th of March 2020 asimported cases one each from Turkey andNorway. The laboratory test confirmingthe two cases was performed at the No-gushi Memorial Institute for Medical Re-search in the capital city Accra. The cu-mulative case count as at 16th July is over26,000 confirmed cases with over 22,000recoveries/discharges, 139 deaths and3716 active cases. In Late May 2020, theGhana Health services reported that over91% of cases were asymptomatic. Also,preliminary data released by the GhanaHealth Service showed about 80% ofdeaths were attributable to co-morbidities.

The current trend in cases reportedshows community infections are prevalentat about 6% in samples tested. The rate ofincrease in the cumulative cases does notappear to have an exponential trend but theabsence of a sustained flattened curvemeans more needs to be done to minimizeCOVID-19 infections. Currently, the bor-ders of Ghana are still closed to the inter-national community; however entry of thecountry through unapproved routes pos-ing serious challenges to the fight againstCOVID. There is also the lack of adher-ence to preventive measures such as socialand physical distancing, wearing facemask and hand washing which the govern-ment has been advocating since the par-tial lockdown was lifted in mid April 2020.The figures 1-3 below shows some details.2021


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Fig. 2. Distribution of COVID-19 cases and 7 days moving average in Ghanaby date sample taken. March - July 2020

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Fig. 3.

42% 58%

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GENDER DISTRIBUTION

Fig. 1. Regional Distribution of Confirmed, Recovery, and Active cases of COVID-19 (16/7/2020)

THE SITUATION OF COVID-19 IN GHANA

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2021

Government Preventive strategiesfor the General Public

Since the day of the confirmation ofthe first cases (12th March) of theCOVID-19 in Ghana, the Governmentand the Ministry of Health together withthe Ghana Health Service have institut-ed various strategies to prevent thespread of the infection. Some of thestrategies include;

1. Intensive General public education

on COVID-19 on symptoms and pre-ventives measures.

2. On the 15th of March publicgathering including conference, schoolsworkshops were suspended.

3. On March 28, 2020, the governmentof Ghana imposed lockdown restrictions intwo regions (Greater Accra and Ashanti re-gions) but it was lifted after three weeks.

4. Travel restrictions were issued onthe same date.

5. Transport operators were advisedto observe social distancing,

6. Stay at home, observe social dis-tancing, and avoid handshaking.

7. Wash your hands often with soapand water for at least 20 seconds.

8. Cover your cough or sneeze witha tissue, dispose of the tissue in aclosed bin, and then wash your hands.

9. Always wear a mask, particularlywhen leaving home.

10. Avoid touching your eyes, nose,and mouth

11. Avoid contact with people whohave fever, cough, or difficulty in breathing.

12. Call the designated emergencyline(s) 112 and 311 for COVID-19 or thenational ambulance service.

reference1. https: //ghanahealthservice.org/ -

covid19/, accessed July 16, 2020.2. https: //mobile.ghanaweb.com -

/GhanaHomePage/NewsArchive/Coro-navirus-91-of-infected-Ghanaians-do-not-develop-symptoms-962428., ac-cessed 30th May 2020

3. https: //www.moh.gov.gh/presi-dent-ak ufo-addo-addresses-nation-on-measures-taken-by-govt-to-combat-the-coronavirus-pandemic/, accessed 30thMay 2020

4. https: //ghanahealthservice.org/ -covid19/archive.php#

52

region

ahafoashantibonobono easteasterncentralGreater accranorthernnorth eastotisavannahupper eastupper westVoltawesternwestern northtotal

cases

9852591072059481110

136902679

12857282704182140200

24988

recovered/discharged

114,786

96198830866

110931707

10248275703502025140

21067

% recovered/discharged

11.22 91.01 89.72 96.59 87.55 78.02 81.03 63.67 77.78 79.69 84.21 97.52 100.00 83.73 94.63 70.00 84.31

active cases

87424117

1142342536901259406711360

3782

abstractKawasaki disease (Kd) is an autoimmune disease with acute

vasculitis, mainly involving the coronary artery, and is current-ly the main cause of acquired heart disease in children.as theincidence of Kawasaki disease increases year by year, its eti-ology and pathogenesis have attracted more and more atten-tion and attention from scientific research and clinical person-nel.epidemiological studies have shown that Kawasaki diseaseis closely associated with innate inheritance and the acquiredenvironment, and that infection is the main predisposingfactor.epigenetic, affected by the gene interaction with the en-vironment, is caused by not changing the gene sequence Inher-itable alterations in cellular phenotypes and altered gene expres-

sion can reasonably explain the interconnection of genetic geneswith acquired factors in Kd.the analysis of epigenetic factorscan provide the diagnosis of Kd and predict the biomarkersof Kd, and can contribute to the development of pharmacoge-nomics and targeted therapies for Kd.this paper analyzes theexisting literature on the epigenetics of dna methylation, mi-crorna, and long-chain non-coding rna, summarizes its re-cent research advances, and discusses how these mechanismsare involved in the pathogenesis and development of Kd andcontribute to the study of biomarkers associated with Kd.

Key words: Kawasaki disease; Epigenetics; DNA methy-lation; Noncoding RNA

wanG cHenYue,Shaanxi Kawasaki disease diagnosis and treatment center,

Shaanxi province people's hospital, Children's third affiliated hospital of xi 'an jiaotong university, shaanxi province, 710068

JIao fuYonG,shaanxi Kawasaki disease diagnosis and treatment center, xi' an jiaotong

university third affiliated hospital, shaanxi province, 710068

fenG JIanYInG.shaanxi Kawasaki disease diagnosis and treatment center,

shaanxi people's hospital, the third affiliated hospital of xi' an jiaotong university, shaanxi province, 710068

ProGress In tHe ePIGenetIcs of KawasaKI dIsease

Kawasaki disease (KD), also knownas mucocutaneous lymph node syn-drome, was first reported by Japanesedoctor Dr. Tomisaku Kawasaki in 1967.The main clinical manifestation is per-sistent fever for more than 5 days, lipand oral mucosal changes, pleomorphicskin rash, non-suppurative lym-phadenopathy in the neck, conjunctivalhyperemia in both eyes, rigid edema ofhands and feet, and peeling of the fin-gertips [1]. KD mainly affects childrenunder 5 years of age. The incidence ofAsian children is higher than that in Eu-ropean and North American countries,and there are obvious gender differences,more men than women [1]. Accordingto the results of the national epidemio-logical survey of Kawasaki disease inJapan, the incidence of Kawasaki dis-ease in children under 5 years of agefrom 2015 to 2016 was (309.0~330.2)per 100,000 [2]. The results of the epi-demiological survey of Kawasaki dis-ease in South Korea showed that the in-cidence of Kawasaki disease in childrenunder 5 years of age in 2014 was 194.7per 100,000 [3]. The results of the re-gional epidemiological survey in mycountry showed that the incidence ofKawasaki disease in children under 5years old was (40.9~55.1) per 100,000in Beijing from 2000 to 2004 [4];(30.3~71.9)per 100,000 in Shanghaifrom 2008 to 2012 [5]. The main patho-logical changes of KD are inflammato-ry lesions of small and medium bloodvessels throughout the body, especial-ly coronary arteries [6]. The standardtreatment for KD is intravenous gammaglobulin combined with high-dose as-pirin. Although it can significantly re-duce the incidence of coronaryaneurysms, there are still coronary ar-teries abnormalities (CAAs) [7].

In recent years, studies at home andabroad have found that the incidence ofKD is significantly related to environ-mental infections, genetic susceptibil-ity and immune response. Epidemiolog-ical and clinical reports indicate that KDcan be triggered by streptococcus,staphylococcus aureus, mycoplasma,chlamydia, boca virus, rhinovirus, ro-tavirus, measles virus, adenovirus, par-vovirus B19, fungi, etc.[8-12]. Thesusceptibility to KD is closely related togenetic factors. The role of epigenetics

in diseases where genetic inheritanceand environmental factors influenceeach other has been extensively explored[13-14]. The concept of epigeneticswas first proposed by Waddington in1942. It is a process of studying howgenotypes produce phenotypes. Throughvarious mechanisms such as DNA andhistone chemical modification, RNA in-terference, chromatin remodeling, etc.,it affects and regulates the function andcharacteristics of genes, determines theway of gene expression, and can bepassed on to offspring through cell di-vision and proliferation cycles [15]. Atpresent, the research on epigenetics athome and abroad mainly focuses on theregulation mechanism of gene expres-sion changes. Some scholars haveshown that epigenetic regulation anddysfunction are increasingly importantin human physiology and disease, andthey play an important role in thepathogenesis of rheumatic immune dis-eases, tumors, cardiovascular diseasesand other diseases [16-20]. Relatedstudies have shown that epigenetics ismore sensitive to environmental stim-uli and plays an important role in the oc-currence and development of environ-mental-related diseases. In recent years,some scholars have conducted relatedresearch on the epigenetic regulation ofgenes involved in the pathogenesis ofKD. Epigenetic modification can occurin several ways, including covalentmodification of cytosine (such as DNAmethyltransferase methylation), post-transcriptional modification of histones(such as acetylation, phosphorylation,phosphorylation, methylation, citrulli-nation, citrullination, ubiquitination,ribosylation and subunitization) andthe regulation of RNA-based transcrip-tion mechanisms [21]. This article fo-cuses on the epigenetics research relat-ed to KD, and then provides new ideasfor the pathogenesis of KD, early recog-nition, biomarkers, and new treatments.

1.tHe role of dna MetHYlatIon In KdDNA methylation is an important part

of epigenetics. It is the earliest discov-ered and most typical epigenetic mod-ification. It plays an important role inmaintaining cell structure, function,genetic factors and disease occurrence

and is the most widely studied epigenet-ic modification in KD. The mechanismof DNA methylation is regulated by aset of DNA methyltransferases (DN-MTs) and other accessory proteins.Under the action of DNMTs, S-adeno-sylmethionine (SAM) is used as amethyl donor, it combines with the C5position of cytosine to form a chemicalmodification process of 5-methylcyto-sine (5mC) [22]. This modification re-action mainly occurs at the cytosine-gua-nine (G) dinucleotide (CpG) site [23].The promoter region, some exons, andintron-rich regions of CpG dinucleotidesof housekeeping genes are called CpGislands. In the entire genome, CpG is-lands are usually located in the promot-er region of genes [24]. The covalentbinding of methyl groups to the CpG is-lands of the genome can regulate geneexpression without changing the genesequence, thereby affecting protein ex-pression. DNMTs family includingDNMTI, DNMT3A, DNMT3B,DNMT3L, DNMT3L-AS1. DNMTInot only maintains DNA methylationlevel, but also plays an important rolein the expression of T lymphocyte dif-ferentiation stage. The main function ofDNMT3A and DNMT3B is to initiatemethylation[25-26], its epigeneticchanges play a very important role inimmune pathogenesis. In the humangenome, methylated genes are usuallyrelated to actively transcribed genes. Hy-permethylation of CpG islands in thepromoter region can lead to long-termstable gene suppression by recruitingtranscription repressors or masking thebinding of transcription activators [27].At the overall or individual gene level,the dynamic changes of DNA methyla-tion are essential for normal develop-ment and cell differentiation in diseases[28].

Huang et al. conducted genomicDNA methylation and gene expressionanalysis on KD and found that the ex-pression levels of DNMT1 andDNMT3A in KD patients were signif-icantly lower than those in the normalcontrol group, and the transient DNAmethylation process occurred in theacute stage of KD [29]. Li et al. studiedthe changes in DNA methylation beforeand after IVIg administration in KD pa-tients, and proved that IVIg treatment

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mainly changes DNA methylation by re-ducing methylated CPG markers, andthat genes that change DNA methylationare also clearly related to inflamma-tion[30]. Chen et al. studied the differ-ence in methylation between KD pa-tients and normal controls and found thatthe methylation of the CpG region of thetwo is significantly different [31]. Dif-ferent methylated regions contain genesinvolved in inflammatory response, in-nate immunity and chemokine signalingpathways [31]. KD-related epigeneticchanges can be observed in FCGR2A,matrix metalloproteinases (MMPs),toll-like receptors (TLRs), NOD-like re-ceptors, HAMP and other genes, provid-ing a new basis for the pathophysiolo-gy of KD.

TLRs are one of the initial respon-ders involved in the activation of the in-flammatory response by the immunesystem, and they are mainly involvedin non-specific immune and inflamma-tory responses. TLRs widely recognizethe characteristic pattern moleculespresent on bacteria (lipopolysaccharide)and viruses (dsDNA/RNA, ssDNA/ -RNA), and mediate inflammation andcytokine by activating protein kinases(such as IRAK1/4, TBK and IKKi, etc.)biosynthesis. Except TLR3 and TLR7in the acute phase of KD, the mRNAexpression of TLRs in KD patients hasincreased. However, compared with thenormal control group, the expressionlevels of methylation pattern moleculeson TLR1, 2, 4, 6, 8, and 9 in the acutephase of KD patients were lower. Af-ter IVIg treatment, this difference ismore significant [32]. Studies haveshown that stimulating TLR2 andTLR4 with LPS can regulate the ex-pression of IL-2, IL-6, IL-10, MCP-1,TNF-α and INF-β in the KD mousemodel. This observation provides ev-idence that KD is triggered by bacte-rial infection [33-34].

In the acute phase of KD, the activa-tion of macrophages from M1 to M2 hasbeen studied. In recent years, genechip arrays have been used to analyzethe transcriptome of patients with acuteKD. In addition to the markers associ-ated with M2 macrophages, the expres-sion of TLR2 and IL2RA (M1macrophages) has increased (such asMS4A4A, MS4A6A, TLR1, TLR8,

TLR5, CD36, CCR2 and ARG1). Thepromoter regions of these genes are ina state of hypomethylation. IVIg treat-ment for KD patients further enhancesthe expression pattern of these genes byenriching the hypomethylation state. Ab-normal neutrophil activation is also re-lated to KD. Increased expression ofCD177, a neutrophil activation markerwith abnormal methylation patterns,was observed in KD patients. The lev-el of CD177 in the VIg(IVIg)-sensitiveKD patient group decreased, but the lev-el of the IVIg resistant KD patientgroup increased [35].

Fc receptors in immune cells [im-munoreceptor tyrosine-based activa-tion motif (ITAM) related receptorfamily] can bind to antibodies orantigen-antibody complexes to helpregulate phagocytosis, degranulationand cytokine biosynthesis [36, 37]. Inrecent years, studies have found thatchanges in the expression level andfunction of Fc receptors are related tothe occurrence of rheumatic immunediseases [38-40]. The genome-widestudy (GWAS) has confirmed thatthe FCGR2A gene is a susceptibilitygene for KD. FCGR2A mainly en-codes the immunoglobulin IgG (Fc re-gion receptor II-a) receptor which iswidely expressed in activated immunecells. Studies have shown that themethylation level of this gene affects thebinding of IgG2 to its receptor [41]. Alatest GWAS study found that, comparedwith the control group, the FCGR2Agene of KD patients has 15.54% epige-netic regulation of hypomethylationmode. Compared with IVIg-sensitiveKD patients, IVIg-insensitive patientsalso have significantly higher levels ofhypomethylation [42].

2. tHe role of MIcrornas In KawasaKI dIseaseMicroRNAs (miRNAs) are endoge-

nous, single-stranded non-coding smallRNAs (18-25 nucleotides long), whichplay an important role in controllingmRNA translation. Non-coding RNA istranscribed but not converted into pro-tein, but as an epigenetic mechanism toregulate gene expression. They regulatepost-transcriptional gene expression bycombining the translation part, and

have the function of inhibiting the tran-scription and translation of target mRNAor being able to cut target mRNA andpromote its degradation [43, 44]. MostmiRNAs are highly conservative, se-quential and tissue specific. The expres-sion of miRNA is controlled by the epi-genetic mechanism, which itself alsocontrols the epigenetic mechanism,forming an "epigenetics-miRNA regu-latory loop", and the abnormality of itsregulation link is related to many dis-eases [45].

miRNA has a unique expressionpattern, so it is used as a new non-inva-sive biomarker for disease diagnosis[46]. It has been reported that miRNAscan be released in peripheral blood, andthese miRNAs are related to certain spe-cific pathophysiological conditions[47]. Therefore, peripheral serum miR-NAs are widely used as diagnostic andtherapeutic biomarkers for various dis-eases. According to reports, the expres-sion of abnormal miRNAs is closely re-lated to immune diseases, cardiovascu-lar diseases, inflammation and tumors[48-51]. Many studies at home andabroad have shown that miRNAs playan important role in the pathogenesis ofKD [52]. Studies have shown that thereare differences in the expression ofmiRNA in KD patients. In the acutephase of KD, the expression of miR-143,miR-199b-5p, miR-618, miR-223 andmiR-145 is significantly higher [53-56].Another study showed that in KD pa-tients, serum miR-200c and miR-371-5p levels were significantly higher thanhealthy controls. These miRNAs mayplay an important role in the pathogen-esis of KD and can serve as potentialbiomarkers of KD [57]. Scholars havestudied the role of serum miRNA, suchas miR-1246, miR-4436b-5p, miR-197-3p and miR-671-5p, as biomarkersin KD [57-60]. Zhang et al. conducteda study on 102 patients with KD. Andfound that the serum levels of miR-200cand miR-371-5p were significantly in-creased in the acute phase of KD; in pa-tients with IVIG-resistant KD, theirlevels were also higher; the study alsoshowed that after treatment, its level de-creased from before [61]. In anotherstudy by Zhang et al., plasma miR-328,miR-575, miR-134, and miR-671-5phave been shown to be potential organ-

54

isms for diagnosing KD and potentialbiomarkers for predicting the outcomeof IVIg treatment by affecting the ex-pression of inflammatory genes [62].Wang et al. showed that in KD, hsa-let-7b-5p and hsa-miR-223-3p were slight-ly down-regulated, while miR-200c,miR-197-3p and miR-671-5p levelswere up-regulated [63]. Research by Liet al. showed that, compared withhealthy controls, the expression of 18miRNAs in the plasma of KD patientsis different. miR-125a-5p is signifi-cantly increased in the plasma of KD pa-tients. It induces vascular endothelial cellapoptosis by regulating the target geneMKK7, and plays a role in the pathogen-esis of KD [64].

3. tHe role of lonG non-codInG rnas In KawasaKI dIseaseLong non-coding RNAs (lncRNAs)

are non-coding RNAs with a lengthgreater than 200 nucleotides, whichparticipate in the regulation of variousprocesses in cells by regulating genetranscription. More than 27,000 lncR-NAs have been found in the humangenome, and new studies have shownthat their functions are closely relatedto the development of human diseases[65-68]. Ko et al. studied the changes inthe expression of lncRNA in 37 KD pa-tients, and the results showed that thetranscription of XLOC_006277 in IVIg-sensitive KD patients was too high in theacute phase and decreased after IVIgtreatment; Higher levels ofXLOC_006277 transcription were alsofound in KD patients who later devel-oped CAAs [69].

Studies have found that lncRNAcan enhance the inflammatory responseby increasing the transcription of pro-inflammatory cytokines and other in-flammatory target genes or enhancinginflammatory signals. THRIL (TNF- andhnRNPL related immunomodulatorylncRNA) is one of many lncRNAs in-duced by TLR2 activation [70].CXCL10 is one of the genes regulatedby THRIL that has been discovered sofar. It is up-regulated at the acute stageof KD patients and has been confirmedas a biomarker of KD [71]. In a studyof 17 patients with KD, it was found thatin the acute phase of KD, when the level

of TNFα increases, the expression oflinc1992/thirl is low, so linc1992/thrilis considered to be a new biomarker forimmune activation of KD.

lncRNAs are induced to expressduring inflammatory response and reg-ulate gene transcription during the in-flammatory response. At present, thereare few studies on KD and lncRNAs, butstudies have shown that KD is closelyrelated to changes in the expression oflncRNAs. In order to understand the bi-ological functions and roles of lncRNAsin KD, more research is still needed todiscover new treatment strategies andevaluate as biomarkers.

In summary, KD, as a relativelycommon immunoinflammatory diseasein children, is often accompanied bycoronary artery damage, and even severecomplications such as coronaryaneurysm rupture, myocardial infarction,and sudden death, which affect thegrowth and development of children,and it brings a heavy psychological andfinancial burden to the family. KD iscontrolled by both heredity and environ-ment. Changes in the external environ-ment closely affect the occurrence anddevelopment of KD, so further re-search on this disease is needed interms of epigenetics.

The current understanding of epige-netics in KD is still preliminary. This ar-ticle describes several new biomarkersfor KD diagnosis and disease prediction.Most of the studies are based on single-center studies with a limited number ofpatients, and a larger sample size isneeded for verification. As the switch ofgene regulation, epigenetics can providenew ideas for the pathogenesis of KD,early identification, biomarkers, newtreatments and other aspects of relatedresearch on epigenetic regulation mech-anisms.

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The new coronavirus (SARS-CoV-2)has caused huge losses to human life andeconomy [1-2]. 334,981 confirmedCOVID-19 cases and 14,652 deathswere reported in 190 countries and terri-tories, but data on the epidemiological andclinical characteristics of pediatric patientsare limited. Children have become sus-ceptible to 2019-nCoV infection due toimmature immune function. As of 24: 00on February 7,2020,285 children withnew-type coronavirus pneumonia were re-ported nationwide, including 10 new-borns. Epidemiological investigationssuggest that the population is generallysusceptible to the new coronavirus, andsome children have a clear family gath-ering history [3-4]. On March 3, the Na-tional Health Commission stated in theupdated "Pneumonitis Diagnosis andTreatment Program for New Coron-avirus Infection (Trial Version 7)" thatchildren, infants, and young childrenwere also affected. Some children andneonatal cases may have atypical symp-toms, manifested as gastrointestinalsymptoms such as vomiting and diarrhea,or only manifested as poor spirit and short-ness of breath. Mild children showed onlylow fever, mild fatigue, and no clinicalmanifestations of pneumonia.

obJectIVes and MetHodssubject retrospective case sum-

mary.Five children who were diagnosed

with SARS-CoV-2 new coronavirusinfection through nucleic acid testing

suMMarYobjective to explore the clinical, laboratory, imaging features and main

points of diagnosis and treatment of 5 children with novel coronavirus infec-tions caused by family clusters. Methods a retrospective analysis of clini-cal data of five cases of children infected with sars-coV-2 in family clus-ter outbreak at Henan children's Hospital (children's Hospital affiliated toZhengzhou university) from January to february 2020. Results five chil-dren from four families were included, involving 20 family members infect-ed with the novel coronavirus. Patients: 2 males and 3 females. age from5 days to 8 years and 6 months. four of the five patients showed low to mod-erate fever. fever lasted 2 to 18 days. example 3 had no other clinical man-ifestations such as fever. Type: one case of asymptomatic infection, threecases of mild, and one case of critical illness. Peripheral blood lymphocytesdecreased in four exceptions. the hemoglobin and erythrocytes in patient 1were reduced, and the d2 polymer in patient 1 was 22 times higher than theother four patients. c-reactive protein and calcitonin were normal in 5 pa-tients. Patient 1 had a blood cell sedimentation rate of 40, and the other fourpatients were normal. Influenza a and b virus of five patients were normal.the novel coronavirus nucleic acid by throat swabs and blood tests were pos-itive. all five patients underwent chest radiographs and ct examinations.three of the chest radiographs showed rough lung texture, but ct case 1showed small patchy shadows in multiple sites, cases 2 and 3 showed patchyshadows of the right lung, and cases 4 and 5 were all normal. five childrenwere treated with interferon nebulization and oral chinese medicine, and fourpatients were treated with ribavirin. two patients took oral lopinavir / riton-avir orally (1.5ml, 2 times / d×5d) antiviral treatment. five patients exceptthe Icu were treated in the remaining 4 cases only supported symptomatictreatment, all cured and discharged and followed up were normal.

conclusIons: In children with novel coronavirus infection, there aremostly mild common types, which can also be asymptomatic and less criti-cal. Patients’ peripheral blood lymphocytes decreased. In critically patients,d2 polymer increased significantly, c-reactive protein and procalcitonin werenot necessarily abnormal. except heavy and critically, other light general typesare mainly supported by symptomatic treatment, and the prognosis is most-ly good. attention should be paid to avoid transmission among family mem-bers, and timely monitoring and evaluation of the pediatric status of infect-ed families in order to detect and diagnose early.

Key words: children; novel coronavirus; family cluster infection; diagnosisand treatment

ZHou cHonGcHen, luo sHuYInG,Henan Provinvcial Children’s Hospital (Children'sHospital Affiliated to Zhengzhou University, Henan

Zhengzhou 450018, China)

Ma leI, XIao QI,Children’s Hospital, Shaanxi Provincial People’s

Hospiital, Shaanxi Xi’an 710068, China

ZHou YIbo, ZHen XInGGanG, fenGYInGJun, lI MIn,

Henan Provinvcial Children’s Hospital (Children's Hospital Affiliated to Zhengzhou University, Henan Zhengzhou 450018, China)

JIao fuYonG,Children’s Hospital, Shaanxi Provincial People’s Hospiital,

Shaanxi Xi’an 710068, China

clInIcal analYsIsof 5 cases of cHIldren wItH sars-coV-2 InfectIon In faMIlY clusteroutbreaK

and other treatment in Henan ProvincialChildren's Hospital (Children's Hospi-tal Affiliated to Zhengzhou University)from January to February 2020 were en-rolled as research subjects. This studywas approved by the Ethics Committeeof Zhengzhou Children's Hospital andinformed consent was obtained from thechildren's families.

MetHod1. Diagnostic criteria. (1) Both

throat swabs and blood nucleic acidtests were positive. (2) The diagnosticcriteria were conducted in accordancewith the first edition of the ChineseJournal of Pediatrics "Children's 2019New Coronavirus Infection Diagnosisand Prevention Suggestions" on a tri-al basis.

2. According to the ICD-10 number,query and retrieve clinical data throughelectronic medical records.

The gender, age, epidemiology,laboratory examination and imag-ing data (chest X-ray and CT MRI)of the children were collected and an-alyzed.

3. Clinical types According to the in-fection status of children and the clin-ical characteristics of confirmed diag-nosis, they are divided into five types [6-

7]. Asymptomatic infection, mild, com-mon, severe, critical.

statIstIcal MetHodsDescriptive analysis, measurement

data are expressed as M (range).

resultI. General InformationFive children were from four fami-

lies, and epidemiological suggestion wascaused by cluster infection among fam-ily members, which involved 20 fami-ly members, including family membersincluding grandparents, parents, and sis-ters.

Gender: 3 girls and 2 boys. Agerange: 5 days-8 years and 6 months).There was 1 neonate at 5 days, 1 caseat June, 1 case at 7 years old, 1 case at6 years old, and 1 case at 8 years old inJune.

Case 1 The child's parents lived inWuhan until birth. Department G1P1,born 38 + 5 weeks after cesarean sec-tion, A's score and other unknown. OnJanuary 22, the child returned toXinyang, Henan with his parents fromWuhan. In the afternoon of the same day,the mother of the child felt cold andlethargic, but she was not diagnosed andtreated. She had a cesarean section on

January 31, and a positive nucleic acidtest on February 1, confirmed a new typeof coronavirus infection. This suggeststhat the mother had a new coronavirusinfection before cesarean section. Al-though the new coronavirus infection oc-curred only 5 days after birth, it was notcaused by vertical mother-to-child infec-tion, because the mother was infectedwith the new coronavirus before cesare-an section.

clinical manifestations and labo-ratory tests

Fever is the main symptom of mostchildren. Except for Case 3, fever is lowto moderate, with a maximum body tem-perature of 38.6°C. Case 3 No fever, norunny nose, cough, diarrhea and othersymptoms.

The total number of neonatal leuko-cytes in case 1 was 12.41, and the oth-er 4 cases ranged from 4.79 to 9.02. Thenumber of lymphocytes was 6.88 exceptCase 1. One of them was 3.52 and theother three were between 2.28 and2.71. Before the second crossover ofchildren's white blood cells, lympho-cytes should be predominant, but thelymphocytes in this group were lower,suggesting that it is related to viral in-fection.

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Table 1

General information and clinical manifestations of 5 children with novel coronavirus infection

12345

MfMff

5d6M

7Y6M6Y7M8Y6M

2/230/119/22/22/2

53255

542089

YYYYY

3838.1

normal38.637.4

nnnnn

YYnnn

nnnnn

185n22

2916161515

№ gender

age date tohospital

epidemiology Main clinical manifestations days offever

days of beingho s pitalized

number of hou -sehold infections

days between ex p o - s ure and diagnosis

wuhanrelated

fever(℃)

sneeze cough vomiting and diarrhea

Table 2

Laboratory and imaging (chest X-ray, chest CT) examination of 5 children with novel coronavirus infection

№

1

2

3

4

5

wbc(×109/l)

12.95

4.79

9.02

4.82

5.02

blood routinen(%)

0.505%

0.175%

0.613%

0.427%

0.388%

l(%)

0.495

0.772

0.319

0.247

0.271

rbc(×1012/l)

3.07

5.05

5.23

4.52

4.60

HGb(g/l)

101 g/l

127 g/l

148 g/l

126 g/l

135 g/l

Plt(×109/l)

356

451

447

283

261

crP(mg/l)

<0.5

0.5

<0.5

na

na

Pct(ng/dl)

0.092

0.11

0.039

na

na

esr(mm/h)

40

11

12

na

na

flu virusa/b

na

-

-

na

na

alt(u/l)

46.7

21.8

48.4

na

na

ast(u/l)

37.8

55.3

32.8

na

na

ldH(u/l)

na

na

261.3

na

na

cK-Mb(u/l)

48.3

na

14.7

na

na

d-2polymer

22.48

0.4

0.2

na

na

chest radi-ograph

rough lungtexture

rough lungtexture

rough lungtexture

normal

normal

chest ct

Multiple smallpatches

Multiple smallpatches

Patchy shadowof right lung

normal

normal


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60

Case 1 Hemoglobin and red bloodcells were reduced, hemoglobin 101g,red blood cells 3.12 suggested anemia.Two patients had platelets> 470.

Five patients with alanine amino-transferase, aspartate aminotransferase,lactate dehydrogenase, and creatine ki-nase isoenzymes were normal.

Case 1 newborn D-dimer 22.48, sig-nificantly higher than other children.

Third, imaging examinationAll 5patients underwent chest radiographand CT. Three of the chest radiographsshowed rough lung texture, but CTcase 1 showed multiple small patchyshadows in both lungs, cases 2 and 3 CTshowed right lung patchy shadows,and cases 4 and 5 (siblings) showed noabnormalities in CT.

treatMentAll 5 cases were treated with α-2b in-

terferon nebulization and oral Chinesemedicine. All but ribavirin was used ex-cept for Example 2. Except for theneonate of Example 1, the remaining 4cases were all mild, without IC 入, me-chanical ventilation, gamma globulin,and other treatments. Only sympto-matic treatment was supported. All pa-tients were cured and discharged. Fol-low-up was normal. Examples 1 and 2received oral antiviral therapy withlopinavir / ritonavir (1.5ml, 2 times / d× 5d). No oseltamivir phosphate wasused in 5 cases [6-9].

The total length of hospital stay was91 days, with an average of 18.2 days.Case 1 was hospitalized for 29 days.Cases 2 and 3 are 16 days, and Cases 4and 5 are 15 days. Fever days were 28days, with an average of 5.6 days.

dIscussFamilial cluster infection 5 children

from four family epidemiology suggesta family cluster infection, of which 20family members were involved in the in-fection. Including grandparents, grand-

ma, father, mother and sister. Amongthem, the neonates were critically illonly 5 days after birth. Before birth, hisparents were in Wuhan. After the moth-er became infected with the new coro-navirus pneumonia, she had a fever andthen had a cesarean section. A positivecheckup confirmed the diagnosis.

Clinically, fever is the main manifes-tation. Four children (80%) had feverranging from cough, asthma, vomitingand diarrhea. This shows that fever is themost common manifestation of neona-tal coronavirus infection in children. It'salso a signal and clue. It is the first per-formance that should be taken serious-ly. Italian studies report that fever is themost common manifestation of 83% -98%, while cough and shortness ofbreath account for 31% -55%. None ofthe 5 children had congenital, geneticand metabolic diseases [8-11].

According to its symptoms and clin-ical manifestations, it is divided intoasymptomatic infection, mild, com-mon, severe, and critical. Studies sug-gest that children with new type of coro-navirus infection have five characteris-tics clinically. First, the number of in-fections is smaller than that of adults.Second, symptoms and clinical manifes-tations are lighter than those of adults.Third, there are fewer complicationsthan adults. Fourth, recovery is fasterthan that of adults, and fifth has a bet-ter prognosis. This may be related to lessexposure of children than adults, pedi-atric immune function is not yet fully de-veloped, and pediatric infections aremild and inaccurate, and the diagnosiscannot be found in time and is easilymissed.

The minimum age is 5 days afterbirth. The parents lived in Wuhan untilthe child was born. Department G1P1,born 38 + 5 weeks after cesarean sec-tion, A's score and other unknown. Be-fore admission, the parents of the childreturned to Xinyang, Henan from

Wuhan on January 22, and the motherof the child felt cold and lethargic in theafternoon. A cesarean section was per-formed on January 31, and a new coro-navirus infection was confirmed onFebruary 1 with a positive nucleic acidtest, indicating that the mother had a newcoronavirus infection during childbirth.

Although the new coronavirus infec-tion occurred only five days after birth,it suggested that it was not caused byvertical infection of mothers and infants.Because the mother was infected withthe new coronavirus before cesarean sec-tion.

Five cases had family members witha history of infection. Fever is the mainsymptom of most children. Except forExample 3, fever is low to moderate,with a maximum body temperature of38,6. Example 3 had no fever, no run-ny cough or vomiting.

The clinical and immunologicalcharacteristics of children need attention,and further research and discussion areneeded. One patient in this group had noclinical manifestations despite a nucle-ic acid test and a family member whowas diagnosed with a new coronavirusinfection. It should be noted that chil-dren with asymptomatic infection shouldbe vigilant, because those with nosymptoms or mild symptoms are like-ly to become a hidden source of infec-tion should be paid attention to. It hasbeen reported that most of the early lym-phocytes were reduced in adults andlower in 4 cases. Leukocytes in childrenunder 5 years of age have two crosses.Lymphocytes are normally higher thanneutrophils. So if the lymphocytes de-crease, it may be related to viral infec-tion.

Increased D-dimer is an indicator ofserious infection. The D-dimer in thisgroup of cases was as high as 22.248.It is 22 times higher than other cases, butthere is no significant difference betweenCRP, PCT mild and critical illness. In

Table 3Treatment of 5 children with novel coronavirus infection

№

12345

Heartfailure

nnnnn

Icu

Ynnnn

mechanicalventilation

Ynnnn

supportiveoxygen therapy

Ynnnn

nebulized inhaledinterferon alpha-2b

YYYYY

rib-avirin

YnYYY

lopinavir/ ritonavir

YYnnn

oselta -mivir

nnnnn

cefop-erazone

Ynnnn

Gluco-corticoid

nnnnn

Immunoglo -bulin (IVIG)

YYnnn

chinese her -bal medicine

YYYYY

adult patients, AST, ALT, lactate dehy-drogenase, isoenzymes, etc. increased,but no significant increase in childrenin this group. Positive nucleic acid testis an important basis for the diagnosisof new crown infection. In this group of5 children, throat swabs, blood nucle-ic acid tests were positive twice, and nonegative children. The patient was dis-charged from hospital with a negativesecondary test, and continued to be sep-arated and observed at home for twoweeks after discharge. [3-7]

It has been reported that the nucleicacid test may be negative in the earlystage, so the chest radiograph and CT ofepidemiological history and symptomssuggest that children with new crownsshould be repeatedly tested for nucleicacid to avoid missed diagnosis. Nega-tive throat swabs but positive analswabs have been reported to indicate along period of exclusion of the virusfrom the intestinal tract. Chest radi-ographs of 3 patients in this groupshowed rough lung texture, but CTexamination showed patchy consolida-tion shadows in multiple parts of bothlungs or right lung.

It shows that chest CT is earlier andmore diagnostic value than chest radi-ograph. In view of the low sensitivity ofnucleic acid detection, in order to pre-vent missed diagnosis, epidemiologicaland clinical manifestations should becombined, and combined diagnosis ofnucleic acid examination and chest CTshould be used to reduce missed diag-nosis [7-8].

In terms of treatment. In view of thefact that children with neo-crown infec-tion are less ill and have a better prog-nosis, they are mainly family-gath-ered. For ordinary, asymptomatic, mildcases, special medication is not empha-sized. Except for case 1 who was treat-ed in the ICU in the group, the remain-ing 4 cases were closely observed af-ter hospitalization, and they were curedafter being supported by symptomatictreatment. No special changes were ob-served after two weeks of follow-up.Example 1 The patient recovered andwas discharged from hospital despitethe onset of disease on 5 days after birthand treatment with mechanical ventila-tion. The application of antiviral drugssuch as ribavirin in children with newcrown infection suggests that furtherstudies on efficacy, safety, and toxic side

effects are needed. Patients 1, 2 orallytook lopinavir / ritonavir orally (1.5ml,2 times / dX5d antiviral treatment.None of the 5 patients received os-eltamivir phosphate [6-10].

Except for neonates in this group, theremaining four cases were not treatedwith antibiotics, and emphasis wasplaced on avoiding blind or incorrect useof antibacterial drugs. Reasonable selec-tion of antibiotics should be based onbacterial infection and bacterial cultureand drug sensitivity tests. For critical-ly ill patients, a short course of smalldoses of gamma ball and glucocorticoidcan be given. The application of tradi-tional Chinese medicine should betreated with individualized syndromesaccording to the age, physique, and con-dition of the child. It is recommendedto take traditional Chinese medicine in-stead of injecting traditional Chinesemedicine preparations.

A2b interferon nebulization, as amedication for respiratory diseases, iscurrently widely used, but the clinicalefficacy of novel coronavirus infectionis still lacking theoretical and clinical ev-idence of rigorous scientific researchsuch as randomized double-blind place-bo control. Therefore, further clinicalrigorous scientific research is needed toprovide scientific theoretical and exper-imental evidence for clinical applica-tions. Moreover, atomization may in-crease the risk of aerosol infection,which deserves further discussion anddiscussion.

references[1] Wuhan Municipal Health Com-

mittee. Wuhan Municipal Health Com-mittee on current pneumonia in our citySituation report of the epidemic[EB/OL]. (2019- 12- 31) [2020- 02- 01].http: //wjw.wuhan.gov.cn/ front/web/ -showDetail/2019123108989.

[2] World Health Organization.Home care for patients with suspectednovel coronavirus (nCoV) infectionpresenting with mild symptoms andmanagement of contacts [EB/OL](2020-01-20) [2020-02-03] .https://www.who.int/publications-detail/ho -me-care - for - patients - with - suspect-ed - novel - coronavirus - (ncov) -infec-tion - presenting - with - mild - symp-toms - and - management - of -contacts.

[3] National Health Committee of thePeople's Republic of China. As of 20:

00 on February 10, the latest situationof epidemic situation of new coronaviruspneumonia [EB/OL] . (2020-02-11)[2020- 02- 11] . http: //www.gov.cn/xin-wen/2020- 02/11/content_5477103.htm.

[4] National Health Commission ofthe People's Republic of China. Noticeon prevention and control of pneumoniain children and pregnant women withnew coronavirus infection [EB/OL] .(2020- 02- 02) [2020- 02- 02] .http://www.nhc.gov.cn/fys/s7902/202002/de2d62a5711c41ef9b2c4b6f4d1f2136.shtml.

[5] National Health Commission ofthe People's Republic of China. Noticeon Issuing a COVID-19 Infected Pneu-monia Diagnosis and Treatment Plan(Trial Version 5) [EB/OL] (2020- 02-05) [2020- 02- 05]. http: //www.nhc. -gov.cn / yzyg j / s7653p/202002/ -3b09b894ac 9b4204a 79db5b8912d -4440. shtml.

[6] Recommendations for diagnosisand prevention of new coronavirus in-fections in the Chinese Medical Asso-ciation Pediatrics Branch 2019(TrialVersion 1) [J] 中华儿科杂志, 2020, 58(3) : 169-174.

[7] J F -W Chan, Yuan SF, K - HKok, et al. A familial cluster of pneumo-nia associated with the 2019 novelcoronavirus indicating person - to - per-son transmission: a study of a familycluster [J] Lancet, 2020, 395 (10223) :514-523.

[8] Cai Jiehao, Wang Xiangshi, GeYanling, et al. Shanghai's first childrenwith new coronavirus infection [J] Chi-nese Journal of Pediatrics, 2020, 58 (2):86-87.

[9] Bin Cao, Yeming Wang, DanningWen, et al. A Trial of Lopinavir–Riton-avir in Adults Hospitalized with SevereCovid-1 March 18, 2020 DOI: 10. -1056/ NEJMoa2001282

[10] WHO Infection Prevention andControl Guidance for COVID-19 avail-able at https: //www.who.int/emergen-cies/diseases/novel-coronavirus-2019/technical-guidance/infection-pre-vention-and-control

[11] Bordi Licia, Nicastri Emanuele,Scorzolini Laura et al

Differential diagnosis of illness in pa-tients under investigation for the nov-el coronavirus (SARS-CoV-2), Italy,February 2020. Euro Surveill. 2020;25(8): pii=2000170. https: //doi.org/ -10 .2807 /1560-7917 .ES .2020 . -25.8.2000170

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Kawasaki disease is also called themucocutaneous lymph node syndrome,common in 6 months to 6 years old chil-dren, its’ main clinical manifestation isacute or persistent fever, oral cavity mu-cous membrane inflammation, eye con-junctival congestion, swollen lymphnodes, etc. The main pathologicalchange is a systemic inflammatory le-sions of small and medium-sized bloodvessels, especially the coronary arteries.In the long term, it may cause coronaryartery thrombosis and ischemic heartdisease in children, which seriouslythreatens to children's normal growthand development and physical health[1,14]. In addition, in the acute phase ofKawasaki disease in children, peri-carditis, myocarditis and other symp-toms may also occur, which further in-duces serious complications includingheart failure [19], directly threatening thelife and health of children [12]. Kawasa-ki disease is a global disease, and the in-cidence varies by race and country, but

the incidence of Kawasaki disease is rel-atively high in Asian populations. It isrelatively common in pediatric clinic,and the incidence has been increasingin recent years [2,16]. In recent years,there has been a further understandingand development of kawasaki diseasenursing measures and methods. In orderto promote the quality of medical nurs-ing for Kawasaki disease, this paper issummarized as follows.

I. HolIstIc care for KawasaKI dIsease1.1 diet nursing: For suckled children,

pay attention to the supplementation ofrelevant nutrients, for weaned children,to maintain a balanced nutrition. Due tofever and high energy consumption,children should be given high nutritiousand digestible diet, mainly of semi-liquidfood, such as egg cake and soybeanmilk, etc. Spicy and stimulating foodshould be banned. Eat small, frequentmeals at a controlled speed to avoid stim-

ulating oral mucosa, and fatty acids andamino acids should be properly supple-mented to ensure daily nutrient intake [4].

1.2 skin and mucous membranenursing: Keep the skin dry and clean,scrub daily, and clean the sweat in time af-ter sweating; Wear soft clothing, often cutnails, avoid scratching the skin; Bed sheetneat and soft; Clean buttocks and surround-ing skin after use. Finger and toe stiffnessand swelling are common complicationsof such children, which generally do notneed intervention and can disappear spon-taneously in about 7 days, but the infectiousrash that may occur during this periodshould be avoided. Calamine lotion shouldbe applied externally for early scarletfever-like rash with obvious itching; If chil-dren have acra and perianal peeling, theyshould regularly clean their skin and lim-it their hand and foot movement to preventskin damage, local infection and other com-plications caused by scratching skin; Chil-dren with Kawasaki disease can have lipflushing, dryness, bleeding and other con-ditions, use normal saline to clean the chil-dren's mouth daily, more than twice a day,to avoid the occurrence of oral ulcer; Lipbalm for lip dry and peeling; Oral ulcerpowder is used to give oral care to childrenwith ulcer; For obvious eye conjunctivalhyperemia, avoid light stimulation and rinsewith normal saline [4].

1.3 complications nursing: Fever isthe main symptom of Kawasaki diseasein children. Clinical temperature monitor-ing was strengthened after admission, andthe temperature was measured once 2hours. After the high temperature drop,take the temperature again in half an hour.Drink more water to prevent febrile con-vulsion. For patients with body temper-ature > 390C, physical cooling can beadopted on the basis of routine aspirin

abstractKawasaki disease is one of the main causes of acquired heart disease in chil-

dren. the damage degree of the heart coronary artery determines the main ther-apeutic methods and follow-up time of children. the main clinical manifesta-tions of Kawasaki disease are acute or persistent fever, oral cavity mucous mem-brane inflammation, eye conjunctival congestion, swollen lymph nodes, etc. Inrecent years, the diagnosis and treatment experience of Kawasaki disease hasbeen popularized, among which clinical nursing is the key to ensure and improvethe treatment effect.the nursing types are mainly divided into holistic nursingfor Kawasaki disease, evidence-based nursing for Kawasaki disease, clinical path-way nursing for Kawasaki disease and internet-based continuous nursing, in-cluding: diet, skin mucosa, medication methods and other issues.In order to ex-plore the effective nursing methods of Kawasaki disease, this paper comprehen-sively describes the current research status and intervention methods of Kawasa-ki disease nursing at home and abroad, so as to provide theoretical referencefor the nursing work of Kawasaki disease in the later stage.

Key words: Kawasaki disease; Systemic vasculitis; Nursing; New progress

ZHanG HonG, lIu HonGMeI, Department of vascular surgery,

Shaanxi Provincial People's Hospital, Xi’an 710068, China

denG feIdan,Class of Prevention 71, Xi 'an Jiaotong University,

Xi’an 710049, China

ZHanG XIbIn, nIu QIan, Ma JI,Department of vascular surgery, Shaanxi Provincial

People's Hospital, Xi’an 710068, China

correspondence: JIao fuYonG, department of vascular surgery, shaanxi Provincial People's Hospital, Xi’an 710068, china,

email: [email protected]

new ProGressIn nursInG researcH of KawasaKI dIsease

treatment. Note to monitor the bodytemperature once every 4 hours, adjust theindoor temperature and humidity ap-propriately, and encourage children todrink more water; Physical coolingthrough alcohol bath, ice pillow, an-tipyretic patch, and appropriate medica-tion; Monitor vital signs, complexion,pupils and consciousness, and pay atten-tion to possible abnormalities. During hos-pitalization should limited movement, restin bed, and careful observation of diseasedevelopment.For children with pre-exist-ing coronary artery dilatation or coronaryaneurysm, carefully observe of bloodpressure, heart rate, breathing, complex-ion, consciousness, and observe whetherhad tachycardia, arrhythmia and so on,when it is necessary to give continuousecg monitoring, close observation of thepatient's ecg, alert to early changes of car-diovascular, always ask whether chest dis-tress and shortness of breath, and malaiseof the precordial area.

1.4 Psychological nursing: Com-municate with children and their familieswith friendly tone and relaxed language,comfort and encourage children.Edu-cate parents about the disease and the ef-fects of treatment to reduce tension andhelp build confidence in treatment. Be-fore using drug, explain the nature of thedrug, the mechanism of action, the pos-sible symptoms, the causes of the adversereactions and in what case need to informthe staff to the family members in detailto remove the unnecessary tension and ex-plain even if children appear symptomsalso need not nervous, just inform med-ical staff, who will deal with the situationand monitor the entire infusion process toavoid anxiety, fear and suspicion amongfamily members. In terms of psycholog-ical intervention, due to the repeated ill-ness of the children, the fever lasts for along time, and the high cost of hospital-ization, the family members of the chil-dren will inevitably have anxiety. Thenursing staff should introduce the child'scondition, the doctor's treatment plan andthe outcome of the disease to the familyin detail, patiently listen to the child's fam-ily's appeals, and assist them to solve.

1.5 out-of-hospital nursing: pay at-tention to discharge guidance, remind thereturn visit after discharge, guide childrento take medicine on time and in quantity,can not stop or reduce at will. Details tobe filled in the discharge guidance card in-clude: the usage and dosage of oral drugs;time of review: 1, 3, 6, 9 months after eachreview; pay attention to diet nutrition, pre-vent colds; do not carry out strenuous ac-

tivities within 1 year to avoid recurrenceor aggravation of the disease; vaccinationis not allowed within 9 months [5,17].

1.6 Medication nursing: make clear thedosage, way of administration and time ofmedication, explain the matters needing at-tention and possible adverse reactions,closely observe whether there are abnormalconditions such as drug eruption, and im-mediately stop the drug for treatment afterdiscovery. At present, the commonly useddrugs for pediatric kawasaki disease includegamma globulin, aspirin, etc. [2,18].Thetransfusion of gamma globulin should becarried out according to the operationstandard of blood products, and parentsshould be informed of the pre-transfusionexamination. Input strictly aseptic opera-tion, before using other drugs to wash pipewith normal saline, and out of the box. In-fusion speed should be slow, generally un-der 3 years old 10 ~ 20 drops /min, over 3years old 20 ~ 30 drops /min. Pay attentionto observation, once nausea, vomiting, pal-pitation, chest tightness, sweating andother symptoms, can slow down infusionspeed or stop infusion; If symptoms wors-en, such as shortness of breath, cyanosis,urticaria, etc, immediately stop medication,give oxygen, keep warm, and cooperatewith the physician to give anti-allergy treat-ment. When using aspirin, it is necessaryto emphasize the accuracy of dosage, giveit on time, and do not increase or decreaseor stop taking it at will. Communicate theeffects of medications and possible reac-tions to parents to get their cooperation.Gen-erally choose enteric-soluble aspirin, shouldbe taken in 15 minutes after meals, infantsafter grinding and dissolution, when nec-essary, with aluminum hydroxide, whiledrinking more water. During medication,children should be closely observed for drugeruption, skin, mucous membrane, gumbleeding and stool color, and regular reex-amination of blood routine, coagulationfunction and liver function, etc [15].

II. eVIdence-based nursInG for KawasaKI dIseaseEvidence-based nursing is an impor-

tant branch of evidence-based medicine,meaning "to follow the evidence of nurs-ing", may be defined as carefully, accu-rately and wisely apply the best availableresearch evidence. Combine perfectlyyears of clinical experience, nursingskills and patient's values and principlesat the same time, to develop nursing meas-ures. Its core is to carry out nursing workbased on the best evidence [6].Kawasa-ki disease evidence-based nursing as an

ideal practical activity, can maximum lim-it satisfy the needs of children and parents,on the basis of clinical practice of nurs-ing problems, look for evidence in the rel-evant research literature, then make a crit-ical evaluation on the validity, reliabili-ty, clinical application and universality ofthe evidence, and pick out the best evi-dence, to solve the actual problem of chil-dren. In order to improve the quality ofnursing, then sublimation of nursing the-ory and practice on an evidence-based ba-sis. By looking for scientific evidence ofKawasaki disease and consulting a largenumber of professional related materials,nurses also promoted the update of pro-fessional knowledge.

The specific methods of implement-ing evidence-based nursing interventionare as follows [6]: (1) Look for evidence-based evidence: combined with the liter-ature report, comprehensive clinical nurs-ing actual need, put forward the follow-ing evidence-based nursing basis:Evidence 1: In the process of the treat-ment for children with injection of gam-ma globulin, can cause adverse reactionssuch as rash, fever, headache, impact ondiagnosis and treatment; Evidence 2:After the onset of children, gastrointesti-nal dysfunction, need to be focused; Evidence 3: The families of children withinsufficient knowledge of the disease, cannot accurately participate in the care ofchildren. (2) Put forward nursing coun-termeasures: combined with the above ev-idence-based nursing evidence, put for-ward the necessary nursing rectificationmeasures. Evidence 1: Nursing coun-termeasures: According to the high fever,rash and other symptoms caused by thetreatment process, the causes of adversereactions were analyzed, and the possi-ble safety risks in the process of drug usewere deeply explored. Necessary meas-ures were taken for scientific intervention.At the same time, nurses continue to im-prove their own nursing skills, have a clearunderstanding of the adverse reactions ofgamma globulin, and timely convey to thechildren's families. Be aware of risks andsign the informed consent for medication,to avoid causing family members do notunderstand, resulting in poor communi-cation between nurses and patients relateddisputes. Evidence 2: Nursing coun-termeasures: Timely observation of thechildren's skin and body temperature,combined with the change of indicatorsto judge the condition. For children withabnormal defecation, nursing staff tothe children during the treatment of gas-trointestinal function of the correct judg-

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ment, in order to avoid damage to the in-testinal mucosa, enteric preparations canbe appropriately given, fully protect thegastrointestinal function. The frequencyof stool movement and stool character ofchildren were observed, in order to detectpotential risks in time, such as toxic re-action. The vital signs of the children wereclosely monitored, and the drugs werestopped in time when abnormalities werefound, and the corresponding treatmentwas carried out. (3) Evidence 3: Nursingcountermeasures: Communicate closelywith family members, inform them oftheir important role in the treatment ofchildren, and give full play to their initia-tive. Inform family members of Kawasa-ki disease related knowledge, demonstratenursing operation points. Family mem-bers' emotions should be channelled sothat they can participate in the child care.Prior to discharge, do a good job of guid-ance, and agree on the time of return tothe hospital.

III. clInIcal PatHwaY nursInG for KawasaKI dIseaseThe clinical treatment of Kawasaki

disease in children is mainly drug ther-apy, clinical nursing plays a prominentrole in the treatment, and combined withthe clinical path, the nursing effectwill effectively improve.

Clinical pathway nursing is imple-mented in the following process [7]: Es-tablish a clinical pathway group: Headnurse as the leader, Nurse-in-charge as thedeputy leader, 4 responsible nurses as theteam members, assign tasks according toindividual work area and nursing expert-ise; (2) Evaluation before nursing: Assessthe condition and nursing first, then to un-derstand the basic condition of children, thepast medical history, medication history,analysis of possible nursing problems, toscreen the nursing risks; (3) Evidence-based support: According to the problemsfound, through the search of literature andintegration of previous nursing records,seek for targeted nursing methods; (4)Nursing implementation and records:Group discussion of nursing plan and makenursing process table, in strict accordancewith the nursing process table implemen-tation of nursing. After complete the cor-responding nursing measures, marking andobserving the effect of implementationrecord. Last, check the process tablewhether there are nursing errors; (5) Nurs-ing evaluation: According to the nursingrecords and children's family feedback,evaluate the nursing effect, and continu-ously improve the nursing plan.

The clinical path was applied to thenursing of the research group, the imple-mentation of nursing measures is moreorganized, nursing division of labor isclear. The use of nursing process table,to avoid the absence of nursing measures,continuous improvement of the nursingplan, quality control effect is more ide-al, and nursing quality is significantly im-proved. Clinical pathway can improve theefficiency and scientificity of nursing.

IV. Internet-based contInuous nursInGIn recent years, with the development

of mobile network tools, Internet-basedcontinuing nursing services have beengradually applied in out-of-hospital nurs-ing health education for patients withchronic diseases [13].The level of care-givers' disease knowledge can affect theircare ability, and providing caregivers withdisease knowledge will help them to pro-vide professional and scientific homecare services for patients with chronic dis-eases. In order to improve the medicationcompliance of children with Kawasaki dis-ease coronary artery injury after dischargeand reduce the family care burden of thechildren, continuity of care and health guid-ance can be provided for them, to improvethe treatment compliance of the children[8]. In recent years, with the emergence ofthe Internet, internet-based continuousnursing intervention can effectively savemedical materials and is not affected bytime and space, so that continuous nurs-ing services can be better carried out [9].

First, set up a network platform man-agement team [10]: the team members in-cluded 1 head nurse, 1 Senior title cardio-vascular specialist doctor, 3 specialistnurses in charge, 1 psychological consult-ant and 2 network engineers.The headnurse and cardiovascular specialist are re-sponsible for developing home health ed-ucation programs for the children, and thenurses and psychological consultants an-swer related questions for the children andtheir caregivers through wechat everyTuesday and Thursday. Vascular special-ists are responsible for providing treatment,examination, dietary guidance, daily lifeguidance, medication guidance and oth-er post-discharge issues for children andcaregivers through mobile APP or wechatgroup.The network engineers shall be re-sponsible for the operation training andmaintenance guidance of wechat group,wechat official account and mobile APPfor the team members.

Then, build a network communicationplatform [10]: (1) WeChat group: estab-

lish WeChat group called "health commu-nication group of Kawasaki disease",through weekly rotation, the supervisornurses communicate with the children onthe wechat network platform, patiently an-swer questions raised by children andcaregivers, and encourage caregivers toexchange Kawasaki disease nursingexperience in wechat group.Wechat of-ficial account: establish Kawasaki diseasewechat official account, children andcaregivers when they are admitted to hos-pital, let them follow the public account,which includes disease knowledge, ques-tion answering, classic case sharing, on-line booking and other functions. Thehealth education content uploaded on theofficial account should be verified by thehead nurse and cardiovascular specialist.

Specific contents of continuous nurs-ing [10]: (1) Hospitalization: establishhealth education archives of childrenwith Kawasaki disease, including gender,age, course of the disease, cardiovascu-lar damage, medication (including thepreparation methods, types, adverse drugreactions), caregivers’ education degree,contact information, healthy condition,etc. To confirme that caregivers canskilled use of smart phones and WeChatpublic, and invite specialist doctor to joinWeChat group APP. (2) 1 ~ 3 months af-ter discharge: children with kawasaki dis-ease coronary artery injury need to takeanticoagulants such as warfarin and as-pirin after discharge. Anticoagulants areeasy to cause bleeding, When taking themthe dosages should be controlled well andmedication should be strictly followed asprescribed by the doctor. Some childrenmay develop rashes and other adverse re-actions after taking aspirin, and their per-formance should be closely monitoredduring taking aspirin. During the medica-tion period, caregivers can send the med-ication situation and medication reactionof the child to the wechat group in theform of photos or videos. Specialist doc-tors can make a preliminary diagnosis ofthe child through the pictures or videos,and determine whether the child needs togo to the hospital according to the diag-nosis results. Medical staff conducted re-mote online video health education forchildren and caregivers once a week toimprove their awareness of disease. (3)3 months after discharge: inform childrenand caregivers of daily Kawasaki diseasehealth care, prevention of adverse behav-ior events and other knowledge throughwechat platform or mobile APP. Due tothe prolonged discharge, the coordinationdegree and medication compliance of chil-

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dren and their families for regular follow-up visit will decrease. The medical staffconducts online videos for the childrenand their caregivers through Wechatgroups every 4 weeks, so as to know themedication status and the outcome con-dition of the children. 1 ~ 2d before thefollow-up, the children and caregiverswere reminded to make online registra-tion and appointment for various exam-inations through Wechat group. Accord-ing to the cardiovascular conditions of thechildren, the diet plan, exercise plan andthe time to return to school were deter-mined, and the caregivers were instruct-ed to learn to observe the symptoms ofangina pectoris or myocardial infarction.For the elderly children, we should payattention to the clinical symptoms,whether there is chest pain, chest tightnessand other discomfort. For the youngchildren, we should pay attention towhether there is dysphoria, loss of ap-petite, depression and other manifesta-tions. For children with heavy family bur-den, psychological counselors shouldbe arranged to conduct psychological in-tervention on children and caregiversthrough online platforms, so as to reducetheir bad emotions and promote theirphysical and mental health.

V. suMMarYKawasaki disease in children, also

known as cutaneous mucosal lymphnode syndrome, can lead to small andmedium-sized vascular lesions through-out the body, which is a vasculitis syn-drome. It can cause serious damage to thecoronary arteries in children, and is oneof the important causes of coronary arterydisease in children. It is also a potentialthreat to the onset of coronary heart dis-ease in children as adults. Clinical main-ly adopts drug therapy, clinical nursing isthe key to ensure and improve the effectof drug therapy. Holistic nursing is a com-prehensive and meticulous nursing mode,which can meet the nursing needs of pa-tients from more dimensions, effectivelyimprove the physical and mental conditionsof children, and has a high clinical appli-cation rate. Compared with traditional nurs-ing methods, Kawasaki disease evidence-based nursing model has more obvious ef-fect. It can meet the needs of children'smedical treatment, further strengthen thecorrect cognition of family members, andachieve satisfactory clinical nursing effect.The clinical pathway can improve the ef-ficiency and scientificity of nursing. Inter-net-based continuous nursing throughWechat, mobile App and other channels,

regularly push Kawasaki disease basicknowledge, updating drugs knowledge,and regularly use pictures and video tomake disease knowledge become more im-age, vivid, make caregivers can better un-derstand the disease knowledge, can pro-vide a more comprehensive, targetednursing service for children and caregivers,thus improve the caregivers diseaseawareness, So that it can better urgechildren to take medication, so as to im-prove their medication compliance [20].

In short, in recent years, with the in-depthresearch on the pathogenesis of Kawasa-ki disease and the accumulation of thera-peutic experience, as well as the backgroundof mobile networking era, various nursingtechniques and methods for Kawasakidisease change and development, timely ap-plication, Kawasaki disease nursing qual-ity effectively improved, children benefitsignificantly, it is worth promoting.

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Newburger J W, et al. Diagnosis, Treat-ment, and Long-Term Management ofKawasaki Disease: A Scientific State-ment for Health Professionals From theAmerican Heart Association[J]. Cir-culation, 2017, 135(17).

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[3] 廉世宽. 丙种球蛋白治疗小儿川崎病的临床疗效及其安全性[J]. 临床合理用药杂志, 2021, 14(12): 112-114.

[4] 刘琳琳. 优质护理模式应用于小儿川崎病护理中的应用[J]. 健康必读, 2021(15): 21.

[5] 李艳琴, 憨贞慧. 比较不同用量丙种球蛋白联合阿司匹林肠溶片治疗小儿川崎病的临床观察及护理[J]. 河南大学学报(医学版), 2020,39(02): 99-101.

[6] 姚静, 徐明国, 王威, 等. 循证护理在川崎病患儿中的应用[J]. 泰山医学院学报, 2020, 41(10): 768-769.

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[8] 何依凤. 微信平台结合医护一体化护理对川崎病患儿治疗依从性及护理满意度的影响[J]. 基层医学论坛, 2020, 24(15): 2219-2220.

[9] 王丽, 王霞, 吴佳, 等. 出院后延续护理在川崎病患儿中的应用分析[J]. 母婴世界, 2021(4): 289.

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脉损伤患儿家庭照顾负担的影响[J].齐鲁护理杂志, 2021, 27(01): 110-113.

[11] Andrea Vergara1, 2, EmanueleMonda1, Cinzia Mautone3, FrancescaRenon1, et al; Rare case of Kawasakidisease with cardiac tamponade and gi-ant coronary artery aneurysms;. Cardi-ology in the Young 31: 865–866. doi:10.1017/S1047951120004989; Firstpublished online: 11 February 2021.

[12] Danfeng Zhang1, 2, LingjuanLiu1, 2, Xupei Huang3 * and Jie Tian1,2 *; Insights Into Coronary Artery Le-sionsin Kawasaki Disease; Frontiers inPediatrics; published: 25August 2020doi: 10.3389/fped.2020.00493

[13] Frank Zhu1 & Jocelyn Y. Ang2, 3; 2021 Update on the Clinical Man-agement and Diagnosis of KawasakiDisease; PEDIATRIC INFECTIOUSDISEASES; Current Infectious Disea -se Reports (2021) 23: 3 https: //doi. -org/10.1007/s11908-021-00746-1;

[14] Priya R. Soni1 & Magali NovalRivas1, 2 & Moshe Arditi1, 2, 3; A Co -m prehensive Update on Kawasaki DiseaseVasculitis and Myocarditis; PEDIATRICRHEUMATOLOGY; Current Rheumatol-ogy Reports (2020) 22: 6 https://doi.org/10.1007/s11926-020-0882-1;

[15] Eileen Rife1 & AbrahamGedalia2; Kawasaki Disease: an Update;VASCULITIS; Current RheumatologyReports (2020) 22: 75 https: //doi.org -/10.1007/s11926-020-00941-4

[16] Tina Sosa, MD; Laura Brower,MD; Allison Divanovic; Diagnosis andManagement of Kawasaki Disease;JAMA Pediatrics Published online Jan-uary 22, 2019.

[17] David Ferreira, BMed a, b, *, RenaNg, BMed c, Elise Lai, BMed c et al;Kawasaki Disease in the Australian Pop-ulation: An Australian Tertiary HospitalExperience;, Lung and Circulation (2021),https: //doi.org/10.1016/j.hlc. 2020.12.016;

[18] Surjit Singh1 & Avinash Sharma1& Fuyong Jiao2; Kawasaki Disease: Is-sues in Diagnosis and Treatment - A De-veloping Country Perspective; Indian J Pe-diatr (February 2016) 83(2): 140–145DOI10.1007/s12098-015-1890-4.

[19] Fuyong Jiao1, Ankur Kumar Jin-dal2, Vignesh Pandiarajan2 et al; Theemergence of Kawasaki disease inIndiaand China; Global Cardiology Science-and Practice 2017: 21 http: //dx.doi.org -/10.21542/gcsp.2017.21;

[20]Fuyong Jiao1 & Xiaohua Yan1& Xiaofang Wu2; The Xi’an Experienceof Kawasaki Disease – Lessons Learntover 5 years; Indian J Pediatr; DOI10.1007/s12098-016-2100-8.

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IntroductIonPuberty is a transitional period for the

child to become a young adult. Disordersof puberty can impact physical andpsychosocial well-being and also riskfactors of various diseases later in adultlife. The most visible changes during pu-berty are increased growth velocity andthe development of secondary sexual

characteristics. The first sign of puber-tal initiation is breast development ingirls and testicular enlargement in boys.The landmark studies of Marshal andTanner1, which classified puberty intofive stages in girls and boys, have beenwidely used to assess pubertal develop-ment. Precocious puberty is the onset ofone or more pubertal signs at an age of

2-2.5 standard deviations (SD) earlierthan population reference data. In the ma-jority of studies, increased body mass in-dex (BMI) is related to precocious pu-berty in girls. Delayed puberty is consid-ered as the absence of sexual maturationsigns by an age of more than 2-2.5 stan-dard deviation values above the mean ofthe population. Constitutional delay ofgrowth and puberty is the most commoncause of delayed puberty in boys. In clin-ical practice, assessment of pubertalstages for each child is extremely use-ful, but should all times be related to up-dated and reliable reference data from thesame population2. The growth and pu-bertal development of an individualchild is a dynamic statement of his or hergeneral condition or health. Puberty isa transitional period for a child to becomea young adult. Disorders of puberty canimpact physical and psychosocial well-being and also risk factors of various dis-eases later in adult life. The most visi-ble changes during puberty are in-creased growth velocity and the devel-opment of secondary sexual character-istics.

The sequence of pubertal events is re-markably consistent across countries andethnic groups, although the timing variesby country. The timing of puberty is in-fluenced partly by genetics, but largely bynutrition and economic development3.

Growth patterns and anthropometricmeasurements of school-aged childrenin Mongolia are well-known from pre-vious several nationwide studies. Sec-ular trends in height and weight were ob-served in each study, but changes in thetiming of puberty are still unknown.Therefore, we need to study the timing

(abstract)Key words: physical development, puberty, anthropometric measurement, sec-

ular trend

background: Growth patterns and anthropometric measurements of school-aged children in Mongolia are well-known from previous several nationwide stud-ies. Secular trends in height and weight were observed in each study, but changesin the timing of puberty are still unknown.

the objective of the study: To perform a physical development assessment ofschool-age children, establish the median age pubertal stages both in girls and boys.And determine relationships of pubertal stages and anthropometric measurements.

Methods: A cross-sectional study of the growth and pubertal stages of healthy385 school-aged children (aged 7-17 years) who live in the suburban area of Ulaan-baatar. Pubertal stages were determined by Tanner and Marshal’s method. Heightand weight were also recorded, and BMI was calculated. Mean age at pubertalstages were estimated using probit analysis. Mean age at menarche was calculat-ed by status quo method.

results: The prevalence of obesity and overweight were 6.5%, 12.0% respec-tively. And 4.9% of total students were underweight, 11.7% were stunted. The me-dian age of onset of Tanner stages 2 for breast development was 9.58, and pubichair stage 2 was 10.94 in girls. The median age at menarche was 12.26. The me-dian age of testicular enlargement (Tanner 2 stage) and pubic hair Tanner 2 stagewere at 10.96 and 13.30 years, respectively. BMI, waist circumference, and hipcircumference had a medium to strong correlation with pubertal stages and menar-che in girls. Height was strongly correlated with pubertal stages in boys.

conclusions: The prevalence of obesity and overweight (24.1%) are highestamong elementary school students, and stunting (13.3-14.5%) is twice higher inmiddle and high school students. Breast and pubic hair development start at 9.58and 10.95 in girls, the median age at menarche is 12.26, and testicular and pubichair development starts at 10.29 and 13.30 in boys, respectively. Hip circumferencein girls (r=0.809, р<0.05), height in boys (r=0.843, р<0.05) had strongly corre-lated with pubertal stages.

PHYsIcal GrowtH andPubertal deVeloPMentof scHool-aGed cHIldren In ulaanbaatar

DIFFERENT

tunGalaG osGonbaatar, erdenetuYa Ganbaaatar,

Mongolian National University of Medical Sciences,School of Medicine, Department of Pediatrics

[email protected]

and tempo of puberty in healthy Mon-golian children and look for any possi-ble downward secular trends in puber-tal development.

obJectIVeTo perform physical development

assessment of school-age children, es-tablish the mean age of pubertal stagesboth in girls and boys.

To determine relationships ofpubertal stages and anthropometricmeasurements.

MetHodsA cross-sectional study of the

growth and pubertal stages of healthy385 school-aged children (aged 7-17years) living in the suburban area ofUlaanbaatar. The school is located15km from the center of Ulaanbaatar.

Pubertal stages were determined ac-cording to Tanner and Marshal’s methodby visual inspection and palpation. Tes-ticular size was measured by Prader’s or-chidometer. Height was measured usinga mobile stadiometer to the nearest 1 mmand weight was measured by electron-ic scale to the nearest 100 gram. Andbody mass index (BMI) was calculated.

Mean age at pubertal stages were es-timated using probit analysis. Mean ageat menarche was calculated by statusquo method.

resultsThe prevalence of obesity and over-

weight were 6.5% and 12.0%. And4.9% of total students were under-weight, 11.7% were stunted.

The prevalence of obesity and over-weight (24.1%) are highest among el-ementary school students, and stunting(13.3-14.5%) is twice higher in middleand high school students.

The median age of onset of Tannerstages 2 for breast development was9.58, and pubic hair stage 2 was 10.94in girls. The median age at menarchewas 12.26.

The median age of testicular enlarge-ment (Tanner 2 stage) and pubic hairTanner 2 stage were at 10.96 and 13.30years, respectively.

Hip circumference in girls (r=0.809,р<0.05), height in boys (r=0.843,р<0.05) had strongly correlated with pu-bertal stages.

dIscussIonAccording to the fifth national nutri-

tional survey, the prevalence of over-weight was 22.2% and the prevalence ofobesity was 6.4% among primary schoolchildren in Mongolia. Overweight preva-lence was higher in boys (26.6%) com-pared to girls (17.8%)4. In our survey,the prevalence of overweight was low-er in the suburban area of Ulaanbaatar,the capital city of Mongolia.

We compared the anthropometricmeasurements of school-aged childrenwith previous several studies. To com-pare the study conducted from 50 yearsago with our current result, mean heightincreased by 9.2 cm in boys, 8.9 cm ingirls. And mean weight increased by 8.9kg in boys, 5.7 kg in girls, respective-ly 5, 6. And the age at peak height ve-locity occurred 1-2 years earlier in oursurvey. A previous study in Ulaan-

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Table 1Mean height and weight of students.

Male

female

Gender Heightweight

bMIHeightweight

bMI

class р valueelementary

134.034.719.3133.630.417.0

Middle

148.042.519.3151.144.019.1

High

170.861.020.7159.955.121.7

0.010.010.2150.010.010.01

Table 2Nutritional status of students.

bMI normaloverweightobesityunderweight

Heightnormal stunting

9717167

12710

70.8%12.4%11.7%5.1%

92.7%7.3%

13223711

14825

76.3%13.3%4.0%6.4%

85.5%14.5%

66621

6510

88.0%8.0%2.7%1.3%

86.7%13.3%

n % n % n %elementary Middle High

class р value

0.015

0.134

Graphic 1Mean age at Menarche

17

16

15

14

13

121920 1940 1960 1980 2000 2020

13,3

12,26

14,26

16


2021

baatar shows that 69.5% of boys, 71.7%of girls' anthropometric measurementswere in the normal range7. But in thecurrent study, 70.6% of boys, 82.0% ofgirls were normal to their age.

The mean age at menarche is avery sensitive indicator of an individ-

ual’s general health and socioeconom-ic status. The first survey of the growthand pubertal development in Mongo-lia was conducted in 1920 by a Russ-ian researcher8. The mean age atmenarche was 16 years old in girls. Acentury later, in our study, a girl's

mean age of menarche decreased to12.2 years old.

conclusIonsThe prevalence of obesity and

overweight are highest among elemen-tary school students, and stunting istwice higher in middle and high schoolstudents.

Downward secular trend of growthand pubertal development is still ob-served in Mongolia. The mean age atmenarche is decreased by four years inthe last 100 years. Age of pubertalstage milestones are decreasing, and me-dian height and weight are increasing.

BMI, waist circumference and hipcircumference had a medium to strongcorrelation with pubertal stages andmenarche in girls. Height was stronglycorrelated with pubertal stages in boys.

references1. Marshall WA, Tanner JM. Varia-

tions in pattern of pubertal changes ingirls. Arch Dis Child.1969; 44 (235):291– 303

2. A. Juul, G. Teilmann, T. Scheike,N. T. Hertel, K. Holm, E. M. Laursen,K. M. Main and N. E. Skakkebæk Pu-bertal development in Danish children:comparison of recent European andUS data, International journal of androl-ogy 2006; 29: 247-255

3. Hochberg, Z., Belsky, J. Evo-devo of human adolescence: beyond dis-ease models of early puberty. BMC Med11, 113 (2013).

4. Fifth national nutrition survey re-port, 2017, https: //www.unicef.org/mon-golia/media/1116/file/NNS_V_undsen_tailan_EN.pdf

5. Narantsog, Ch, Malchilkhuu, D.Physical growth measurements and in-tellectual quality among school agedchildren. E720006, master degree dis-sertation, Ulaanbaatar, Mongolia 2007

6. Amgalan G, Burmaa B, Baigali J,Erdenechimeg E, “Physical growth andanthropometric measurent of School-aged children” Mongolian health sci-ence, 2008, 1(143)

7. Munkhzaya M, Undram L, Ser-OdK, et al. (2018) The Secular GrowthChanges in Height and Weight of Mon-golian Children over the Past 50 Years.Int J Marine Biol Res 3(1): 1-7.

8. Lhagvajav Ch, Mean menarchealage of Mongolia girls. Mongolian healthscience, 1970, 3(3)

68

Table 4Correlation between growth measurements and pubertal stage.

** р <0.01* р<0.05

Gender female

breast stageMenarche Pubic hair stage

MaleGenital stagePubic hair stage

bMI

.592**

.501**

.574**

.151*0.143

Hip circumference

.809**

.698**

.774**

Pearson’s correlation waist circumference

.639**

.548**

.616**

.339**

.290**

Height

.791**

.678**

.743**

.843**

.774**

Table 3Pubertal development.

2345

2345

2345

2345

5th percentile

8.099.1510.6212.16

9.2110.0611.7212.95

10.05

8.0210.5312.7012.81

10.3712.2612.8715.17

9.78

25th percentile

8.9710.2111.7813.34

10.2311.2612.6913.97

11.35

9.3611.9013.9014.28

12.1013.3414.4916.84

11.30

50th percentile

9.5810.9512.5914.17

10.9412.1013.3714.67

12.26

10.2912.8614.7415.29

13.3014.0915.6218.00

12.36

age 75th percentile

10.1911.6813.3914.99

11.6512.9314.0415.37

13.17

11.2113.8115.5816.31

14.5014.8416.7519.16

13.416

95th percentile

11.0612.7414.5516.17

12.6714.1315.0116.38

14.47

12.5515.1916.7817.78

16.2315.9218.3720.83

14.93

breast stage

Pubic hair stage (Girls)

Menarche

Genital stage (boys)

Pubic hair stage (boys)

Voice change

2021


an oVerVIew,Acute carbon monoxide poisoning

(ACMP) is a common disease in winterin northern China, mainly occurring in ru-ral areas with underdeveloped econom-ic conditions, and its mortality and dis-ability rate are high. More than 2.5 mil-lion people die of carbon monoxidepoisoning every year in the world. Ac-cording to national statistics, the numberof people who die of gas poisoningevery year in China is about 1,500 peo-ple. Because of the cold winter, and thedoors and Windows are also very tight,especially the substandard coal or notburning, people die of chronic poisoningin their sleep at night.http: //www.so.com -/s?q =%E5%9C%A8%E4%B8%AD -%E5 %9B%BD&ie=utf-8&src=inte -rnal_we nda_recommend_textnhttp://www.so.com /s?q=%E7%85% A4%E6 -%B0%94% E4%B8%AD%E6%AF% -92&ie=utf-8&src=internal_wenda_rec-ommend_textnhttp: //www.so. com -/s?q=% E4%BA%BA%E6% 95%B0&ie -=utf-8& src=inte rn al_wenda_ recom -mend _textnhttp: //www.so.com /s?q=% -

E5 %86%AC %E5%AD%A3&ie=utf-8&src=inter nal_wenda_recomm end_te -xtnh ttp: //www.so.com /s?q=%E9%97% -A8%E7% AA%97&ie=utf-8&src=inte -rnal_wenda_re com mend_textnhttp://www.so .com /s?q=%E5%9C %A8% -E5% A4%9 C%E9%87%8C&ie=utf-8&src=internal_wenda_recommend_textnhttp: //www.so.com/s?q= %E6% 85% -A2% E6%80% A7%E4%B8% AD% -E6% AF%92&ie=utf-8&src=intern -al_wenda_recommend_textn CO poi-soning is still one of the highest acute poi-soning cases in incidence, disability andmortality so far, and the incidence of De-layed encephalopathy after acute carbonmonoxide poisoning (DEACMP) hasbeen reported in China by 10% to 30%[1], 13% to 50% abroad[2].The causes ofpoisoning are mostly coal burning forheating, including coal burning for heat-ing, improper use of gas water heater, gasleakage and so on. Hemoglobin (Car-boxy-hemoglobin (COHb) forms whenthe body inhales CO, which affects theretention, transport, and use of oxygen inthe body. All tissues and cells in the body

are impaired, especially those organs withhigh oxygen demand, such as the brainand heart.By clinical comprehensivetreatment, most patients can recover, butthe more "fake" period of severe CO poi-soning patients after 60 days (2 -) easyto appear with dementia, mental symp-toms and extrapyramidal abnormal braindysfunction, known as delayed en-cephalopathy in acute carbon monoxidepoisoning (DEACMP), reported inci-dence of 10% to 30%, and domestic for-eign reported 13% to 50%[3]. Patients of-ten have cognitive and memory disordersand other sequelae, severe cases candie.Clinical manifestations include cog-nitive impairment, dysmorrhea, forcedcrying, forced laughter, Chorea andParkinson's disease[4,5].The pathogen-esis of DEACMP is still unclear, whichmay be related to vascular damagecaused by ischemia and hypoxia, oxygenfree radical damage, cell apoptosis, cy-totoxicity and other possible mecha-nisms[4]. The treatment of CO poison-ing is based on reducing the damage byeliminating CO and reversing cellularmetabolic disorders.The occurrence ofthis disease will lead to the decrease orloss of the working ability of patients,which will greatly affect the quality of lifeof patients, and also bring a heavy bur-den to patients, families and society.

II. case rePortGas poisoning is northern winter, es-

pecially northern rural heating, a kindof accident that often occurs, gas poison-ing is to point to carbon monoxide in gasand hemoglobin binding inside humanbody, and bring about hemoglobin in-side human body, cannot be in contactwith oxygen and make the organizationhypoxia, place produces the criticalsituation that endangers life seriously.

abstractobjective to investigate the course, symptoms and advantages of early com-

prehensive treatment of carbon monoxide (co) poisoning in a child with de-layed encephalopathy due to family carbon monoxide poisoning.Methods themedical history, physical examination, imaging examination and later recov-ery of the child in our hospital during rehabilitation treatment.to summa-rize the benefits of early comprehensive treatment for delayed encephalopa-thy due to carbon monoxide poisoning in children.results the local hyper-baric oxygen treatment of co poisoning in the child was not good, and therewere coma, convulsion, paralysis and other delayed encephalopathy.after be-ing transferred to our hospital for comprehensive treatment, the conditiongradually recovered. conclusion It is important to strengthen the clinical ob-servation of co poisoning patients, especially children, to find the damageof delayed encephalopathy and various organs in time, and to timely com-prehensive treatment.

Key words: Carbon monoxide poisoning; Delayed encephalopathy; Hyper-baric oxygen.

XIanPenG Yan, Xuan wan, XIaoHua Yan, JIanYInG fenG,JIeMIn wanG, fuYonG JIaoChildren’s Hospital, Shaanxi provincial People’s Hospital, 710068, Xi’an, China

corresponding author: fufonG JIao,email: [email protected]

a case rePort of faMIlY cluster carbon

MonoXIde PoIsonInGwItH delaYed

encePHaloPatHY and lIterature reVIew


2021

There has been a lot of rain this year. Ina certain area of northern Shaanxi, theweather suddenly turned cold in May,and the cave dwelling was even colder.My parents were living in the countytown, so I was left behind by a familyof four children (grandpa is 54, grand-ma is 52, boy is 5, girl is 3) to make acharcoal fire for warmth that night.Dadcalled home nobody answer the nextday, around two o 'clock in the afternoongo home only to find that the four gaspoisoning, emergency hospital, whengrandpa, girls, and poisoning the heav-iest unfortunately died in the process ofhospital, the lightest grandma symptoms,hyperbaric oxygen therapy better soonafter 1 week, life care, I have a headache,the grandson of fever, vomiting, threedays after hyperbaric oxygen therapywith limbs twitch, coma, local poortreatment effect to our hospital. Aftermore than 20 days of mental stimulation,grandma showed a slow reaction, wasreluctant to speak, suffered from mem-ory loss and incontinence. Consideringcarbon monoxide poisoning, tardy en-cephalopathy was hospitalized in the re-habilitation department of our hospital.

III. (1) General InforMatIon (case IntroductIon of cHIldren)Male child, 5 years old, chief com-

plaint: carbon monoxide poisoning for6 days, accompanied by fever andvomiting for 2 days. History of presentillness: Six days ago, four children in afamily were found to have carbonmonoxide poisoning and were in coma.They were immediately hospitalized inSuide District, Yulin First Hospital for"hyperbaric oxygen and supportivetreatment" (the specific treatmentprocess and examination were not

known, but the family members spokeabout it). Local head CT: basicallynormal. 2 days ago with fever, vomit-ing, the highest temperature of 38.50C,vomiting for gastric contents, the jetshape, about 5-6 times (unknown), ac-companied by intermittent right and in-voluntary shaking head, no obviouscough, head CT: no exception (familiesof oral, did not see the result), chest CT:double lung exudation and inflamma-tion, because of the treatment the effectnot beautiful.Children with irregularbreathing, limb involuntary shaking, thecondition is critical. Since the onset ofthe disease, no cough, no rash, no dys-pnea, nasal feeding, poor mental, large,normal urine.

Physical examination: T: 36.30C, P:100 times/min, R: 22 times/min, Wt:20kg, SO2: 95%, BP: 90/60mmhg.Nor-mal development, moderate nutrition,shallow coma, strong stimulation re-sponse, occasionally can wake up, sim-ple response "ah, ah", the whole bodyskin and mucosa no yellow, rash, bleed-ing points, no edema.No enlargementwas observed in superficial lymphnodes of the body. The skull is normalin size and has no deformity. The eyemoves freely, the pupil is as big as thecircle, about 3mm, and the response tolight reflection and regulationexists.Normal hearing in both ears, noabnormal secretion in external audito-ry canal, no tenderness in mastoidprocess. Nasal septum unbiased, lip rud-dy, pharyngeal hyperemia, tonsil II de-gree is big, neck soft, no resistance, tra-cheal middle and carotid pulse withoutexception, thoracic symmetry withoutexception, percussion sound clear, dou-ble lung auscultation breath soundsclear, audible and sputum song, heartrate 100 / cent, law of qi, each valve aus-cultation area did not smell and patho-logic murmur.The abdomen is flat, the

abdominal wall is soft, no tenderness orrebound pain, the liver, spleen and ribsare not touched, the whole abdominalpercussion is drum sound, no percussivepain in the liver and kidney area, and thebowel sounds are normal. No obviousabnormality was found in anus and ex-ternal genitalia.The spine was physio-logically curved, the muscle tension ofthe lower limbs was low, musclestrength could not be judged in the seda-tive state, physiological reflex existed,and pathological reflex was not elicit-ed. Outpatient auxiliary examination:Blood routine examination: WBC:10.1×109/ L, N: 0.85, L: 0.07, M: 0.08,PLT: 116 x 109/ L, RBC: 3.86 x 1012/L,HGB: 109g/L, CRP: normal, procalci-tonin: 5.42ng/ml, coagulation series:FDP 7.48mg/L, D-dimer: 1.41 mg/L, ar-terial blood gas: PH: 7.4 PCO2:43.7mmHg PO2: 23.5mmhg BE:2mmol/L SO2: 99.8%, chest CT: dou-ble lung texture weight gain blur.

(2) Admission diagnosis: 1. Delayedencephalopathy due to carbon monox-ide poisoning; 2. Bronchopneumonia;3.Sepsis.

Assisted in-hospital examination: re-examination of blood gas analysis: Potas-sium 2.2Mmol /L sodium 144mmol/L lac-tic acid 1mmol /L PH 7.51 PCO2 21.3mmHg PO2 120mmHg BE-4.8mmol /Lelectrocardiogram: no obvious abnor-malities; reexamination of electrolyte ionanalysis: Potassium 3.3mmol/L sodium134mmol /L liver function and myocar-dial enzyme: ALT 334U/L AST 156U/LCK 2596U/L CK-MB 55U/L LD 899U/L,coagulation test: normal, PCT 3.9ng/ml,no abnormal glucose.After admission, cra-nial MRI was urgently checked (Figure 1):left cerebral hemisphere swelling, abnor-mal signal shadow of left cerebral hemi-sphere, right frontotemporal parietal lobeand corpus callosum, which were consid-ered as hypoxic-ischemic encephalopathy.Severe cerebral hemisphere swelling,brain line extrusion to the right. 10 dayslater, head MRI was rechecked (Figure 2):abnormal changes in left cerebral hemi-sphere, bilateral basal ganglia region,thalamus, right frontal lobe and lateral ven-tricular posterior horn were consistent withthe manifestations of carbon monoxidetoxic encephalopathy. Cerebral hemi-sphere swelling was basically restored.Electroencephalogram: abnormal elec-troencephalogram (eeg) (background eegrhythm slowed down significantly in the

70

MRI at 1 week after poisoning (1) Treatment in the later half moon (2)

whole brain region and bilateral cerebralhemispheres were significantly asym-metric, and no abnormalities were ob-served in the rest). 1 week review of pro-calcitonin: normal; liver function reviewat discharge: ALT 51U/L AST 121U/L;myocardial enzyme spectrum: CK 108U/LCK-MB 51U/L.

(3) Treatment: "ceftriaxone sodium(T)" anti-infection for 1 week, midazo-lam sedation and support treatment for2 days. At the same time, HBO, dexam-ethasone, citicoline, physiotherapy andacupuncture were used to improvebrain function, protect liver, nourish my-ocardium, maintain internal environmentbalance, hyperbaric oxygen and rehabil-itation treatment.

(4) Results: After three days of com-prehensive treatment, the child wasconscious and unable to speak, withcomplete paralysis of the right upper andlower limbs. After continuous hyperbar-ic oxygen rehabilitation, the physicalstrength of the child gradually recovered.After one month of hospitalization, thechild was discharged with normalspeech and intelligence, and was able tocommunicate with others at a relative-ly slow speed.Right upper and lowerlimbs can be lifted, support can stand fora short time, can not walk.

IV. dIscussIonAcute carbon monoxide poisoning is

an emergency, early effective treatmentis very important, the most serious is theoccurrence of delayed encephalopathy,and then severe death. The incidence ofcarbon monoxide poisoning in childrenis small, but the disability rate is high. Af-ter admission, the child was in coma andparalysis, with obvious mri brain edemaon imaging, midline shift, severe braindamage, accompanied by myocardial andliver damage, which were very rare. Af-ter effective comprehensive treatmentsuch as HBO, dexamethasone, citicoline,physiotherapy and acupuncture, the chil-dren recovered gradually for one month.They could stand on their hands andcould not walk. They could talk to eachother and communicate with others at arelatively slow speed.Compared with hergrandma, she showed the importance ofearly intervention. Her early symptomswere mild, delayed encephalopathy ap-peared half a month later, which wasmanifested as unclear consciousness,quadrplegia, incontinence and other

manifestations. Meanwhile, she wasconsidered to be related to the recoveryof viscera functions and basic diseases ofthe old. Because children are smaller andventilate faster, they absorb carbon diox-ide faster than adults, but for the same rea-son, they remove it faster. [7-8]. Themechanism of hyperbaric oxygen ther-apy: (1) hyperbaric oxygen can acceler-ate the dissociation of carbon oxygen he-moglobin and promote the elimination ofCO.(2) Hyperbaric oxygen can rapidlyincrease the blood oxygen content of thebody, improve blood oxygen partialpressure, and quickly correct the hypox-ia state of the body tissues.(3) Hyperbar-ic oxygen can quickly correct tissuehypoxia, improve aerobic oxidation, re-duce organic acid, and fundamentally im-prove acidosis.(4) Hyperbaric oxygen canreduce intracranial pressure to preventcerebral edema after hypoxia.(5) Hyper-baric oxygen can rapidly control cerebraledema, which is of positive significanceto the recovery of CO poisoning causedby shock, brain, kidney, liver and otherimportant organ function damage. (6) Hy-perbaric oxygen has obvious preventionand treatment effect on late onset en-cephalopathy caused by CO poisoning.Since the pathogenesis of DEACMP isstill unclear, treatment is also based onits possible pathogenesis. Currently, nu-tritive nerve, improved circulation, hor-mone immunosuppression combinedwith HBO and rehabilitation therapy arewidely used clinically.The main patho-logical basis of DEACMP is diffuse de-myelination of the white matter of thebrain, proliferation of capillary endothe-lial cells in brain tissue and abnormal neu-rotransmitter metabolism in the brain[9].Most scholars believe that the brain is themost vulnerable to damage due to the lackof tissue hypoxia after ACMP and thevigorous metabolism due to the lack ofvascular anastomosis.Adenosine triphos-phate is rapidly depleted in the absenceof oxygen, the sodium pump does notwork properly, and sodium ions accumu-late in cells, causing edema in brain cells.The microvascular wall endothelial cellsswell and denaturate, and the accumula-tion of acid metabolites in the brain in-creases the vascular permeability, result-ing in the interstitial edema of brain cells.Blood oozes from the walls of blood ves-sels or extravasates in veins, occlusive en-darteritis and microthrombogenesis,which in turn leads to necrosis of brain

cells and demyelinating changes in thewhite matter[10]. HBO is widely used inthe treatment of delayed encephalopathydue to carbon monoxide poisoning inChina. A number of clinical studieshave shown that HBO is effective in im-proving clinical symptoms and signs, andimproving the cure rate and recovery rate.However, due to ethical problems, aprospective non-HBO treatment groupcannot be designed as a controlgroup[11]Et al. conducted a retrospectivecohort study on 56 and 23 DEACMP pa-tients who received different times ofHBO treatment, and found that early andlong course of HBO treatment could im-prove the prognosis of patients.Foreignscholars from Taiwan in 2010[12]HBOtreatment five times a week during hos-pitalization was applied to 9 DNS pa-tients, and HBO treatment was found toimprove the prognosis of DEACMP.Japanese scholars in 2014[13]Threemen over the age of 50 who developedDNS 25 days after CO poisoning weretreated with HBO for 30 times, and theimprovement in nerve damage was sig-nificantly improved.There are stud-ies[14][15][16]The mechanism of gluco-corticoid therapy for DEACMP is as fol-lows: it can stabilize biofilm, increasevascular densification, reduce endothe-lial cell edema and endovascular inflam-mation, and produce immunosuppressiveeffect, so as to effectively prevent de-myelination lesions.At the same time, canalso expand spasmodic contraction ofblood vessels, improve the blood circu-lation in the brain and prevent the degen-eration and necrosis of brain cells. Ad-ditional, glucocorticoid still can im-prove the excitability of nerve center, re-duce carbon monoxide to the damage ofcentral nerve cell, improve central nervesymptom thereby. Therefore, glucocor-ticoid has a practical and effective effecton brain protection.

In summary, both hyperbaric oxygenand glucocorticoid have certain curativeeffects on ACMP and DEACMP, but asmall amount of adverse reactions are in-evitable.As a vulnerable group, chil-dren with delayed encephalopathy ac-companied by serious imaging damagewill have high mortality rate, high pos-sibility of sequelae and high expectationof parents, which should be paid enoughattention to by doctors.Therefore, adversereactions should be closely monitored andsymptomatic treatment should be con-

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72

ducted in the clinical treatment of ACMPand DEACMP children.In addition,treatment should be carried out in strictaccordance with the formulated treatmentplan. Meanwhile, changes in the condi-tion should be closely observed and thetreatment plan should be timely adjust-ed in order to get the best effect of treat-ment. At present, the pathogenesis ofDEACMP is not very clear, and the re-search on this disease is still in the ear-ly stage of exploration. It is hoped thatthere will be a specific treatment for thisdisease in the near future.

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LY, et al. Increased Long-Term Risk ofDementia in Patients With CarbonMonoxide Poisoning: A Population-Based Study [J]. Medicine, 2016, 95 (3):e2549.

[2] Akyol S, Erdogan S, Idiz, N, et al.The role of reactive oxygen species andoxidative stress in carbon monoxide isan in-depth analysis [J]. Redox Rep,2014, 19 (5): 180-189

[3] Pepe G, Castelli M, Nazerian P,et al. Delayed neuropsychological se-quelae after carbon monoxide poison-ing: Predictive risk factors in the Emer-gency Department.A retrospectivestudy[J].Scand J Trauma programmedc Emerg Med, 2011, 19(1): 16.

[4] Wang X, et al. MRI and clinicalmanifestations of delayed encephalopa-

thy after carbon monoxide poisoning.Pak J Pharm Sci. 2016; 29 (6 Suppl):2317 - 20.

[5] Sung YF, et al. Generalizedchorea due to delayed encephalopathyafter acute carbon monoxide intoxication.Ann Indian Acad Neurol. 2015; 18 (1):

The 108-10.Wu PE, Juurlink DN. Carbon amend-

ment [J]. CMAJ. 2014, 186(8): 611.[7] Hampson NB, Piantadosi CA,

Thom SR, Weaver LK. Practice recom-mendations in the diagnosis, manage-ment, and prevention of carbon monox-ide poisoning. Am J Respir Crit CareMed. 2012 Dec 1; 186 (11): 1095-1101.

[8] Rose JJ, Wang L, Xu Q, et al. Car-bon monoxide poisoning: pathogenesis,management, and future directions ofdherapy. Am J Respir Crit Care Med.2017 Mar 1; 195 (5): 596-606.

[9] Kim J H, Chang K H, Song I C,et al. Delayed encephalopathy of acutecarbon monoxide intoxication: 22.Am JNeuron adiol, 2003, 24(8): 1592-1597.

[10] Chu K, Jung K H, Kim H J, etal. Diffusion-weighted MRI and99m Tc-HMPAO SPECT in delayed relapsingtype of carbon monoxide poisoning: Ev-idence of delayed cytotoxic edma[J].EurNeuro, 2004, 51(2): 98-103.

[11] Zhao Yongjun, Liu Yangsheng-sheng. Analysis of factors affecting theoccurrence and prognosis of delayed en-cephalopathy after CARBON monox-ide poisoning [J].Journal of Changchun

University of Chinese Medicine, 2013,29 (2): 317-318.

[12] Chang DC, Lee JT, Lo CP, et al.Hyperbaric oxygen ameliorates de-layed neuropsychiatric syndrome ofcarbon monoxide poisoning[J]. Under-sea & Hyperbaric Medicine Journal ofthe Undersea & Hyperbaric Medical So-ciety Inc, 2010, 37 (1): 23 to 33.

[13] Watanuki T, Matsubara T,Higuchi N, et al. [Clinical examinationof 3 patients with delayed neuropsychi-atric encephalopathy induced by carbonmonoxide poisoning, who recoveredfrom severe neurocognitive impair-ment by repetitive hyperbaric oxygentherapy][J]. Seishin shinkeigaku zasshi= Psychiatria et neurologia Japonica,2014, 116 (8): 659-69.

[14] Xiang W P, Xue H, Wang B J.Delayed encephalopathy of acute carbonintoxication in rats: Potential mechanismand intervention of dexamethasone[J].Pakistan Journal of PharmaceuticalSciences, 2014, 27(6): 2025-2028.

[15] Li Haijun, Zhang Ming, ZhangDongqin, et al.Effect of early hormoneintervention on delayed encephalopathyafter carbon monoxide poisoning [J].Journal of clinical emergency, 2015,16(4): 256-259.

[16] Wang Haitao.Clinical observa-tion on comprehensive treatment ofdelayed encephalopathy after carbonmonoxide poisoning [J]. Modern HealthPreservation, 2015(18): 102.

Breastfeeding is the best source ofnutrition for infants and young chil-dren and is one of the most effectivemeasures to ensure the healthy growth

and development of children. Theabundant anti-infective substancesin breast milk can prevent the infec-tion of digestive tract and respirato-

ry tract, and effectively reduce the in-fant mortality rate. Breastfeedingpromotes early cognitive and non-cognitive development in infants.

JIale wanG,Class 4 of master degree 2020, Xi'an Medical University

HaotIan Xu,Department of Pediatrics, Heyang County Hospital,

Shaanxi province

YunYI lIanG,School of Public Health, Xi'an Jiaotong University Health Science Center

fuYonG JIao,Children’s Hospital of shaanxi provincial people’s Hospital 4,

Shaanxi Children's Health Promotion Association

corresponding author: fuYonG JIaoe-mail: [email protected]

researcHProGress of breastfeedInG In cHIna

China has cooperated with the WorldHealth Organization and other organ-izations to promote a series of inter-national standards and policies onbreast-feeding, and advocates andpromotes effective measures to pro-tect, promote and support breast-feeding. Therefore, the pure breast-feeding rate of 0-6 months babies inChina has been significantly im-proved along with the development ofsocial and economic level, and it ishigher in rural areas than in cities.

The World Health Organization(WHO), the United Nations Chil-dren's Fund (UNICEF) and other in-ternational organizations have formu-lated a series of international stan-dards and policies on breastfeeding,including the International Code ofMarketing of Breast Milk Substi-tutes and the Baby-Friendly HospitalInitiative, to advocate and promote ef-fective measures to protect, promoteand support breastfeeding in all coun-tries around the world. The WorldHealth Organization (WHO) to theglobal initiative: encourage mothersto exclusively breastfeed for sixmonths, and then gradually add com-plementary food breastfeeding to 2years old or more. By 2020, 50 percent of babies should be exclusivelybreastfed up to the age of six months,according to the Guidelines for theDevelopment of Chinese Children.The benefits of breastfeeding to thegrowth and development of infants areself-evident, this paper through thestudy of the current situation andprogress of breastfeeding, improvemothers' awareness of breastfeed-ing, improve the rate of breastfeedingin China.

I. adVantaGes of breastfeedInG The various nutrients contained

in breast milk are most suitable for thedigestion and absorption of infants,and have the highest bioavailability.It can meet the physiological needs ofinfants at different stages, and can notbe replaced by any other food.

Breast milk can reduce the in-cidence of neonatal diseases. Breastmilk is an essential nutrient for in-

fants. Breast milk, especiallycolostrum, contains immune sub-stances, which can meet the growthand development needs of infants 4 to6 months after birth. Infants and in-fants are prone to various diseases dueto lack of breastfeeding.

Breastfeeding is associated withthe incidence of breast cancer. Stud-ies have shown that less or no breast-feeding mothers have an increasedrisk of breast cancer. When breast-feeding, the mother's physical contactwith the baby enhances the commu-nication between the mother and thebaby, enhances the baby's sense of se-curity, and promotes the healthy de-velopment of the baby's physical andsocial adaptability.

2. tHe current sItuatIon of breastfeedInG The current situation of breast-

feedingAccording to data on breastfeeding

rates in China, breastfeeding levelsvary from place to place, with 41 percent of babies exclusively breastfedwithin six months, 71 per cent contin-uing to breastfeed at the age of oneand 45 per cent breastfeeding at theage of two.

482/5000 The current situation of breast-

feeding in ChinaAccording to a report by the Unit-

ed Nations Children's Fund(UNICEF), from 2012 to 2014, therate of exclusive breastfeeding for ba-bies under 6 months of age in Chinawas low. According to a survey report(2019) released by the China Devel-opment Research Foundation, therate of exclusive breastfeeding with-in six months in China is generallylow.

In 1998, when the World Bank sur-veyed China, breastfeeding ratesstood at 67 percent.

In February 2019, the China Devel-opment Research Foundation releasedthe Investigation Report on FactorsInfluenting Breastfeeding in China,which focused on infants under 1 yearof age, and examined exclusivebreastfeeding of infants aged 0-5

months (i.e., within 6 months), con-tinued breastfeeding of infants aged6-11 months, and early exposure toearly opening of milk within 1 hourafter birth. The survey data showedthat the rate of exclusive breastfeed-ing within six months was highest inbig cities, followed by rural areas andsmall and medium-sized cities. Ac-cording to a report on the influencingfactors of breastfeeding in China re-leased by the China DevelopmentResearch Foundation in February2019, the exclusive breastfeedingrate of infants within six months inChina is low. The exclusive breast-feeding rate was the highest in bigcities, reaching 36 percent. The low-est rate for small and medium-sizedcities was just 23 percent. Accordingto the 2018 Investigation Report onthe Publicity and Sales of Breast-milkSubstitutes released by the ChinaConsumers Association, the propor-tion of exclusive breastfeeding has de-creased compared with a decade ago.In 2018, 49.05 percent of babieswere exclusively breastfed by moth-ers, compared with 52.4 percent in2007.

In recent years, the data of breast-feeding rate in different regions ofChina show that the situation ofbreastfeeding is different in differentregions, provinces and cities. In 2010,a survey was conducted in some sec-ondary and tertiary hospitals inShanghai, among which 24.8% ofwomen were exclusively breastfed. In2012, the rate of exclusive breastfeed-ing among 260 newborns in FeichengCity People's Hospital of Shandongwas 76.2%. In the same year, a sur-vey of Longhua Community inShanghai found that the rate of exclu-sive breastfeeding was 41.9%. LiYunfang et al. investigated the feed-ing methods of four baby-friendlyhospitals in Weinan City, and foundthat the rate of exclusive breastfeed-ing was 48.7%. In 2012, a study se-lected five regions in North China,East China, Northwest China, South-west China and Northeast China, in-cluding Tongliao City of Inner Mon-golia, Changzhou City of JiangsuProvince, Ningxia City of Gansu

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2021

Province, Bijie District of GuizhouProvince and Harbin City of Hei-longjiang Province. The resultsshowed that the average rate of exclu-sive breastfeeding in the five citieswas 62.56%

A 2012 survey of breastfeeding inurban, urban and rural areas in Guang-dong province found that 75.6 percentand 65.8 percent of babies aged 4months and 6 months were breastfed,respectively

According to a 2012 survey ofbreastfeeding in Hong Kong, a 2013survey of nine counties and cities inZhejiang province found that the rateof exclusive breastfeeding was 30.3%.In 2014, a survey was conducted onthe feeding patterns of women inNanhu Community of ChangchunCity, and the rate of exclusive breast-feeding in the area was 50.8%.

A 2016 survey in Shenzhen foundthat the exclusive breastfeeding ratewithin six months was 61.2%.

A 2015 survey of breastfeeding inBeijing found that 51.6% of infantswithin four months were exclusivelybreastfed. A 2017 survey in Shenzhenfound that 61.2 percent of babieswithin six months were exclusivelybreastfed. Breastfeeding varies,though. The Program for the Devel-opment of Children in China (2011-2020) set the goal of "50 percent ormore exclusive breastfeeding for in-fants aged 0-6 months" in 2011.

3. tHe InfluencInG factors of breastfeedInGAt present, China's exclusive

breastfeeding rate is very low, 28.1%of the people think it is the maternalown reasons, such as the lack ofmilk, etc. 22.9% of the people, choosebreastfeeding knowledge populariza-tion is not enough; 20.4 percent attrib-uted it to poor feeding conditions.

Many people have misconceptionsabout breastfeeding, thinking that aslong as you give your baby breastmilk is breastfeeding, in fact, this isnot comprehensive. The World HealthOrganization recommends optimalbreastfeeding: all babies should bebreastfed within one hour of birth and

exclusively breastfed for six monthswithout water or any other liquid orsolid food. Nutritionally adequateand safe complementary foods arestarted after six months, while breast-feeding continues until two years ofage or beyond., of course, this is themost ideal way of feeding, and in factin addition to some social factors,many mothers breastfeeding is a lackof enough knowledge of science, in-cluding breast milk secretion regular-ity, neonatal physical characteristicsand methods of promoting lactation,and insufficient understanding of thebenefits and the importance of breast-feeding, this also is they don't stick tobreastfeeding. This, coupled with theinfluence of older or traditional child-rearing attitudes, creates more barri-ers for mothers to breastfeed. Manymothers think it's good to give formu-la to their children. If there is a tem-porary shortage of milk, do not giveup easily. Mixed feeding can be car-ried out first, and then by increasingthe number of sucking, breastfeedingmothers can reasonably replenishwater (6-8 glasses of water a day) topromote milk secretion, so as to en-sure a good supply of milk andachieve the ultimate exclusive breast-feeding.

IV. ProGress In breastfeedInG In cHIna4, New progress has been made in

breastfeeding in China. In recentyears, with the development of theeconomy and the overall improvementof the national education level, thecountry has paid more and more at-tention to breastfeeding. With theestablishment of the China Breast-feeding Action Alliance, China has setMay 20 as the National BreastfeedingPublicity Day every year. In 2013, thefirst breast milk bank in the mainlandof China was established inGuangzhou. In January 2017, YiliGroup and 10 major domestic hospi-tals including Peking Union MedicalCollege Hospital jointly promotedthe establishment of a standardizedand standardized Chinese breast milkbank. In August 2017, the National

Breastfeeding New Progress TrainingCourse was successfully held in JinanWomen. In April 2019, the "Interna-tional Conference on BreastfeedingNew Progress and Cases in China"was successfully held. In August2020, the Chinese Nutrition Societyissued the "Standards for the Estab-lishment and Management of Hu-man Milk Banks in Medical Institu-tions". Although there is a long wayto go to improve breastfeeding rates,national and social efforts are beingmade to improve breastfeeding. Fromthe perspective of policy, both theOutline of China's Child Development(2011-2020), the National NutritionPlan (2017-2030) and the ActionPlan for Healthy Children (2018-2020) have clearly stated that thebreastfeeding rate of 0-6 months ba-bies in China should reach more than50% by 2020. Actively, China has cre-ated more than 7,300 baby-friendlyhospitals to better publicize the ben-efits of breast-feeding, teach breast-feeding skills, and help women buildtheir confidence in breast-feeding. Inaddition, maternal and child facilitiesare also actively supporting. TakingBeijing as an example, by August2018, more than 4,000 maternal andchild facilities had been establishedin public places such as airports andlarge railway stations, as well as in en-terprises and institutions.

5. tHe suMMarYIt is not difficult to see from the

data and reports of various studies onbreast milk at home and abroad thatbreastfeeding in China still needs tocontinue efforts, which should rely onthe joint efforts of the whole society,such as constantly improving publicbreastfeeding facilities, giving scien-tific guidance and more psychologi-cal care to breastfeeding mothers, andpopularizing more breastfeedingknowledge. It is believed that througha series of corresponding measures,we will continue to promote the im-provement of the current situation ofbreastfeeding in China, improve thebreastfeeding rate, and lay a solidfoundation for the healthy growth ofthe next generation.

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2021


corresPondence We report about a 5 day old new-

born with critically pneumonia SARS-CoV-2 after cesarean section infect-

ed by a family cluster infection. Amale newborn was admitted 22 daysafter delivery due to "intermittentfever for 17 days". That means that on

the fifth day after delivery, due to Ce-sarean section, the newborn began tofever. In short, history of pregnancyand delivery modus was G1P1, 22days ago (31 jan 2020). The newbornwas delivered in 38 + 5 weeksgestation by c-section. Amniotic fluid,umbilical cord and placenta was nor-mal, APGAR score at 1,5 and 10 min-utes normal. 18 days ago (04 feb2020) the child developed fever witha peak of 38.00c. The child showedchoking cough, had no runningnose, no vomiting, no diarrhoea,any convulsions or skin rashes.

17 days ago, on 02 of February2020, the fever in outpatient clinic inXinyang Center Hospital processed. Aswab test for SARS-CoV-2 virus nu-cleic acid testing was positive.15days ago, on 6th of february 2020,fever was present once up to 37.70c.17 days before the child see a doctorin the center of the Xinyang Hospital.The medical treatment was based on

PRACTICING PHYSICIANS

„coVId-19 PneuMonIa:tHe first case of successful

treatMent of a crItIcal Ill

newborn after cesarean sectIon“

fuYonG JIao,Children's Hospital, Shaanxi Provincial People's Hospital, Xiatong University, Xi` an, China.Working in research cooperation since 2019

cHonGcHen ZHou, YIbo cHenG, sHuYInG luo,Henan Provincial Children`s Hospital (Children`s Hospital affiliated to Zhengzhou University), Henan, Zhengzhou, China

leI Ma,Children's Hospital, Shaanxi Provincial People's Hospital, Xiatong University, Xi` an, China.Working in research cooperation since 2019

XInGGanG ZHen, YInGJun fenG, MIn lI, Henan Provincial Children`s Hospital (Children`s Hospital affiliated to Zhengzhou University), Henan, Zhengzhou, China

stefan bIttMann,Department of Pediatrics, Ped Mind Institute, Gronau, Germany. Working in research cooperation since 2019

abstract:In the XXI century a great attention should be devoted to the prob-

lems of global heating, resulting in natural calamities and spread of dif-ferent diseases. therefore, measures against expected epidemic shouldbe taken.

science and security must be determined together with social-econom-ic and ecological environment. together with each of these two factors sci-ence may have both positive and negative sides. thus, in my opinion, sci-ence of the XXI century should serve the mankind at high level of urban-ization, safety of each citizen of this country and carry on preventive meas-urements against possible negative influence. Introduction of high tech-nologies in investigations, existence of precise medical statistical database,creation of modern computer programs and their usage(prognosis of dis-ease course, establishment of risk factors and groups, etc) – that is all onthe basis of which it will be possible to solve many problems existing in theXXI century.

Kevword: Pediatrics, Security, Disease, Preventive measurements Chil-dren’s rights.


2021

ribavirin, cephalosporin, immunoglob-ulin (2.5 g, application 5 days), albu-min (3 g, application of 3 days), atom-ization interferon, Lopinavir/Ritonavir(0.5 ml /per time, all 12h). Under thesemedication the child had temperaturefluctuations with highest temperatureof 37.50c, discontinuous, when admin-istering oxygen inhalation throughnasal catheter oxygen intolerance.The child had no failure to thrive, buthad choking cough. For furthertreatment, with a diagnosis of"COVID-19" the newborn wasadmitted to our hospital fromemergency ambulance. In this mo-ment of admittance, the child'smental reaction was poor, butsleep was normal, the newbornshowed normal stool and normalurine.

————The parents had been living in

Wuhan City, before the baby wasborn. On January 22, the parentsof the baby returned toXinyang City from Wuhan. Inthe afternoon of that day, themother felt cold and drowsy. Thefather and grandfather of the childwere diagnosed with COVID-19on April 4th. The baby's grand-mother was diagnosed on Febru-ary 25. Physical examinationshowed full month appearance, weightof 3600g, body temperature was36.50c, pulse rate 172 times/min,respiration rate of 40 times/min. Theblood pressure was initially measuredby 74/36mm Hg, height was 51cm.There was no malformation in theskull, the anterior fontanelle was2.5cm × 2.5cm, the posteriorfontanelle was closed, flat and soft,and the tension was normal. Bilater-al pupil showed isocorie, the reflex tolight existed. The breath was smoothunder oxygen inhalation by nasalcatheter was performed. No expirato-ry dyspnoea was found. The threeconcave signs were negative.

The breath sounds in both lungswere rough. Heart rhythm was uni-form, heart sounds were strong, nomurmur was heard, abdomen wassoft, umbilical cord did not fall off,

liver reached 1.5cm below rightcostal, soft, spleen was not reached,bowel sounds were normal. The ex-tremities were warm at the end, withfree movement, normal muscle tone,and primitive reflexes. Laboratoryblood routine examination showedleukocyte 12.95× 109/L, erythrocyte3.07×1012/L, hemoglobin 101 g/L,platelet 356×109/L, lymphocyte per-centage 49.5 %, c-reactive protein

quantitative determination <0.5 mg/L.Liver and kidney function, myocardialenzymes, electrolytes: total bilirubin13.7 umol/L, conjugated bilirubin2.7 umol/L, unconjugated bilirubin11.0 umol/L, alanine transaminase46.7 U/L, glutamate transaminase37.8 U/L, creatine kinase isoenzyme48.3 U/L, potassium 6.75 mmol/L.

Computertomography showed localthickening of double lung texture,small patch density increased shadows.A fuzzy edge was found. Chest CT re-viewed on March 1 showed, that thelung film was more clearly absorbedthan before. After admission, the childwas placed in the isolation ward fortreatment and have been given a warmbox insulation.The newborn had nasalcatheter application of oxygen, inter-feron injection by oral cavity and am-broxole at the same time. The heart rate

was closely monitored. Respiration,blood pressure, electrolyte were alsoclosely monitored. Furosemide wasgiven as diuretic, cefoperazone wasgiven. Sedation, heart strengthening,diuretic, fluid limitation, circulationimprovements were initiated. IN thenext days, the child's body temperaturewas normal, no cough, no dyspnea,good nursing, normal defecation andurination. Further two time nucleic acid

tests were negative and thecondition of the newborn wassignificantly improved. They werefollowed up for two weeks afterdischarge. Finally, the baby recov-ered normal, and the spirit andaspect was finally very good. Norise of temperature of fever wasfound in course.

In conclusion, because of thefamily gathering, the clinical diag-nosis and treatment characteristicsof a new coronary pneumoniacombined with psychological ex-haustion caused by non-mother-to-child transmission after cesareansection were analyzed. It is a de-scription of a case of neonatal se-vere coronavirus pneumonia 5days after cesarean section inChildren's Hospital affiliated toZhengzhou University. As a resultthe neonate lived for 5 days withfebrile COVID-19 infection. How-

ever, the children turned into micro-se-vere, coronavirus pneumonia, com-bined with psychological failure, afterrescue treatment, accounting and test-ing twice negative at discharge. Ce-sarean section and family members in-fection easy caused neonatal criticalpneumonia, and this should strength-en the diagnosis and treatment. Thiscase shows impressingly the course ofa COVID-19 infected neonate due tocluster infection of the whole family.

Picture 1: Computertomography ofthe lungs in newborn with COVID-19infection

Corresponding Author:STEFAN BITTMANN M.D., M.A.,Head of the Department of Pedi-atrics and Ped Mind Institute

D-48599 GronauGermany

76

Ground glass opacity in a newborn infected withCOVID-19

2021


1. bacKGround:A novel coronavirus pneumonia

(COVID-19) outbreak in Wuhan inmid December 2019, which caused bythe infection of a new coronavirus——severe acute respiratory syndromecoronavirus type 2 (SARS-CoV-2).The WHO announced that COVID-19was a public health emergencies of in-ternational concern in January 30,2020. Then, it quickly spread aroundthe world and was accepted as a pan-demic on March 11, 2020 [1]. As ofJune 11, 2020, more than 7.3 millionpeople worldwide have been diag-nosed with COVID-19. COVID-19epidemiology shows that the popula-tion is generally susceptible, but theproportion of children affected seemsto be much smaller than that of adults,and only 2% of cases are described aspatients under 20 years old [2]. Theepidemiology report describes novelcoronavirus pneumonia cases diag-nosed in children, and more than 90%

abstractobjective: to explore the differences and connections between 156 chil-

dren with Kawasaki disease (Kd) from 6 sub-centers during the outbreakand the 48 patients with Kd reported during the epidemic period in relevantcountries. Methods: retrospectively analyzed the relationship between theclinical manifestations and laboratory examinations of children with Kd whowere hospitalized after the outbreak and children with Kd reported in oth-er countries during the outbreak. results: there are many cases of Kd in chil-dren in china, of which 83.6% are complete and 16.4% are incomplete, butthey are not sars-coV-2 infections. this is different from the Kd childrenrecently discovered in european and american countries, but the clinical man-ifestations are similar. the inflammatory index of patients with Kd-like symp-toms reported in the literature is much higher than that of normal Kd pa-tients. among them, the proportion of patients with crP>200mg/l is as highas 46%; secondly, combined with diagnostic criteria, we found that typicalKd patients have Plt is higher than normal, but the Plt levels of patientswith Kd-like symptoms that we have counted in the literature are mostly with-in the normal range.

conclusion: the etiology of Kawasaki disease is unclear, but the relation-ship between the new crown and Kawasaki needs further study. due to thecharacteristics of immunity, children are prone to infection and develop mul-tisystem inflammatory syndrome in children (MIsc) and Kd-like manifes-tations. therefore, timely diagnosis and correct treatment should be madeto reduce the damage of coronary artery.

Key word: Kawasaki disease; COVID-19; MIS-C;

lIn-na wanG,Postgraduate of Class 7Grade18, School of Clinical Medicine,

Xi’an Medical University, Xi’an, 710068, China

fu-YonG JIao,Children's Hospital, Shaanxi Provincial People’s Hospitall, Xi’an

Medical University, Xi’an, 710068, China (Corresponding author: Jiao F-Y, Email: [email protected])

Yu weI,Class 1 Grade14, School of Clinical Medicine, Xi’an Medical University, Xi’an, 710068, China

YInG-Jun fenG,Henan Children's Hospital, Zhengzhou University, Henan, China

JInG-lI ZHanG,Hebei Children's Hospital, Hebei, China

ZHao-XIa ZHanG,Department of Pediatrics, Shenzhen People’s Hospital, Jinan University, Shenzhen, China

sHu-bIn tanG,Baoji Maternal and Child Health Hospital, Baoji, China

Ya-lI lI,Department of Pediatrics, Hanzhong 3201 Hospital, Hanzhong, China

PenG-JIanG KanG, Ya-le ZHanG,Xianyang Children's Hospital, Xianyang, China

HuI-ronG lI,Yulin Children's Hospital, Yulin, China

MultIcenter clInIcal studY of 156 cHIldren wItH KawasaKI dIsease durInGcoVId-19


2021

of them are asymptomatic, mild ormoderate [3].

In the past few weeks, there havebeen significant clusters of KD-likesymptoms in children in the UnitedKingdom, the United States and Italy,with similar test results reported, andsome of these children have confirmedSARS-CoV2 infection by RT-PCR.Kawasaki disease (KD), also known asmucocutaneous lymph node syndrome,is an acute febrile disease in childrenwith systemic vasculitis as the mainpathological change. It is commonlyseen in children under 5 years old, andusually manifested as fever, rash, diffusemucosal inflammation, non exudativeconjunctivitis, cervical lymph node le-sions and limb changes [4]. The diseasecauses inflammatory changes in thewalls of small and medium-sized arter-ies in any part of the body. However,coronary artery is mainly involved. Inuntreated KD children, up to 25% mayhave coronary artery disease, whichleads to serious complications, such ascoronary artery dilatation, coronaryaneurysm and acute myocardial infarc-tion [5].

KD is a disease with unclear etiol-ogy. At present, it has been reportedthat KD is related to infection and im-mune-mediated, which mainly in-

vades coronary artery, and is relatedto susceptible genes. A study in 2014showed that HCoV-229E may be apossible pathogen of Kawasaki disease[6]. Epidemiology shows that the in-cidence of typical KD is higher inAsian children. However, more than50% of children with KD-like syn-drome reported during the outbreakwere African Caribbean [7]. It is stip-ulated that all hospitalized childrenshould undergo nucleic acid test.Therefore, all hospitalized KD chil-dren have been tested for COVID-19.156 of our KD children are not infect-ed with COVID-19.All the nucleicacid tests are negative. KD or KD-likesymptoms have not been observed inpediatric patients since the outbreak ofnew crown pneumonia in China,which has increased the possibility ofracial background and genetic suscep-tibility.

In an article published in the Lanceton May 7, 2020, eight critically illchildren characterized of severe in-flammation were described in detail.However, not all children have con-firmed the infection or exposure toCOVID-19 [7]. In Bergamo, Italy, 20children were diagnosed with KD,roughly equivalent to the total num-ber of cases in the region for more

than three years [8]. The Frenchhealth minister reported that about 15children had KD symptoms in hospi-tals in Paris [8]., The New York CityDepartment of Health issued a healthalert on May 4, 2020, describing 15cases of multisystem inflammatorysyndrome characterized of KD ortoxic shock syndrome (TSS) [9]. NewYork said it was investigating 85 cas-es of "multisystem inflammatory syn-drome in children associated withCOVID-19" [10]. Shelley rifagan saidthey noticed that eight children hadunprecedented high inflammatoryshock, similar to atypical Kawasakidisease, Kawasaki shock syndrome ortoxic shock syndrome in 10 daysfrom mid April 2020. Among them,two children tested positive for SARS-CoV-2.And they support that suchchildren should receive early attentionfrom the community and be given pri-ority early recognition of the disease[7]. The US Centers for Disease Con-trol and Prevention published an of-ficial name on May 14, 2020, callingthe disease " multisystem inflamma-tory syndrome in children (MIS-C)"[11].

2. MaterIals and researcH MetHods:2.1 Methods:Since the outbreak of novel coron-

avirus pneumonia in Wuhan in mid De-cember 2019, we have jointly conduct-ed 4 centers to investigate the diagno-sis and treatment of KD children, in-cluding Shaanxi, Henan, Hebei andGuangzhou. 156 cases of KD were di-agnosed and treated, including 95boys and 61 girls, with a male to fe-male ratio about 1.6: 1. Among them,children aged 1-5 years were the main,followed by infants ≤ 1 year old, andchildren aged 11-18 years were theleast.

Inclusion criteria: Fever persisting ≥5days, plus at least four out of five of thefollowing principal features

Bilateral bulbar conjunctivalcongestion;②Hyperemia of oral cavity and pha-

ryngeal mucosa (lip redness, lipchapped, bayberry tongue);③ Pleomorphic rash;

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Table 1

④ Changes in extremities, includ-ing erythema and edema in palmoplan-tar and finger-end (toe-end) in acutestage and membranous desquamationof the transitional area of the nail bedof the finger(toe) in the convalescentstage;⑤ Acute non suppurative lym-

phadenopathy of neck.Exclusion criteria:① Congenital heart disease② Viral myocarditis③ Rheumatic carditis and other

connective tissue diseases④Hematological diseases (leukemia,

etc.)⑤ Incomplete data and incorrect di-

agnosisPatients with Kawasaki like symp-

toms were defined according to theAmerican Heart Association's 2017criteria, including classic (≥ 5 days offever plus 4 or more clinical criteria,including bilateral bulbar non ex-udative conjunctivitis, lip or oralchanges, non suppurative cervicallymph node lesions, pleomorphicrash, erythema on the palms andsoles of the feet, hand foot induration,or both) and incomplete types. For theincomplete type (≥ 5 days of feverplus the above two or three clinicalcriteria), the value of erythrocytesedimentation rate (ESR) or C-reac-tive protein (CRP), or both, can beused as an indicator, also includinganemia, thrombocytosis after 7 daysof fever, hypoproteinemia, hyper-transaminaemia, leukocytosis, asep-tic pyuria, or showing coronary he-mangioma or cardiac insufficiency byechocardiography (left ventriculardysfunction, mitosis) related addition-al diagnostic criteria [12].

According to the following criteria[13]: Dilation: diameter ≥ 2.5SD;small aneurysms: localized dilationwith internal diameter ≤ 4 mm (5-year-old children: the inner diameterof one segment is 1.5 times of theadjacent segment) Z score ≥ 2.5 to <5; medium aneurysm: aneurysm diam-eter > 4 mm and < 8 mm (children ≥5 years: segment diameter is 1.5-4times of adjacent segment) Z score ≥ 5t<10; giant aneurysm: display inner diam-eter of 8 The Z-score of aneurysms

(children ≥ 5 years old: the inner diam-eter of one segment is more than 4 timesthat of adjacent segments) was ≥ 10 mm.According to the results of echocardio-graphy, KD children were divided intothree groups: normal group, coronary ar-tery dilation group and coronary arteryaneurysm group.

2.2.research methods:Retrospectively analyzed the relation-

ship between the clinical manifestations

and laboratory examinations of childrenwith KD who were hospitalized after theoutbreak and children with KD report-ed in other countries during the outbreak.

We summarized the information ofKD patients during the epidemic peri-od and drew a table.

In the three groups of coronary ar-tery damage, the initial diagnosis andreturn visit were not the same, the dif-ference was statistically significant. Af-ter further comparison, it was found

2021


Table 2

Initial diagnosis38 (23.4%)28 (17.9%)26 (16.7%)27 (17.3%)9 (5.7%)4 (2.6%)

32 (20.5%)32 (20.5%)2 (1.3%)8 (5.1%)12 (7.7%)31 (19.9%)15 (9.6%)2 (1.3%)

20 (12.8%)44 (28.2%)

within 3cases≥8002cases≥110024 (15.4%)8 (5.1%)

18 (11.5%)5 (3.2%)11 (7.1%)

one of them was up to 2974 (2.6%)12 (7.7%)24 (15.4%)19 (12.2%)7 (4.5%)

---

-

22 (14.1%)42 (26.9%)

0 (0%)

malefemale≤1 year

1-5 years6-10 years11-18 years

normalcoronary artery dilatation

aneurysm＜60

60~9090~120>120≤100

100~300

≥300

normal>30>60>100>120

normal>30>60>100>120

≥1 month≥3 months≥6 months

≥1year

recoverybetter

death

Gender

age

extent ofcoronaryar tery da -ma geHemoglo-bin (HGb)/g/l

Platelet(Plt) ×109/l

c-reactiveprotein(crP)/mg/l

erythro-cyte sedi-mentationrate(esr)/mm/h

follow upmonths

treatmenteffect

return visit57 (36.5%)33 (22.2%)35 (22.4%)47 (30.1%)7 (4.5%)1 (0.7%)

57 (36.5%)20 (12.8%)3 (8.4%)6 (3.8%)

16 (10.3%)50 (32.1%)18 (11.5%)3 (3.8%)

31 (19.9%)

53 (34.0%)

57 (36.6%)17 (10.9%)8 (5.1%)2 (1.3%)6 (3.8%)

54 (34.6%)9 (5.8%)13 (8.3%)8 (5.1%)6 (3.8%)

39 (43.3%)24 (26.7%)15 (16.7%)13 (13.3%)

one of them was followedup for 7 years

54 (35.3%)36 (23.1%)1 (0.6%)

the child died after stren-uous exercise and was notinfected with sars-coV-2


2021

that the difference was statisticallysignificant (P = 0.003) between the chil-dren of normal and coronary artery di-latation (P = 0.003), and the return vis-it of coronary artery dilatation was re-duced; but there was no significant dif-ference between the children of normaland aneurysm, coronary artery dilata-tion and aneurysm (P > 0.0167). Itshowed that most of the coronary ar-teries were normal in the initial diag-nosis and return visit cases, and mostof the cases were normal in the returnvisit, with significant difference, indi-cating that most of these children recov-ered after early treatment.It is suggest-ed that the scheme of early treatmentand the application of drugs are correct.The follow-up and treatment should bestrengthened before return visit.

In this special case, children withfever need to go through layers ofscreening to exclude covid-19.In Chi-na, we have two kinds of nucleic acidtest methods, real-time fluorescentRT-PCR and gene sequencing, butmost of us use the former method. Realtime fluorescent RT-PCR is real-timefluorescent reverse transcription poly-merase chain reaction. It reverses theextracted viral genomic RNA intocomplementary DNA (cDNA) firstly.Then, the specific primers were used toamplify the nucleic acid sequence ofthe pathogen using cDNA as tem-plate. Because the fluorescent dye canbe integrated into the product synchro-

nously during the amplificationprocess, researchers can detect the in-tensity of the fluorescence signal in realtime. The most widely used gene se-quencing is called Next generationsequencing (NGS). We are more famil-iar with this technology is Non-inva-sive Prenatal Testing (NIPT). In the di-agnosis of new coronavirus, NGStechnology makes the viral RNA intoa DNA library that can be recognizedand analyzed by the sequencer, andthen simultaneously tests millions ofnucleic acid sequences on the se-quencer. Real time fluorescent RT-PCR needs to be carried out in P2 lev-el laboratory, and three-level protectionshould be implemented in operatorarea. The samples were mainly collect-ed from respiratory tract because of itshigh positive rate. The sample types in-clude throat swab, nasopharynx swaband sputum. It were collected accord-ing to the Laboratory Guidelines forNovel Coronavirus Pneumonia issuedby National Health Commission. Forpharyngeal swab collection, two plas-tic rod swabs with polypropylene fiberheads were used to wipe the posteriorpharyngeal wall at the same time. Theswab head was immersed into a tubecontaining 3ml virus preservation so-lution. The tail was discarded and thetube cover was tightened. For na-sopharyngeal swab collection, a plas-tic rod swab with a polypropylenefiber head should be inserted into the

posterior wall of the nasopharynx cav-ity. It will stay for a moment and thenslowly rotate to exit. Take anotherpolypropylene fiber swab and collectthe other nostril in the same way. Thetwo swabs were immersed in the sametube containing 3ml virus preservationsolution, the tail was discarded, and thetube cover was tightened

The diagnosis and treatment of chil-dren with fever in China is divided intothe following steps:

(1) Sub examination: all the childrenneed to be examined by professionalnurses, which can be divided into twocategories: those without fever can goto the general outpatient department;those with fever should go to the feverclinic;

(2) Follow up patients: because KDchildren need regular review of cardiacultrasound, but the hospital takes pre-vention and control measures duringthe epidemic, so these patients whoneed to be reexamined need to use:① Online booking;② The patients were treated in the

local hospital nearby;③ Video remote consultation;④ Online outpatient appointment;⑤ Hospitalized in non designated

hospitals.According to the above triage

method, KD patients were diagnosedand treated in time, and the cure ratewas greatly improved. There was nodelay in the treatment of KD childrenbecause of the epidemic situation.Therefore, during the epidemic period,we should also develop a reasonableprogram for the treatment of noncovid-19 children, so as not to delay thebest treatment time.

1. There was no significant differ-ence in gender of KD children betweenChina and other countries.

2. There was significant differencein age groups between China and oth-er countries. After further comparison,it was found that the number of KDchildren under 5 years old in China wasthe most, while that of other countrieswas over 6 years old, and the differencewas statistically significant.

3. There was significant differencein CRP count between Chinese and oth-er countries. After further comparison,

80

Table 3

50454035302520151050

≤ 1 year 1-5 years 6-10 years

age

Initial diagnosis

no.

ofca

ses

11-18 years

return visit

47

26

35

27

9 74

1

it was found that the number of CRPcount of children with KD in China wassignificantly different between the twogroups of ≤ 100, >100 and ≥22. It wasmost in the two groups of ≤100 in Chi-na, while that in other countries wasmost in the two groups of > 100.

4. There was significant differencein platelet count between Chinese andother countries. Further comparisonshowed that the differences amongthe groups were statistically significant.The number of platelet count of KDchildren in China was the most in ≥ 300group, while that in other countries wasin 100-300 group.

3. results:① KD in China is lighter than that

in foreign countries② Most of KD nucleic acids in

China were negative③ The PLT of KD in foreign coun-

tries did not increase or decrease,while that of KD in China increased④WBC and CRP increased in KD

laboratories both in China and othercountries.⑤ The D-dimer of KD in foreign

countries was significantly high, whichcan be up to 4000 in certain child

We compared the KD patients treat-ed during the epidemic period with 48KD patients reported by relevant coun-tries during the epidemic period. Thestudy found that the inflammatory in-dexes of patients with KD-like symp-toms reported in the literature weremuch higher than those of normal KDpatients, and the proportion of pa-tients with CRP > 200mg /L was ashigh as 46%. Secondly, combined withthe diagnostic criteria, we found thatthe PLT of typical KD patients washigher than normal (The PLT of 2 cas-es were more than 1100×109/L; 44 weremore than 300×109/L accounting for28.2%.The return visit patient were 53cases (34%).), but most of the PLT lev-els of patients with KD-like symptomsin the literature were within the normalrange. And the PLT of KD children inChina is higher than normal level,which reported in Britain, France andItaly were mostly at or below the nor-mal level.P < 0.05, comparing with KDchildren in China, there was significant

difference.Besides, there were signif-icant differences among the three de-grees of coronary artery damage.Thecases of coronary artery dilatation andthe normal accounted for 20.5% in theinitial diagnosis group, while that of theaneurysm were only 1.3%. In the returnvisit group, 36.5% were normal, 12.8%were coronary dilation, and 8.4% wereaneurysms. It is suggested that most ofthe children with coronary artery dilata-tion or aneurysms in the follow-upgroup were recovered after effectivetreatment.

4. dIscussIon:Since Mr. Tomisaku Kawasaki pro-

posed KD, scholars have been commit-ted to exploring the etiology of KD.However, the etiology of KD is still un-clear. Many scholars believe that KDis related to infection. Therefore, ear-ly diagnosis and treatment should begiven to children with KD during theepidemic period, so as to reduce thedamage to the heart as much as possi-ble. We should strengthen the follow-up and correct treatment. The coronaryartery damage of most patients recov-ered after 6-18 months. However, the

giant aneurysm can just recover grad-ually after 2-3 years. In this study, a 12-year-old boy with a giant coronaryaneurysm died suddenly after strenu-ous exercise two years later.

According to the severity of the dis-ease, MISC is a multisystem inflamma-tory reaction, so the children weremost with severe condition, multiple or-gans damage, and whose laboratory in-flammatory index increased significant-ly. More and more children with MIS-C have been reported worldwide sincelate April 2020. Besides persistentfever, diarrhea and various degrees ofrash, conjunctivitis and limb edema,there are also shock and myocardialdysfunction [7]. Both MIS-C and KDare characterized by fever, skin changesand coronary artery involvement. Thesimilarity of the two diseases poses anew challenge to the diagnosis andtreatment of KD children during theepidemic. None of the KD patients inour four centers during the outbreakwere COVID-19 patients, which wasdifferent from the KD like symptomsof children infected with SARS-CoV-2 reported by other countries. A signif-icant feature of KD is high and persist-

2021


Table 4

all patients were preliminary checking at thepre screening triage table

nurses measure temperature andinquiry epidemiology during pre

examination

t<37.30c t≥37.30c

Have a epidemiological contacthistory (those who have con-tact history in the epidemicarea within 14 days or have

pneumonia symptoms of two ormore people around them)

suspected case

nurses report to the infection control office

transfer to designated medical institutions

report to national Health commission

Generalout-patient

service

no epidemi-ological con-tact history

Have a epidemio-logical contact his-

tory

no epidemi-ological con-tact history

Perfect nucleic acid detec-tion, complete chest ctwhen cough symptoms


2021

ent fever, and poor response to an-tipyretic drugs. Most children recovercompletely after a few weeks, but ear-ly treatment is necessary to prevent pos-sible complications. A serious compli-cation is coronary artery aneurysm,whose rupture can lead to thrombosisand myocardial infarction [14]. More-over, it has been found that the aggra-vation of endothelial inflammationand injury / function after SARS-CoV-2 infection may be realizedthrough endothelial ACE2. Systemic in-flammatory response to pneumoniamay enhance the inflammatory re-sponse in coronary artery lesions, lead-ing to endothelial dysfunction [15], sothis may be an important reason forKD-like symptoms in COVID-19 pa-tients. The results of this study foundthat the levels of inflammatory mark-ers similar to those of KD patients re-ported by other countries were signif-icantly higher than normal, and PLTlevels were mostly within the normalrange, which was different from thelaboratory results of typical KD chil-dren.It may reflect the particularlystrong immune response to SARS-CoV-2 [16].

The emergence of KD patients withpositive SARS-CoV-2 test poses anew challenge to pediatricians andtheir parents. During the epidemic pe-riod, due to the inability to go out andfear of the hospital, KD patients weremisdiagnosed, missed diagnosis andfailed to get timely treatment. In addi-tion, new requirements were put for-ward for the detection of SARS-CoV-2. In this case, the detection of SARS-

CoV-2 hass more important meaningfor KD patients. Therefore, we shouldearly identify the presence of KD-likepatients, give active treatment in orderto reduce the incidence of coronary ar-tery aneurysm, and improve the curerate.

The sample size of this study issmall, so more epidemiological andclinical data are needed to measure theprevalence of this condition, to assessthe correlation between KD and SARS-CoV-2, and to determine whether KD-like syndrome in other countries is aunique clinical syndrome or a form ofKawasaki disease.

reference:1. Fuyong Jiao, Kawasaki Disease,

Beijing: People's Medical PublishingHouse, 1st editor (1-18), 2013.

2. Lu R, Zhao X, Li J, Niu P, YangB, Wu H, et al. Genomic characterisa-tion and epidemiology of 2019 novelcoronavirus: implications for virusorigins and receptor binding. Lancet,2020, 22; 395(10224): 565-574.

3. Wu Z, McGoogan JM. Character-istics of and Important Lessons Fromthe Coronavirus Disease 2019(COVID-19) Outbreak in China: Sum-mary of a Report of 72314 CasesFrom the Chinese Center for DiseaseControl and Prevention. JAMA. 2020.

4. Dong Y, Mo X, Hu Y, et al. Epi-demiological Characteristics of 2143Pediatric Patients With 2019 Coron-avirus Disease in China. Pediatrics.2020.

5. Jiao FY, Yan XH, Wu XF. TheXi’an Experience of Kawasaki Disease

– Lessons Learnt over 5 years[J], In-dian J Pediatr, 2016, 83(10): 1195-6.

6. Karim E, Lin J, Jiao FY, Guo N,Yuan ZY, Kawasaki Disease: GlobalBurden and Genetic Background[J],Cardiol Res, 2020; 11(1): 9-14

7. Shirato K, Imada Y, Kawase M etal. Possible involvement of infectionwith human coronavirus 229E, butnot NL63, in Kawasaki disease. J MedVirol, 2014; 86: 2146-2153.

8. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, TheocharisP. Hyperinflammatory shock in childrenduring COVID-19 pandemic. Lancet,2020; 395(10237): 1607–1608. doi:10.1016/S0140-6736(20)31094-1.

9. Rising cases of kids with Kawasa-ki disease possibly linked to coron-avirus 2020 [accessed 5/6/2020]. Avail-able from: https: //english.kyodonews. -net /news/2020/04/05476c47050f-rising-cases-of-kids-with-kawasaki-disease-possibly-linked-to-virus.html.

10. 2020 Health Alert #13: PediatricMulti-System Inflammatory SyndromePotentially Associated with COVID-192020 [Available from: https: //www1. -nyc. gov /assets/doh/downloads/ -pdf/han/ alert/2020/covid-19-pediatric-multi-system-inflammatory-syn-drome.pdf

11. Healio New York announces de -a ths of children from illness linked toCOVID-19 https: //www.healio.com/ -pediatrics/emerging-diseases/news/on-line/%7B31277551-82e1-499f-b7cc-380b49ef7248%7D/new-york-an-nounces-deaths-of-children-from-ill-ness-linked-to-covid-19.

12. Centers for Disease Control andPrevention. Multisystem inflammato-ry syndrome in children (MIS-C) asso-ciated with coronavirus disease 2019(COVID-19). CDC Health Alert Net-work publication CDCHAN-00432.May 14, 2020. Accessed May 27, 2020.https: //emergency.cdc.gov /han/2020/ -han00432.asp

13. McCrindle BW, Rowley AH,Newburger JW, et al. Diagnosis, treat-ment, and long-term management ofKawasaki disease: a scientific statementfor health professionals from the Amer-ican Heart Association. Circulation,2017; 135: e927–99.

14. Alessandra M, Isabella TJ, Do-nato R, et al, Kawasaki disease: guide-

82

Table 5

malefemale

≤11-5 6-10 11-18

normal＞30＞100＞200≤100

100-300≥300

Gender

age (y)

c-reactiveprotein(crP)/mg/l

Platelet(Plt)×109/l

95 (60.9%)61 (39.1%)61 (39.1%)74 (47.4%)16 (10.3%)5 (3.2%)

81 (51.9%)51 (32.7%)23 (14.7%)1 (0.7%)5 (3.2%)53 (34%)

98 (62.8%)

30 (62.5%)18 (37.5%)6 (12.5%)13 (27.1%)17 (35.4%)12 (25%)6 (12.5%)7 (14.6%)13 (27.1%)22 (45.8%)13 (27.1%)28 (58.3%)7 (14.6%)

0.040

41.931

87.269

44.790

0.842

＜0.05

＜0.05

＜0.05

china other countries c2/ fisher's exact test p value

lines of the Italian Society of Pediatrics,part I - definition, epidemiology, etio -pathogenesis, clinical expression andmanagement of the acute phase, ItalianJournal of Pediatrics, 2018; 44: 102

15. B.W. McCrindle, A.H. Rowley,J.W. Newburger, J.C. Burns, A.F. Bol-ger, M. Gewitz, A.L. Baker, M.A.Jackson, M. Takahashi, P.B. Shah, T.Kobayashi, M.H. Wu, T.T. Saji, Pahl E.Diagnosis, Treatment, and long-termmanagement of Kawasaki disease: ascientific statement for health profes-sionals from the American heart asso-ciation, Circulation, 2017; 135 (17):e927–e999.

16. Varga Z, Flammer AJ, Steiger P,et al, Endothelial cell infection and en-dotheliitis in COVID-19, Lancet, 2020;395(10234): 1417–1418.

17. Toubiana J, Poirault C, Corsia A,Bajolle F, Fourgeaud J. et al. Outbreakof Kawasaki disease in children duringCOVID-19 pandemic: a prospectiveobservational study in Paris, France.theBMJ, 2020; 369, m2094.doi: https://doi.org/10.14740/cr993 Karim Elak-abawia, b, e, Jing Linc, e, FuyongJiaod, et al

18. Kawasaki Disease: Global Bur-den and Genetic Background CardiolRes. 2019; 000(000): 000-000

19. Jiao F, Yan X, Wu X. The Xi’anExperience of Kawasaki Disease–Le -sso ns Learnt over 5 years[J]. The Indi-an Journal of Pediatrics, 2016, 83(10):1195-1196. Fuyong Jiao*, Stefan Bitt -mann. A new classification of clinicalfindings and treatment options ofSARS-CoV-2 infection in childrenfrom China[J]. Advances in PediatricResearch Jiao et al. 2020 | 7: 37

20. Karim Elakabawi, Jing Lin,Fuyong Jiao, Ning Guoa, Zuyi Yuan.20. Fuyong Jiao: Global Burden andGenetic Background[J]. Elmer PressCardiol Res. 2020, 11(1): 9-14

21. Fuyong Jiao.Kawasaki disease- New manifestation of COVID-19 inchildren[J]. Chinese Journal of Con-temporary Pediatrics. 2020, 22 (7) :682-683

22. Stefan Bittmann, Anne Weis-senstein, Gloria Villalon, ElenaMoschüring-Alieva, Elisabeth Luchter:Association of COVID-19 coronavirusand Kawasaki syndrome like featuresin 1-5 years old children.The Neuro-science Chronicles, Neurosci Chron2020; 1(1): 4-5.

23. Stefan Bittmann, Anne Weis-senstein, Gloria Villalon, ElenaMoschüring-Alieva, Lara Bittmann,Elisabeth Luchter: Treatment Options

in COVID-19: The Role of Bioavail-able Antiviral Ribonucleoside Analo-gon NHC in vitro Journal of Regener-ative Biology and Medicine, 2020;2(2): 1-2.024

24. Stefan Bittmann, ElisabethLuchter, Elena Moschüring Alieva,Anne Weissenstein, Gloria Villalon ANeurotropic Potential for Brain Dam-age in COVID-19 BIOMEDICALJournal of Scientific & Technical Re-search, 27(1)-2020. BJSTR. MS.ID. -004437.

25. Covid-19-The Role of Chil-dren and Search for Effective TreatmentOptions with Promising view to An-giotensin II Inhibitors American Jour-nal of Biomedical Science and Re-search 2020 - 8(4). (MS.ID.001273.DOI: 10.34297/AJBSR.2020.08. -001273)

26. Stefan Bittmann, ElisabethLuchter, Elena Moschüring-Alieva,Gloria Villalon, Anne Weissenstein:COVID 19: Camostat and The Role ofSerine Protease Entry Inhibitor TM-PRSS2 Journal of Regenerative Biol-ogy and Medicine, 2020; 2(2): 1-2

27. Bittmann S: COVID-19 inAdults and Children: The Clock isTicking.Journal of Regenerative Biol-ogy and Medicine, 2020; 2(2): 1-2.

2021


abstractshaanxi Provincial diagnosis and

treatment center of Kawasaki dis-ease clinical research centerfor Pe-diatric Medicine diseasesof shaanxiProvince the children's Hospital ofsPPH

chinese Journal of contempo-rary Pediatrics

expert committee of advancedtraining for Pediatrician, china Ma-ternal and children’s Health associ-ation

General Pediatrician Group, soci-ety of Pediatrician, chinese doctor

assocIatIon abstractKawasaki disease is anacute, self-limit-

ed arteritis that main lyoccurs in children un-der 5 years of age. Intravenous immunoglob-ulin (IVIG) hasbecomean effective treat-mentregimen, which can effectivelyreducethe incidence of cardiovascular complica-tions. However, the reisnoconsensusorclinical guidelinesfortheapplication of IVI-Gin Kawasaki disease. Thisconsensus was-

formulated on the basis of domestic andin-ternationalresearchprogresson Kawasakidiseasein children, and specific suggestionswereprovidedon the clinical application strat-egy of IVI Gin child hood Kawasaki dis-easeasafirst-linetreatmentdrugand the pre-ventionandtreatmentof adverse reactions.

Keyword: Kawasaki disease (KD) ;Self-limited Vasculitis; Intravenousim-munoglobulin(IVIG); Expertconsensus; Children correspond author: fuYonG JIao

cHInese PedIatrIc eXPert consensuson tHe use

of IntraVenous IMMunoGlobulIn In KawasaKI dIsease


2021

84

Aim Social Pediatric Protection Fundis to execute programs of social pedia-tric development and maintain rights andhealthcare of Children, Mothers andAdolescents. Fund has great organiza-tional experience, technical equipmentand skilled members. Most of the mem-bers are Professors at TSMU, whohave clinical and educational experien-ce of 15-20 years and were one of thefirst, Before the independence, to readlectures about congenital infections,sexually transmitted diseases and pre-vention of HIV. Fund is also coopera-

ting with physicians, psychologists,Lawyer (who operate in field of socialassistance) and Public figures. By thejoint forces of all the people above saidSPPF is able to hold free medical exa-minations, juridicial consultations, cha-rity events, informational lectures abouthealthy way of life, congenital infection,HIV, Social subjects and etc.

Since 1997 more than 93.000 Child-ren and Hundreds of older people havebeen medically for free in the frameworkof charity events.

Before Independence, The activemembers of SPPF and theirconsortium in 1980-1990 ex-amined above 124 000 Child-ren, all over Georgia.

actIVItIesFrom 1992 to 1998 was

periodically holding humani-tarian examinations. From1998 with the help of SocialPediatrics Protection Fundstarted charity activities, in

which Georgian pediatrists were partici-pating. Activities included: Instrumentaland laboratory research of patients in dif-ferent regions of Georgia, Medical gifts,several funded emergency operations.

07.01.98 – 07.02.99 Tbilisi, - over9200 children were examined.

23-24.01.99 East Georgia, - over3500 children were examined.

12-13-14.02.99 Tbilisi, - over 100children were examined and gifted me-dicines. Free consultations by professorswere held by Mother and Child Dia-gnostic Centre and other hospitals oncea week, consultations in leading pedi-atric clinics of the city once in a mon-th. In these activities were also partici-pating: 1. Institute of skin and vein 2.Sci-entific Institute of Parasitology and ot-hers.

12-13-14.03.99 expedition in Poti andAbasha (Qedisi, Marani and other), -950 children were examined and giftedmedicines.

29-30. 01-07.08.99 – 4400 childrenwere examined and gifted medicines.

23-24-25.08.99 KhobiandZugdidi,- Free instrumental and laboratory ex-aminations were funded. Also medici-nes against louse and itch were given.

04.04.99 - Expedition in Pasanauri –over 400 children were examined.

07.05.99 – Expedition in Lanchkhu-ti – Free instrumental and laboratory ex-aminations were held and medicineswere gifted.

“tHe role of tHe socIal PedIatrIcs ProtectIonfund In GeorGIan PedIatrIcs - 1998-2021“

tHe socIal PedIatrIc ProtectIon funddate of foundation: 30.09.1998date and number of registration: #147 9.10. 1998waddress: Tbilisi, Ljubljana 21, 0154tel.: 995 593337154e-mail: [email protected]; [email protected]: Prof. George ChakhunashviliJob of contact: Chairman of The Boardbranches of fund: Mtskheta; Kutaisi; Gori.; Abasha.; Batumi.; Sagarejo; Gur-

jaani; Telavi; Tchiatura; Zugdidi; Territory of Operation: Georgia (eu)

GEORGIAN PEDIATRICS IS 100 YEARS OLDGEORGIAN PEDIATRICS IS 100 YEARS OLD

G. cHaKHunasHVIlI,MD.PhD.D.Sc. Professor, Academician

(Chairman of the Social Pediatrics Protection Fund of Georgia)

INFORMATION

18.05.99 Rustavi, - 250 childrenwere examined and gifted medicines.

22.06.99 Sagarejo, - 250 childrenwere examined and gifted medicines.

13-14.08.99 Chokhatauri, - over1500 children were examined.

15.08.99 Bakhmaro, - over 2000children were examined.

16.08.99 Adjara high-mountain regi-ons, - over 750 children were examined.

17.08.99 Tbilisi, – Examinations inHomeless children house.

16.10.99 Dusheti region, - over 200children were examined and gifted me-dicines.

2000.26.02.2000 Gori, - over 500 children

were examined. Different medicineswere given out.

23.03.2000 Axalgori, - 30 childrenwere examined.

01.04.2000 Marneuli region (Wer-akvi), - General blood analysis, instru-mental examinations – echoscopy, en-cephalography were done. Over 1500children were examined.

15.04.2000 Gurjaani, - 1200 childrenwere examined, medicines were given out.

29.04.2000 Rustavi, - 300 childrenwere examined.

05.06.2000 – Children from Avcha-la colony were examined.

20-28.07.2000 – Children in Tskhne-ti Orphanage were examined.

21-22-23.07.2000 – Examinations inAbasha and Samtredia region.

7-8.08. 2000, Bakhmaro-Beshumi –1925 children were examined.

2001.15.03.2001. Children of employees

of Rustavi Nitrogen Factory were exa-mined.

23.06.2001. Children of employeesof Rustavi Nitrogen Factory were exa-mined.

14-15-16.09.2001 Baghdati region(Sairme, Witelkhevi, Rokhi, Ochba,Xani, Zegani, Saqraula) – over 2500children were examined.

2002.10.03.2002 Axalgori, - 250 children

were examined.20-04.2002 Sighnaghi, - 450 child-

ren examined.23-24-25-26.05.2002 Khulo, - 600

children and 100 adults were examinedwith the help of Patriarchy.

27-28-29.06.2002 Tbilisi, - 400 child-ren were examined in different Hospi-tals.

16-17-18-19.07.2002 KodorisKheo-ba, - 250 children were treated.

3-4-5-6.08.2000 Tusheti (Dikolo,Omalo, Shenaqo) – 200 children weretreated.

2003.05.03.2003 Samtskhe-Javakheti, -

1250 children were examined.17.04.2003 Werovani, - 450 children

were examined.20.05.2003 Borjomi, - 870 children

were examined.25.06.2003 Mta-Tusheti, - 320 child-

ren were examined.30.07.2003 Bakhmaro, - 630 child-

ren were examined.20.08.2003 Zestaponi, - 210 children

were examined.07.09.2003 Racha, - 170 children

were examined.18.102003 Dmanisi, - 180 children

were examined.

2004.March, April, May – Kaspi, Gurjaa-

ni, Telavi, Akhmeta, Lagodekhi, Sig-hnaghi, Bodbe, Aspindza, Axaltsikhe,Borjomi, Tbilisi, Zestaponi, Kharagau-li, Chiatura – over 1728 children wereexamined. In different regions (Zugdi-di, Khulo, Khelvacharui, Qeda, Lanchk-huti, OzurgetiIngiri), SPPF held chari-ty activities with the help of Patriarchy– over 2400 children were examined andmedicines were given out.

2005.Marneuli region – 700 children and

80 adults were examined.18th of July, Kaspi – 450 children

were examined.8th of October, Mtskheta – 300

children were examined.14-15-16th of October, Lentekhi –

850 children and 250 adults were exa-mined.

2006.18th of February –20 Painter Union

families were examined.March – over 100 refugee children

were examined.April – Charity activities were held

by ambassadors in Guria.31th of May – 450 children were ex-

amined in Rustavi.1-2th of June - Open door day in

TSMU, 400 children were examined.They were held free consultations andlaboratory examinations.

9-10th of June, Kaspi - 300 childrenwere examined.

1th of July, Ckhinvali region – 500children of war participants were exa-mined. In September-October – 120children.

2021



2021

In November – over 200 of Journa-list’s families were examined.

2007.Marneuli – Free consultations for

100 children. Childrens with Scoliosiswere shown. They got espander giftsand were recommended how to treatscoliosis.

Dusheti – 250 children were exami-ned.

Akhalsheni–85 children were heldconsultations.

9-10th of June, Kaspi – 300 childrenwere examined.

1th of July, Ckhinvali region – 500children of war participants were exa-mined. In September-October – 120children.

In November – over 200 of Journa-list’s families were examined.

2008.1st of June – Open door day

(200 children were examined).2nd of June – Teddy bear

(300 children examined).14th of June, Akhmeta (QaQu-

coba) - 450 children were exami-ned and gifted medicines. Alsoexaminations like echoscopy ofabdominal cavity and ECG wereheld.

27th of June – restoration ofGeorgian Section.

20th of August - STOP RUS-SIA (meeting at Igoeti)

1st of September, Tbilisi –STOP RUSSIA (meeting ofchain)

4th of October – free consultationsand examinations. Painters and artistsmaster classes were held.

6th of December – 110 childrenwere examined in Bergman Clinicswith echoscopy of abdominal cavity,ECG and other.

2009.13.06.2009, Khashuri – 750 children

were examined.26.12.2009, Barisakho – 80 children

were examined.

2010.4th of July – Open door day for fa-

mily members of war victims (50 child-ren were examined).

10th of July, Karaleti – 200 childrenwere examined and medicines were gi-ven out.

4th of November – St. King Ta-mar orphanage children were exami-ned.

3-4th of December,Tbilisi– 400 sport-smen children were examined.

2011.1st of June,Tbilisi – 200 children

were examined.24th of December,Tbilisi – 200

children were examined.

2012.1st of June,Tbilisi – 350 children

were examined.22th of December,Tbilisi – 250

children were examined.Since 1997 more than 93.000 Child-

ren and Hundreds of older people havebeen medically for free in the frameworkof charity events.

2013.1-4.06.2013. Tbilisi, Batumi,

Gori, Telavi – 1250 childrenwere examined.

17-21.12.2013. Tbilisi – 350children were examined.

2014.1st of June, Tbilisi – 150

children were examined.28th of December, Tbilisi – 50

children were examined.

2015.1st of June, Tbilisi – 350 chil-

dren were examined.11.12.2015. Chkorotscu –

1300 children were examined.

86

2016.3035 children were examined.






Since 1997-2012 more than93.000 Children and Hundreds ofolder people have been medicallyfor free in the framework of cha-rity events.

Before Independence, The acti-ve members of SPPF and their con-sortium in 1980-1990 examinedabove 124 000 Children, all overGeorgia.

Till today over 228 050 chil-dren were examined and thou-sands of old people. Charity activ-ities continue.

sIMPosIuMs and conferences Held bY tHe socIal

PedIatrIc ProtectIon fund:1992. First pediatric cardiology con-

ference – “believe the reality of betterfuture”.

01.06.1999. II conference – “Healt-hy child & peaceful Caucasus”.

25.12.1999. III conference – “Today’seconomic directions in pediatric and itsperspective”. XXI century Pediatricsshould be the start of invalid prophylax-is.

01.06.2000. IV conference – “Childmust have right to be protected sinceembryo”.

27.03.2001. Meeting in ombuds-man’s office – “Under aged criminals,their rights and reality”.

01.06.2001. V conference dedicatedto Children Protection National Day.

32.03.1999. 01.06.2000. 01.06.2001“Child treatment in XXI century”23.04.1999. 01.06.2000“Child treatment in XXI century”“Orthopedic school”

17.12.1999. Mucoviszidose treat-ment and diagnostics.

01.06.2000. Young Pediatrists XVIIIconference.

28.02.2001. Urgent questions ofTherapy of respiratory diseases in pe-diatrics.

01.06.2001. “Child has right to beprotected since embryo”.

01.06.2001. “Child, adult and familyviolence”.

13.02.2002. “Human genome pro-ject”.

10.03.2002. Akhalgori, - Presentati-onof toner drink “Lomisi”.

06.11.2002. National Conference:Medical and social problems of peoplewho suffer from mucoviszidose and me-tabolism disorder.

07.11.2002. “Contemporary aspectsof inborn diseases”.

04.04.2003. “Urgent pediatric ques-tions” (IX conference).

01.06.2003. Internet conference (Xconference) – Social Pediatrics Protec-tion Fund gave out journals and maga-zines called “Social Pediatrics” (Inwhich is written about social, medical,pedagogic, psychological, religious andother urgent problems).

19.12.2003. Second Georgian Cardi-ology Congress.

22.10.2004. “Urgent Pediatric ques-tions” dedicated to SPPF president,Victor Moroshkin.

01.06.2004. Second National Inter-net Conference.

01.06.2005. Urgent Pediatric ques-tions.

09.09.2005. Tbilisi Marriot, - SecondNational Conference “Healthy child &Peaceful Caucasus”.

1st of June, 2006. – SPPF conferen-ce. XXIII Congress of Young PediatristsLeague.

31.05.2007. III congress of PediatricCardiology.

07.12.2007. SPDF XVII conference.07.10.2008. Conference – “Section

of child and adult”.20.12.2008. SPPF and ESMNS se-

cond conference.12.06.2009. SPPF XX conferen-

ce.01.06.10. Second conference of

Georgian surgeons and XXII con-ference of Tsalka.

03.12.2010. Conference dedi-cated to I. Kvachadze 85th anniver-sary.

01.06.2011. SPPF XXVI confe-rence.

23-24.12.2011. SPPF XXVIIconference.

01.06.2012. IV congress of Pe-diatric Cardiology.SPPF XXVIIIconference.

21-22.12.2012. SPPF XXIXconference

1-4.06.2013. SPPF XXX confe-rence

17-21.12.2013. SPPF XXXI confe-rence

1-2.06.2014. SPPF XXXII conferen-ce

27-28.12.2014. SPPF XXXIII con-ference

1-2.06.2015. SPPF XXXIV confer-ence

11.12.2015. SPPF XXXV confer-ence

1.06.2016. SPPF XXXVI conference9-10.12.2016. SPPF XXXVI confer-

ence01.06.2017. SPPF XXXVIII confer-

ence05.12.2017. SPPF XXXIX confer-

ence01.06.2018. SPPF XL conference07.12.2018. SPPF XLI conference01.06.2019. SPPF XLII conference14.12.2019. SPPF XLIII conference31.05.2020. SPPF XLIV conference20.12.20. SPPF XLV conference01.06.2021. SPPF XLVI conference18.12.21. SPPF XLVII conferenceThe most important in the work of

the Foundation are the creative work2021



2021

of Professor Irakli Tsitsishvili andProfessor Avtandil Kvezereli-Kopadze(Pictures-1-2-3-4-5-6-8-), whose un-stinting work to the last day of his lifeset a perfect example for the youth -first of all, And with all things how youmust work in many ways for your land

to bring up worthy descendants.Againthank you to them and to the happinessthat we have had in the relationship ofsuch true persons.God enlighten theirsouls.

Newspapers and magazines havebeen published since 1998 at the direct

initiative of the Social Pediatrics Protec-tion Fund.

At the same time, the Social Pedi-atrics Protection Fund continues the pathof the Hospital Pediatrics Department ofTSMU (both charitable and public),whose department was headed by GreatPediatrician, Doctor of Medical Sci-ences, Professor Ioseb Kvachadze.Georgian Pediatrics had its own profes-sor, Mr. Ioseb Kvachadze, who in-formed us of the possibilities of our in-tellectual potential from the high trib-unes of the world's congresses manytimes during that closed Soviet period(believe me, it was only the bumblebee).Figure N9 shows the members of the al-most unchanged department from 1981-1991.

Thus, the Social Pediatrics ProtectionFund continues its creative work, andmost importantly, its priority for youngpeople to be involved in its functioningremains unresolved.

First sit on the chairs from the left: assistant leilaKomshiashvili, assistant nunu shelia, assistant tamartsereteli, Professor Irakli tsitsishvili, Head of the depart-ment Professor Ioseb Kvachadze, associate ProfessorKristine Kutelia, assistant tamaz Marinashvili, assis-tant tina beradze, laboratory assistant nana Gvarjal-adze.

In the second row stand from the left: (third) clinical res-ident nino lapiashvili, assistant Jana sakvarelidze, assis-

tant nutsa tatishvili, assistant Marine chikovani, clinicalresident tsisana Giorgadze

In the third row stand from the left: (third) assistant Gior-gi chakhunashvili, (fifth) assistant tamaz Gozalishvili,Postgraduate student davit telia, assistant nugzar uberi,Postgraduate student Marine Giorgadze, laboratory as-sistant lia Kvatadze, who in Georgian pediatrics and notonly in Georgia, have made a flawless contribution to thedevelopment of their directions.

88

European center of traditional Chinese medicine (TCM) in Prague,Czech and xi’an, China

”Children’s rights must be defended since embryo”

Georgian Pediatrics is 100 years old

pediatrics - sppf.info

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