To elucidate the genetic characterization and molecular epidemiological features of Echovirus 19 （El9） isolates collected from an outbreak associated with hand, foot and mouth disease （HFMD） in Tai＇an city of Sha...To elucidate the genetic characterization and molecular epidemiological features of Echovirus 19 （El9） isolates collected from an outbreak associated with hand, foot and mouth disease （HFMD） in Tai＇an city of Shandong Province of China from July to September, 2003. Methods Thirty seven Echovirus 19 isolates were isolated from stool specimens and throat swabs collected during the outbreak, then major capsid （VP1） genomic sequence was determined, and phylogenetic tree was done based on the VP1 sequences among these 37 and other El9 viruses deposited in the Genbank. Also a representative strain named CHN-SD03-TN12 was selected for sequencing of 5′-untranslated regions （5′-UTR）. Results The identity rate was about 98.9%-100% among all these 37 El9 viruses. The genetic relationships between these 37 El9 isolates and other strains reported were also depicted. The identity rate was about 78.4%-78.9% compared with El9 reference strain Burke. The substitutions in the sequence of 5′-UTR resulted in changes in the conjectural properties of 5′-UTR of El9 viruses. Condusion The genetic features of El9 viruses isolated during the outbreak in Shandong Province in 2003 may be associated with a genetic and antigenic drift that changes the virulence of the Shandong isolates, but the molecular changes in Shandong El9 viruses contributing to their phenotype remain to be further illuminated. However, the sequences described in this paper substantiate the changes taken place in capsid VPI and 5′UTR regions. These substitutions may contribute to their tropism and virulence, and play a significant role in pathogenesis and clinical manifestations of the disease.展开更多
Hand,foot,and mouth disease(HFMD)recently emerged as a global public threat.The licensure of inactivated enterovirus A71(EV-A71)vaccine was the first step in using a vaccine to control HFMD.New challenges arise from c...Hand,foot,and mouth disease(HFMD)recently emerged as a global public threat.The licensure of inactivated enterovirus A71(EV-A71)vaccine was the first step in using a vaccine to control HFMD.New challenges arise from changes in the pathogen spectrum while vaccines directed against other common serotypes are in the preclinical stage.The mission of a broad-spectrum prevention strategy clearly favors multivalent vaccines.The development of multivalent vaccines was attempted via the simple combination of potent monovalent vaccines or the construction of chimeric vaccines comprised of epitopes derived from different virus serotypes.The present review summarizes recent advances in HFMD vaccine development and discusses the next steps toward a safe and effective HFMD vaccine that is capable of establishing a crossprotective antibody response.展开更多
Hand,foot and mouth disease(HFMD)is a common infectious disease that usually affects children less than 5 years of age.HFMD is caused by human enteroviruses(HEVs).HEVs,members of the Enterovirus genus of the Picornavi...Hand,foot and mouth disease(HFMD)is a common infectious disease that usually affects children less than 5 years of age.HFMD is caused by human enteroviruses(HEVs).HEVs,members of the Enterovirus genus of the Picornaviridae(small RNA virus)family.展开更多
Enterovirus 71(EV71)infection is more likely to cause hand,foot and mouth disease(HFMD)in children,which can lead to neurogenic complications and higher mortality.As a commonly used clinical medicine,Reduning injectio...Enterovirus 71(EV71)infection is more likely to cause hand,foot and mouth disease(HFMD)in children,which can lead to neurogenic complications and higher mortality.As a commonly used clinical medicine,Reduning injection(RDN)helps to shorten the symptoms of patients with HFMD and facilitate the early recovery of children.However,the regulatory mechanism of RDN on the HFMD immune system disorder caused by EV71 remains to be discussed.This study collected detailed treatment data of56 children with HFMD who entered the affiliated Children’s Hospital of Nanjing Medical University during 2019.Retrospective analysis of clinical data showed that the symptoms of the RDN treatment group were improved compared with the untreated group.To explore its mechanism,the relevant detection indicators were detected by flow cytometry,enzyme-linked immunosorbent assay and realtime quantitative PCR.It was found that the number and function of innate immune(ILCs)and adaptive immunity(Th1,Th2 and secreted cytokines)were reduced,suggesting that RDN plays a role by regulating cellular immunity.The in vitro differentiation inhibition test further confirmed that RDN affected Th1 differentiation by inhibiting the expression of transcription factors on the basis of Th1 cell differentiation in vitro.展开更多
Enteroviruses(EVs)belong to the family Picornaviridae and are divided into 15 species:enterovirus A–L and rhinovirus A–C(http://www.picornaviridae.com).EV-C consists of 23 serotypes,including poliovirus 1-3,CVA1,CVA...Enteroviruses(EVs)belong to the family Picornaviridae and are divided into 15 species:enterovirus A–L and rhinovirus A–C(http://www.picornaviridae.com).EV-C consists of 23 serotypes,including poliovirus 1-3,CVA1,CVA11,CVA13,CVA17,CVA19,CVA20,CVA21,CVA22,CVA24,EVC95,EV-C96,EV-C99,EV-C102,EV-C104,EV-C105.展开更多
Dear Editor,Hand,foot and mouth disease(HFMD)is one of the most common infectious diseases,particularly in the Asia-Pacific region.In the past two decades,HFMD rises to prominence for its heavy burden,with over one mi...Dear Editor,Hand,foot and mouth disease(HFMD)is one of the most common infectious diseases,particularly in the Asia-Pacific region.In the past two decades,HFMD rises to prominence for its heavy burden,with over one million cases reported annually.Before 2013,enterovirus A71(EV-A71)and Coxsackievirus A16(CVA16)were the main pathogens leading to HFMD in the mainland of China(Yang et al.,2017).In recent years,non-EV-A71-non-CVA16 other enteroviruses,such as Coxsackievirus A6(CVA6),Coxsackievirus A10(CVA10)and Coxsackievirus A4(CVA4),were frequently reported and replaced EV-A71 and CVA16 becoming the major causative agents of HFMD(Zhou et al.,2021;Wang et al.,2022).展开更多
In this manuscript the authors have studied the application value of White blood cell morphology combined with neutrophils alkaline phosphatase staining integral value in treatment of pediatric HFMD combined with infe...In this manuscript the authors have studied the application value of White blood cell morphology combined with neutrophils alkaline phosphatase staining integral value in treatment of pediatric HFMD combined with infection. They showed that comparing the NAP positive rate of HFMD co-infection with the NAP positive rate of other three groups respectively—reference group, HFMD group and anti-infection HFMD group—the t value is 25.7964, 28.2326, 28.3696 and the values of P are 0.0000;Comparing the NAP integral value of HFMD co-infection with the NAP integral value of other three groups respectively, which are reference group, HFMD group and anti-infection HFMD, the t value is 35.8687, 36.2664, 36.1374 and the values of P are 0.0000. They concluded that it is useful to apply WBC morphological examination combined with the positive rate and integral value of NAP staining to diagnose and treatment HFMD.展开更多
Coxsackievirus B3(CVB3)is the pathogen causing hand,foot and mouth disease(HFMD),which manifests across a spectrum of clinical severity from mild to severe.However,CVB3-infected mouse models mainly demonstrate viral m...Coxsackievirus B3(CVB3)is the pathogen causing hand,foot and mouth disease(HFMD),which manifests across a spectrum of clinical severity from mild to severe.However,CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis,failing to replicate human HFMD symptoms.Although several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys,there is no comprehensive data on CVB3.In this study,we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different routes.The results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip,leading to nasopharyngeal colonization,acute severe pathological injury,and typical HFMD symptoms.Notably,the nasal drip group exhibited a longer viral excretion cycle and more severe pathological damage.In the subsequent study,rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms,viral excretion,serum antibody conversion,viral nucleic acids and antigens,and the specific organ damages,particularly in the heart.Surprisingly,there were no significant differences in myocardial enzyme levels,and the clinical symptoms resembled those often associated with common,mild infections.In summary,the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced HFMD.These models could serve as a basis for understanding the disease pathogenesis,conducting pre-trial prevention and evaluation,and implementing post-exposure intervention.展开更多
Objective:To observe the curative effect of Modified Ganlu Xiaodu Dan and Kuhuang San combined with interferon on the treatment of HFMD of damp-heat accumulation toxin syndrome and its effects on liver function, myoca...Objective:To observe the curative effect of Modified Ganlu Xiaodu Dan and Kuhuang San combined with interferon on the treatment of HFMD of damp-heat accumulation toxin syndrome and its effects on liver function, myocardial enzymes, inflammatory factors and immunoglobulin.Merhods:From June 2018 to November 2018, 74 children with damp-heat accumulation toxin syndrome who were diagnosed with hand, foot and mouth disease have been randomly divided into the observation group (38 cases) and the control group (36 cases).The control group is given conventional Western medicine symptomatic treatment, and sprayed on the oral cavity with IFN- atomized inhalation or IFN- 2b spray. On the basis of the control group, the observation group is given Modified Ganlu Xiaodu Dan, and Kuhuangsan for washing body. 7 d is a course of treatment. The recurrence time of the two groups, the time of rash regression and the efficacy of the children have been observed. The changes of liver function, myocardial zymogram, inflammatory factors and immunoglobulin are compared before and after treatment.Results: The efficacy of the observation group was 92.1% higher than that of the control group (83.3%), and the difference was statistically significant. The time required for the body temperature of the observation group (2.64±0.57) d was lower than that of the control group (3.12±0.62) d, and the time required for the rash to resolve was (4.18±0.69) d, which was lower than that of the control group (5.25±0.73) d. Statistically significant. The levels of ALT, AST, CK-MB, IL-4 and IL-6 in the observation group were lower than those in the control group after treatment, the difference was statistically significant. The serum IgA and IgM levels in the observation group were higher than those in the control group after treatment. Conclusion: Modified Ganlu Xiaodu Dan and Kuhuang San combined with interferon for the treatment of HFMD of damp-heat accumulation toxin syndrome have a sound curative effect and it can improve liver function, protect cardiomyocytes, reduce inflammatory factors, and regulate immune function for children.展开更多
In the era of the pandemic of coronavirus disease 2019(COVID-19),the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infects infants and children with mild or atypical symptoms[1,2].The new variations in SA...In the era of the pandemic of coronavirus disease 2019(COVID-19),the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infects infants and children with mild or atypical symptoms[1,2].The new variations in SARS-CoV-2 recently found in the United Kingdom greatly increased the risk of infection among children[3].Although previous evidence showed that children rarely developed severe symptoms from COVID-19,the hospitalization rate was 24.5%and the ICU admission rate was 2.5%among children in the United States[4].Further,there is a lack of evidence regarding the influence of the recently appeared SARS-CoV-2 variations.Thus,it is of great significance to monitor and track the COVID-19 infection among children.展开更多
基金This work was supported by Chinese Center for Disease Control and Prevention and Ministry of Health,China.
文摘To elucidate the genetic characterization and molecular epidemiological features of Echovirus 19 （El9） isolates collected from an outbreak associated with hand, foot and mouth disease （HFMD） in Tai＇an city of Shandong Province of China from July to September, 2003. Methods Thirty seven Echovirus 19 isolates were isolated from stool specimens and throat swabs collected during the outbreak, then major capsid （VP1） genomic sequence was determined, and phylogenetic tree was done based on the VP1 sequences among these 37 and other El9 viruses deposited in the Genbank. Also a representative strain named CHN-SD03-TN12 was selected for sequencing of 5′-untranslated regions （5′-UTR）. Results The identity rate was about 98.9%-100% among all these 37 El9 viruses. The genetic relationships between these 37 El9 isolates and other strains reported were also depicted. The identity rate was about 78.4%-78.9% compared with El9 reference strain Burke. The substitutions in the sequence of 5′-UTR resulted in changes in the conjectural properties of 5′-UTR of El9 viruses. Condusion The genetic features of El9 viruses isolated during the outbreak in Shandong Province in 2003 may be associated with a genetic and antigenic drift that changes the virulence of the Shandong isolates, but the molecular changes in Shandong El9 viruses contributing to their phenotype remain to be further illuminated. However, the sequences described in this paper substantiate the changes taken place in capsid VPI and 5′UTR regions. These substitutions may contribute to their tropism and virulence, and play a significant role in pathogenesis and clinical manifestations of the disease.
基金sponsored by the National Natural Science Foundation of China(81672018)the National 13th Five-Year Grand Program on Key Infectious Disease Control(2017ZX10202102)+2 种基金the 13th Five-Year National Science and Technology Major Project for infectious Diseases(2017ZX10305501-002)Shanghai Pujiang Program(19PJ1409100)the Technology Service Platform for Detecting High level Biological Safety Pathogenic Microorganism Supported by Shanghai Science and Technology Commission(18DZ2293000)。
文摘Hand,foot,and mouth disease(HFMD)recently emerged as a global public threat.The licensure of inactivated enterovirus A71(EV-A71)vaccine was the first step in using a vaccine to control HFMD.New challenges arise from changes in the pathogen spectrum while vaccines directed against other common serotypes are in the preclinical stage.The mission of a broad-spectrum prevention strategy clearly favors multivalent vaccines.The development of multivalent vaccines was attempted via the simple combination of potent monovalent vaccines or the construction of chimeric vaccines comprised of epitopes derived from different virus serotypes.The present review summarizes recent advances in HFMD vaccine development and discusses the next steps toward a safe and effective HFMD vaccine that is capable of establishing a crossprotective antibody response.
基金supported by the Chinese National Science and Technology Major Project [2017ZX10104001]Fujian Provincial Natural Science Foundation [NO.2016J01350]the Department of Science and Technology,Fujian Province [NO.2016Y0011]
文摘Hand,foot and mouth disease(HFMD)is a common infectious disease that usually affects children less than 5 years of age.HFMD is caused by human enteroviruses(HEVs).HEVs,members of the Enterovirus genus of the Picornaviridae(small RNA virus)family.
基金supported by the National Natural Science Foundation of China(Nos.81973221 and 81603647)the Innovation Team of the“Double-First Class”Disciplines(No.CPU2018GF08)+2 种基金the Medical Science and Technology Development Foundation of Nanjing Medical University(No.2017NJMUZD055)High-Level Talents in Six Industries in Jiangsu(No.SWYY010)Young and Middle-aged Academic Leader for Universities of Qinglan Project of Jiangsu(No.1170040009)。
文摘Enterovirus 71(EV71)infection is more likely to cause hand,foot and mouth disease(HFMD)in children,which can lead to neurogenic complications and higher mortality.As a commonly used clinical medicine,Reduning injection(RDN)helps to shorten the symptoms of patients with HFMD and facilitate the early recovery of children.However,the regulatory mechanism of RDN on the HFMD immune system disorder caused by EV71 remains to be discussed.This study collected detailed treatment data of56 children with HFMD who entered the affiliated Children’s Hospital of Nanjing Medical University during 2019.Retrospective analysis of clinical data showed that the symptoms of the RDN treatment group were improved compared with the untreated group.To explore its mechanism,the relevant detection indicators were detected by flow cytometry,enzyme-linked immunosorbent assay and realtime quantitative PCR.It was found that the number and function of innate immune(ILCs)and adaptive immunity(Th1,Th2 and secreted cytokines)were reduced,suggesting that RDN plays a role by regulating cellular immunity.The in vitro differentiation inhibition test further confirmed that RDN affected Th1 differentiation by inhibiting the expression of transcription factors on the basis of Th1 cell differentiation in vitro.
基金supported by the Basic Research Projects of Yunnan Province,China [Grant Number:202002AA100009 and 2017FA006]
文摘Enteroviruses(EVs)belong to the family Picornaviridae and are divided into 15 species:enterovirus A–L and rhinovirus A–C(http://www.picornaviridae.com).EV-C consists of 23 serotypes,including poliovirus 1-3,CVA1,CVA11,CVA13,CVA17,CVA19,CVA20,CVA21,CVA22,CVA24,EVC95,EV-C96,EV-C99,EV-C102,EV-C104,EV-C105.
基金supported by the key research project of Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai(Grant no:GWVI-3,GWVI-11.1-09)approved by the Ethics Committees of Shanghai Municipal Center for Disease Control and Prevention(Ethics Number,2023-44)。
文摘Dear Editor,Hand,foot and mouth disease(HFMD)is one of the most common infectious diseases,particularly in the Asia-Pacific region.In the past two decades,HFMD rises to prominence for its heavy burden,with over one million cases reported annually.Before 2013,enterovirus A71(EV-A71)and Coxsackievirus A16(CVA16)were the main pathogens leading to HFMD in the mainland of China(Yang et al.,2017).In recent years,non-EV-A71-non-CVA16 other enteroviruses,such as Coxsackievirus A6(CVA6),Coxsackievirus A10(CVA10)and Coxsackievirus A4(CVA4),were frequently reported and replaced EV-A71 and CVA16 becoming the major causative agents of HFMD(Zhou et al.,2021;Wang et al.,2022).
文摘In this manuscript the authors have studied the application value of White blood cell morphology combined with neutrophils alkaline phosphatase staining integral value in treatment of pediatric HFMD combined with infection. They showed that comparing the NAP positive rate of HFMD co-infection with the NAP positive rate of other three groups respectively—reference group, HFMD group and anti-infection HFMD group—the t value is 25.7964, 28.2326, 28.3696 and the values of P are 0.0000;Comparing the NAP integral value of HFMD co-infection with the NAP integral value of other three groups respectively, which are reference group, HFMD group and anti-infection HFMD, the t value is 35.8687, 36.2664, 36.1374 and the values of P are 0.0000. They concluded that it is useful to apply WBC morphological examination combined with the positive rate and integral value of NAP staining to diagnose and treatment HFMD.
基金supported by several key projects,the Medical and Health Science and Technology Innovation Project of the Chinese Academy of Medical Sciences(CIFMS,2016-I2M-2-001)the National Resource Center for Non-Human Primates,Major Science and Technology Special Projects in Yunnan Province,Kunming Science and Technology Innovation and Service Capacity Enhancement Program Key Projects(2016-2-R-07674)+3 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS,2018-I2M-3-002 and 2021-I2M-1-024)the National Key R&D Project of China(2021YFF0702804)Peking Union Medical College-Central University Basic Scientific Research Business Fee(Project number.:3332023079)Yunnan Province Applied Basic Research Special Project-General Project(project number:202401CF070048,202301AT070367).
文摘Coxsackievirus B3(CVB3)is the pathogen causing hand,foot and mouth disease(HFMD),which manifests across a spectrum of clinical severity from mild to severe.However,CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis,failing to replicate human HFMD symptoms.Although several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys,there is no comprehensive data on CVB3.In this study,we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different routes.The results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip,leading to nasopharyngeal colonization,acute severe pathological injury,and typical HFMD symptoms.Notably,the nasal drip group exhibited a longer viral excretion cycle and more severe pathological damage.In the subsequent study,rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms,viral excretion,serum antibody conversion,viral nucleic acids and antigens,and the specific organ damages,particularly in the heart.Surprisingly,there were no significant differences in myocardial enzyme levels,and the clinical symptoms resembled those often associated with common,mild infections.In summary,the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced HFMD.These models could serve as a basis for understanding the disease pathogenesis,conducting pre-trial prevention and evaluation,and implementing post-exposure intervention.
文摘Objective:To observe the curative effect of Modified Ganlu Xiaodu Dan and Kuhuang San combined with interferon on the treatment of HFMD of damp-heat accumulation toxin syndrome and its effects on liver function, myocardial enzymes, inflammatory factors and immunoglobulin.Merhods:From June 2018 to November 2018, 74 children with damp-heat accumulation toxin syndrome who were diagnosed with hand, foot and mouth disease have been randomly divided into the observation group (38 cases) and the control group (36 cases).The control group is given conventional Western medicine symptomatic treatment, and sprayed on the oral cavity with IFN- atomized inhalation or IFN- 2b spray. On the basis of the control group, the observation group is given Modified Ganlu Xiaodu Dan, and Kuhuangsan for washing body. 7 d is a course of treatment. The recurrence time of the two groups, the time of rash regression and the efficacy of the children have been observed. The changes of liver function, myocardial zymogram, inflammatory factors and immunoglobulin are compared before and after treatment.Results: The efficacy of the observation group was 92.1% higher than that of the control group (83.3%), and the difference was statistically significant. The time required for the body temperature of the observation group (2.64±0.57) d was lower than that of the control group (3.12±0.62) d, and the time required for the rash to resolve was (4.18±0.69) d, which was lower than that of the control group (5.25±0.73) d. Statistically significant. The levels of ALT, AST, CK-MB, IL-4 and IL-6 in the observation group were lower than those in the control group after treatment, the difference was statistically significant. The serum IgA and IgM levels in the observation group were higher than those in the control group after treatment. Conclusion: Modified Ganlu Xiaodu Dan and Kuhuang San combined with interferon for the treatment of HFMD of damp-heat accumulation toxin syndrome have a sound curative effect and it can improve liver function, protect cardiomyocytes, reduce inflammatory factors, and regulate immune function for children.
基金supported by the Guangxi Natural Sci-ence Foundation(2017JJA140773y).
文摘In the era of the pandemic of coronavirus disease 2019(COVID-19),the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infects infants and children with mild or atypical symptoms[1,2].The new variations in SARS-CoV-2 recently found in the United Kingdom greatly increased the risk of infection among children[3].Although previous evidence showed that children rarely developed severe symptoms from COVID-19,the hospitalization rate was 24.5%and the ICU admission rate was 2.5%among children in the United States[4].Further,there is a lack of evidence regarding the influence of the recently appeared SARS-CoV-2 variations.Thus,it is of great significance to monitor and track the COVID-19 infection among children.
