Objective:To explore which pattern recognition receptors(PRRs)play a key role in the development of hand,foot,and mouth disease(HFMD)by analyzing PRR-associated genes.Methods:We conducted a comparative analysis of PRR...Objective:To explore which pattern recognition receptors(PRRs)play a key role in the development of hand,foot,and mouth disease(HFMD)by analyzing PRR-associated genes.Methods:We conducted a comparative analysis of PRR-associated gene expression in human peripheral blood mononuclear cells(PBMCs)infected with enterovirus 71(EV-A71)which were derived from patients with HFMD of different severities and at different stages.A total of 30 PRR-associated genes were identified as significantly upregulated both over time and across different EV-A71 isolates.Subsequently,ELISA was employed to quantify the expression of the six most prominent genes among these 30 identified genes,specifically,BST2,IRF7,IFI16,TRIM21,MX1,and DDX58.Results:Compared with those at the recovery stage,the expression levels of BST2(P=0.027),IFI16(P=0.016),MX1(P=0.046)and DDX58(P=0.008)in the acute stage of infection were significantly upregulated,while no significant difference in the expression levels of IRF7(P=0.495)and TRIM21(P=0.071)was found between different stages of the disease.The expression levels of BST2,IRF7,IFI16 and MX1 were significantly higher in children infected with single pathogen than those infected with mixed pathogens,and BST2,IRF7,IFI16 and MX1 expression levels were significantly lower in coxsackie B virus(COXB)positive patients than the negative patients.Expression levels of one or more of BST2,IRF7,IFI16,TRIM21,MX1 and DDX58 genes were correlated with PCT levels,various white blood cell counts,and serum antibody levels that reflect disease course of HFMD.Aspartate aminotransferase was correlated with BST2,MX1 and DDX58 expression levels.Conclusions:PRR-associated genes likely initiate the immune response in patients at the acute stage of HFMD.展开更多
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） is a common contagious illness which occurs worldwide both sporadically and in epidemics. The disease mainly affects, children and the typical symptoms, which may resolve spontan...Hand, foot, and mouth disease （HFMD） is a common contagious illness which occurs worldwide both sporadically and in epidemics. The disease mainly affects, children and the typical symptoms, which may resolve spontaneously, include mucocutaneous papulovesicular lesions on the hands, feet, mouth, and buttocks. In rare cases, however, the patients may also develop neurological complications such as neurogenic pulmonary edema,展开更多
Objectives Hand,foot and mouth disease(HFMD)is a widespread infectious disease that causes a significant disease burden on society.To achieve early intervention and to prevent outbreaks of disease,we propose a novel w...Objectives Hand,foot and mouth disease(HFMD)is a widespread infectious disease that causes a significant disease burden on society.To achieve early intervention and to prevent outbreaks of disease,we propose a novel warning model that can accurately predict the incidence of HFMD.Methods We propose a spatial-temporal graph convolutional network(STGCN)that combines spatial factors for surrounding cities with historical incidence over a certain time period to predict the future occurrence of HFMD in Guangdong and Shandong between 2011 and 2019.The 2011-2018 data served as the training and verification set,while data from 2019 served as the prediction set.Six important parameters were selected and verified in this model and the deviation was displayed by the root mean square error and the mean absolute error.Results As the first application using a STGCN for disease forecasting,we succeeded in accurately predicting the incidence of HFMD over a 12-week period at the prefecture level,especially for cities of significant concern.Conclusions This model provides a novel approach for infectious disease prediction and may help health administrative departments implement effective control measures up to 3 months in advance,which may significantly reduce the morbidity associated with HFMD in the future.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
Objective To realize the characteristics of "zheng" differentiation-treatment for hand, foot and mouth disease(HFMD), a new methodology of syndrome differentiation for different stages of HFMD has been explo...Objective To realize the characteristics of "zheng" differentiation-treatment for hand, foot and mouth disease(HFMD), a new methodology of syndrome differentiation for different stages of HFMD has been explored. Methods Total of 2 325 cases with HFMD were recorded by distributing them into exterior syndrome stage, interior syndrome stage, severe syndrome stage and recovered syndrome stage, respectively, and the main symptoms and subsidiary symptoms of different stages of HFMD have been observed. The major and minor pathogenesis of HFMD in different stages were obtained, and compared with the "2010 Guideline for the Diagnosis and Treatment of HFMD". Results It was found that the major pathogenesis of exterior stage was defined as "the invation of the wenevil to the defender of the body with the collaterals got involved ", and the minor as "qi deficiency"; in interior stage, "the fury of Gan-Yang" was the main pathogenesis, and "qi in chaos and qi deficiency" was the minor; in severe syndrome stage, "the damage of heart, liver and lung" was the main pathogenesis, and "qi in chaos" was the minor; and the pathogenesis of recovered stage was "qi-yin deficiency". Compared with the "2010 Guideline for the Diagnosis and Treatment of HFMD", it showed that "the obstruction of the fei-pi qi by the mixture of shi-re evil" and "the mixture of shi-re" in vivo was quite difficult to be explained in completely different context in the general situation; in the severe stage, the TCM clinical characteristics of syndrome differentiation might lose; in the early acute severe cases, the phenomenon that xin-yang and fei-qi almost ran out was difficult to be observed, then, the line between the severe and the acute severe became vague.Conclusions The theory of syndrome differentiation by stages of HFMD was reasonable in the actual situation of clinical description on HFMD which was expected to be further tested and widely applied in the "zheng" differentiation-treatment of HFMD in the future.展开更多
In recent years,the number of hand,foot,and mouth disease(HFMD)cases in China has continued to grow,and the disease has become a serious public health issue.Xinjiang Uygur Autonomous Region is located in the arid area...In recent years,the number of hand,foot,and mouth disease(HFMD)cases in China has continued to grow,and the disease has become a serious public health issue.Xinjiang Uygur Autonomous Region is located in the arid areas of Northwest China,where the epidemiological trend of HFMD is gradually increasing and characterized by geographical heterogeneity.In this study,based on the HFMD case data in all counties and cities in Xinjiang,we employed statistical and GIS spatial analyses,and geographic probe models to characterize the spatiotemporal differentiation of HFMD epidemics in Xinjiang during the period of 2009–2018,and quantitatively analyzed the factors influencing the spatial differentiation of HFMD epidemics.The results showed that HFMD incidence rate in Xinjiang had non-stationary temporal characteristics on the interannual and monthly scales,and the monthly variation characteristics of HFMD epidemic were quite different in southern and northern Xinjiang.The spatial distribution characteristics of HFMD epidemics showed a north–south spatial differentiation pattern with the Tianshan Mountains as the boundary;cold spot and hot spot of HFMD epidemics in Xinjiang have shifted from scattered to concentrated,and the spatial differentiation pattern had gradually stabilized.Moreover,the dominant factors influencing the spatial differentiation of HFMD epidemics in Xinjiang were socioeconomic factors,such as per capita GDP and urbanization rate,while the basic factors affecting its spatial differentiation were natural environmental factors.The spatial differentiation and evolution patterns of HFMD epidemics differed between northern and southern Xinjiang.Specifically,the leading role of socioeconomic factors is more obvious in southern Xinjiang than in northern Xinjiang,while natural environmental factors(e.g.,dryness and relative humidity)contribute to the prevalence of HFMD epidemics in northern Xinjiang,and the perturbing effect of these factors was more prominent than other factors.The results of this study can provide a scientific basis for the prevention of HFMD epidemics and early warning of HFMD epidemics in Xinjiang.展开更多
EV71-type virus is one of the main pathogens causing the occurrence of hand,foot and mouth disease(HFMD),and VP1 protein,a factor that directly determines the antigenicity of the virus,has been isolated.The tomato was...EV71-type virus is one of the main pathogens causing the occurrence of hand,foot and mouth disease(HFMD),and VP1 protein,a factor that directly determines the antigenicity of the virus,has been isolated.The tomato was selected as a bioreactor for the production of an edible EV71 vaccine designed for the VP1 capsid protein.Using molecular biology techniques,the fusion gene EV71-VP1 was cut from vector PGEX-4T-2,a vector containing the p2300-EV71 gene with CaMV35S promoter and TL regulatory elements was constructed,and the hypocotyl and cotyledons of tomato were transformed using Agrobacterium(EHA105)-mediated method,screened,elongated and rooted,and finally 20 resistant tomato plants were obtained.Five transgenic positive seedlings were obtained by digestion and PCR assay,among which three plants were detected by RT-PCR to be capable of transcriptional translation at the RNA level.The experimental results aimed to explore new material support for the preparation of transgenic plant oral vaccines against EV71 infection and provide a theoretical basis for accelerating the development of transgenic plant vaccines in the future.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
文摘Objective:To explore which pattern recognition receptors(PRRs)play a key role in the development of hand,foot,and mouth disease(HFMD)by analyzing PRR-associated genes.Methods:We conducted a comparative analysis of PRR-associated gene expression in human peripheral blood mononuclear cells(PBMCs)infected with enterovirus 71(EV-A71)which were derived from patients with HFMD of different severities and at different stages.A total of 30 PRR-associated genes were identified as significantly upregulated both over time and across different EV-A71 isolates.Subsequently,ELISA was employed to quantify the expression of the six most prominent genes among these 30 identified genes,specifically,BST2,IRF7,IFI16,TRIM21,MX1,and DDX58.Results:Compared with those at the recovery stage,the expression levels of BST2(P=0.027),IFI16(P=0.016),MX1(P=0.046)and DDX58(P=0.008)in the acute stage of infection were significantly upregulated,while no significant difference in the expression levels of IRF7(P=0.495)and TRIM21(P=0.071)was found between different stages of the disease.The expression levels of BST2,IRF7,IFI16 and MX1 were significantly higher in children infected with single pathogen than those infected with mixed pathogens,and BST2,IRF7,IFI16 and MX1 expression levels were significantly lower in coxsackie B virus(COXB)positive patients than the negative patients.Expression levels of one or more of BST2,IRF7,IFI16,TRIM21,MX1 and DDX58 genes were correlated with PCT levels,various white blood cell counts,and serum antibody levels that reflect disease course of HFMD.Aspartate aminotransferase was correlated with BST2,MX1 and DDX58 expression levels.Conclusions:PRR-associated genes likely initiate the immune response in patients at the acute stage of HFMD.
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supported by National Foundation of China (project No.2013ZX10004-202)National Basic Research Program of China (973 Program,2011CB504902)National Natural Science Foundation of China (project Nos.30900063,81101303,81373049)
文摘Hand, foot, and mouth disease （HFMD） is a common contagious illness which occurs worldwide both sporadically and in epidemics. The disease mainly affects, children and the typical symptoms, which may resolve spontaneously, include mucocutaneous papulovesicular lesions on the hands, feet, mouth, and buttocks. In rare cases, however, the patients may also develop neurological complications such as neurogenic pulmonary edema,
基金supported by grants from the Key Technologies Research and Development Program from the Ministry of Science and Technology[grant number:ZDZX-2018ZX102001002-003-003]the Beijing Natural Science Foundation[project number:L192014]
文摘Objectives Hand,foot and mouth disease(HFMD)is a widespread infectious disease that causes a significant disease burden on society.To achieve early intervention and to prevent outbreaks of disease,we propose a novel warning model that can accurately predict the incidence of HFMD.Methods We propose a spatial-temporal graph convolutional network(STGCN)that combines spatial factors for surrounding cities with historical incidence over a certain time period to predict the future occurrence of HFMD in Guangdong and Shandong between 2011 and 2019.The 2011-2018 data served as the training and verification set,while data from 2019 served as the prediction set.Six important parameters were selected and verified in this model and the deviation was displayed by the root mean square error and the mean absolute error.Results As the first application using a STGCN for disease forecasting,we succeeded in accurately predicting the incidence of HFMD over a 12-week period at the prefecture level,especially for cities of significant concern.Conclusions This model provides a novel approach for infectious disease prediction and may help health administrative departments implement effective control measures up to 3 months in advance,which may significantly reduce the morbidity associated with HFMD in the future.
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 the development and construction project of State Administration of l Traditional Chinese Medicine (200907001-3)the key science and technology project of Shenzhen (201003134, 201002110)
文摘Objective To realize the characteristics of "zheng" differentiation-treatment for hand, foot and mouth disease(HFMD), a new methodology of syndrome differentiation for different stages of HFMD has been explored. Methods Total of 2 325 cases with HFMD were recorded by distributing them into exterior syndrome stage, interior syndrome stage, severe syndrome stage and recovered syndrome stage, respectively, and the main symptoms and subsidiary symptoms of different stages of HFMD have been observed. The major and minor pathogenesis of HFMD in different stages were obtained, and compared with the "2010 Guideline for the Diagnosis and Treatment of HFMD". Results It was found that the major pathogenesis of exterior stage was defined as "the invation of the wenevil to the defender of the body with the collaterals got involved ", and the minor as "qi deficiency"; in interior stage, "the fury of Gan-Yang" was the main pathogenesis, and "qi in chaos and qi deficiency" was the minor; in severe syndrome stage, "the damage of heart, liver and lung" was the main pathogenesis, and "qi in chaos" was the minor; and the pathogenesis of recovered stage was "qi-yin deficiency". Compared with the "2010 Guideline for the Diagnosis and Treatment of HFMD", it showed that "the obstruction of the fei-pi qi by the mixture of shi-re evil" and "the mixture of shi-re" in vivo was quite difficult to be explained in completely different context in the general situation; in the severe stage, the TCM clinical characteristics of syndrome differentiation might lose; in the early acute severe cases, the phenomenon that xin-yang and fei-qi almost ran out was difficult to be observed, then, the line between the severe and the acute severe became vague.Conclusions The theory of syndrome differentiation by stages of HFMD was reasonable in the actual situation of clinical description on HFMD which was expected to be further tested and widely applied in the "zheng" differentiation-treatment of HFMD in the future.
基金supported by the National Natural Science Foundation of China(41861037)the Third Xinjiang Scientific Expedition Program(2021xjkk0902).
文摘In recent years,the number of hand,foot,and mouth disease(HFMD)cases in China has continued to grow,and the disease has become a serious public health issue.Xinjiang Uygur Autonomous Region is located in the arid areas of Northwest China,where the epidemiological trend of HFMD is gradually increasing and characterized by geographical heterogeneity.In this study,based on the HFMD case data in all counties and cities in Xinjiang,we employed statistical and GIS spatial analyses,and geographic probe models to characterize the spatiotemporal differentiation of HFMD epidemics in Xinjiang during the period of 2009–2018,and quantitatively analyzed the factors influencing the spatial differentiation of HFMD epidemics.The results showed that HFMD incidence rate in Xinjiang had non-stationary temporal characteristics on the interannual and monthly scales,and the monthly variation characteristics of HFMD epidemic were quite different in southern and northern Xinjiang.The spatial distribution characteristics of HFMD epidemics showed a north–south spatial differentiation pattern with the Tianshan Mountains as the boundary;cold spot and hot spot of HFMD epidemics in Xinjiang have shifted from scattered to concentrated,and the spatial differentiation pattern had gradually stabilized.Moreover,the dominant factors influencing the spatial differentiation of HFMD epidemics in Xinjiang were socioeconomic factors,such as per capita GDP and urbanization rate,while the basic factors affecting its spatial differentiation were natural environmental factors.The spatial differentiation and evolution patterns of HFMD epidemics differed between northern and southern Xinjiang.Specifically,the leading role of socioeconomic factors is more obvious in southern Xinjiang than in northern Xinjiang,while natural environmental factors(e.g.,dryness and relative humidity)contribute to the prevalence of HFMD epidemics in northern Xinjiang,and the perturbing effect of these factors was more prominent than other factors.The results of this study can provide a scientific basis for the prevention of HFMD epidemics and early warning of HFMD epidemics in Xinjiang.
基金Supported by the Natural Science Foundation of Heilongjiang Province(LH2021C032)。
文摘EV71-type virus is one of the main pathogens causing the occurrence of hand,foot and mouth disease(HFMD),and VP1 protein,a factor that directly determines the antigenicity of the virus,has been isolated.The tomato was selected as a bioreactor for the production of an edible EV71 vaccine designed for the VP1 capsid protein.Using molecular biology techniques,the fusion gene EV71-VP1 was cut from vector PGEX-4T-2,a vector containing the p2300-EV71 gene with CaMV35S promoter and TL regulatory elements was constructed,and the hypocotyl and cotyledons of tomato were transformed using Agrobacterium(EHA105)-mediated method,screened,elongated and rooted,and finally 20 resistant tomato plants were obtained.Five transgenic positive seedlings were obtained by digestion and PCR assay,among which three plants were detected by RT-PCR to be capable of transcriptional translation at the RNA level.The experimental results aimed to explore new material support for the preparation of transgenic plant oral vaccines against EV71 infection and provide a theoretical basis for accelerating the development of transgenic plant vaccines in the future.
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.
