BACKGROUND Hepatitis delta virus(HDV)infection is the most severe form of chronic viral hepatitis,yet sex-based clinical differences remain poorly defined.Understanding these differences may inform disease management ...BACKGROUND Hepatitis delta virus(HDV)infection is the most severe form of chronic viral hepatitis,yet sex-based clinical differences remain poorly defined.Understanding these differences may inform disease management and guide research.AIM To investigate sex-related differences in demographic and clinical characteristics of patients with chronic HDV infection in a nationwide,real-world Italian setting.METHODS We analyzed demographic,clinical,and virological data from 513 hepatitis B surface antigen/anti-HDV-positive patients,consecutively enrolled between 2019 and 2024,across 58 liver clinics in the Italian PITER HDV cohort.A propensity score-weighted logistic regression model evaluated the association between sex and cirrhosis and/or hepatocellular carcinoma.RESULTS Among 513 patients(61.6%male),median age(56.0 years)and age distribution were similar by sex(P=0.41).Cirrhosis was frequent:73.4%vs 66.0%(anti-HDV-positive)and 77.8%vs 74.2%(HDV RNA-positive)in males and females,respectively.HDV RNA levels were comparable(P=0.93).The highest proportion of females with cirrhosis(33.8%)was in the 56-60-year group,similar to males(34.9%).Among patients with cirrhosis aged≤40 years,females,(80.9%of whom of non-Italian origin),were more represented than males(16.1%vs 6.5%respectively,P<0.05).Male sex was associated with cirrhosis(odds ratio=1.85;95%confidence interval:1.004-3.40).Among HDV RNA-positive patients,males more often had hepatocellular carcinoma,elevated gammaglutamyl transpeptidase,alcohol use,diabetes,hypertension,steatotic liver disease,and hepatitis C virus/human immunodeficiency virus coinfection.Interferon eligibility was similar.CONCLUSION HDV-infected females develop cirrhosis earlier,without liver disease cofactors,while males show advanced liver disease with multiple cofactors.Tailored care for young migrant women and cofactor-guided management for men may improve HDV outcomes,promoting equity.展开更多
Since first isolation in 1947 from the Zika forest in Uganda, Zika virus(ZIKV) has been principally known as a benign agent associated with sporadic human infections in a restricted number of African countries. Howeve...Since first isolation in 1947 from the Zika forest in Uganda, Zika virus(ZIKV) has been principally known as a benign agent associated with sporadic human infections in a restricted number of African countries. However, during 2015–2016,an Asian lineage of ZIKV caused an unprecedentedly large outbreak in the Americas and sizeable numbers of exported cases across the globe. In this review, we critically appraise the recent advances in molecular epidemiological studies of ZIKV performed to date, and we highlight the pivotal role played by genomic surveillance in elucidating the origins,dissemination and evolution of the Asian lineage of ZIKV in Asia and in the Americas.展开更多
Globally, coxsackievirus B4 (CV-B4) has been continuously isolated and evidence suggests an association with the development of pancreatitis and type I diabetes. In addition, CV-B4 is also associated with myocarditi...Globally, coxsackievirus B4 (CV-B4) has been continuously isolated and evidence suggests an association with the development of pancreatitis and type I diabetes. In addition, CV-B4 is also associated with myocarditis and severe central nervous system (CNS) complications, which remain poorly studied and understood. In the present study, we established an institute for Cancer Research (ICR) mouse model of CV-B4 infection and examined whether CV-B4 infection resulted in a predisposition to myocarditis and CNS infection. We found high survival in both the treatment and control group, with no significant differences in clinical outcomes observed. However, pathological lesions were evident in both brain and heart tissue of the CV-B4-infected mice. in addition, high viral loads were found in the neural and cardiac tissues as early as 2 days post infection. Expressions of IFN-y and IL-6 in sera were significantly higher in CV-B4-infected mice compared to uninfected negative controls, suggesting the involvement of these cytokines in the development of histopathological lesions. Our murine model successfully reproduced the acute myocarditis and cerebral cortical neuron edema induced by CV-B4, and may be useful for the evaluation of vaccine candidates and potential antivirals against CV-B4 infection.展开更多
This study sought to identify potential therapeutic targets in herpes simplex keratitis(HSK) patients with active and inactive infection by investigating peripheral cytokine production. Peripheral blood mononuclear ce...This study sought to identify potential therapeutic targets in herpes simplex keratitis(HSK) patients with active and inactive infection by investigating peripheral cytokine production. Peripheral blood mononuclear cells(PBMCs) and serum were prepared from healthy controls and HSK patients during active infection or following treatment(inactive infection). Serum antibody titres were determined by ELISA. Protein expression levels were analysed by Western blot. Cytokine levels were determined by multiplex ELISA. Active corneal herpes simplex virus type 1(HSV-1) infection resulted in significantly elevated peripheral levels of IL-1β in HSK patients compared to healthy controls, and remained significantly increased following treatment. Elevated production of IL-1β in inactive patients was associated with significantly increased levels of IRF3 and STAT1, key proteins involved in promoting anti-viral immune responses. Our data suggest that inflammation persists beyond the period that it is clinically evident and that enhanced peripheral production of IL-1β may have implications for HSV-1 viral clearance in active and inactive HSK patients.展开更多
We compared the numbers of nucleotide substitutions occurring in the non-coding regions and coding regions of Ebola virus genomes and found that non-coding regions contain indispensable phylogenetic and evolutionary i...We compared the numbers of nucleotide substitutions occurring in the non-coding regions and coding regions of Ebola virus genomes and found that non-coding regions contain indispensable phylogenetic and evolutionary information. The omission of genetic data from non-coding regions can lead to unreliable phylogenies and inaccurate estimates of evolutionary parameters.展开更多
Nonpharmaceutical interventions(NPIs)have been commonly deployed to prevent and control the spread of the coronavirus disease 2019(COVID-19),resulting in a worldwide decline in influenza prevalence.However,the influen...Nonpharmaceutical interventions(NPIs)have been commonly deployed to prevent and control the spread of the coronavirus disease 2019(COVID-19),resulting in a worldwide decline in influenza prevalence.However,the influenza risk in China warrants cautious assessment.We conducted a cross-sectional,seroepidemiological study in Shandong Province,Northern China in mid-2021.Hemagglutination inhibition was performed to test antibodies against four influenza vaccine strains.A combination of descriptive and meta-analyses was adopted to compare the seroprevalence of influenza antibodies before and during the COVID-19 pandemic.The overall seroprevalence values against A/H1N1pdm09,A/H3N2,B/Victoria,and B/Yamagata were 17.8%(95%CI 16.2%–19.5%),23.5%(95%CI 21.7%–25.4%),7.6%(95%CI 6.6%–8.7%),and 15.0(95%CI 13.5%–16.5%),respectively,in the study period.The overall vaccination rate was extremely low(2.6%).Our results revealed that antibody titers in vaccinated participants were significantly higher than those in unvaccinated individuals(P<0.001).Notably,the meta-analysis showed that antibodies against A/H1N1pdm09 and A/H3N2 were significantly low in adults after the COVID-19 pandemic(P<0.01).Increasing vaccination rates and maintaining NPIs are recommended to prevent an elevated influenza risk in China.展开更多
基金Supported by the Investigator Sponsored Research Grant from Gilead Sciences,No.IN-IT-980-6816the Fondazione Italiana per la Ricerca sul Cancro(AIRC),No.IG 2020 ID 24858.
文摘BACKGROUND Hepatitis delta virus(HDV)infection is the most severe form of chronic viral hepatitis,yet sex-based clinical differences remain poorly defined.Understanding these differences may inform disease management and guide research.AIM To investigate sex-related differences in demographic and clinical characteristics of patients with chronic HDV infection in a nationwide,real-world Italian setting.METHODS We analyzed demographic,clinical,and virological data from 513 hepatitis B surface antigen/anti-HDV-positive patients,consecutively enrolled between 2019 and 2024,across 58 liver clinics in the Italian PITER HDV cohort.A propensity score-weighted logistic regression model evaluated the association between sex and cirrhosis and/or hepatocellular carcinoma.RESULTS Among 513 patients(61.6%male),median age(56.0 years)and age distribution were similar by sex(P=0.41).Cirrhosis was frequent:73.4%vs 66.0%(anti-HDV-positive)and 77.8%vs 74.2%(HDV RNA-positive)in males and females,respectively.HDV RNA levels were comparable(P=0.93).The highest proportion of females with cirrhosis(33.8%)was in the 56-60-year group,similar to males(34.9%).Among patients with cirrhosis aged≤40 years,females,(80.9%of whom of non-Italian origin),were more represented than males(16.1%vs 6.5%respectively,P<0.05).Male sex was associated with cirrhosis(odds ratio=1.85;95%confidence interval:1.004-3.40).Among HDV RNA-positive patients,males more often had hepatocellular carcinoma,elevated gammaglutamyl transpeptidase,alcohol use,diabetes,hypertension,steatotic liver disease,and hepatitis C virus/human immunodeficiency virus coinfection.Interferon eligibility was similar.CONCLUSION HDV-infected females develop cirrhosis earlier,without liver disease cofactors,while males show advanced liver disease with multiple cofactors.Tailored care for young migrant women and cofactor-guided management for men may improve HDV outcomes,promoting equity.
基金supported by the National Key Science and Technology Projects of China (2017ZX10104001-006)the National Science and Technology Major Project (2018ZX10101004-002)supported by the Taishan Scholars program of Shandong Province (ts201511056)
文摘Since first isolation in 1947 from the Zika forest in Uganda, Zika virus(ZIKV) has been principally known as a benign agent associated with sporadic human infections in a restricted number of African countries. However, during 2015–2016,an Asian lineage of ZIKV caused an unprecedentedly large outbreak in the Americas and sizeable numbers of exported cases across the globe. In this review, we critically appraise the recent advances in molecular epidemiological studies of ZIKV performed to date, and we highlight the pivotal role played by genomic surveillance in elucidating the origins,dissemination and evolution of the Asian lineage of ZIKV in Asia and in the Americas.
基金supported by the Natural Science Foundation of Shandong Province(ZR2015JL026)the National Natural Science Foundation of China(81601773)supported by the Taishan Scholars program of Shandong Province(ts201511056)
文摘Globally, coxsackievirus B4 (CV-B4) has been continuously isolated and evidence suggests an association with the development of pancreatitis and type I diabetes. In addition, CV-B4 is also associated with myocarditis and severe central nervous system (CNS) complications, which remain poorly studied and understood. In the present study, we established an institute for Cancer Research (ICR) mouse model of CV-B4 infection and examined whether CV-B4 infection resulted in a predisposition to myocarditis and CNS infection. We found high survival in both the treatment and control group, with no significant differences in clinical outcomes observed. However, pathological lesions were evident in both brain and heart tissue of the CV-B4-infected mice. in addition, high viral loads were found in the neural and cardiac tissues as early as 2 days post infection. Expressions of IFN-y and IL-6 in sera were significantly higher in CV-B4-infected mice compared to uninfected negative controls, suggesting the involvement of these cytokines in the development of histopathological lesions. Our murine model successfully reproduced the acute myocarditis and cerebral cortical neuron edema induced by CV-B4, and may be useful for the evaluation of vaccine candidates and potential antivirals against CV-B4 infection.
基金Supported by the Health Research Board and the Royal Victoria Eye and Ear Hospital Research Foundation through the Medical Research Charities Group(No.1409)
文摘This study sought to identify potential therapeutic targets in herpes simplex keratitis(HSK) patients with active and inactive infection by investigating peripheral cytokine production. Peripheral blood mononuclear cells(PBMCs) and serum were prepared from healthy controls and HSK patients during active infection or following treatment(inactive infection). Serum antibody titres were determined by ELISA. Protein expression levels were analysed by Western blot. Cytokine levels were determined by multiplex ELISA. Active corneal herpes simplex virus type 1(HSV-1) infection resulted in significantly elevated peripheral levels of IL-1β in HSK patients compared to healthy controls, and remained significantly increased following treatment. Elevated production of IL-1β in inactive patients was associated with significantly increased levels of IRF3 and STAT1, key proteins involved in promoting anti-viral immune responses. Our data suggest that inflammation persists beyond the period that it is clinically evident and that enhanced peripheral production of IL-1β may have implications for HSV-1 viral clearance in active and inactive HSK patients.
基金supported by the National Natural Science Foundation of China(81470096)the Doctoral Starting up Foundation of Taishan Medical Collegesupported by a grant from the International Development Research Centre
文摘We compared the numbers of nucleotide substitutions occurring in the non-coding regions and coding regions of Ebola virus genomes and found that non-coding regions contain indispensable phylogenetic and evolutionary information. The omission of genetic data from non-coding regions can lead to unreliable phylogenies and inaccurate estimates of evolutionary parameters.
基金supported by the Academic Promotion Programme of Shandong First Medical University(No.2019QL006)the Natural Science Foundation of Shandong Province(Nos.ZR2020QH133,ZR2020MH339,and ZR2021MC001).
文摘Nonpharmaceutical interventions(NPIs)have been commonly deployed to prevent and control the spread of the coronavirus disease 2019(COVID-19),resulting in a worldwide decline in influenza prevalence.However,the influenza risk in China warrants cautious assessment.We conducted a cross-sectional,seroepidemiological study in Shandong Province,Northern China in mid-2021.Hemagglutination inhibition was performed to test antibodies against four influenza vaccine strains.A combination of descriptive and meta-analyses was adopted to compare the seroprevalence of influenza antibodies before and during the COVID-19 pandemic.The overall seroprevalence values against A/H1N1pdm09,A/H3N2,B/Victoria,and B/Yamagata were 17.8%(95%CI 16.2%–19.5%),23.5%(95%CI 21.7%–25.4%),7.6%(95%CI 6.6%–8.7%),and 15.0(95%CI 13.5%–16.5%),respectively,in the study period.The overall vaccination rate was extremely low(2.6%).Our results revealed that antibody titers in vaccinated participants were significantly higher than those in unvaccinated individuals(P<0.001).Notably,the meta-analysis showed that antibodies against A/H1N1pdm09 and A/H3N2 were significantly low in adults after the COVID-19 pandemic(P<0.01).Increasing vaccination rates and maintaining NPIs are recommended to prevent an elevated influenza risk in China.