Journal of Medical Virology最新文献

{"title":"Identification of a Novel Alkaloid Zj6-11 as a Potent Inhibitor of Influenza Virus Infection via Repression of Virus-Induced Mitochondria-Dependent Apoptosis","authors":"Hanbai Liang,&nbsp;Ying Zhang,&nbsp;Wenhao Sun,&nbsp;Xiaomei Xiao,&nbsp;Xiwen Zhao,&nbsp;Bin Tan,&nbsp;Jian Zhang,&nbsp;Xun Song,&nbsp;Zhengdan He,&nbsp;Liang Ye","doi":"10.1002/jmv.70230","DOIUrl":"https://doi.org/10.1002/jmv.70230","url":null,"abstract":"<div>\u0000 \u0000 <p>Influenza A virus (IAV) remains a major global public health threat, especially with the emergence of antiviral resistance, highlighting the urgent need for novel therapeutics. Alkaloids are known for their antiviral properties, and chemical synthesis has become a key strategy in developing new alkaloid compounds. In this study, we synthesized a series of novel alkaloids using the Ugi reaction and assessed their antiviral potential and mechanisms. Through screening and validation, Zj6-11 was identified as a promising compound that effectively inhibits IAV infection in vitro. Molecular docking and binding affinity assays showed that Zj6-11 binds with high affinity to IAV nucleoprotein (NP) and inhibits its interaction with nucleic acids. Further, in vitro nuclear translocation assays confirmed that Zj6-11 suppresses NP nuclear import. Mechanistically, Zj6-11 significantly inhibits IAV-induced apoptosis and mitigates mitochondrial membrane potential dysfunction. Zj6-11 also inhibits cytochrome c release, reduces the expression of cleaved Caspase-9 and Caspase-3, and suppresses IAV-induced apoptosis-inducing factor (Aif) expression, suppressing IAV-induced mitochondrial apoptosis. More importantly, Zj6-11 plays a crucial role in protecting mice from IAV infection and reducing IAV pathogenicity. Our study provides mechanistic insights into Zj6-11's control of IAV infection in vitro and in vivo, offering new perspectives for antiviral therapy development.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Multiorgan Proteomics Characteristics of the Diverse Fatal Phase in Super Elderly Patients With SARS-CoV-2 Infection: A Descriptive Study","authors":"Shuxia Wang,&nbsp;Jin Sun,&nbsp;Yazhuo Hu,&nbsp;Wei Zhang,&nbsp;Bangguo Qin,&nbsp;Man Li,&nbsp;Nan Zhang,&nbsp;Shengshu Wang,&nbsp;Tingyu Zhou,&nbsp;Miao Liu,&nbsp;Cong Ma,&nbsp;Xinli Deng,&nbsp;Yongyi Bai,&nbsp;Geping Qu,&nbsp;Lin Liu,&nbsp;Hui Shi,&nbsp;Bo Zhou,&nbsp;Ke Li,&nbsp;Bo Yang,&nbsp;Suxia Li,&nbsp;Fan Wang,&nbsp;Jinling Ma,&nbsp;Lu Zhang,&nbsp;Yajuan Wang,&nbsp;Li An,&nbsp;Wenhui Liu,&nbsp;Qing Chang,&nbsp;Ru Zhang,&nbsp;Xi Yin,&nbsp;Yang Yang,&nbsp;Qiangguo Ao,&nbsp;Qiang Ma,&nbsp;Shuangtong Yan,&nbsp;Haili Huang,&nbsp;Peng Song,&nbsp;Shu Zhao,&nbsp;Linggen Gao,&nbsp;Wenning Lu,&nbsp;Lining Xu,&nbsp;Li Lei,&nbsp;Keyu Wang,&nbsp;Qing Song,&nbsp;Zhijian Zhang,&nbsp;Xiangqun Fang,&nbsp;Yao He,&nbsp;Qi Zhang,&nbsp;Jianjun Jia,&nbsp;Ping Zhu","doi":"10.1002/jmv.70207","DOIUrl":"https://doi.org/10.1002/jmv.70207","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aims to identify the risk factors associated with clinical outcomes and the proteomic changes in organs related to fatal SARS-CoV-2 infection within the super-elderly population. This retrospective analysis included all elderly individuals with COVID-19 admitted to the Second Medical Center of PLA General Hospital from December 2022 to January 2023. The follow-up period ended on March 30, 2023. During this time, epidemiological, demographic, laboratory, and outcome data were analyzed descriptively. Proteomic sequencing was performed on super-elderly patients who died from COVID-19 at different stages of the disease. A total of 352 elderly COVID-19 patients, with a mean age of 89.84 ± 8.54 years, were included in this study. During a median follow-up period of 98 days, 79 patients died. Deceased patients were older and more likely to have cardiovascular and cerebrovascular diseases, with a lower prevalence of lipid-lowering therapy. The number of deaths in the acute and post-acute phases were 34 and 45, respectively. Proteomics data suggest that the immune systems of patients who died in the acute phase underwent a more rapid and severe onslaught. Patients in the post-acute phase showed higher levels of viral genome replication and a more robust immune response. However, the over-activation of the immune system led to systemic organ dysfunction. Effective management of comorbidities may improve the prognosis of COVID-19 in super-elderly patients. The continuous replication of the SARS-CoV-2 virus and its subsequent impact on the immune system are critical determinants of survival time in this demographic.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RSV-Bacterial Co-Infection Is Associated With Increased Illness Severity in Hospitalized Children - Results From a Prospective Sentinel Surveillance Study","authors":"Ana Rita Torres,&nbsp;Vânia Gaio,&nbsp;Aryse Melo,&nbsp;Miguel Lança,&nbsp;Marta Barreto,&nbsp;Licínia Gomes,&nbsp;Inês Azevedo,&nbsp;Teresa Bandeira,&nbsp;David Lito,&nbsp;Raquel Guiomar,&nbsp;Ana Paula Rodrigues,&nbsp;VigiRSV group","doi":"10.1002/jmv.70209","DOIUrl":"https://doi.org/10.1002/jmv.70209","url":null,"abstract":"<div>\u0000 \u0000 <p>During the autumn/winter respiratory syncytial virus (RSV) epidemics, bacterial co-infection is common and affects the disease severity. We aimed to understand the relationship between RSV-bacterial co-infections and clinical severity since the RSV seasonality change after COVID-19 pandemic. We conducted a prospective, sentinel surveillance study at 20 sites in Portugal in children under 2 years hospitalized with RSV, between April 21 and January 23. Effect of co-infection with potentially pathogenic bacteria (PPB) on the length of hospitalization and disease severity was investigated using multivariate linear and log-binomial regression models. Among 678 RSV hospitalizations, 67.4% occurred in children under 6 months and 15.3% in preterm; 20.4% tested positive for PPB; median length of hospitalization was 5 days (IQR: 3–7days). Children coinfected with PPB had a higher rate of ICU admission (29.7% vs. 3.5%, <i>p</i> &lt; 0.001), resulting in more prolonged hospitalizations (7 vs. 5 days, <i>p</i> &lt; 0.001) and a 13-fold risk of having severe disease (RR: 13.2, 95% CI:7.3–23.9). RSV-bacterial co-infection was associated with increased length of hospitalization and severe illness during off-season epidemics. This risk is probably overestimated, as laboratory testing for bacterial infections is usually higher in severely ill-appearing children. Measures to prevent outgrowth of pathogenic bacteria within the respiratory tract should be discussed.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenovirus-Specific T Cells in Adults Are Frequent, Cross-Reactive to Common Childhood Adenovirus Infections and Boosted by Adenovirus-Vectored Vaccines","authors":"Rookmini Mukhopadhyay,&nbsp;Arnold W. Lambisia,&nbsp;Jennifer P. Hoang,&nbsp;Benjamin J. Ravenhill,&nbsp;Charles N. Agoti,&nbsp;Benjamin A. Krishna,&nbsp;Charlotte J. Houldcroft","doi":"10.1002/jmv.70222","DOIUrl":"https://doi.org/10.1002/jmv.70222","url":null,"abstract":"<p>Human adenoviruses (HAdVs) cause diverse disease presentations as pathogens and are also used as viral vectors for vaccines and gene therapy products. Pre-existing adaptive immune responses to HAdV are known to influence symptom severity, viral clearance and the success of viral vectored products. Of note, approximately 50% of the UK's adult population has received at least one dose of a chimpanzee adenovirus vectored SARS-CoV-2 vaccine (ChAdOx1) since January 2021. We used FluoroSpot analysis to quantify the interferon-gamma (IFNγ) and interleukin-2 (IL2) responses of healthy blood donors to HAdV species A, B, C, D and F and chimpanzee adenovirus Y25, related to HAdV species E. We find that cellular immune responses to multiple species of human adenovirus are ubiquitous among healthy adult blood donors and that stimulating PBMC with whole hexon peptide libraries induces a significantly greater IFNγ and IL2 response than using selected peptide pools alone. We then compared the cellular immune responses of ChAdOx1 recipients and control donors using PBMC collected in 2021 and found that homotypic and heterotypic IFNγ responses were significantly boosted in ChAdOx1 recipients but not controls. Finally, we show that in PBMC derived from blood donors, IFNγ responses are made to both conserved and variable regions of the hexon protein. Future vaccination campaigns using adenoviral vectored vaccines will need to account for the pre-existing exposure of recipients to both circulating HAdVs and vaccines such as ChAdOx1, which convey polyfunctional antiviral T cell responses to even low seroprevalence HAdV types.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70222","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral Load of Human Papillomavirus (HPV) During Pregnancy and Its Association With HPV Vertical Transmission","authors":"Eméra Alice Bénard,&nbsp;Ana Maria Carceller,&nbsp;Marie-Hélène Mayrand,&nbsp;Jacques Lacroix,&nbsp;Joseph Niyibizi,&nbsp;Louise Laporte,&nbsp;Emilie Comète,&nbsp;François Coutlée,&nbsp;Helen Trottier,&nbsp;The HERITAGE study group","doi":"10.1002/jmv.70221","DOIUrl":"https://doi.org/10.1002/jmv.70221","url":null,"abstract":"<p>Little is known on the dynamics of human papillomavirus (HPV) viral load during pregnancy and on the impact of viral load on HPV vertical transmission. We described viral loads for several genotypes during pregnancy and analyse its association with vertical transmission. Data were analysed from the HERITAGE study, a cohort of pregnant women recruited between 2010 and 2016 in three centres in Canada. Vaginal samples were collected at the first and third trimesters of pregnancy, placental samples were collected at birth, and conjunctival, oral, pharyngeal, and genital samples were collected in children at birth and 3 months were tested for HPV DNA and viral load by Linear Array essay. The association between viral load and vertical transmission was measured using logistic regression. Odd ratios (ORs) and their 95% Confidence intervals (CI) were adjusted for age of the mother. We included women in the cohort infected with the 13 most common genotypes during pregnancy (<i>n</i> = 287). A decrease in HPV viral load was observed during pregnancy (median difference between the third and first trimester of pregnancy = −0.005 copies/cell [<i>p</i> &lt; 0.05]). Women with more than 2 HPV copies/cell (compared to those with ≤ 2 copies) at first trimester had a statistically significant higher risk of vertical transmission (adjusted OR = 6.41; 95% CI: 1.10–37.34 for any genotypes and OR = 17.17; 95% CI: 1.18–250.28 for HPV-16). Viral load values analysed continuously or categorized with different cut-offs showed comparable results. HPV viral load varied during pregnancy and was strongly associated with HPV vertical transmission. The results provide a better understanding of risk factors associated with vertical transmission.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70221","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143186525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Intriguing Role of Short-Form TSLP by Zeitvogel et al.","authors":"Remo Poto,&nbsp;Gianni Marone,&nbsp;Gilda Varricchi","doi":"10.1002/jmv.70224","DOIUrl":"https://doi.org/10.1002/jmv.70224","url":null,"abstract":"","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143186526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bilayer or Not: Revisiting the Structural Nature of HBV Subviral Particles","authors":"Haitao Liu,&nbsp;Sonal Garg,&nbsp;Jianming Hu,&nbsp;Joseph Che-Yen Wang","doi":"10.1002/jmv.70212","DOIUrl":"https://doi.org/10.1002/jmv.70212","url":null,"abstract":"<p>Hepatitis B virus (HBV) subviral particles (SVPs) are primarily stabilized by protein–protein interactions, with discrete lipid patches playing a supporting role, rather than forming a conventional lipid bilayer, challenging classical assumptions about viral membrane architecture.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70212","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143112141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of the Inflammasome by the SARS-CoV-2 Accessory Protein ORF9b, Abrogated by Small-Molecule ORF9b Homodimerization Inhibitors","authors":"Erika Zodda,&nbsp;Mònica Pons,&nbsp;Natàlia DeMoya-Valenzuela,&nbsp;Cristina Calvo-González,&nbsp;Cristina Benítez-Rodríguez,&nbsp;Blanca D. López-Ayllón,&nbsp;Achraf Hibot,&nbsp;Alice Zuin,&nbsp;Bernat Crosas,&nbsp;Marta Cascante,&nbsp;María Montoya,&nbsp;María D. Pujol,&nbsp;Jaime Rubio-Martínez,&nbsp;Timothy M. Thomson","doi":"10.1002/jmv.70145","DOIUrl":"https://doi.org/10.1002/jmv.70145","url":null,"abstract":"<div>\u0000 \u0000 <p>Viral accessory proteins play critical roles in viral escape from host innate immune responses and in viral inflammatory pathogenesis. Here we show that the SARS-CoV-2 accessory protein, ORF9b, but not other SARS-CoV-2 accessory proteins (ORF3a, ORF3b, ORF6, ORF7, ORF8, ORF9c, and ORF10), strongly activates inflammasome-dependent caspase-1 in A549 lung carcinoma cells and THP-1 monocyte-macrophage cells. Exposure to lipopolysaccharide (LPS) and ATP additively enhanced the activation of caspase-1 by ORF9b, suggesting that ORF9b and LPS follow parallel pathways in the activation of the inflammasome and caspase-1. Following rational in silico approaches, we have designed small molecules capable of inhibiting the homodimerization of ORF9b, which experimentally inhibited ORF9b-ORF9b homotypic interactions, caused mitochondrial eviction of ORF9b, inhibited ORF9b-induced activation of caspase-1 in A549 and THP-1 cells, cytokine release in THP-1 cells, and restored type I interferon (IFN-I) signaling suppressed by ORF9b in both cell models. These small molecules are first-in-class compounds targeting a viral accessory protein critical for viral-induced exacerbated inflammation and escape from innate immune responses, with the potential of mitigating the severe immunopathogenic damage induced by highly pathogenic coronaviruses and restoring antiviral innate immune responses curtailed by viral infection.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143112035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infectious Subgenomic Amplicon Strategies for Japanese Encephalitis and West Nile Viruses","authors":"Prince Pal Singh,&nbsp;Nguyen Phuong Khanh Le,&nbsp;Uladzimir Karniychuk","doi":"10.1002/jmv.70205","DOIUrl":"10.1002/jmv.70205","url":null,"abstract":"<p>Classical methods for constructing infectious cDNA clones of flaviviruses are often hindered by instability and toxicity. The Infectious-Subgenomic-Amplicons (ISA) method is an advancement which utilizes overlapping DNA fragments representing viral genomic sequence and in-cell recombination to bypass bacterial plasmid assembly. However, the ISA method has limitations due to the toxicity of some ISA DNA fragments in bacteria during synthetic production. We validated modified ISA strategies for producing toxic ISA Japanese encephalitis virus (JEV) and West Nile virus (WNV) DNA fragments. Three approaches were explored, including subdividing toxic DNA fragments into two sub-fragments for synthetic clonal production, using a low-copy bacterial plasmid, and subdividing the toxic DNA fragments into four short overlapping sub-fragments, each up to 1.8 kb. The latter novel approach in ISA applications enabled the synthesis of entirely bacteria-free ISA DNA fragments. Our results demonstrate that subdividing toxic fragments into sub-fragments smaller than 1.8 kb for synthesis is the efficient strategy, circumventing the need for bacterial plasmids and ensuring rapid production of synthetic flaviviruses. This method also shortens the production timeline. We also compared the efficacy of JEV and WNV ISA in zinc finger antiviral protein 1 (ZAP) wild-type and knockout cells and found that knockout cells may be more effective for ISA rescue of flaviviruses, including CpG-enriched strains for live attenuated vaccines. The validated modified ISA strategies provide an efficient approach for producing synthetic JEV and WNV. This will enable rapid research during outbreaks of emerging flaviviruses by facilitating the quick generation of new virus variants.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Reprogramming in Epstein–Barr Virus Associated Diseases","authors":"Tiffany Melanie Yee,&nbsp;Liang Wei Wang","doi":"10.1002/jmv.70197","DOIUrl":"10.1002/jmv.70197","url":null,"abstract":"<div>\u0000 \u0000 <p>Epstein–Barr virus (EBV) is the first human cancer-causing viral pathogen to be discovered; it has been epidemiologically associated with a wide range of diseases, including cancers, autoimmunity, and hyperinflammatory disorders. Its evolutionary success is underpinned by coordinated expression of viral transcription factors (EBV nuclear antigens), signaling proteins (EBV latent membrane proteins), and noncoding RNAs, which orchestrate cell transformation, immune evasion, and dissemination. Each of those activities entails significant metabolic rewiring, which is achieved by viral subversion of key host metabolic regulators such as the mammalian target of rapamycin (mTOR), MYC, and hypoxia-inducible factor (HIF). In this review, we systemically discuss how EBV-encoded factors regulate metabolism to achieve viral persistence and propagation, as well as potential research questions and directions in EBV-driven metabolism.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}