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Enhanced pathogenicity and transmissibility of H9N2 avian influenza virus in mammals by hemagglutinin mutations combined with PB2-627K

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Virologica Sinica 2023年第1期38卷 47-55页

作者： Kaituo Liu Yaqian Guo Huafen Zheng Zhuxing Ji Miao Cai Ruyi Gao Pinghu Zhang Xiaowen Liu Xiulong Xu Xiaoquan Wang Xiufan Liu Joint International Research Laboratory of Agriculture and Agri-Product Safety The Ministry of Education of ChinaYangzhou UniversityYangzhou225009China Animal Infectious Disease Laboratory College of Veterinary MedicineYangzhou UniversityYangzhou225009China Jiangsu Co-innovation Center for Prevention and control of Important Animal Infectious Diseases and Zoonosis Yangzhou UniversityYangzhou225009China Jiangsu Key Laboratory of Zoonosis Yangzhou225009China Institute of translational Medicine Key Laboratory of Geriatric Disease Prevention and Control of Jiangsu ProvinceMedical CollegeYangzhou UniversityYangzhou225009China

H9N2 avian influenza viruses(AIVs)circulate globally in poultry and have become the dominant AIV subtype in China in recent ***,we demonstrated that the H9N2 virus(A/chicken/Eastern China/SDKD1/2015)naturally harbors a mammalian-adaptive molecular factor(627K)in the PB2 protein and is weakly pathogenic in ***,we focused on new markers for virulence in mammals.A mouse-adapted H9N2 virus was serially passaged in mice by infecting their *** expected,infected mice showed clinical symptoms and died at passage six.A comparison between the wild-type and mouse-adapted virus sequences identified amino acid substitutions in the hemagglutinin(HA)protein.H9N2 viruses with the T187P t M227L double mutation exhibited an increased affinity to human-type(SAα2,6Gal)receptors and significantly enhanced viral attachment to mouse lung tissues,which contributed to enhancing viral replication and virulence in ***,HA with the T187P t M227L mutation enabled H9N2 viral transmission in guinea pigs via direct *** pathogenicity in mice is a polygenic *** results demonstrated that these HA mutations might be combined with PB2-627K to significantly increase H9N2 virulence in mice,and this enhanced virulence was achieved in other H9N2 AIVs by generating the same combination of *** summary,our study identified novel key elements in the HA protein that are required for H9N2 pathogenicity in mice and provided valuable insights into pandemic preparedness against emerging H_(9)N_(2)strains.

关键词： H9N2 Hemagglutinin(HA) PB2-627K Mammalian adaptation Pathogenicity Transmissibility

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Gastric cancer: Epidemiology, risk factors and prevention strategies

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Chinese Journal of Cancer Research 2020年第6期32卷 695-704页

作者： Lei Yang Xiangji Ying Shuo Liu Guoqing Lyu Zekuan Xu Xi Zhang Huichao Li Qingyu Li Ning Wang Jiafu Ji Key Laboratory of Carcinogenesis and translational Research(Ministry of Education/Beijing) Beijing Office for Cancer Prevention and ControlPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and translational Research(Ministry of Education/Beijing) Center of Gastrointestinal CancerPeking University Cancer Hospital&InstituteBeijing 100142China Department of Gastrointestinal Surgery Peking University Shenzhen HospitalShenzhen 518036China Department of General Surgery the First Affiliated Hospital of Nanjing Medical UniversityCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 210029China

Gastric cancer(GC) is a global health problem, with more than 1 million people newly diagnosed with GC worldwide each year. GC is more prevalent in less developed countries than in more developed countries. About half of all GC cases worldwide occur in East Asia, notably China. Globally, overall incidence rates of GC are declining, which is potentially attributed to a decrease in Helicobacter pylori(H. pylori) infection and the use of refrigeration to preserve foods rather than salt. GC is a multifactorial disease, and its occurrence and development were impacted by environmental and genetic factors. H. pylori infection is the primary risk factor for GC, especially for non-cardia. The prognosis of GC is poor due to stages at the first diagnosis. The 5-year survival rate is less than 10% when patients are diagnosed at an advanced stage, but the rate is as high as 85% if patients are detected at an earlier stage. Endoscopic screening can potentially prevent GC by early diagnosis and early treatment and has been widely adopted in screening programs in East Asian countries, such as Japan and Korea. This review summarizes updated epidemiological aspects, risk factors, and prevention strategies of GC in recent years to help researchers determine the most effective intervention strategies for reducing risk of GC.

关键词： Gastric cancer epidemiology risk factor prevention strategy

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Precision screening for esophageal squamous cell carcinoma in China

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Chinese Journal of Cancer Research 2020年第6期32卷 673-682页

作者： Zhonghu He Yang Ke Key Laboratory of Carcinogenesis and translational Research(Ministry of Education/Beijing) Laboratory of GeneticsPeking University Cancer Hospital&InstituteBeijing 100142China

Esophageal squamous cell carcinoma(ESCC)is the predominant subtype of esophageal cancer in China,and this neoplasm is associated with high morbidity and mortality as well as clear geographical *** primary prevention for ESCC lacks a clear intervention target,secondary prevention,also known as screening and early diagnosis and early treatment,has become the mainstay of ESCC prevention and control in *** screening in China has been subject to decades of evaluation and ***,the ESCC screening strategy currently adopted in China has encountered a developmental *** this review,we have summarized studies and significant findings for ESCC screening and proposed advancement of screening strategies as follows:1)evidence from randomized controlled trials is needed to support the effectiveness and health economic value of endoscopic screening for ESCC;2)the current traditional screening and surveillance strategies warrant reform,and a risk-prediction-based precision strategy should be established;and 3)a deeper understanding of the value of opportunistic screening in the prevention and control of ESCC in China is called *** to the low absolute prevalence of precancerous lesions,substantial investment of resources and nonnegligible risks of invasive screening techniques,precision and individualization should be the main direction of cancer screening programs for the *** advocate cooperation on the part of Chinese scientists to solve this major China-specific health problem in the next decades.

关键词： Esophageal cancer organized screening opportunistic screening cost-effectiveness risk stratification

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OIP5 Interacts with NCK2 to Mediate Human Spermatogonial Stem Cell Self-Renewal and Apoptosis through Cell Cyclins and Cycle Progression and Its Abnormality Is Correlated with Male Infertility

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Research 2024年第1期2023卷 455-469页

作者： Yinghong Cui Wei Chen Li Du Zuping He The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province The Research Center of Reproduction and Translational Medicine of Hunan ProvinceHunan Normal University School of MedicineChangsha 410013HunanChina

Spermatogonial stem cells(SSCs)have important applications in both reproduction and regenerative ***,specific genes and signaling transduction pathways in mediating fate decisions of human SSCs remain ***,we have demonstrated for the first time that OIP5(Opa interacting protein 5)controlled the self-renewal and apoptosis of human *** sequencing identified that NCK2 was a target for OIP5 in human SSCs,and interestingly,OIP5 could interact with NCK2 as shown by Co-IP(co-immunoprecipitation),IP-MS(mass spectrometry),and GST pulldown ***2 silencing decreased human SSC proliferation and DNA synthesis but enhanced their ***,NCK2 knockdown reversed the influence of OIP5 overexpression on human ***,OIP5 inhibition decreased the numbers of human SSCs at S and G2/M phases,while the levels of numerous cell cycle proteins,including cyclins A2,B1,D1,E1 and H,especially cyclin D1,were remarkably ***,whole-exome sequencing of 777 patients with nonobstructive azoospermia(NOA)revealed 54 singlenucleotide polymorphism mutations of the OIP5 gene(6.95%),while the level of OIP5 protein was obviously lower in testes of NOA patients compared to fertile ***,these results implicate that OIP5 interacts with NCK2 to modulate human SSC self-renewal and apoptosis via cell cyclins and cell cycle progression and that its mutation and/or lower expression is correlated with *** such,this study offers novel insights into molecular mechanisms underlying the fate determinations of human SSCs and the pathogenesis of NOA,and it provides new targets for treating male infertility.

关键词： OIP5 Apoptosis reversed

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Nab-paclitaxel plus capecitabine as first-line treatment for advanced biliary tract cancers:An open-label,non-randomized,phase II clinical trial

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World Journal of Gastroenterology 2024年第30期30卷 3564-3573页

作者： Ling-Xiao Xu Jia-Jia Yuan Ran Xue Jun Zhou Department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing)Peking University Cancer Hospital and InstituteBeijing 100142China

BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment *** To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic *** This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical *** patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease *** primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and *** A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were *** response assessment was impeded for one patient due to premature demise from tumor *** the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were *** Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.

关键词： Nab-paclitaxel Capecitabine Biliary tract cancer Objective response rate Phase II clinical trial

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Increased circulating zonulin in children with biopsy-proven nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2014年第45期20卷 17107-17114页

作者： Lucia Pacifico Enea Bonci Lidia Marandola Sara Romaggioli Stefano Bascetta Claudio Chiesa Department of Pediatrics and Child Neuropsychiatry Sapienza University of Rome Department of Experimental Medicine Sapienza University of Rome Institute of translational Pharmacology National Research Council

AIM: To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD).

关键词： Zonulin Intestinal permeability Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Children

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SARS-CoV-2 vaccine research and immunization strategies for improved control of the COVID-19 pandemic

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Frontiers of Medicine 2022年第2期16卷 185-195页

作者： Yiming Shao Yingqi Wu Yi Feng Wenxin Xu Feng Xiong Xinxin Zhang Chinese Center for Disease control and Prevention Beijing 102206China Changping Laboratory Beijing 102206China Department of Infectious Diseases Research Laboratory of Clinical VirologyNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Policy Science Central Committee of the Chinese Peasants and Workers Democratic PartyBeijing 100011China

The record speed at which Chinese scientists identified severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and shared its genomic sequence with the world,has greatly facilitated the development of coronavirus disease(COVID-19)diagnostics,drugs,and *** is unprecedented in pandemic control history to develop a dozen successful vaccines in the first year and to immunize over half of the global population in the second year,due to the efforts of the scientific community,biopharmaceutical industry,and regulatory agencies *** challenges are both great and multidimensional due to the rapid emergence of virus variants and waning of vaccine *** strategies need to adapt to these challenges to keep population immunity above the herd immunity threshold,by increasing vaccine coverage,especially for older adults and young people,and providing timely booster doses with homologous or heterologous vaccine *** research should be undertaken to develop more effective vaccines against SARS-CoV-2 variants and to understand the best prime-boost vaccine combinations and immunization strategies to provide sufficient and sustainable immune protection against COVID-19.

关键词： COVID-19 pandemics SARS-CoV-2 vaccination

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Hepatitis C virus-specific cytotoxic T cell response restoration after treatment-induced hepatitis C virus control

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World Journal of Gastroenterology 2015年第12期21卷 3480-3491页

作者： Juan-Ramón Larrubia Elia Moreno-Cubero Joaquín Miquel Eduardo Sanz-de-Villalobos translational Hepatology Unit Guadalajara University Hospital University of Alcalá Department of Medicine and Medical Specialties University of Alcalá Department of Biology of Systems University of Alcalá

Hepatitis C virus(HCV)-specific cytotoxic T cell(CTL) response plays a major role in viral control during spontaneous infection resolution. These cells develop an exhausted and pro-apoptotic status during chronic onset, being unable to get rid of HCV. The role of this response in contributing to sustained viral response(SVR) after anti-HCV is controversial. Recent studies show that after successful interferon-based anti-HCV treatment, HCV traces are still detectable and this correlates with a peak of HCV-specific CTL response activation, probably responsible for maintaining SVR by subsequent complete HCV clearing. Moreover, SVR patients' serum is still able to induce HCV infection in na?ve chimpanzees, suggesting that the infection could be under the control of the immune system after a successful treatment, being transmissible in absence of this adaptive response. At least theoretically, treatmentinduced viral load decrease could allow an effective HCV-specific CTL response reestablishment. This effect has been recently described with anti-HCV interferonfree regimes, based on direct-acting antivirals. Nevertheless, this is to some extent controversial with interferon-based therapies, due to the detrimental immunoregulatory α-interferon effect on T cells. Moreover, HCV-specific CTL response features during anti-HCV treatment could be a predictive factor of SVR that could have clinical implications in patient management. In this review, the recent knowledge about the role of HCV-specific CTL response in the development of SVR after anti-HCV treatment is discussed.

关键词： Hepatitis C virus Chronic hepatitis Hepatitis C vi

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Methodological quality(risk of bias) assessment tools for primary and secondary medical studies: What are they and which is better?

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Military Medical Research 2020年第3期7卷 359-370页

作者： Lin-Lu Ma Yun-Yun Wang Zhi-Hua Yang Di Huang Hong Weng Xian-Tao Zeng Center for Evidence-Based and translational Medicine Zhongnan HospitalWuhan University169 Donghu RoadWuchang DistrictWuhan 430071HubeiChina Department of Evidence-Based Medicine and Clinical Epidemiology the Second Clinical CollegeWuhan UniversityWuhan 430071China Center for Evidence-Based and translational Medicine Wuhan UniversityWuhan 430071China Global Health Institute Wuhan UniversityWuhan 430072China

Methodological quality(risk of bias)assessment is an important step before study initiation ***,accurately judging study type is the first priority,and the choosing proper tool is also *** this review,we introduced methodological quality assessment tools for randomized controlled trial(including individual and cluster),animal study,non-randomized interventional studies(including follow-up study,controlled before-and-after study,before-after/pre-post study,uncontrolled longitudinal study,interrupted time series study),cohort study,case-control study,cross-sectional study(including analytical and descriptive),observational case series and case reports,comparative effectiveness research,diagnostic study,health economic evaluation,prediction study(including predictor finding study,prediction model impact study,prognostic prediction model study),qualitative study,outcome measurement instruments(including patient-reported outcome measure development,content validity,structural validity,internal consistency,cross-cultural validity/measurement invariance,reliability,measurement error,criterion validity,hypotheses testing for construct validity,and responsiveness),systematic review and meta-analysis,and clinical practice *** readers of our review can distinguish the types of medical studies and choose appropriate *** one word,comprehensively mastering relevant knowledge and implementing more practices are basic requirements for correctly assessing the methodological quality.

关键词： Methodological quality Risk of bias Quality assessment Critical appraisal Methodology checklist Appraisal tool Observational study Qualitative study Interventional study Outcome measurement instrument

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The role of neutrophils in triptolide-induced liver injury

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Chinese Journal of Natural Medicines 2018年第9期16卷 653-664页

作者： WANG Xin-Zhi ZHANG Shen-Ye XU Yao ZHANG Lu-Yong JIANG Zhen-Zhou Jiangsu Key Laboratory of Drug Screening Jiangsu Center for Pharmacodynamics Research and Evaluation China Pharmaceutical University Nanjing 210009 China Faculty of Health and Medical Science University of Copenhagen Copenhagen Denmark Key Laboratory of Drug Quality control and Pharmacovigilance China Pharmaceutical University Ministry of Education Nanjing 210009 China Jiangsu Key Laboratory of Traditional Chinese Medicine Evaluation and translational Research Nanjing 210009 China

Triptolide(TP) induces severe liver injury, but its hepatotoxicity mechanisms are still unclear. Inflammatory responses may be involved in the pathophysiology. Neutrophils are the first-line immune effectors for sterile and non-sterile inflammatory responses. Thus, the aim of the present study was to investigate the neutrophilic inflammatory response in TP-induced liver injury in C57 BL/6 mice. Our results showed that neutrophils were recruited and accumulated in the liver, which was parallel to or slightly after the development of liver injury. Neutrophils induced release of myeloperoxidase and up-regulation of CD11 b, which caused cytotoxicity and hepatocyte death. Hepatic expressions of CXL1, TNF-α, IL-6, and MCP1 were increased significantly to regulate neutrophils recruitment and activation. Up-regulation of toll like receptors 4 and 9 also facilitated neutrophils infiltration. Moreover, neutrophils depletion using an anti-Gr1 antibody showed mild protection against TP overdose. These results indicated that neutrophils accumulation might be the secondary response, not the cause of TP-induced liver injury. In conclusion, the inflammatory response including neutrophil infiltration may play a role in TP-induced hepatotoxicity, but may not be severe enough to cause additional liver injury.

关键词： Triptolide Liver injury Inflammatory response Neutrophil Depletion

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