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Clinical characteristics of critical patients with pandemic influenza A(H1.1. virus infection in Chengdu,China

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2012年第1期13卷 49-55页

作者： Li-hui DENG1.2,Yi-lan ZENG3,Ping FENG1.Ya-ling LIU3,Li-chun WANG1.2,Yun BAI3,Hong TANG1.2(1.enter of infectious {1.,West China hospital of Sichuan University,Chengdu 61.041.China)(2Division of infectious {1.,State Key Laboratory of Biotherapy,Sichuan University,Chengdu 61.041.China)(3Chengdu infectious Disease hospital,Chengdu 61.041.China) Center of infectious {1. West China Hospital of Sichuan University Chengdu 610041 China

Objective： The critical illness of pandemic influenza A （H1.1. virus infection may be associated with relatively poor outcomes. The objective of this study is to describe clinical features and factors associated with the deaths of critical patients. Methods： Medical records of 26 critical patients with H1.1.infection admitted from Sept. 1.to Dec. 31. 2009, were retrospectively reviewed. Diagnosis was established by real-time reverse transcdptase- polymerase chain reaction （RT-PCR） assay. Results： The mean age of the patients was （40.4＋1..4） years and 73.1. of them were male. Clinical manifestations included fever, cough, and sputum production. The laboratory findings included leukocytosis, lymphopenia, C-reaction protein, and lactic dehydrogenase elevation. In this series, 1. subjects survived and 9 died. The parameters between the deaths and survivors were compared, which included acute physiology and chronic health evaluation II （APACHE II） scores （23.8＋1..1.vs. 1..3_＋6.6, P〈0.05）, sequential organ failure assessment （SOFA） scores （1..3_＋3.0 vs. 6.6_＋3.3, P〈0.05）, and multiple organ dysfunction syndrome （MODS） scores （7.4＋2.5 vs. 3.3＋1.7, P〈0.05）. The cases of deaths had higher incidences of cardiovascular failure （1.0% vs. 41.2%, P〈0.05）, renal failure （55.6% vs. 1..7%, P〈0.05）, encephalopathy （44.4% vs. 5.9%, P〈0.05）, hepatic failure （33.3% vs. 5.9%, P〈0.05）, and septic shock （33.3% vs. 1..6%, P〈0.05）. Conclusions： The critical patients with H1.N1.infection have high APACHE II, SOFA, and MODS scores, which may be associated with an increased risk of death and complex clinical courses.

关键词： Critical illness H1.1 Infection Influenza A virus Mortality

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Real life efficacy and safety of direct-acting antiviral therapy for treatment of patients infected with hepatitis C virus genotypes 1. 2and 3 in northwest China

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World Journal of Gastroenterology 2019年第44期25卷 6551-6560页

作者： Ying Yang Feng-Ping Wu Wen-Jun Wang Juan-Juan Shi Ya-Ping Li Xin Zhang Shuang-Suo Dang Department of infectious {1. the Second Affiliated Hospital of Xi’an Jiaotong University

BACKGROUND Regimens involving direct-acting antiviral agents(DAAs)are recommended for the treatment of infection with hepatitis C virus(HCV)genotypes 1.2 and *** real-world data is still not enough,especially in *** To investigate the efficacy and safety of DAA-based regimens in a real-life setting in *** This study included 366 patients infected with HCV genotypes 1.2 and 3,with or without cirrhosis,who were observed between May 201. and December *** were treated with ledipasvir and sofosbuvir(SOF)(genotype 1.with or without ribavirin(RBV),SOF and RBV(genotype 2),or SOF and daclatasvir(genotype 3),with or without RBV,for 1. or more *** participants’sustained virological responses(SVR)at post-treatment week 1.(SVR1.)was the primary *** occurrence of adverse events and drug-drug interactions were *** In the 366 patients,genotype 1.59.0%)was the most common genotype,followed by genotypes 2(34.4%)and 3(6.6%).Liver cirrhosis was diagnosed in 1.4(42.1.)***(1..7%)patients were ***-to-treat analysis revealed that SVR1. was 86.3%(31./366).For modified intention-totreat analysis,SVR1. was achieved in 96.6%of overall patients(31./327),96.3%in patients with genotype 1.97.5%in those with genotype 2,and 95.0%in those with genotype *** of the treatment failures were due to lack of follow-up(3cases had non-responses,1.had virological breakthrough,1. relapsed and 36 did not participate in the follow-up).There was no significant difference in SVR between different genotypes and liver statuses(P1.(P0.05 for all).The cumulative hepatocellular carcinoma occurrence and recurrence rate after using the DAAs was 0.9%.Most of the

关键词： Hepatitis C virus Direct-acting antiviral agents Efficacy Safety Drug-drug interactions Real-life experience

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O-GlcNAcylation of YTHDF2 promotes HBV-related hepatocellular carcinoma progression in an N^(6)-methyladenosine-dependent manner

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1208-1223页

作者： Yang Yang Yu Yan Jiaxin Yin Ni Tang Kai Wang Luyi Huang Jie Hu Zhongqi Feng Qingzhu Gao Ailong Huang Institute for Viral Hepatitis Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education)Department of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqingChina

Hepatitis B virus(HBV)infection is a major risk factor for hepatocellular carcinoma(HCC),but its pathogenic mechanism remains to be *** RNA N^(6)-methyladenosine(m^(6)A)reader,YTH(YT521.B homology)domain 2(YTHDF2),plays a critical role in the HCC ***,the function and regulatory mechanisms of YTHDF2 in HBV-related HCC remain largely ***,we discovered that YTHDF2 O-GlcNAcylation was markedly increased upon HBV infection.O-GlcNAc transferase(OGT)-mediated O-GlcNAcylation of YTHDF2 on serine 263 enhanced its protein stability and oncogenic activity by inhibiting its ***,YTHDF2 stabilized minichromosome maintenance protein 2(MCM2)and MCM5 transcripts in an m^(6)A-dependent manner,thus promoting cell cycle progression and HBV-related HCC ***,targeting YTHDF2 O-GlcNAcylation by the OGT inhibitor OSMI-1.significantly suppressed HCC *** together,our findings reveal a new regulatory mechanism for YTHDF2 and highlight an essential role of YTHDF2 O-GlcNAcylation in RNA m^(6)A methylation and HCC *** description of the molecular pathway has the potential to yield therapeutic targets for suppression of HCC progression due to HBV infection.

关键词： hepatocellular markedly DF2

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Antiviral treatment of hepatitis C virus infection and factors affecting efficacy

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World Journal of Gastroenterology 2013年第47期19卷 8963-8973页

作者： Yan Zhu Song Chen Institute of infectious {1. Southwest Hospitalthe Third Military Medical University

Hepatitis C virus(HCV)infection is the leading cause of chronic liver-related diseases,including cirrhosis,liver failure,and hepatocellular ***,no effective vaccine is available for HCV *** glycol interferon-α(PegIFN-α)in combination with ribavirin(RBV)is the standard of care(SOC)for chronic hepatitis ***,the efficacy of PegIFN-αand RBV combination therapy is less than 50%for genotype 1.CV,which is the dominant virus in *** addition,IFN and RBV have several severe side ***,strategies to improve sustained virological response(SVR)rates have been an important focus for clinical *** serine protease inhibitors telaprevir and boceprevir were approved by the United States Food and Drug Administration in *** addition of HCV protease inhibitors to the SOC has significantly improved the efficacy of treatments for HCV *** direct-acting antiviral drugs currently in late-stage clinical trials,both with and without pegIFN and RBV,have several advantages over the previous SOC,including higher specificity and efficacy,fewer side effects,and the ability to be administered orally,and might be optimal regimens in the *** affecting the efficacy of anti-HCV treatments based on IFN-αinclude the HCV genotype,baseline viral load,virological response during treatment,host IL28B gene polymorphisms and hepatic ***,determining the effect of the above factors on DAA therapy is *** this review,we summarize the development of antiHCV agents and assess the main factors affecting the efficacy of antiviral treatments.

关键词： Hepatitis C virus Treatment Interferon Protease inhibitors IL28B protein Polymorphisms Viral load Genotype Hepatic steatosis

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Impact of cirrhosis-related complications on posttransplant survival in patients with acute-on-chronic liver failure

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Hepatobiliary & Pancreatic diseases International 2023年第1期22卷 64-71页

作者： Chun-Xia Zhu Lu Yang Hong Zhao Yan Zhang Sheng Tu Jing Guo Dong Yan Chen-Xia Hu Hai-Feng Lu Kai-Jin Xu Jian-Rong Huang Lan-Juan Li State Key Laboratory for Diagnosis and Treatment of infectious {1. National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of Medicine79 Qingchun RoadHangzhou 310003China

Background:Acute-on-chronic liver failure(ACLF)is a life-threatening syndrome defined as acute decompensation in patients with chronic liver *** transplantation(LT)is the most effective *** aimed to assess the impact of cirrhosis-related complications pre-LT on the posttransplant prognosis of patients with ***:This was an observational cohort study conducted between January 201. and December *** characteristics,cirrhosis-related complications at LT and patient survival post-LT were *** liver recipients with ACLF were followed for 1.year ***:A total of 21. LT recipients with ACLF were enrolled,including 75(35.4%)patients with ACLF-1.64(30.2%)with ACLF-2,and 73(34.4%)with *** median waiting time for LT was 1.(4-24)*** most prevalent cirrhosis-related complication was ascites(78.8%),followed by hepatic encephalopathy(57.1.),bacterial infections(48.1.),hepatorenal syndrome(22.2%)and gastrointestinal bleeding(1..3%).Survival analyses showed that patients with complications at LT had a significantly lower survival probability at both 3 months and 1.year after LT than those without complications(all P1..Moreover,the TACC model showed a comparable ability for predicting the outcome post-LT to the other four prognostic models(chronic liver failure-consortium ACLF score,Chinese Group on the Study of Severe Hepatitis B-ACLF score,model for end-stage liver disease score and Child-Turcotte-Pugh score).Conclusions:The presence of cirrhosis-related complications pre-LT increases the risk of death post-LT in patients with *** TACC model based on the number of cirrhosis-related complications pre-LT could stratify posttransplant survival

关键词： Acute-on-chronic liver failure Liver transplantation Cirrhosis-related complication Prognosis Transplant timing

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PCK1.dysregulation in cancer: Metabolic reprogramming, oncogenic activation, and therapeutic opportunities

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Genes & diseases 2023年第1期10卷 101-112页

作者： Jin Xiang Kai Wang Ni Tang Key Laboratory of Molecular Biology for infectious {1.(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

The last few decades have witnessed an advancement in our understanding of multiple cancer cell pathways related to metabolic *** of the most important cancer hallmarks,including aerobic glycolysis(the Warburg effect),the central carbon pathway,and multiple-branch metabolic pathway remodeling,enables tumor growth,progression,and *** carboxykinase1.PCK1.,a key rate-limiting enzyme in gluconeogenesis,catalyzes the conversion of oxaloacetate to ***1.expression in gluconeogenic tissues is tightly regulated during *** tumor cells,PCK1.is regulated in a cell-autonomous manner rather than by hormones or nutrients in the extracellular ***,PCK1.as ananti-oncogenic role in gluconeogenic organs(the liver and kidneys),but a tumor-promoting role in cancers arising from non-gluconeogenic *** studies have revealed that PCK1.has metabolic and non-metabolic roles in multiple signaling networks linking metabolic and oncogenic *** PCK1.expression results in the activation of oncogenic pathways,accompanied by metabolic reprogramming,to maintain *** this review,we summarize the mechanisms underlying PCK1.expression and regulation,and clarify the crosstalk between aberrant PCK1.expression,metabolic rewiring,and signaling pathway *** addition,we highlight the clinical relevance of PCK1.and its value as a putative cancer therapeutic target.

关键词： Gluconeogenesis Metabolism Oncogenesis PCK1 Tumor

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Longitudinal gut fungal alterations and potential fungal biomarkers for the progression of primary liver disease

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Science China(Life Sciences) 2024年第6期67卷 1183-1198页

作者： Shiman Jiang Lvwan Xu Yanfei Chen Zheyue Shu Longxian Lv Yuxi Zhao Kefan Bi Sisi Yang Qiangqiang Wang Lanjuan Li State Key Laboratory for Diagnosis and Treatment of infectious {1. National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Liver disease,a major health concern worldwide,is a serious and progressive ***,we not only established a mouse model of DEN+CCl4-induced primary liver disease but also collected clinical human samples to investigate longitudinal alterations in the gut *** liver disease advanced,gut integrity was disrupted,and the mycobiota was disturbed in the mouse *** metabolites associated with hepatocellular carcinoma(HCC)differed from those associated with the cirrhotic phase as follows:levels of stercobilin and aflatoxin B1.dialcohol were reduced,while levels of triterpenoids,bafilomycin A1.and DHEA were increased in the HCC *** abundance of the phylum Chytridiomycota increased as the chronic liver disease progressed and was then replaced by the phylum Ascomycota in *** on the results from clinical human samples,the genus Candida(Ascomycota)(in humans)and the genus Kazachstania(Ascomycota)(in mice)occupied a dominant position in the HCC group,while other fungi were *** increased abundance of *** and depletion of *** may be hallmarks of the progression of liver cirrhosis to early ***,the administration of *** and *** in the LC-HCC progression could accelerate or retard the progression of ***,gut fungi have the potential to serve as a noninvasive clinical biomarker and even a treatment method.

关键词： gut mycobiome liver disease longitudinal studies hepatocarcinogenesis fungal biomarker

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Review of the pharmacological effects of astragalosideⅣand its autophagic mechanism in association with inflammation

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World Journal of Clinical Cases 2022年第28期10卷 10004-10016页

作者： Ying Yang Meng Hong Wen-Wen Lian Zhi Chen State Key Laboratory for Diagnosis and Treatment of infectious {1. National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

Astragalus membranaceus Bunge,known as Huangqi,has been used to treat various diseases for a long ***Ⅳ(AS-Ⅳ)is one of the primary active ingredients of the aqueous Huangqi *** experimental models have shown that AS-Ⅳexerts broad beneficial effects on cardiovascular disease,nervous system diseases,lung disease,diabetes,organ injury,kidney disease,and gynaecological *** review demonstrates and summarizes the structure,solubility,pharmacokinetics,toxicity,pharmacological effects,and autophagic mechanism of AS-Ⅳ.The autophagic effects are associated with multiple signalling pathways in experimental models,including the PI3KI/Akt/m TOR,PI3KⅢ/Beclin-1.Bcl-2,PI3K/Akt,AMPK/m TOR,PI3K/Akt/m TOR,SIRT1.NF-κB,PI3K/AKT/AS1.0,and TGF-β/Smad signalling *** on this evidence,AS-Ⅳcould be used as a replacement therapy for treating the multiple diseases referenced above.

关键词： AstragalosideⅣ Pharmacological effect Autophagy Inflammation

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Mitochondrial Damage and Drp1.Overexpression in Rifampicin-and Isoniazid-induced Liver Injury Cell Model

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Journal of Clinical and Translational Hepatology 2019年第1期7卷 40-45页

作者： Fangfang Li Juan Zhou Yi Li Kewei Sun Jun Chen Department of Liver diseases Third Hospital of ShenzhenShenzhenGuangdongChina Department of Digestive diseases First Hospital of ChenzhouChenzhouHunanChina Department of infectious {1. The Affiliated Zhuzhou Hospital Xiangya Medical College CSUZhuzhouHunanChina Liver diseases Center Department of Infectious DiseasesThe Second Xiangya HospitalCentral South UniversityChangshaHunanChina Department of infectious {1. First Hospital of Hunan University of Chinese MedicineChangshaHunanChina

Background and Aims:Rifampicin(RFP)and isoniazid(INH)are widely used as anti-tuberculosis ***,the mechanisms underlying the involvement of reactive oxygen species and mitochondria in RFP-and INH-related hepatotoxicity have not been established *** study aimed to observe the intracellular mechanisms leading to mitochondrial dysfunction and morphological changes in RFP-and INH-induced hepatocyte ***:Cell injury,changes in mitochondrial function,and expression and activation of dynamin related protein 1.Drp1.,known as the main protein for mitochondrial fission,were analyzed in cultured QSG7701.cells exposed to RFP and ***:INH and RFP treatment induced pronounced hepatocyte injury and increased cell *** the similar context of aspartate aminotransferase elevation and adenosine triphosphate synthesis decrease,changes in mitochondrial membrane permeability and reactive oxygen species in hepatocytes induced by RFP were significantly different from those induced by INH(p1.in RFP-induced cell injury,which was not occurred with exposure to ***:RFP-induced hepatotoxicity may be closely related to mitochondrial dysfunction and Drp1.mediated mitochondrial fission.

关键词： Anti-tuberculosis drug-induced liver injury Drp1 Mitochondrial dysfunction Mitochondrial fission

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Go-Ichi-Ni-San 2:A potential biomarker and therapeutic target in human cancers

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World Journal of Gastrointestinal Oncology 2022年第10期14卷 1892-1902页

作者： Dan-Dan Shan Qiu-Xian Zheng Zhi Chen State Key Laboratory for Diagnosis and Treatment of infectious {1. National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

Cancer incidence and mortality are increasing globally,leading to its rising status as a leading cause of *** Go-Ichi-Ni-San(GINS)complex plays a crucial role in DNA replication and the cell *** GINS complex consists of four subunits encoded by the GINS1.GINS2,GINS3,and GINS4 *** findings have shown that GINS2 expression is upregulated in many diseases,particularly *** example,increased GINS2 expression has been found in cervical cancer,gastric adenocarcinoma,glioma,non-small cell lung cancer,and pancreatic *** correlates with the clinicopathological characteristics of the *** addition,high GINS2 expression plays a pro-carcinogenic role in tumor development by promoting tumor cell proliferation and migration,inhibiting tumor cell apoptosis,and blocking the cell *** review describes the upregulation of GINS2 expression in most human tumors and the pathway of GINS2 in tumor ***2 may serve as a new marker for tumor diagnosis and a new biological target for therapy.

关键词： Go-Ichi-Ni-San Go-Ichi-Ni-San 2 Cancer Biomarker Clinicopathological characteristics Molecular mechanism

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