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Impact of SNP-SNP interactions of DNA repair gene ERCC5 and metabolic gene GSTP1 on gastric cancer/atrophic gastritis risk in a Chinese population

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World Journal of Gastroenterology 2018年第5期24卷 602-612页

作者： Liang Sang Zhi Lv Li-Ping Sun Qian Xu Yuan Yuan Department of Ultrasound the First Hospital of China Medical UniversityShenyang 110001Liaoning ProvinceChina Tumor Etiology and Screening Department of Cancer institute and General Surgery the First Affiliated Hospital of China Medical UniversityShenyang 110001Liaoning ProvinceChina Key Laboratory of Cancer Etiology and Prevention Liaoning Provincial Education DepartmentChina Medical UniversityShenyang 110001Liaoning ProvinceChina National clinical Research center for digestive diseases Xi’an 710032Shaanxi ProvinceChina

AIM To investigate the interactions of the DNA repair gene excision repair cross complementing group 5(ERCC5) and the metabolic gene glutathione S-transferase pi 1(GSTP1) and their effects on atrophic gastritis(AG) and gastric cancer(GC) *** Seven ERCC5 single nucleotide polymorphisms(SNPs)(rs1047768, rs2094258, rs2228959, rs4150291, rs4150383, rs751402, and rs873601) and GSTP1 SNP rs1695 were detected using the Sequenom MassA RRAY platform in 450 GC patients, 634 AG cases, and 621 healthy control subjects in a Chinese *** Two pairwise combinations(ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) influenced AG risk(P_(interaction) = 0.008 and 0.043, respectively), and the ERCC5 rs2094258-GSTP1 rs1695 SNP pair demonstrated an antagonistic effect, while ERCC5 rs873601-GSTP1 rs1695 showed a synergistic effect on AG risk OR = 0.51 and 1.79, respectively). No pairwise combinations were observed in relation to GC risk. There were no cumulative effects among the pairwise interactions(ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) on AG susceptibility(P_(trend) > 0.05). When the modification effect of Helicobacter pylori(H. pylori) infection was evaluated, the cumulative effect of one of the aforementioned pairwise interactions(ERCC5 rs873601-GSTP1 rs1695) was associated with an increased AG risk in the case of negative H. pylori status(P_(trend)= 0.043).CONCLUSION There is a multifarious interaction between the DNA repair gene ERCC5 SNPs(rs2094258 and rs873601) and the metabolic gene GSTP1 rs1695, which may form the basis for various inter-individual susceptibilities to AG.

关键词： Excision repair cross complementing group 5 Glutathione S-transferase pi 1 Atrophic gastritis Gastric cancer Single nucleotide polymorphisms

Mechanisms of Steatosis-Derived Hepatocarcinogenesis:Lessons from HCV Core Gene Transgenic Mice

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Engineering 2021年第12期7卷 1797-1805页

作者： Pan Diao Fangping Jia Xiaojing Wang Xiao Hu Takefumi Kimura Takero Nakajima Toshifumi Aoyama Kyoji Moriya Kazuhiko Koike Naoki Tanaka Department of Metabolic Regulation Shinshu University School of MedicineMatsumoto 390-8621Japan State Key Laboratory for Diagnosis and Treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesDepartment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003China Department of Gastroenterology Lishui HospitalZhejiang University School of MedicineLishui 323000China Department of Pathophysiology Hebei Medical UniversityShijiazhuang 050017China Department of Gastroenterology Shinshu University School of MedicineMatsumoto 390-8621Japan Molecular Signaling Section Laboratory of Bioorganic ChemistryNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaMD 20892USA Department of Infection Control and Prevention The University of TokyoTokyo 113-0033Japan Department of Gastroenterology The University of TokyoTokyo 113-0033Japan International Relations Office Shinshu University School of MedicineMatsumoto 390-8621Japan Research center for Social Systems Shinshu UniversityMatsumoto 390-8621Japan

Hepatitis C virus(HCV)is a major cause of chronic hepatitis,liver cirrhosis,and hepatocellular carcinoma(HCC)*** the structural proteins of HCV,the HCV core protein has the ability to regulate gene transcription,lipid metabolism,cell proliferation,apoptosis,and autophagy,all of which are closely related to the development of *** mice carrying the HCV core gene exhibited age-dependent insulin resistance,hepatic steatosis,and HCC that resembled the clinical characteristics of chronic hepatitis C *** dietary modifications,including calorie restriction and diets rich in saturated fatty acids,trans fatty acids,or cholesterol,were found to influence hepatic steatogenesis and tumorigenesis in HCV core gene transgenic *** strategies modulated hepatocellular stress and proliferation,in addition to hepatic fibrotic processes and the microenvironment,thereby corroborating a close interconnection between dietary habits and steatosis-related *** this review,we summarize the findings obtained from mouse models transgenic for the HCV genome,with a special focus on HCV core gene transgenic mice,and discuss the mechanisms of steatogenesis and hepatocarcinogenesis induced by the HCV core protein and the impact of dietary habits on steatosis-derived HCC development.

关键词： Steatosis Hepatocellular carcinoma Trans fatty acid Saturated fatty acid Dietary restriction HCV core protein

T cell-depleting nanoparticles ameliorate bone loss by reducing activated T cells and regulating the Treg/Th17 balance

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Bioactive Materials 2021年第10期6卷 3150-3163页

作者： Xiaoshan Yang Fuxing Zhou Pingyun Yuan Geng Dou Xuemei Liu Siying Liu Xiangdong Wang Ronghua Jin Yan Dong Jun Zhou Yajie Lv Zhihong Deng Shiyu Liu Xin Chen Ying Han Yan Jin State Key Laboratory of Military Stomatology&National clinical Research center for Oral diseases&Shaanxi International Joint Research center for Oral diseases Center for Tissue EngineeringSchool of StomatologyFourth Military Medical UniversityXi’anShaanxi710032China Xijing Hospital of digestive diseases&State Key Laboratory of Cancer Biology Fourth Military Medical UniversityXi’anShaanxi710032China Department of Gynecology and Obstetrics Xijing HospitalFourth Military Medical UniversityXi’anShaanxi710032China School of Chemical Engineering and Technology Shaanxi Key Laboratory of Energy Chemical Process IntensificationInstitute of Polymer Science in Chemical EngineeringXi’an Jiao Tong UniversityXi’anShaanxi710049China Department of Dermatology Tangdu HospitalFourth Military Medical UniversityXi’anShaanxi710038China

Estrogen deficiency is one of the most frequent causes of osteoporosis in postmenopausal *** chronic inflammatory conditions caused by estrogen deficiency,activated T cells contribute to elevated levels of proinflammatory cytokines,impaired osteogenic differentiation capabilities of bone marrow mesenchymal stem cells(BMMSCs),and disturbed regulatory T cell(Treg)/Th17 cell ***,therapeutic strategies that re-establish immune homeostasis in this disorder have not been well ***,we produced T cell-depleting nanoparticles(TDNs)that ameliorated the osteopenia phenotype and rescued the osteogenic deficiency of BMMSCs in ovariectomized(OVX)*** consist of monocyte chemotactic protein-1(MCP-1)-encapsulated mesoporous silica nanoparticles as the core and Fas-ligand(FasL)as the *** showed that the delicate design of the TDNs enables rapid release of MCP-1 to recruit activated T cells and then induces their apoptosis through the conjugated FasL both in vitro and in *** signals recognized by macrophages help skew the Treg/Th17 cell balance and create an immune tolerant state,further attenuating the osteogenic deficiency of BMMSCs and the osteopenia ***,we found that the therapeutic effects of TDNs were partially mediated by apoptotic T cell-derived extracellular vesicles(ApoEVs),which promoted macrophage transformation towards the M2 *** findings demonstrate that TDNs may represent a promising strategy for treating osteoporosis and other immune disorders.

关键词： Nanoparticles Activated T cell Immune tolerance Apoptotic extracellular vesicles Osteoporosis

A toolbox for genetic manipulation in intestinal Clostridium symbiosum

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Synthetic and Systems Biotechnology 2024年第1期9卷 43-54页

作者： Pengjie Yang Jinzhong Tian Lu Zhang Hui Zhang Gaohua Yang Yimeng Ren Jingyuan Fang Yang Gu Weihong Jiang CAS-Key Laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant SciencesShanghai Institute of Plant Physiology and EcologyChinese Academy of SciencesShanghai200032China University of Chinese Academy of Sciences Beijing100049China Xianghu Laboratory Hangzhou311231China NHC Key Laboratory of digestive diseases Division of Gastroenterology and HepatologyShanghai Institute of Digestive DiseaseRenji HospitalSchool of MedicineShanghai Jiao Tong University145 Middle Shandong RoadShanghai200001China Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen518120China The Wallenberg Laboratory Department of Molecular and Clinical MedicineSahlgrenska AcademyUniversity of GothenburgBruna Straket 16Gothenburg41345Sweden

Gut microbes are closely related with human health,but remain much to *** symbiosum is a conditionally pathogenic human gut bacterium and regarded as a potential biomarker for early diagnosis of intestinal ***,the absence of an efficient toolbox that allows diverse genetic manipulations of this bacterium limits its in-depth ***,we obtained the complete genome sequence of *** ATCC 14940,a representative strain of *** this basis,we further developed a series of genetic manipulation methods for this ***,following the identification of a functional replicon pBP1 in *** ATCC 14940,a highly efficient conjugative DNA transfer method was established,enabling the rapid introduction of exogenous plasmids into ***,we constructed a dual-plasmid CRISPR/Cas12a system for genome editing in this bacterium,reaching over 60% repression for most of the chosen genes as well as efficient deletion(>90%)of three target ***,this toolbox was used for the identification of crucial functional genes,involving growth,synthesis of important metabolites,and virulence of *** ATCC *** work has effectively established and optimized genome editing methods in intestinal ***,thereby providing strong support for further basic and application research in this bacterium.

关键词： Gut Clostridium symbiosum Toolbox Gene overexpression Gene deletion Gene regulation

Fecal microbiota transplantation in clinical practice:Present controversies and future prospects

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hLife 2024年第6期2卷 269-283页

作者： Hongliang Tian Xinjun Wang Zhixun Fang Long Li Chunyan Wu Dexi Bi Ning Li Qiyi Chen Huanlong Qin Department of Colorectal Disease Tenth People’s Hospital of Tongji UniversityShanghaiChina Shanghai Institution of Gut Microbiota Research and Engineering Development Tenth People’s Hospital of Tongji UniversityShanghaiChina clinical Research center for digestive diseases Tongji UniversityShanghaiChina Bengbu First People’s Hospital AnhuiChina Research institute of Intestinal diseases Tongji University School of MedicineShanghaiChina Department of Pathology Tenth People’s Hospital of Tongji UniversityShanghaiChina Realbio Genomics institute ShanghaiChina

The gut microbiota,serving as the only“organ”that humans can share,has been extensively applied in the treatment of various intestinal and extraintestinal diseases through fecal microbiota transplantation(FMT)*** optimizing the donor selection strategy,FMT exhibited the highest effectiveness(more than 90%)in treating acute intestinal inflammations,such as recurrent Clostridium difficile ***,the efficacy diminishes when addressing intestinal functional diseases(more than 60%),chronic intestinal inflammations or organic diseases(less than 60%),and extraintestinal diseases,particularly those lacking any gastrointestinal symptoms(less than 50%).Ongoing efforts to enhance the therapeutic response of FMT across diverse diseases represent a central focus of current clinical *** review concentrates on donor selection,recipient management,precise donor-recipient matching,antagonistic mechanism of native bacteria to transplanted bacteria,and targeted treatment strategies for different diseases,with the aim of providing practical strategies to improve the clinical efficacy of FMT.

关键词： fecal microbiota transplantation clinical research colonization antagonism

Role of gut microbiota in functional constipation

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Gastroenterology Report 2021年第5期9卷 392-401,I0001页

作者： Shengsheng Zhang Ruixin Wang Danyan Li Luqing Zhao Lixin Zhu digestive Disease center Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijingP.R.China Department of Colorectal Surgery Guangdong Institute of GastroenterologyGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesThe Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China

Functional constipation(FC)is common,yet the etiology is not *** evidence suggests an association between FC and abnormal gut *** relationship between the gut microbiota and the gut transit is likely *** review summarizes the current evidence regarding the impact of gut microbiota on the pathogenesis of *** modulating the colonic motility,secretion,and absorption,gut microbiota may contribute to the development of FC through microbial metabolic activities involving bile acids,short-chain fatty acids,5-hydroxytryptamine,and *** support of the key roles of the gut microbiota in FC,treatment with probiotics,prebiotics,synbiotics,and traditional Chinese medicine often result in compositional and functional changes in the gut *** studies on the pathogenesis of FC and the therapeutic mechanism of microecological agents will provide a knowledge base for better management of FC.

关键词： gut microbiota functional constipation bile acids SCFA serotonin traditional Chinese medicine

Prospective single-blinded single-center randomized controlled trial of Prep Kit-C and Moviprep:Does underlying inflammatory bowel disease impact tolerability and efficacy?

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World Journal of Gastroenterology 2021年第11期27卷 1090-1100页

作者： Waled Mohsen Astrid-Jane Williams Gabrielle Wark Alexandra Sechi Jenn-Hian Koo Wei Xuan Milan Bassan Watson Ng Susan Connor Department of digestive diseases Gold Coast University HospitalGold Coast4215QueenslandAustralia Department of Gastroenterology and Hepatology Liverpool HospitalSydney 2170New South WalesAustralia South West Sydney clinical School University of New South WalesSydney 2170New South WalesAustralia Ingham institute Applied Medical Research Sydney 2170New South WalesAustralia

BACKGROUND Colonoscopy remains the gold standard for detection of colonic *** optimal evaluation depends on adequate bowel *** with inflammatory bowel disease(IBD),require frequent endoscopic assessment for both activity and dysplasia *** commonly used bowel preparations in Australia are Prep Kit-C(Pc)and Moviprep(Mp).Little is known about tolerability,efficacy and safety of split protocols of Mp and Pc in both IBD and non-IBD *** To primary aim was to compare the tolerability,efficacy and safety of split protocols of Mp and Pc in patients having a *** secondary aim was to compare the efficacy,tolerability and safety of either preparation in patients with or without *** Patients were randomized to Pc or Mp bowel *** completed a questionnaire to assess *** was assessed using the Ottawa Bowel Preparation *** electrolytes and renal function were collected one week prior to colonoscopy and on the day of *** Of 338 patients met the inclusion *** 168 patients randomized to Mp and 170 to *** efficacy of bowel preparation(mean Ottawa Bowel Preparation Score)was similar between Mp(5.4±2.4)and Pc(5.1±2.1)(P=0.3).Mean tolerability scores were similar in Mp(11.84±5.4)and Pc(10.99±5.2;P=0.17).125 patients had IBD(73 had Crohn’s Disease and 52 had Ulcerative colitis).Sixtyfour IBD patients were allocated to Mp and 61 to *** non-IBD patients,104 were allocated to Mp and 109 to *** mean tolerability score in the IBD group was lower than the non-IBD group(mean tolerability scores:IBD:10.3±5.1 and non-IBD:12.0±5.3;P=0.01).IBD patients described more abdominal pain with Mp when compared with Pc;(Mp:5.7±4.4 vs Pc:3.6±2.6,P=0.046).Serum magnesium level increased with Pc compared with Mp in all patients(mean increase in mmol/L:Mp:0.03±0.117 and Pc:0.11±0.106;P<0.0001).CONCLUSION In this study,the efficacy,tolerability and safety of Mp and Pc were simila

关键词： Bowel preparation Inflammatory bowel disease Tolerability Efficacy Moviprep Prep Kit-C

Carboxyl Ester Lipase Protects Against Metabolic Dysfunction-Associated Steatohepatitis by Binding to Fatty Acid Synthase

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Engineering 2024年第10期41卷 204-215页

作者： Yang Song Wei Zhong Harry Cheuk-Hay Lau Yating Zhang Huayu Guan Mingxu Xie Suki Ha Diwen Shou Yongjian Zhou Hongzhi Xu Jun Yu Xiang Zhang Department of Medicine and Therapeutics Institute of Digestive DiseaseState Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong 999077China Shenzhen Research institute The Chinese Unviersity of Hong KongShenzhen 518057China Department of Gastroenterology&institute for Microbial Ecology&Xiamen Key Laboratory of Intestinal Microbiome and Human Health&clinical Research center for Gut Microbiota and digestive diseases of Fujian Province Zhongshan Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361004China Division of Gastroenterology and Hepatology Renji HospitalSchool of MedicineShanghai Jiaotong UniversityShanghai 200025China Department of Gastroenterology and Hepatology Guangzhou Digestive Disease CenterGuangzhou First People’s HospitalGuangzhou 510180China

Carboxyl ester lipase(CEL),a pivotal enzyme involved in lipid metabolism,is recurrently mutated in obese ***,we aimed to elucidate the functional significance,molecular mechanism,and therapeutic potential of CEL in metabolic dysfunction-associated steatohepatitis(MASH).Hepatocyte-specific carboxyl ester lipase gene(Cel)knockout(Cel^(DHEP))and wildtype(WT)littermates were fed with cholinedeficient high-fat diet(CD-HFD)for 16 weeks,or methionine-and choline-deficient diet(MCD)for three weeks to induce *** chromatography–mass spectrometry and co-immunoprecipitation were employed to identify the downstream targets of ***-HFD/MCD-fed WT mice received intravenous injections of CEL-adeno-associated viral,serotype 8(AAV8)to induce specific overexpression of CEL in the *** observed a decrease in CEL protein levels in MASH induced by CD-HFD or MCD in ***^(DHEP) mice fed with CD-HFD or MCD exhibited pronounced hepatic steatosis,inflammation,lipid peroxidation,and liver injury compared to WT littermates,accompanied by increased hepatic nuclear factor kappa-light-chain-enhancer of activated B cell(NF-jB)***,Cel knockdown in mouse primary hepatocytes and AML12 cells aggravated lipid accumulation and inflammation,whereas CEL overexpression exerted the opposite ***,CEL directly bound to fatty acid synthase(FASN),resulting in reduced FASN SUMOylation,which in turn promoted FASN degradation through the proteasome ***,inhibition of FASN ameliorated hepatocyte lipid accumulation and inflammation induced by Cel knockdown in vivo and in ***-specific CEL overexpression using AAV8-Cel significantly mitigated steatohepatitis in mice fed with CD-HFD or *** protects against steatohepatitis development by directly interacting with FASN and suppressing its expression for de novo *** overexpression confers a therapeutic benefit in steatohepatitis.

关键词： Metabolic dysfunction-associated steatohepatitis Carboxyl ester lipase Fatty acid synthase De novo lipogenesis Treatment

Baseline Characteristics and Treatment Patterns of the Patients Recruited to the China Registry of Hepatitis B

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Journal of clinical and Translational Hepatology 2019年第4期7卷 322-328页

作者： Shan Shan Hong You Junqi Niu Jia Shang Wen Xie Yuexin Zhang Xun Li Hong Ren Hong Tang Huiguo Ding Xihong Wang Yuemin Nan Xiaoguang Dou Tao Han Lingyi Zhang Xiaoqing Liu Cunliang Deng Jilin Cheng Xiaozhong Wang Qing Xie Shumei Lin Yan Huang Youqing Xu Yong Xiong Wu Li Xuebing Yan Hongxin Piao Wenxiang Huang Qinghua Lu Weijin Gong Shiping Li Xiaoxuan Hu Xiaolan Zhang Shourong Liu Yufang Li Dongliang Yang Hai Li Caixia Yang Mingliang Cheng Liaoyun Zhang Huanwei Zheng Xinhua Luo Feng Lin Lei Wang Guanghua Xu Xiaoyuan Xu Lai Wei Jinlin Hou Zhongping Duan Hui Zhuang Xizhong Yang Yuanyuan Kong Jidong Jia the CR-HepB study group,Beijing,China Liver Research center Beijing Friendship HospitalCapital Medical UniversityBeijing Key Laboratory of Translational Medicine on Liver CirrhosisNational Clinical Research Center for Digestive DiseasesBeijingChina Department of Hepatology First Hospital of Jilin UniversityChangchunJilinChina Department of Infectious diseases Henan Provincial People's HospitalZhengzhouHenanChina center of Liver diseases Beijing Ditan HospitalCapital Medical UniversityBeijingChina Department of Infectious diseases First Affiliated Hospital of Xinjiang Medical UniversityUrumqiXinjiangChina Department of General Surgery The First Hospital of Lanzhou UniversityLanzhouGansuChina Department of Infectious diseases The Second Affiliated Hospital of Chongqing Medical UniversityChongqingChina center of Infectious diseases West China Hospital of Sichuan UniversityChengduSichuanChina Department of Gastroenterology and Hepatology Beijing Youan HospitalCapital Medical UniversityBeijingChina center of Infectious diseases The Third People's Hospital of TaiyuanTaiyuanShanxiChina Department of Traditional and Western Medical Hepatology The Third Hospital of Hebei Medical UniversityShijiazhuangHebeiChina Department of Infectious diseases Shengjing Hospital of China Medical UniversityShenyangLiaoningChina Department of Hepatology Tianjin Third Central HospitalTianjin Medical UniversityTianjinChina Department of Hepatology Lanzhou University Second HospitalLanzhouGansuChina Department of Infectious diseases Peking Union Medical College HospitalBeijingChina Department of Infectious diseases The Affiliated Hospital of Southwest Medical UniversityLuzhouGansuChina Department of Gastroenterology Shanghai Public Health Clinical CenterShanghaiChina Department of Hepatology Xinjiang Uygur Autonomous Region Traditional Chinese Medicine HospitalUrumqiXinjiangChina Department of Infectious diseases Shanghai Ruijin HospitalJiao Tong University School of MedicineShanghaiChina Department of Infectious diseases Th

Background and Aims: Chronic hepatitis B virus(HBV)in-fection remains a major public health problem ***,we describe the baseline characteristics and treatment pro-files of HBV-infected patients recruited to the China Registry of Hepatitis ***: Inclusion criteria were patients with different stages of chronic HBV infection and complete key *** criteria were patients with hepatocellular *** baseline clinical,laboratory and treatment pro-files were ***: Finally,40,431 patients were *** median age was 43 years,with 65.2%being men and 51.3%being positive for hepatitis B e antigen(HBeAg).The most common initial diagnosis was chronic hep-atitis B(81.0%),followed by cirrhosis(9.3%),inactive carrier of hepatitis B surface antigen(HBsAg)(6.7%),and immune tolerant phase of hepatitis B infection(3.0%).Among the 21,228 patients who were on treatment,88.0%,10.0%and 2.0%received nucleos(t)ide analogues(NAs),interferon or combination of NAs and interferon,*** propor-tion of patients who received preferred NAs(entecavir or te-nofovir disoproxil fumarate)had increased from 13.5%in 2003 to 79.7%in ***: We concluded that middle-aged men accounted for most of the patients with chronic hepatitis B in this cross-sectional *** half of the patients were *** were the most com-monly used therapy,and use of the preferred NAs had steadily increased in the past decade.

关键词： Hepatitis B Treatment Registry