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17-Dehydroxyholothurin A, a New Sulfated Triterpene Glycoside from Sea Cucumber Holothuna impatiens

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Chinese Chemical Letters 2006年第11期17卷 1454-1456页

作者： Peng SUN Yang Hua YI Ling LI Min GUI Hai Feng TANG da zhi zhang Shi Long zhang Research Center for Marine Drugs Pharmacy School Second Military Medical University Shanghai 200433 Division of Antitumor Pharmacology State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 201203 Department of Pharmacy Xijing Hospital 4th Military Medical University Xi＇an 710032 Departrnent of Organic Chemistry Pharmacy School Second Military Medical University Shanghai 200433

Abstract： A new sulfated triterpene glycoside named as 17-dehydroxyholothurin A 1 was isolated from the sea cucumber Holothuria impatiens. Its structure was elucidated on the basis of spectroscopic data （2D NMR and MS） and chemical evidence. Compound 1 showed cytotoxic activity against cancer cell lines MKN-28, MFC-7, KB, HL-60 and Hep G2 with IC50 values of 1.98, 4.53, 2.01, 4.69 and 2.80 ×10^-6 tool/L, respectively.

关键词： Sea cucumber Holothuria impatiens 17-dehydroxyholothurin A triterpene glycoside.

Liver-infiltrating CD11b−CD27− NK subsets account for NK-cell dysfunction in patients with hepatocellular carcinoma and are associated with tumor progression

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Cellular & Molecular Immunology 2017年第10期14卷 819-829页

作者： Qiong-Fang zhang Wen-Wei Yin Yang Xia Ya-Yang Yi Qiu-Feng He Xing Wang Hong Ren da-zhi zhang Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016PR China Department of Urinary Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016PR China Department of Hepatobiliary Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016PR China Department of Orthopaedics Surgery The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010PR China

Natural killer(NK)cells have a vital role in killing hepatocellular carcinoma(HCC)cells;however,the mechanism underlying tumor-infiltrating NK(TINK)-cell dysfunction remains poorly *** flow cytometry staining,we precisely characterized the frequency,phenotype and function of NK subsets distinguished by CD27 and CD11b in 30 patients with HCC in comparison to 30 healthy ***,we found a substantial proportion of liver-infiltrating CD11b−CD27−(DN)NK subsets in tumor tissue from HCC ***,these relatively expanded DN NK subsets exhibited an inactive and immature *** detecting the expression of CD107a and interferon-gamma(IFN-γ)on NK subsets and NK cells,we demonstrated that DN NK subsets exhibited a poor cytotoxic capacity and deficient potential to produce IFN-γin comparison to the other three subsets,which contributed to the dysfunction of TINK cells in HCC *** addition,we found that the presence of DN NK cells was closely associated with the clinical outcomes of HCC patients,as the frequency of DN NK cells among TINK cells was positively correlated with tumor stage and size.A large percentage of DN NK cells among TINK cells was an independent prognostic factor for lower survival in the 60-month follow-up *** conclusion,a substantial proportion of CD11b−CD27−NK subsets among TINK cells accounts for NK-cell dysfunction in patients with HCC and is associated with tumor *** study may provide a novel therapeutic target for the treatment of patients with HCC.

关键词： CD11b CD27 dysfunction NK subsets

Clinical characteristics and current management of hepatitis B and C in China

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World Journal of Gastroenterology 2014年第37期20卷 13582-13590页

作者： Yong-Tao Sun Yue-Xin zhang Hong Tang Qing Mao Xiao-Zhong Wang Ling-Yi zhang Hong Chen Ying-Na Zhong Shu-Mei Lin da-zhi zhang Department of Infectious Diseases Tangdu HospitalAffiliated to the Fourth Military Medical University the First Affiliated Hospital of Xinjiang Medical University West China Hospital Sichuan University the First Affiliated Hospital of the Third Military Medical University Traditional Chinese Medicine Hospital of Xinjiang Uygur Administrative Region the Second Affiliated Hospital of Lanzhou University the First Affiliated Hospital of Lanzhou University People’s Hospital of Xinjiang Uygur Administrative Region the First Affiliated Hospital of Xi'an Jiaotong University the Second Affiliated Hospital of Chongqing Medica University

AIM: To describe a population of outpatients in China infected by hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and assess their current management status. METHODS: A multicenter, cross-sectional study of HBV- and/or HCV-infected patients was conducted from August to November, 2011 in western China. Patients >= 18 years of age with HBV and/or HCV infections who visited outpatient departments at 10 hospitals were evaluated, whether treated or not. data were collected on the day of visit from medical records and patient interviews. RESULTS: A total 4010 outpatients were analyzed, including 2562 HBV- infected and 1406 HCV-infected and 42 HBV/HCV co-infected patients. The median duration of documented infection was 7.5 years in HBV- infected and 1.8 years in HCV-infected patients. Cirrhosis was the most frequent hepatic complication (12.2%), appearing in one-third of patients within 3 years prior to or at diagnosis. The HCV genotype was determined in only 10% of HCV-infected patients. Biopsy data were only available for 54 patients (1.3%). Antiviral medications had been received by 58.2% of patients with HBV infection and 66.6% with HCV infection. Nucleos(t) ide analogs were the major antiviral medications prescribed for HBV- infected patients (most commonly adefovir dipivoxil and lamivudine). Ribavirin + pegylated interferon was prescribed for two-thirds of HCV-infected patients. In the previous 12 mo, around one-fifth patients had been hospitalized due to HBV or HCV infection. CONCLUSION: This observational, real-life study has identified some gaps between clinical practice and guideline recommendations in China. To achieve better health outcomes, several improvements, such as disease monitoring and optimizing antiviral regimens, should be made to improve disease management. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

关键词： Hepatitis B Hepatitis C Clinical characteristics Treatment

Predictive factors for sustained response to interferon treatment in patients with chronic hepatitis C: a randomized, open, and multi-center controlled trial

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Hepatobiliary & Pancreatic Diseases International 2005年第2期4卷 213-219页

作者： Yao Xie dao-Zhen Xu zhi-Meng Lu Kang-Xian Luo Ji-Dong Jia Yu-Ming Wang Gui-Zhen Zhao Shu-Lin zhang da-zhi zhang Ninth Clinical Department Beijing Ditan Hospital Beijing 100011 China. xieyao@***

BACKGROUND:This study was undertaken to investigate the predictive factors of sustained viral response in roferon-A or pegasys treated chronic hepatitis C patients after logistic regression analysis of the factors that might be associated with the therapeutic effects of interferon (IFN).METHODS:All patients enrolled into this randomized, open and multi-center controlled trial were divided into two groups randomly and treated with pegasys and roferon-A for 24 weeks, then followed up for another 24 weeks. Before treatment, hepatitis C virus (HCV) genotype was determined, and HCV-RNA in serum was detected before and at the end of treatment and follow-up. HCV-RNA turning negative was considered the major index for evaluating the therapeutic effect. The clinical characteristics including gender, age, infection route of HCV, treatment with IFN, platelet count, AST/ALT ratio and treatment drugs were analyzed by logistic regression.RESULTS:Intention to treat (ITT) and per-protocol (PP) population groups have 208 and 197 patients respectively. In the PP group, after treatment for 24 weeks, the response rates of female patients aged less than 50 years, infected through non-transfusion, relapsed after IFN treatment, and presented with a AST/ALT ratio/=1, virus load equal or more than 8 x 10(5) IU/ml, and genotype 1 infection, and treated finally with roferon-A. But, at the end of follow-up, the patients with a AST/ALT ratio>/=1 and virus load more than 8 x 10(5) IU/ml had a higher rate of sustained response than did those with a AST/ALT ratio

关键词： hepatitis C virus chronic hepatitis C interferon peg-IFN genotype

Replication of hepatitis B virus in primary duck hepatocytes transfected with linear viral DNA

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World Journal of Gastroenterology 2005年第32期11卷 5019-5021页

作者： Yun-Qing Yao Ding-Feng zhang Ni Tang Ai-Long Huang Xiao-Yi Zou Jiang-Feng Xiao Yun Luo da-zhi zhang Bo Wang Wei-Ping Zhou Hong Ren Qi Liu Shu-Hua Guo Department of Infectious Diseases of the First Affiliated Hospital Chongqing University of Medical Sciences Chongqing 400016 China Institute for Viral Hepatitis Chongqing University of Medical Sciences Chongqing 400010 China

AIM: To explore the expression and replication of hepatitis B virus (HBV) DNA in primary duck hepatocytes (PDHs).METHODS: Complete HBV genome was transfected into PDHs by electroporation (transfected group, 1.19×1012copies of linear HBV DNA/1×107 PDHs). After 1-5 d of transfection, HBsAg and HBeAg in the supernatant and lysate of PDHs were measured with the IMX ***, replicative intermediates of HBV DNA were analyzed by Southern blotting and Dot blotting. PDHs electroporated were used as control ***: HBsAg in the hepatocyte lysates of transfected group was 15.24 (1 d), 14.55 (3 d) and 5.13 (5 d; P/N values, positive≥2.1) respectively. HBeAg was negative (＜2.1). Both HBsAg and HBeAg were negative in the supernatant of transfected group. Dot blotting revealed that HBV DNA was strongly positive in the transfected group and negative in the control group. Southern blot analysis of intracellular total DNA indicated that there were relaxed circular (rc DNA), covalently closed circular (ccc DNA), and single-stranded (ss DNA) HBV DNA replicative intermediates in the transfected group, there was no integrated HBV DNA in the cellular genome. These parameters were negative in control ***: Expression and replication of HBV genes can occur in hepatocytes from non-mammalian *** replication has no critical species-specificity, and yet hepatic-specific regulating factors in hepatocytes may be essential for viral replication.

关键词： Hepatitis B virus Replication Expression Primary duck hepatocytes

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir

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Journal of Clinical and Translational Hepatology 2023年第2期11卷 304-313页

作者： Yi-Qi Liu Chi zhang Jia-Wen Li Li-Hua Cao Zhan-Qing zhang Wei-Feng Zhao Qing-Hua Shang da-zhi zhang An-Lin Ma Qing Xie Hong-Lian Gui Guo zhang Ying-Xia Liu Jia Shang Shi-Bin Xie Jun Li Xu-Qing zhang zhi-Qiang Zou Yu-Ping Chen Zong zhang Ming-Xiang zhang Jun Cheng Fu-Chun zhang Li-Hua Huang Jia-Bin Li Qing-Hua Meng Hai-Bin Yu Yu-Qiang Mi Yan-Zhong Peng zhi-Jin Wang Li-Ming Chen Fan-Ping Meng Wan-Hua Ren Lang Bai Yi-Lan Zeng Rong Fan Xian-zhi Lou Wei-Feng Liang Hui Liu Hui Zhuang Hong Zhao Gui-Qiang Wang Department of Infectious Disease Center for Liver DiseasePeking University First HospitalBeijingChina Department of Hepatology The Third Hospital of QinhuangdaoQinhuangdaoHebeiChina Department of Infectious Disease Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Infectious Disease Xinxiang Medical University Affiliated Third HospitalXinxiangHenanChina No.88 Hospital of Chinese People’s Liberation Army(PLA) JinanShandongChina Department of Infectious Diseases The Second Affiliated Hospital of Chongqing Medical UniversityChongqingChina Department of Infectious Disease China-Japan Friendship HospitalBeijingChina Department of Infectious Diseases Ruijin HospitalSchool of MedicineShanghai Jiaotong UniversityShanghaiChina Department of Gastroenterology The People’s Hospital of Guangxi Zhuang Autonomous RegionNanningGuangxiChina Department of Infectious Diseases The Third People’s Hospital of ShenzhenShenzhenGuangdongChina Department of Infectious Diseases The People’s Hospital of Henan ProvinceZhengzhouHenanChina Department of Infectious Disease The Third Affiliated Hospital of Sun-Yat Sen UniversityGuangzhouGuangdongChina Department of Infectious Diseases Jiangsu Province HospitalThe First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuChina Department of Infectious Diseases The Southwest Hospital of Army Medical UniversityChongqingChina Yantai Infectious Diseases Hospital YantaiShandongChina Department of Hepatology Baoding Infectious Diseases HospitalBaodingHebeiChina Department of Integrated Traditional Chinese Medicine(TCM)and Western Medicine Jinan Infectious Diseases HospitalShandong UniversityJinanShandongChina Department of Integrated TCM and Western Medicine in Hepatology The Sixth People’s Hospital of ShenyangShenyangLiaoningChina Beijing Ditan Hospital Capital Medical UniversityBeijingChina Department of Infectious Diseases Guangzhou Eighth People’s HospitalGuangzhou Medical UniversityGuangzhouGuangdon

Background and Aims:Chronic hepatitis B(CHB)can cause liver fibrosis and lead to cirrhosis and *** the effectiveness of antiviral therapy to reverse liver fibrosis is limited,We aimed to evaluate the effect of An-Luo-Hua-Xian pill(ALHX)on fibrosis regression in CHB patients treated with entecavir(ETV).Methods:Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX(ETV+ALHX)between October 1,2013 and December 31,***,laboratory,and liver histology data before and after 78 weeks of treatment were *** Ishak fibrosis score(F)was used and fibrosis regression required a decrease in F of≥1 after ***:A total of 780 patients were enrolled,and 394 with a second liver biopsy after treatment were included in the per-protocol population,132 in ETV group and 262 in ETV+ALHX *** 78 weeks of treatment,the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients:124/211(58.8%)vs.45/98(45.9%),p=*** percentage of patients with a decreased liver stiffness measurement(LSM)was higher in the ETV+ALHX group:156/211(73.9%)vs.62/98(63.%),p=*** regression analysis showed that ETV combined with ALHX was associated with fibrosis regression[odds ratio(OR)=1.94,p=0.018],and a family history of hepatocellular carcinoma was on the contrary.(OR=0.41,p=0.031).Conclusions:ETV combined with ALHX increased liver fibrosis regression in CHB patients.

关键词： Chronic hepatitis B Liver fibrosis Regression Randomized controlled trial

One hundred and ninety-two weeks treatment of entecavir maleate for Chinese chronic hepatitis B predominantly genotyped B or C

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World Journal of Clinical Cases 2022年第28期10卷 10085-10096页

作者： Jing-Hang Xu Sa Wang da-zhi zhang Yan-Yan Yu Chong-Wen Si Zheng Zeng Zhong-Nan Xu Jun Li Qing Mao Hong Tang Ji-Fang Sheng Xin-Yue Chen Qin Ning Guang-Feng Shi Qing Xie Xi-Quan zhang Jun dai Department of Infectious Diseases Center for Liver DiseasesPeking University First HospitalBeijing 100094China Clinical and Research Center of Infectious Diseases Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Department of Infectious Diseases The Second Affiliated Hospital with Chongqing Medical UniversityChongqing 400010China Jiangsu Chia-tai Tianqing Pharmaceutical Co. LtdNanjing 222006Jiangsu ProvinceChina Department of Infectious Diseases The First Affiliated Hospital with Nanjing Medical UniversityNanjing 210029Jiangsu ProvinceChina Department of Infectious Diseases Southwest China HospitalChongqing 400038China Department of Infectious Diseases West China HospitalChengdu 610041Sichuan ProvinceChina Department of Infectious Diseases The First Affiliated Hospital of Zhejiang UniversityHangzhou 310010Zhejiang ProvinceChina Department of International Medicine Beijing Youan HospitalCapital Medical UniversityBeijing 100069China Department and Institute of Infectious Diseases Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030Hubei ProvinceChina Department of Infectious Diseases Huashan HospitalFudan UniversityShanghai 200040China Department of Infectious Diseases Ruijin HospitalJiaotong University School of MedicineShanghai 200025China

BACKGROUND Entecavir(ETV)is a potent and selective nucleotide analog with significant activity against hepatitis B virus(HBV).ETV maleate is a derivative compound of ETV and was reported to have an efficacy and safety profile that is comparable to ETV(Baraclude)when used in Chinese patients with chronic hepatitis B(CHB)in phase III clinical trials(Clinical *** number,NCT-01926288)at weeks 48,96,and *** To investigate the antiviral potency and safety of ETV maleate at week 192 in Chinese CHB patients predominantly genotyped B or *** In this double-blind study,we randomly assigned patients to receive 0.5 mg/d ETV(Group A)or ETV maleate(Group B)(ratio,1:1),each with a placebo tablet for 48 ***,all patients received open-label treatment with 0.5 mg/d ETV maleate starting at week *** primary efficacy endpoint was the reduction in HBV DNA levels from *** endpoints included the proportion of patients with undetectable HBV DNA(0.05),viral suppression with HBV DNA0.05)and HBe Ag seroconversion(28.77%vs 20.00%,P>0.05)occurred similarly between Groups A and B at week ***,there was a significant difference in the proportion of patients with normal ALT levels(91.14%vs 78.38%,P0.05),percentages of patients who achieved undetectable HBV DNA(100%vs 100%,P>0.05)and rates of ALT normal

关键词： Chronic hepatitis B Entecavir maleate Randomized controlled trial Treatment outcome Mutation Genotype

IGF-1R/β-catenin signaling axis is involved in type 2 diabetic osteoporosis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2019年第10期20卷 838-848页

作者： zhi-da zhang Hui REN Wei-xi WANG Geng-yang SHEN Jin-jing HUANG Mei-qi ZHAN Jing-jing TANG Xiang YU Yu-zhuo zhang De LIANG zhi-dong YANG Xiao-bing JIANG The First Clinical School Guangzhou University of Chinese MedicineGuangzhou 510405China Department of Spinal Surgery the First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405China School of Basic Medicine Guangzhou University of Chinese MedicineGuangzhou 510006China Lingnan Medical Research Center of Guangzhou University of Chinese Medicine Guangzhou 510405China

Insulin-like growth factor-1 receptor(IGF-1 R)is involved in both glucose and bone ***-1 R signaling regulates the canonical Wnt/β-catenin signaling *** this study,we investigated whether the IGF-1 R/β-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis(DOP).Serum from patients with or without DOP was collected to measure the IGF-1 R level using enzyme-linked immunosorbent assay(ELISA).Rats were given streptozotocin following a four-week high-fat diet induction(DOP group),or received vehicle after the same period of a normal diet(control group).Dual energy X-ray absorption,a biomechanics test,and hematoxylin-eosin(HE)staining were performed to evaluate bone mass,bone strength,and histomorphology,respectively,in *** real-time polymerase chain reaction(qRT-PCR)and western blotting were performed to measure the total and phosphorylation levels of IGF-1 R,glycogen synthase kinase-3β(GSK-3β),andβ-*** serum IGF-1 R level was much higher in patients with DOP than in *** rats exhibited strikingly reduced bone mass and attenuated compression strength of the vertebrae compared with the control *** staining showed that the histomorphology of DOP vertebrae was seriously impaired,which manifested as decreased and thinned trabeculae and increased lipid droplets within *** analysis demonstrated that IGF-1 R mRNA expression was significantly up-regulated,and western blotting detection showed that phosphorylation levels of IGF-1 R,GSK-3β,andβ-catenin were enhanced in DOP rat *** results suggest that the IGF-1 R/β-catenin signaling axis plays a role in the pathogenesis of *** may contribute to development of the underlying therapeutic target for DOP.

关键词： Diabetic osteoporosis Insulin-like growth factor-1 receptor(IGF-1R) Signaling axis Pathogenesis

Unsatisfying antiviral therapeutic effect in patients with mother-tochild transmissed chronic hepatitis B virus infection: a prospective multi-center clinical study

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Chinese Medical Journal 2019年第22期132卷 2647-2656页

作者： Jun Li Xiao-Qin Dong Zhao Wu An-Lin Ma Shi-Bin Xie Xu-Qing zhang Zhan-Qing zhang da-zhi zhang Wei-Feng Zhao Guo zhang Jun Cheng Qing Xie Jun Li zhi-Qiang Zou Ying-Xia Liu Gui-Qiang Wang Hong Zhao China Hepatitis B Related Fibrosis Assessment Research Group Department of Infectious Diseases Center for Liver DiseasePeking University First HospitalBeijing 100034China Department of Infectious Diseases Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Department of Infectious Diseases China-Japan Friendship HospitalBeijing 100029China Department of Infectious Diseases The Third Affiliated Hospital Sun Yat-Sen UniversityGuangzhouGuangdong 510000China Department of Infectious Diseases South West Hospital Affiliated to Third Military Medical UniversityChongqing 400038China Department of Hepatology Shanghai Public Health Clinical CenterFudan UniversityShanghai 200083China Department of Infectious Diseases Second Affiliated Hospital of Chongqing Medical UniversityChongqing 404000China Department of Infectious Diseases Xinxiang Medical University Third HospitalXinxiangHenan 453003China Department of Infectious Diseases The People's Hospital of Guangxi Zhuang Autonomous RegionNanningGuangxi 530021China Department of Infectious Diseases Di Tan Hospital Affiliated to Capital Medical UniversityBeijing 100015China Department of Infectious Diseases Rui Jin HospitalShanghai Jiao Tong University School of MedicineShanghai 200090China Department of Infectious Diseases The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 211166China Department of Infectious Diseases Yantai City Hospital for Infectious DiseaseYantaiShandong 264001China Shenzhen Key Laboratory of Pathogen and Immunity State Key Discipline of Infectious DiseaseShenzhen Third People's HospitalShenzhenGuangdong 518034China The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Zhejiang UniversityHangzhouZhejiang 310085China Department of Infectious Diseases Peking University International HospitalBeijing 102206China 不详

Background:Few data are available regarding the progression of liver disease and therapeutic efficacy in chronic hepatitis B(HBV)carriers infected by mother-to-child transmission(MTCT).This study aimed to investigate these two aspects by comparing the adult chronic HBV carriers in MTCT group with those in horizontal transmission ***:The 683 adult chronic HBV patients qualified for liver biopsy including 191 with MTCT and 492 with horizontal transmission entered the multi-center prospective study from October 2013 to May *** results from 217 patients at baseline and 78 weeks post antiviral therapy were ***:Patients infected by MTCT were more likely to have e antigen positive(68.6%vs.58.2%,x^2=-2.491,P=0.012)than those with horizontal ***,in patients with MTCT,levels of alkaline phosphatase(ALP)(P=0.031),Fibroscan(P=0.013),N-terminal propeptide of Type III procollagen(PIIINP)(P=0.014),and Laminin(LN)(P=0.006)were high,in contrast to the patients with horizontal transmission for whom the levels of albumin(ALB)(P=0.041),matrix metalloproteinase-3(MMP-3)(P=0.001)were *** 47.2% of patients with MTCT and 36.8%of those with horizontal transmission had significant liver fibrosis(P=0.013).Following antiviral therapy for 78 weeks,21.2%and 38.0%patients with MTCT and horizontal transmission acquired hepatitis B e antigen(HBeAg)clearance,respectively(P=0.043),and the virological response rates were 54.7%and 74.1%in the MTCT and horizontal groups,respectively(P=0.005).MTCT was a risk factor for HBeAg clearance and virological ***:Adult patients with MTCT were more prone to severe liver diseases,and the therapeutic efficacy was relatively poor,which underlined the importance of earlier,long-term treatment and interrupting perinatal transmission.

关键词： Chronic Hepatitis B virus infection Horizontal transmission Mother-to-child transmission Progression of disease Therapeutic efficacy