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Relationship between virological response and FIB-4 index in chronic hepatitis B patients with entecavir therapy

World Journal of Gastroenterology 2015年第43期21卷 12421-12429页

作者： Ni Li Jing-Hang Xu Min Yu Sa Wang chong-wen si Yan-Yan Yu Department of Infectious Diseases Peking University First Hospital

AIM: To investigate whether long-term low-level hepatitis B virus(HBV) DNA influences dynamic changes of the FIB-4 index in chronic hepatitis B(CHB) patients receiving entecavir(ETV) therapy with partial virological ***: We retrospectively analyzed 231 nucleos-(t)ide(NA) na?ve CHB patients from our previous study(NCT01926288) who received continuous ETV or ETV maleate therapy for three years. The patients were divided into partial virological response(PVR) and complete virological response(CVR) groups according to serum HBV DNA levels at week 48. Seventy-six patients underwent biopsies at baseline and at 48 wk. The performance of the FIB-4 index and area under the receiver operating characteristic(AUROC) curve for predicting fibrosis were determined for the patients undergoing biopsy. The primary objective of the study was to compare the cumulative probabilities of virological responses between the two groups during the treatment period. The secondary outcome was to observe dynamic changes of the FIB-4 index between CVR patients and PVR ***: For hepatitis B e antigen(HBe Ag)-positive patients(n = 178),the cumulative probability of achieving undetectable levels at week 144 was 95%and 69% for CVR and PVR patients,respectively(P sion. The cumulative probability of achieving undetectable levels of HBV DNA for HBe Ag-negative patients(n = 53) did not differ between the two groups. The FIB-4 index efficiently identified fibrosis,with an AUROC of 0.80(95%CI: 0.69-0.89). For HBe Ag-positive patients,the FIB-4 index was higher in CVR patients than in PVR patients at baseline(1.89 ± 1.43 vs 1.18 ± 0.69,P significant difference in the reduction of the FIB-4 index between the CVR and PVR groups from weeks 48 to 144(-0.11 ± 0.47 vs-0.13 ± 0.49,P = 0.71). At week 144,the FIB-4 index

关键词： Chronic hepatitis B Hepatitis B virus DNA Entecavi

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Effects of antiviral agents and HBV genotypes on intrahepaticcovalently closed circular DNA in HBeAg-positive chronichepatitis B patients

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World Journal of Gastroenterology 2008年第8期14卷 1268-1273页

作者： Hai-Ying Lu Li-Wei Zhuang Yan-Yan Yu chong-wen si Jun Li Jian-Jun Zhang Zheng Zeng Xin-Yue Chen Zhong-Hou Han Yong Chen Departnlent of Infectious Diseases Peking University First Hospital Beijing 100034 China Beijing Zhongfuyouxin Beijing 100085 China Beijing You'an Hospital Beijing 100054 China Qinhuangdao Third Hospital Qinhuangdao 066000 Hebei Province China Huai'an Infectious Disease Hospital Huai'an 223300 Jiangsu Province China

AIM： To evaluate the effects of antiviral agents and HBV genotypes on intrahepatic covalently closed circular DNA （ccc DNA） in HBeAg-positive chronic hepatitis B patients.METHODS： Seventy-one patients received lamivudine （n = 35）, or sequential therapy with lamivudine- interferon alpha 2b （IFN-α 2b, n = 24） for 48 wk, or IFN-α 2b （n = 12） for 24 wk. All subjects were followed up for 24 wk. Intrahepatic ccc DNA was measured quantitatively by PCR. HBV genotypes were analyzed by PCR-RFLP.RESULTS： Sequential lamivudine- INF-α therapy, lamivudine and INF-α monotherapy reduced ccc DNA of 1.7 log, 1.4 log and 0.8 log, respectively （P 〈 0.05）. Seventeen out of the 71 patieots developed HBeAg seroconversion, the reduction of ccc DNA in the HBeAg seroconversion patients was more significant than that in the HBeAg positive patients （3.0 log vs 1.6 log, P = 0.0407）. Twenty-four weeks after antiviral therapy withdrawal, 16 patients had a sustained virological response, the baseline intrahepatic ccc DNA in the patients with a sustained virological response was significantly lower than that in the patients with virological rebound （4.6 log vs 5.4 log, P = 0.0472）. HBV genotype C accounted for 85.9% （n = 61）, and genotype B for 14.1% （n = 10）, respectively, in the 71 patients. There was no significant difference in the change of ccc DNA level between HBV genotypes C and B （2.1 log vs 1.9 log）.CONCLUsiON： Forty-eight week sequential lamivudine- INF-α therapy and lamivudine monotherapy reduce ccc DNA more significantly than 24-wk INF-α monotherapy. Low baseline intrahepatic ccc DNA level may predict the long-term efficacy of antiviral treatment. HBV genotypes C and B have no obvious influence on ccc DNA load.

关键词： Covalently closed circular DNA, Hepatitis Bvirus Sequential therapy Lamivudine Interferon

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Intrahepatic HBV DNA as a predictor of antivirus treatment efficacy in HBeAg-positive chronic hepatitis B patients

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World Journal of Gastroenterology 2007年第20期13卷 2878-2882页

作者： Hai-Ying Lu Li-Wei Zhuang Yan-Yan Yu Hadad Ivan chong-wen si Zheng Zeng Jun Li Dong-Ming Hou Xin-Yue Chen Zhong-Hou Han Yong Chen Department of Infectious Diseases Peking University First Hospital Beijing 100034 China Indiana University School of Medicine Indianapolis IN 46202 United States Beijing You'an Hospital Beijing 100054 China Qinhuangdao Third Hospital Qinhuangdao 066000 Hebei Province China Huai'an Infectious Disease Hospital Huai'an 223300 Jiangsu Province China

AIM： To evaluate the effect of antiviral agents on intrahepatic HBV DNA in HBeAg-positive chronic hepatitis B patients. METHODS： Seventy-one patients received treatment with lamivudine, interferon alpha （IFN-α2b） or sequential therapy with lamivudine-IFN-α2b for 48 wk. All subjects were followed up for 24 wk. Serum and intrahepatic HBV DNA were measured quantitatively by PCR. HBV genotypes were analyzed by PCR-RFLP. RESULTS： At the end of treatment, the intrahepatic HBV DNA level in 71 patients decreased from a mean of （6.1 ± 1.0） Iog10 to （4.9± 1.4） Iog10. Further, a larger decrease was seen in the intrahepatic HBV DNA level in patients with HBeAg seroconversion. Intrahepatic HBV DNA level （before and after treatment） was not significantly affected by the patients＇ HBV genotype, or by the probability of virological flare after treatment. CONCLUsiON： Intrahepatic HBV DNA can be effectively lowered by antiviral agents and is a significant marker for monitoring antivirus treatment. Low intrahepatic HBV DNA level may achieve better efficacy of antivirus treatment.

关键词： Intrahepatic HBV DNA Histology Antivira therapy HBV genotype

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Tenofovir disoproxil fumarate in Chinese chronic hepatitis B patients:Results of a multicenter,double-blind,double-dummy,clinical trial at 96 weeks

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World Journal of Clinical Cases 2021年第18期9卷 4690-4699页

作者： Xiao-Fan Chen Ya-Nan Fan chong-wen si Yan-Yan Yu Jia Shang Zu-Jiang Yu Qing Mao Qing Xie Wei Zhao Jun Li Zhi-Liang Gao Shan-Ming Wu Hong Tang Jun Cheng Xin-Yue Chen wen-Hong Zhang Hao Wang Zhong-Nan Xu Ling Wang Jun Dai Jing-Hang Xu Department of Infectious Diseases Center for Liver DiseasesPeking University First HospitalBeijing 100034China Department of Infectious Diseases Henan Provincial People's HospitalZhengzhou 450003Henan ProvinceChina Department of Infectious Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Department of Infectious Diseases Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Department of Infectious Diseases Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai 200025China Department of Infectious Diseases The Second Affiliated Hospital of Southeast UniversityNanjing 210011Jiangsu ProvinceChina Department of Infectious Diseases The First Affiliated Hospital with Nanjing Medical UniversityNanjing 210029Jiangsu ProvinceChina Department of Infectious Diseases The Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina Department of Infectious Diseases Shanghai Public Health Clinical CenterFudan UniversityShanghai 201052China Department of Infectious Diseases West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina Center of Hepatology Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Department of International Medical Beijing Youan HospitalCapital Medical UniversityBeijing 10069China Department of Infectious Diseases Huashan HospitalFudan UniversityShanghai 200040China Department of Infectious Diseases Peking University People's HospitalBeijing 100044China Clinical Center Jiangsu Chia-tai Tianqing Pharmaceutical Co.LtdNanjing 210000Jiangsu ProvinceChina

BACKGROUND Tenofovir disoproxil fumarate(TDF)is a prodrug of a nucleotide *** an antiviral drug,TDF has been proposed in the first-line treatment of chronic hepatitis B(CHB).Qingzhong,a brand name of TDF,commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd.,and Viread,another brand name of TDF,commercialized by GlaxoSmithKline,have both been approved by the State Food and Drug Administration,*** To investigate the efficacy and safety of the two TDF agents in the treatment of Chinese CHB *** This trial was registered at *** with the identifier number of NCT02287857.A total of 330 Chinese CHB patients,among which 232 were hepatitis B e antigen(HBeAg)-positive,were included in this 5-year-long,multicenter,double-blinded,double-dummy,randomized-controlled,noninferiority phase III *** participants were initially randomized into two groups:Group A(n=161),in which the participants received 300 mg Qingzhong once a day for 48 wk;and Group B,in which the participants received 300 mg Viread once a day for 48 *** from week 49,all the participants in Groups A and B received 300 mg Qingzhong once a day until the 96th *** this study,the primary endpoint was the decrease in plasma level of hepatitis B virus(HBV)DNA at the 96th week,while the secondary endpoints were suppression of HBV replication,alanine aminotransferase(ALT)normalization,HBeAg loss,and HBeAg seroconversion *** For the participants with HBeAg-positive CHB,the decrease in mean HBV DNA level relative to the baseline value was comparable between Groups A and B(5.77 vs 5.73 log10 IU/mL,P>0.05)at the 96th *** addition,similar percentages of HBeAg-positive participants in the two groups exhibited undetectable levels of HBV DNA,HBeAg loss,and HBeAg seroconversion(71.05%vs 77.97%,31.00%vs 27.27%,and 20.22%vs 15.79%,respectively,in Group A vs Group B;P>0.05).For the participants with HBeAg-negative CHB,the decrease in mean HBV DNA level r

关键词： Chronic hepatitis B Hepatitis B virus infection Chronic Tenofovir disoproxil

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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(sistance *** Two hundred eighteen patients who were hepatitis B e antigen(HBe Ag)positive and 57 who were HBe Ag negative were analyzed and predominantly presented with genotype B(49.82%)or C(48.73%).For the HBe Ag-positive CHB patients,the mean HBV DNA level decrease(6.61 Log10 IU/m L vs 6.69 Log10 IU/m L,P>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%,Psignificant difference was found between Groups A and B at week 192 in terms of reductions in HBV DNA levels from baseline(6.05 Log10 IU/m L vs 6.03 Log10 IU/m L,P>0.05),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

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Stepwise assembly to construct stable copper(I) cluster-based circularly polarized luminescent MOFs

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Science China Chemistry 2025年

作者： Jing-wen Xie Meng-Ting Wang Yan Jin si Li Jian-Hua Qin Shuang-Quan Zang Tomas C.W.Mak College of Chemistry Henan Key Laboratory of Crystalline Molecular Functional Materials Zhengzhou University College of Chemistry and Chemical Engineering Luoyang Normal University Department of Chemistry The Chinese University of Hong Kong

Circularly polarized luminescence （CPL） materials have been extensively studied in recent years owing to their widespread applications in 3D display,optical storage,optical anti-counterfeiting,and biological imaging,***（I） clusters have emerged as a promising candidate for CPL materials,driven by their cost-effectiveness,superior luminescent properties,precise structure,and low ***,the poor environmental stability of copper（I） clusters renders their synthesis and preservation challenging,thereby significantly impeding their ***,we have designed and synthesised a chiral double-coordinated ligand in order to construct copper（I） cluster nodes that can be further *** anticipated,by utilizing stepwise assembly strategy,a Cu4cluster node co-modified by chiral alkynyl ligands and triphenylphosphine was further assembled with Cd2+ions to obtain 2D layers structure,L/*** L/D-Cu4-Cd exhibits excellent stability and optical properties,including bright yellow emission,solvent-responsive luminescence,and CPL activity with a maximum glumup to 2.0×10-3,which shows potential applications in the WLED and *** interestingly,the material also exhibits deflection ability towards different wavelengths of linearly polarized light,showing certain potential in the preparation of circular polarizer.

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Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu si Wang Weiqi Zhang Jing Qu Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

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三种抗病毒治疗方法对慢性乙型肝炎患者生活质量的影响

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世界华人消化杂志 2007年第16期15卷 1820-1824页

作者：王艳于岩岩斯崇文陈新月韩忠厚陈宇萍北京大学第一医院感染疾病科北京市100034 北京市佑安医院特需科北京市100069 秦皇岛市第三人民医院肝病科河北省秦皇岛市066001 保定市传染病医院肝病科河北省保定市071000

目的:探讨不同治疗方法治疗的慢性乙型病毒性肝炎,对生活质量的影响.方法:选择143例慢性乙型肝炎患者,随即分为序贯治疗组(拉米夫定+干扰素α2b,n= 56)、拉米夫定组(n=60)、干扰素组(n=27).应用标准化的量表(SF36中文版)评定法,对全部... 详细信息

目的:探讨不同治疗方法治疗的慢性乙型病毒性肝炎,对生活质量的影响.方法:选择143例慢性乙型肝炎患者,随即分为序贯治疗组(拉米夫定+干扰素α2b,n= 56)、拉米夫定组(n=60)、干扰素组(n=27).应用标准化的量表(SF36中文版)评定法,对全部调查对象进行健康状况调查问卷.每名治疗对象于治疗前、治疗结束、随访结束分别接受评定3次.结果:三种不同的治疗方法对慢性乙型肝炎患者的生活质量影响不明显,同一治疗方法在治疗前、治疗后、随访后患者的生活质量也无显著性差异;治疗结束和随访结束,不同病毒载量的患者其生活质量亦没有显著性差异.结论:慢性乙型肝炎患者的生活质量与不同的抗病毒治疗方法无关,临床医师应根据患者的病情选择合理、有效的抗病毒方案并辅以积极的心理干预以最终提高患者生活质量.

关键词：慢性乙型肝炎抗病毒治疗 SF36问卷生活质量

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High Fe‑Loading single‑Atom Catalyst Boosts ROS Production by Density Effect for Efficient Antibacterial Therapy

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Nano-Micro Letters 2025年第2期17卷 187-203页

作者： si Chen Fang Huang Lijie Mao Zhimin Zhang Han Lin Qixin Yan Xiangyu Lu Jianlin Shi Department of Cardiology Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200092People’s Republic of China Shanghai Institute of Ceramics Chinese Academy of SciencesShanghai 200050People’s Republic of China Shanghai Frontiers Science Center of Nanocatalytic Medicine School of MedicineTongji UniversityShanghai 200092People’s Republic of China

The current single-atom catalysts(SACs)for medicine still suffer from the limited active site ***,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with *** constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial ***,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading ***,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/*** addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)*** in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound *** work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.

关键词： Nanocatalytic medicine single-atom catalysts Reactive oxygen species(ROS) High metal loading Oxidase catalysis

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耐心资本对企业ESG表现的影响研究

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经济问题 2025年第1期 48-56页

作者：李思飞温磊北京外国语大学国际商学院北京100089

随着ESG理念的逐渐流行,如何提升企业的ESG表现成为社会公众关注的焦点。耐心资本提倡长期的投资理念,与ESG理念相契合,可能成为促进企业ESG表现提升的重要引擎。为此,基于2009—2022年A股上市公司的样本,实证检验了耐心资本对企业ESG... 详细信息

随着ESG理念的逐渐流行,如何提升企业的ESG表现成为社会公众关注的焦点。耐心资本提倡长期的投资理念,与ESG理念相契合,可能成为促进企业ESG表现提升的重要引擎。为此,基于2009—2022年A股上市公司的样本,实证检验了耐心资本对企业ESG表现的影响。研究发现:耐心资本能够促进企业ESG表现提升。机制检验发现,代理成本、融资约束和信息不对称是耐心资本影响企业ESG表现的重要机制;异质性分析发现,耐心资本对分析师关注度高、媒体关注度高以及属于重点污染监控单位的企业ESG表现具有更明显的提升效应;分项检验发现,耐心资本主要促进了企业社会和公司治理表现提升,对于企业环境表现则没有显著影响。研究结论对于培育和壮大耐心资本、促进企业ESG表现提升具有重要的参考价值。

关键词：耐心资本企业ESG表现信息不对称融资约束代理成本

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