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Hepatobiliary & Pancreatic Diseases International 2005年第4期4卷 550-553页

作者： dao-zhen xu, Yao Xie and zheng-Qin Li Beijing Ditan Hospital, Beijing 100011, China Beijing Ditan Hospital Beijing 100011 China. xudzh@***

BACKGROUND: The resolution of hepatitis C, evidenced by normalization of liver function and disappearance of hepatitis C virus RNA from serum as determined by conventional laboratory assays, reflects virus eradication. But in interferon treated patients the HCV RNA in serum sometimes could not show the virus in cells. Such factors as virus genotype, HCV RNA contents in serum, HCV specific cellular immunities after treatment were reported to predict the response to interferon therapy. In most patients, HCV RNA could detect the virus in peripheral blood mononucle-ar cell. The aim of this study was to investigate the predictive value of HCV RNA in PBMC of patients with chronic hepatitis C after interferon treatment. METHODS: Sixteen patients with chronic hepatitis C were treated with interferon for 24 weeks, and they all get complete responses at 12 weeks of treatment. At the end of treatment, the HCV RNA in PBMC and serum were detected by RT-PCR, and after stopping treatment, HCV RNA in serum was monitored continually. RESULTS: In 9 patients who were HCV RNA positive in their PBMC at the end of treatment, 8 showed serum HCV RNA positive after 24 weeks and another 1 after 1 year. In 7 patients with negative HCV RNA in their PBMC, only 2 patients relapsed in serum HCV RNA after 1-year follow-up, and others remained viral response after 3.5 years. CONCLUSION: HCV RNA in PBMC at the end of IFN treatment is a predictor of durable response to antiviral therapy in patients with chronic hepatitis C.

关键词： chronic hepatitis C HCV RNA interferon peripheral blood mononuclear cell

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

HBV DNA level and antigen concentration in evaluating liver damage of patients with chronic hepatitis B

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Hepatobiliary & Pancreatic Diseases International 2003年第3期2卷 418-422页

作者： Yao Xie Hui Zhao Wang-Su Dai dao-zhen xu the Department of Infectious Diseases, Beijing Ditan Hospital. Beijing 100011, China Department of Infectious Diseases Beijing Ditan Hospital Beijing 100011 China. xieyao@***

OBJECTIVE: To investigate the correlations between HBV DNA levels and viral antigen concentrations in patients with chronic hepatitis B and their significance in clinical practice. METHODS: The HBV DNA levels and serological markers of 118 patients with chronic hepatitis B and 87 patients with liver cirrhosis who had not been treated with antiviral drugs were determined as well as the other parameters relevant to liver function. RESULTS: The HBV DNA levels of the patients with chronic hepatitis anti cirrhosis were expressed as geometric mean±SD, 3.83×10~6±1.34 copies/ml anti 6.98×10~5±1.29 copies/ml, and their HBeAg concentrations expressed as the luminescent values rate of sample to control (s/co) were 35.40±1.26 and 4.05±1.28, respectively. The HBV DNA levels in HBeAg positive group were significantly higher than those in HBeAg negative group (P<0.0001). The correlation coefficient between HBV DNA level and HBeAg or HBsAg concentration was only O. 273 anti -0.12. During the recovery of hepatic function, the reduction of ALT or AST in patients with high viral content was significantly lower than that in patients with low viral content. No correlation was observed between HBV DNA and ALT levels. CONCLUSION: There are significant correlations between HBV DNA level anti HBeAg concentration, but the coefficient is lower. HBV DNA level is not significantly related to ALT, but it could affect the recovery of liver function.

关键词： hepatitis B hepatitis B virus antigen HBeAg HBV DNA ALT

Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a

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World Journal of Hepatology 2016年第15期8卷 637-643页

作者： Ming-Hui Li Yao Xie Lu Zhang Yao Lu Ge Shen Shu-Ling Wu Min Chang Cai-Qin Mu Lei-Ping Hu Wen-Hao Hua Shu-Jing Song Shu-Feng Zhang Jun Cheng dao-zhen xu Liver Disease Center Beijing Ditan Hospital Capital Medical University Clinical Test Center Beijing Ditan Hospital Capital Medical University

AIM: To examine the association between interferon(IFN) therapy and loss of hepatitis B surface antigen(HBs Ag) in inactive HBs Ag carriers. METHODS: This was a retrospective cohort study in inactive HBs Ag carriers, who were treatment-naive, with a serum HBs Ag level < 100 IU/m L and an undetectable hepatitis B virus(HBV) DNA level(< 100 IU/m L). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBs Ag, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen(65.0%) of 20 treated patients achieved HBs Ag loss, 12 of whom achieved HBs Ag seroconversion. Mean HBs Ag level in treated patients decreased to 6.69 ± 13.04 IU/m L after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/m L. Serum HBV DNA level remained undetectable(< 100 IU/m L) in all treated patients during the study. HBs Ag level of the control group decreased from 25.72 ± 25.58 IU/m L at baseline to 17.11 ± 21.62 IU/m L at week 96(P = 0.108). In the control group, no patient experienced HBs Ag loss/seroconversion, and two(5.0%) developed HBV ***: IFN treatment results in HBs Ag loss and seroconversion in a considerable proportion of inactive HBs Ag carriers with low HBs Ag concentrations.

关键词： Chronic hepatitis B surface antigen carriers Inactive hepatitis B surface antigen carriers Interferon Peginterferon alfa-2a Hepatitis B surface antigen loss/ seroconversion

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

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Neural Regeneration Research 2025年第4期20卷 917-935页

作者： Dian Jiao Lai xu zhen Gu Hua Yan Dingding Shen Xiaosong Gu Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhouZhejiang ProvinceChina Affiliated Hospital of Nantong University NantongJiangsu ProvinceChina

Epilepsy is a severe,relapsing,and multifactorial neurological *** regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of *** pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota *** results are lacking for conventional treatments for *** resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with ***-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research *** review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of *** also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current *** studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic ***,many new technologies for the diagnosis and treatment of epilepsy are being ***,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

关键词： diagnosis drug treatment electroencephalography epilepsy monitoring epilepsy nerve regeneration neurostimulation non-drug interventions pathogenesis prediction

Characteristic changes in astrocyte properties during astrocyte-to-neuron conversion induced by NeuroD1/Ascl1/Dlx2

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Neural Regeneration Research 2025年第6期20卷 1801-1815页

作者： Qing He zhen Wang Yuchen Wang Mengjie Zhu Zhile Liang Kanghong Zhang Yuge xu Gong Chen GHM Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina

Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders. However, a few recent studies have claimed that neural transcription factors cannot convert astrocytes into neurons, attributing the converted neurons to pre-existing neurons mis-expressing transgenes. In this study, we overexpressed three distinct neural transcription factors––NeuroD1, Ascl1, and Dlx2––in reactive astrocytes in mouse cortices subjected to stab injury, resulting in a series of significant changes in astrocyte properties. Initially, the three neural transcription factors were exclusively expressed in the nuclei of astrocytes. Over time, however, these astrocytes gradually adopted neuronal morphology, and the neural transcription factors was gradually observed in the nuclei of neuron-like cells instead of astrocytes. Furthermore,we noted that transcription factor-infected astrocytes showed a progressive decrease in the expression of astrocytic markers AQP4(astrocyte endfeet signal), CX43(gap junction signal), and S100β. Importantly, none of these changes could be attributed to transgene leakage into preexisting neurons. Therefore, our findings suggest that neural transcription factors such as NeuroD1, Ascl1, and Dlx2 can effectively convert reactive astrocytes into neurons in the adult mammalian brain.

关键词： aquaporin-4 Ascl1 astrocyte cortex Dlx2 gap junction glia-to-neuron conversion neural regeneration NeuroD1 reprogramming

The Predictive Value of On-treatment Virological Response for Sustained Virological Response in Patients with Chronic Hepatitis C Receiving a Personalized Treatment Program

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国际感染病学（电子版） 2013年第2期2卷 60-70页

作者： Ming-hui Li Yao Xie Yao Lu Guo-hua Qiu Lu Zhang Ge Shen Li-wei Zhuang Ju-long Hu Jian-ping Dong Cai-qin Mu Lei-ping Hu Li-jun Chen Xing-hong Li Min Yang Yun-zhong Wu Hui Zhao Shu-jing Song Jun Cheng dao-zhen xu Liver Diseases Center Beijing Ditan HospitalCapital Medical University Department of Infectious Diseases Beijing Haidian Hospital Medical Record Library Beijing Ditan HospitalCapital Medical University Clinical Test Center Beijing Ditan HospitalCapital Medical University

To investigate the effects of individualised treatment with peginterferon alpha-2a(40 kD)plus ribavirin in Chinese patients with *** Total of 297 consecutive Chinese patients were enrolled,including 250 nave cases and 47 cases who were previously *** duration was determined according to viral genotypes,prior treatment history and viral responses at week 4,12 and *** Totally,235 patients(79.1%)completed treatment and 186(87.3%)achieved *** 219 out of 289(75.8%)patients achieved HCV RNA negative at week 4(RVR)and 259 of 276(93.8%)at week *** the 164 patients with RVR who completed follow-up,158(96.3%)achieved *** with RVR had lower baseline viral loads than patients without RVR(P=0.034).The positive predictive value(PPV)of RVR for SVR was 90.7%(OR 2.10 ***-RVR,95%CI:0.50-8.7).Similar outcomes were observed among patients with HCV undetectable at week *** Viral suppression by week 4 is associated with a high rate of treatment success in treatment nave and experienced patients receiving individualized CHC therapy.

关键词： Chronic hepatitis C Early viral kinetics Pegylated interferon Ribavirin Sustained virological response Tailored regimen

肝病患者血清血管紧张素转化酶活性变化的临床意义

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世界华人消化杂志 2007年第23期15卷 2553-2556页

作者：张剑平魏红山孙继云肖凡张毅徐道振成军北京地坛医院传染病研究所北京市100011 北京中医药大学基础医学院北京市100029

目的:探讨病毒性乙型肝炎不同临床分型中血清血管紧张素转化酶(ACE)的变化及临床价值.方法:采用速率法,利用日立7180全自动生化分析仪对各组样本进行血管紧张素转化酶(ACE)活性和凝血酶原活动度(PTA)的测定.结果:病毒性乙型肝炎不同临... 详细信息

目的:探讨病毒性乙型肝炎不同临床分型中血清血管紧张素转化酶(ACE)的变化及临床价值.方法:采用速率法,利用日立7180全自动生化分析仪对各组样本进行血管紧张素转化酶(ACE)活性和凝血酶原活动度(PTA)的测定.结果:病毒性乙型肝炎不同临床分型血清中ACE活性变化的顺序由低到高为:正常对照组(24.71±9.43μmol/L),梗阻性黄疸(28.75±13.04μmol/L)乙肝后肝硬化合并肝癌(43.81±15.01μmol/L),急性病毒性乙型肝炎(46.97±17.40μmol/L),慢性病毒性乙型肝炎(53.01±16.38μmol/L),乙肝后肝硬化(72.29±20.26μmol/L),慢性重型病毒性乙型肝炎(74.12±21.04μmol/L).乙肝后肝硬化患者血清ACE活性显著高于肝硬化合并肝癌的患者,各组肝病患者血清ACE活性都明显高于正常对照组(P<0.01).慢性乙型肝炎患者凝血酶原活动度(PTA)在高于80%,40%-80%之间,低于40%时,ACE活性分别为44.01±11.27μmol/L,57.65±13.22μmol/L,72.62±12.31μmol/L.各组比较有显著性差异(P<0.05).结论:检测病毒性乙型肝炎不同临床分型中血清ACE的活性变化,对于判断肝细胞损伤程度及鉴别肝细胞性与肝外病变有一定的临床意义.

关键词：血管紧张素转化酶病毒性乙型肝炎凝血酶原活动度

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重叠延伸PCR法克隆重组复合干扰素

世界华人消化杂志 2008年第5期16卷 479-483页

作者：刘顺爱浅野龙太郎郭晶晶刘志英余康康徐道振北京地坛医院日本东北大学大学院生物工学蛋白质研究室

目的:用重叠延伸PCR(overlap extension PCR)法获得人工优化的干扰素-重组复合干扰素(consensus interferon,cIFN)基因,用原核表达系统对其进行表达,鉴定表达的cIFN活性.方法:根据大肠杆菌的偏爱密码子,人工设计cIFN的高表达基因,用over... 详细信息

目的:用重叠延伸PCR(overlap extension PCR)法获得人工优化的干扰素-重组复合干扰素(consensus interferon,cIFN)基因,用原核表达系统对其进行表达,鉴定表达的cIFN活性.方法:根据大肠杆菌的偏爱密码子,人工设计cIFN的高表达基因,用overlap PCR法合成cIFN全基因,用基因重组技术构建其原核表达载体pRA-cIFN,在大肠杆菌BL21中进行高效表达,用SDS-PAGE和Western blotting鉴定cIFN表达,用GuHCl阶段透析法进行蛋白变性、复性,用TALON(His)6亲和层析柱进行纯化,用ELISA、MTS比色定量法及血凝抑制试验检测cIFN的免疫活性和生物活性.结果:成功合成了cIFN全基因,其DNA长度与理论长度534 bp相符;用基因重组技术成功构建了cIFN原核表达载体pRA-cIFN,并用大肠杆茵BL21进行了高效表达。SDS-PAGE和Western blotting鉴定结果显示,表达蛋白主要以包涵体形式存在,其分子质量符合理论值23-3 kDa;用GuHCl阶段透析法成功进行包涵体蛋白的复性,亲和层析法纯化后cIFN的ELISA、MTS比色定量法及血凝抑制试验结果显示。表达蛋白具有明显的cIFN免疫学活性、剂量依赖性PLC/PRF/5细胞增殖抑制作用和HBsAg分泌抑制作用.结论:重叠延伸PCR法是获得重组复合基因的有效简便的方法,我们通过重叠延伸PCR法获得并表达的cIFN具有明显的抗病毒、抗细胞增殖活性.

关键词：重组复合干扰素重叠延伸PCR 原核表达活性鉴定

Impact of virus genotype on interferon treatment of patients with chronic hepatitis C: a multicenter controlled study

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Hepatobiliary & Pancreatic Diseases International 2004年第3期3卷 369-374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 and Da-Zhi Zhang Department of Infeetious Diseases , Beijing Ditan Hos-pital, Beijing 100011 , China Department of Infec-tious Diseases, Ruijin Hospital, Shanghai 200025, China De-partment of Infectious Diseases, Naifang Hospital, First Military Medical U-niversity, Guangzhou 510515, China (Luo KX) Center of Liver Disease,Beijing Friendship Hospital, Beijing 100050, China (Jia J D ) Institute ofInfectious Disease, Southwest Hospital, Third Military Medical University,Chongqing 410032, China Department of Infectious Disea-ses, Second Hospital, China Medical University, Shenyang 110004, China Department of Infectious Diseases, First Hospital, Xi’ an Jiao-tong University, Xi’ an 710061 , China ) Liver Disease Centerof Chongqing, Second Hospital, Chongqing Medical University,Chongqing 410010, China Department of Infectious Diseases Beijing Ditan Hospital Beijing 100011 China. xieyao@***

BACKGROUND: Some factors have been reported to besassociated with a greater likelihood of sustained viral re-sponse ( SVR) in the interferon (IFN) treatment of chronichepatitis C. The factors include HCV genotype, HCVRNA level in serum, state of liver disease, baseline bodyweight, age, sex, and race. The aim of this trial was to in-vestigate the influence of HCV genotype on the IFN treat-ment of patients with chronic hepatitis ***: The genotypes of HCV virus were determinedin the patients with chronic hepatitis C from several hospi-tals of China enrolled into the randomized, opened andcontrolled trial of Peg-IFN alpha-2a (pegasys) treatment,controlled with IFN-α-2a (roferon-A). The serum ALTlevels and HCV RNA concentrations of the patients weredetected before and at the end of treatment and during thefollow-up. The influence of HCV genotype on the IFNtreatment of patients with chronic hepatitis C was analyzedin intention-to-treat (ITT) ***: The HCV genotypes of 202 patients were deter-mined. Of these patients, 158(78.22%) were infected withgenotype 1 HCV and 44(21.78%) with genotype *** viral response at the end of treatment (ETVR) andsustained viral response (SVR) rates were 53.80% and25.32% respectively in patients with genotype 1 HCV, butthey were 61.36% and 43.18% in patients with genotypenon-1. The difference of SVR between patients with geno-type 1 HCV and those with genotype non-1 was significant(P =0.021). After being grouped by the used drugs, theETVR rates of patients infected with genotype 1 and non-1HCV were 76.83% and 80.95% in the patients treated withpegasys (P =0.686); but their SVR rates were 35.37% and66.67% (P =0. 01). The viral relapse rate of genotype 1HCV (55.56%) was significantly higher than that of geno-type non-1 HCV (23.53%) (P=0.02). In roferon-A group,the ETVR and SVR rates of patients with genotype 1 HCVwere 28.95% and 14.47% respectively, which were lowerbut not more significant than those of patients with ge

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