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Therapeutic effects of LLT, a novel immunosuppressant, on type Ⅱ collagen- induced arthritis in DBA／1 mice

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中国药理通讯 2005年第2期22卷 36-36页

作者： ruzhou weitang pei-lanhe xiao-yuli yi-fuyang jian-pingzuo LabofImmunopharmacology GraduateSchooloftheChineseAcademyofSciencesStatekeylaboratoryofdrugresearchShanghaiInstituteofMateriaMedicaChineseAcademyofSciencesShanghai201203

AIM To evaluate the therapeutic effects of LLT on the type II collagen-induced arthritis in DBA/1 mice. LLT is a new compound derived from triptolide. LLT had been demonstrated in vitro and in vivo for its immunosuppressive activities, and our results showed LLT with low toxicity and high efficiency. LLTis a more drug-like compound comparing with the parent compound. METHODS Male DBA/1 mice were immunized at the tail base with 125 ( g of Bovine type II collagen emulsified in CFA containing Mycobacterium tuberculosis and boosted with collagen emulsified in IFA 3 weeks later. The severity of arthritis was graded visually and expressed using the arthritic index. The arthritic score of each mouse was obtained by scoring each limb as severity 0 to 4 and taken the sum of the scores of the four limbs.

关键词： LLT 治疗作用免疫抑制剂 Ⅱ型胶原质诱导作用关节炎 DBA/1 老鼠

Epidemiology,clinical and laboratory characteristics of currently alive HIV-1 infected former blood donors naive to antiretroviral therapy in Anhui Province,China

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Chinese Medical Journal 2006年第23期119卷 1941-1948页

作者： XU jian-qing WANG jian-jun HAN Li-feng XU Chen RUAN Yu-hua XU Zhen-hou CHEN Xi LIU Zhen-dong WANG Jun SU Bing DING Xin-ping GAO Bing GU Yong-bin CAO xiao-yun XING Hui HONG Kun-xue PENG Hong ZHAO Quan-bi YUAN Lin FENG yi ZHANG Gui-yun MA Li-ying WU Lan SHAO yi-ming State Key Laboratory for Infectious Disease Prevention and Control National Center for MDS/STD Control and Prevention Chinese Center for Disease Control and Prevention Beijing 100050 China Reference Laboratory National Center for MDS/STD Control and Prevention Chinese Center for Disease Control and Prevention Beijing 100050 China Anhui Provincial Center for Disease Control and Prevention Hefei230000 China fuyang Center for Disease Control and Prevention Fuyang 236000 China yingzhou Center for Disease Control and Prevention Fuyang 236000 China Funan Center for Disease Control and Prevention Fuyang 236000 China

Background Unregulated commercial blood/plasma collection among farmers occurred between 1992 and 1995 in central China and caused the second major epidemic of human immunodeficiency virus type 1 （HIV-1） infection in China. It is important to characterize HIV-l-infected former blood donors and to study characteristics associated with disease progression for future clinical intervention and vaccine development. Methods A cross-sectional study was performed on HIV-l-infected former blood donors （FBDs） and age-matched HIV-seronegative local residents. Demographic, epidemiologic, clinical and key laboratory data were collected from all study participants. Both unadjusted and adjusted multivariate linear regressions were employed to analyze the association of the decrease of CD4^＋ T-cell counts with other characteristics. Results Two hundred and ninety-four HIV-l-infected FBDs and 59 age-matched HIV-seronegative local residents were enrolled in this study. The unregulated blood/plasma collection occurred more than a decade （10.8 --12.8 years） ago, which caused the rapid spread of HIV-1 infection and the high prevalence of co-infection with hepatitis C virus （HCV, 89.5%）, hepatitis B virus （HBV） co-infection was observed in only 11 HIV＋participants （3.7%）. Deterioration in both clinical manifestation and laboratory parameters and increase of viral loads were observed in parallel with the decrease of CD4^＋ T-cell counts. The decrease of total lymphocyte counts （P〈0.001） and hemoglobin levels （P〈0.001） and the appearance of dermatosis （P=0.03） were observed in parallel with the decrease of CD4^＋ T-cell counts whereas viral loads （P〈0.001） and CD8^＋ T-cell counts （P=0.01） were inversely associated with CD4^＋ T-cell counts.Conclusions Co-infection with HCV but not HBV is highly prevalent among HIV-l-infected FBDs. CD4^＋ T-cell counts is a reliable indicator for disease progression among FBDs. Total lymphocyte counts, hemoglobin level and appearance of dermatosis were po

关键词： human immunodeficiency virus blood donors disease progression co-infection hepatitis C

Influence of weight management on the prognosis of steatohepatitis in chronic hepatitis B patients during antiviral treatment

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Hepatobiliary & Pancreatic Diseases International 2021年第5期20卷 416-425页

作者： Xiu-Juan Chang yi-Wen Shi Jing Wang Hua-Bao Liu Yan Chen xiao-Ning Zhu Yong-Ping Chen Zu-jiang Yu Qing-Hua Shang Lin Tan Qin Li Li jiang Guang-Ming xiao Liang Chen Wei Lu xiao-Yu Hu Qing-Hua Long Lin-Jing An Zi-Yuan Zou Vincent Wai-Sun Wong Yong-Ping Yang jian-Gao Fan Department of Liver Disease Chinese PLA General Hospitalthe Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China Center for Fatty Liver Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghai 200092China Department of Liver Disease Affiliated Traditional Chinese Medicine Hospital of Southwest Medical UniversityLuzhou 610072China Department of Liver Diseases Traditional Chinese Medicine Hospital of ChongqingChongqing 400038China Department of Infectious and Liver Diseases Liver Research Centerthe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000China Department of Infectious Disease the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Center of Therapeutic Liver Disease the 960th Hospital of Chinese PLATaian 271000China Liver Disease Department Fuyang 2nd People's HospitalFuyang 236015China Department of Liver Diseases Fuzhou Infectious Diseases HospitalFuzhou 350025China Department of Infectious Diseases Southwest HospitalArmy Military Medical UniversityChongqing 400038China Department of Infectious Diseases Guangzhou 8th People’s HospitalGuangzhou 510060China Department of Hepatic Diseases Shanghai Public Health Clinical CenterShanghai 201508China Department of Liver Diseases Tianjin Second People’s HospitalTianjin Institute of HepatologyTianjin 300192China National Integrative Medicine Clinical Base for Infectious Diseases and Department of Infectious Diseases Affiliated Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610000China Department of Infection and Liver Disease Yichun People’s HospitalYichun 336028China Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina

Background:Although concomitant nonalcoholic steatohepatitis(NASH)is common in chronic hepatitis B(CHB),the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain *** aimed to investigate the outcomes of NASH in CHB patients receiving antiviral ***:In the post-hoc analysis of a multicenter trial,na?ve CHB patients receiving 72-week entecavir treatment were *** evaluated the biochemical,viral and histopathological responses of these *** histopathological features of NASH were also evaluated,using paired liver biopsies at baseline and week ***:A total of 1000 CHB patients were finally enrolled for analysis,with 18.2%of whom fulfilling the criteria of NASH.A total of 727 patients completed entecavir antiviral treatment and received the second *** HBe Ag loss,HBe Ag seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH(P>0.05).Among patients with NASH,the hepatic steatosis,ballooning,lobular inflammation scores and fibrosis stages all improved during follow-up(all P<0.001),46%(63/136)achieved NASH *** with baseline body mass index(BMI)≥23 kg/m2(Asian criteria)[odds ratio(OR):0.414;95%confidence interval(95%CI):0.190-0.899;P=0.012]and weight gain(OR:0.187;95%CI:0.050-0.693;P=0.026)were less likely to have NASH *** patients without NASH at baseline,22(3.7%)developed *** BMI≥23 kg/m2(OR:12.506;95%CI:2.813-55.606;P=0.001)and weight gain(OR:5.126;95%CI:1.674-15.694;P=0.005)were predictors of incident ***:Lower BMI and weight reduction but not virologic factors determine NASH resolution in *** value of weight management in CHB patients during antiviral treatment deserves further evaluation.

关键词： Nonalcoholic steatohepatitis Hepatitis B NASH resolution Antiviral treatment Weight management

Dickkopf-1检测对女性绝经期类风湿关节炎继发骨质疏松的临床诊断价值

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解放军医学杂志 2021年第4期46卷 361-366页

作者：裴子欢黄家翌刘宇晗胡廷婷李小航李旭曾婷婷田永建余建林吴洋谭立明南昌大学第二附属医院检验科/江西省检验医学重点实验室南昌330006 南昌大学第一附属医院检验科南昌330006 安徽省阜阳市人民医院检验科安徽阜阳236000

目的探讨血清Dickkopf-1(DKK1)对女性绝经期类风湿关节炎(RA)继发骨质疏松(OP)的临床诊断价值。方法选择2019年5月-2020年9月在南昌大学第二附属医院确诊的236例绝经期患者,其中,44例RA继发OP患者为RA+OP组,150例无OP的RA患者为RA组,42... 详细信息

目的探讨血清Dickkopf-1(DKK1)对女性绝经期类风湿关节炎(RA)继发骨质疏松(OP)的临床诊断价值。方法选择2019年5月-2020年9月在南昌大学第二附属医院确诊的236例绝经期患者,其中,44例RA继发OP患者为RA+OP组,150例无OP的RA患者为RA组,42例无RA的OP患者为OP组。以该院同期43名绝经期健康女性作为对照组。采用ELISA法检测血清DKK1水平;分别采用毛细管法及速率散射比浊法检测红细胞沉降率(ESR)及C反应蛋白(CRP)水平;采用电化学发光法检测骨代谢指标甲状旁腺素(PTH)、Ⅰ型胶原C-末端肽(CTX)、25-羟维生素D3[25-(OH)D3]、Ⅰ型前胶原N-末端肽(PINP)及骨钙素(OC)水平,采用色谱法检测骨碱性磷酸酶(BALP)水平;采用Lunar Prodigy双能X线骨密度仪检测所有患者包括全髋及腰椎L1-4等部位的骨密度(BMD)、Z分数、T分数;采用ROC曲线下面积分析DKK1对RA、OP及RA继发OP的诊断效能。结果四组间DKK1、ESR、CRP、BMI、PTH、CTX、25-(OH)D3、全髋BMD、全髋T分数、BALP、全髋Z分数、腰椎L1-4 BMD、腰椎L1-4 T分数、腰椎L1-4 Z分数等指标差异均有统计学意义(P<0.01或P<0.05);RA+OP组骨折史与OP组比较差异有统计学意义(P<0.01)。双变量相关性分析及多元线性回归分析结果显示,血清DKK1与ESR、CRP、骨折史及BALP呈正相关(P<0.05),与BMI、全髋BMD、全髋T分数、全髋Z分数、腰椎L1-4 BMD、腰椎L1-4 T分数、腰椎L1-4 Z分数、PINP、25-(OH)D3、PTH等指标呈负相关(P<0.01或P<0.05)。多元线性回归分析结果显示,DKK1与CRP及BMI呈独立正相关(R2=0.048,β=0.034,P=0.003;R2=0.008,β=0.178,P=0.042),与PINP及全髋T分数呈独立负相关(R2=0.003,β=–0.022,P=0.009;R2=0.235,β=–2.375,P=0.000)。ROC曲线分析结果显示,DKK1诊断RA继发OP的最佳截断值为9.21μg/L,灵敏度为93.2%,特异度为91.1%,Kappa一致性指数为0.630,且DKK1对OP的诊断效能高于对RA的效能,Kappa一致性指数较稳定。结论女性绝经期RA继发OP患者血清DKK1水平增高,且对绝经期患者RA继发OP具有较好的诊断价值。

关键词：绝经期类风湿关节炎骨质疏松 Dickkopf-1 骨代谢

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EV71小鼠适应株制备及体内外感染特点

中国实验动物学报 2010年第5期18卷 383-389,I0004,I0005页

作者：朵建英王卫马春梅郝翊徐艳峰许文波董小平王健伟魏强秦川中国医学科学院实验动物研究所北京协和医学院比较医学中心卫生部人类疾病比较医学重点实验室北京100021 中国疾病预防控制中心病毒病预防控制所北京100050 中国医学科学院病原生物学研究所北京100730

目的用1日龄ICR小鼠传代制备EV71小鼠适应株,研究EV71亲代株与小鼠适应株的体内外感染特点,建立EV71感染ICR小鼠动物模型,为病毒疫苗和抗病毒药物的研究提供实用的动物评价工具。方法用1日龄ICR小鼠进行EV71病毒(fuyang-0805)的传代,得... 详细信息

目的用1日龄ICR小鼠传代制备EV71小鼠适应株,研究EV71亲代株与小鼠适应株的体内外感染特点,建立EV71感染ICR小鼠动物模型,为病毒疫苗和抗病毒药物的研究提供实用的动物评价工具。方法用1日龄ICR小鼠进行EV71病毒(fuyang-0805)的传代,得到小鼠传代株。以一定浓度亲代株和传代株病毒分别接种RD、Vero、SY5Y、Caco-2四种细胞,定量方法检测各时间点不同毒株在四种细胞上的复制数量,CCK8方法测定各时间点细胞的存活率;同时,两毒株分别腹腔注射感染1日龄小鼠,定期安乐死动物,采集肺、小肠、骨骼肌、大脑四种器官组织,进行动物体内病毒半定量和定量分析,同时进行各器官组织病理学观察、免疫组织化学鉴定。结果与亲代毒株相比较,小鼠传代株(EV71-MMP4)表现出更强的肌肉来源细胞嗜性与毒性;同时,两毒株腹腔注射感染1日龄小鼠后,EV71-MMP4感染的小鼠体重增长较正常小鼠体重增长缓慢;半定量和定量RT-PCR显示,在小鼠肌肉中的病毒载量于感染后1d和5d达到高峰。EV71-MMP4感染组感染率较高、病毒组织分布较广、感染持续性较好、病毒载量较高,高剂量病毒感染后小鼠小肠、心肌和骨骼肌可观察到细胞空泡变性、淋巴细胞浸润等病理变化。免疫组织化学显示感染后小鼠骨骼肌有EV71病毒特异分布。结论阜阳EV71小鼠适应株表现出较亲代毒株更好的小鼠易感性、细胞毒性,所建立的动物模型可用于EV71病毒致病机制、感染特点的研究和病毒疫苗及药物的评价。

关键词： EV71小鼠适应株 ICR小鼠动物模型

几株不同临床结局肠道病毒71型毒株的分子生物学比较研究

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现代预防医学 2017年第23期44卷 4322-4325+4331页

作者：陈恒朱渝左浩江李怡沅速丽媛程悦黄韦唯张晓春陈振华黄薇孟建彤栾荣生成都市疾病预防控制中心四川大学四川大学华西公共卫生学院(华西第四医院)

目的通过对不同临床结局EV71毒株的生物学及分子生物学特性研究,探索其毒力差异的原因。方法选择5株临床结局分别为无症状、轻症、重症（及其成人密接者）、死亡病例的病毒分离株,观察细胞病变,测定病毒滴度并进一步测定全基因序列,进... 详细信息

目的通过对不同临床结局EV71毒株的生物学及分子生物学特性研究,探索其毒力差异的原因。方法选择5株临床结局分别为无症状、轻症、重症（及其成人密接者）、死亡病例的病毒分离株,观察细胞病变,测定病毒滴度并进一步测定全基因序列,进行同源性分析与蛋白预测。结果各毒株细胞病变相似,TCID50为10;-10;,各毒株间差异不明显。基因测序结果显示,与阜阳株相比,各毒株碱基同源性为95.12%-96.06%;氨基酸同源性约为98%,存在10个一致性突变位点。蛋白预测VP1二级结构存在蛋白结合位点差异,三级结构基本一致。结论不同临床结局EV71毒株细胞毒力与基因差异细微,毒株毒力与临床结局的关系有待更多研究确认。

关键词：临床结局 EV71 比较研究