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Twist1-induced miR-199a-3p promotes liver fibrosis by suppressing caveolin-2 and activating TGF-βpathway

Signal Transduction and Targeted Therapy 2020年第1期5卷 1732-1743页

作者： Xiaoxue Yang Liping Ma Rong Wei Tinghong Ye JianKang Zhou Maoyao Wen ruoting men Rami I.Aqeilan Yong Peng Li Yang Department of Gastroenterology&Hepatology West China HospitalSichuan UniversityChengdu 610041China State Key Laboratory of Biotherapy and Cancer Centre West China HospitalSichuan Universityand Collaborative Innovation Centre for BiotherapyChengdu 610041China School of Bioscience and Technology Chengdu medical collegeChengdu 610500China Department of Immunology&Cancer Research Hebrew University-Hadassah Medical SchoolJerusalemIsrael

The activation of hepatic stellate cells(HSCs)participates in liver fibrosis,and emerging evidences indicate that microRNAs(miRNAs)are abnormally expressed during HSC ***,the potential roles of miRNAs in liver fibrosis still remain ***,this study aimed to investigate the role of miR-199a-3p in liver fibrosis and its underlying *** found that miR-199a-3p expression was dramatically upregulated during HSC activation in vitro,and during liver fibrogenesis in CCl4-treated rats,and its liver expression was increased in the patients with *** the luciferase assay and RT-qPCR,we revealed that the expression of miR-199a-3p in HSCs was driven by the transcription factor Twist1 which could be further induced by TGF-β*** studies showed that inhibition of miR-199a-3p in both human LX2 cells and rat HSCs significantly decreased the expression of fibrotic markers,such as fibronectin and connective tissue growth factor(CTGF),whereas the forced expression of miR-199a-3p exhibited opposite effects,demonstrating the role of miR-199a-3p in promoting HSC ***,miR-199a-3p plays an important role in TGF-βsignalling pathway activation through targeting CAV2 that negatively regulates the expression of transforming growth factor-beta receptor type I(TGFβRI).Importantly,administration of antagomiR-199a-3p in the CCl4-treated mice significantly ameliorated hepatic *** conclusion,Twist1-induced miR-199a-3p mediates the activation of HSCs by suppressing CAV2 expression and subsequently increasing TGFβRI expression to promote TGF-β*** findings highlight the therapeutic potential of miR-199a-3p for hepatic fibrosis.

关键词： Twist1 miR hepatic

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Factors and cytokine signatures associated with the response to therapy in patients with primary biliary cholangitis-autoimmune hepatitis overlap syndrome:a real-world study

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Chinese Medical Journal 2023年第6期136卷 735-736页

作者： Xiaoli Fan Yi Shen Fan Yang Xinyu Xiang Ruiqi Wu ruoting men Li Yang Department of Gastroenterology and Hepatology Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal CancerWest China HospitalSichuan UniversityChengduSichuan 610041China

To the Editor:Autoimmune liver disease is a chronic immune-mediated liver *** term“overlap syndrome”(OS)is used to describe the conditions in which patients simultaneously or consecutively present with features of primary biliary cholangitis(PBC)or primary sclerosing cholangitis and autoimmune hepatitis(AIH).[1]PBC-AIH OS is described most frequently,[2]with a prevalence of approximately 8%to 20%in adult patients with either pure PBC or AIH.

关键词： AIH patients cholangitis

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Sequential therapy or standard triple therapy for Helicobacter pylori infection:a systematic review and meta-analysis

Sequential therapy or standard triple therapy for Helicobact...

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第十七届西南地区消化病学术会议暨2014贵州省消化病及消化内镜学术年会

作者： Li Feng MaoYao Wen YongJun Zhu ruoting men Li Yang Division of Digestive Diseases West China Hospital of Sichuan University Division of Digestive Diseases Affiliated Hospital of North Sichuan Medical Collage

BACKGROUND:The effectiveness of standard triple therapy(STT)for the eradication of Helicobacter pylori(HP)has decreased *** therapy(SQT)is a new regimen proposed to address this ***:To compare the efficacy of SQT versus STT for HP ***:We performed a systematic review of the literature and pooled-data *** eradication rates were based on an intention-to-treat(ITT)and per-protocol(PP)*** risk ratios(RR)of eradication rate were pooled,with a 95%***:A total of 33 trials met the inclusion *** ITT and PP eradication rates were 80.4%and 88.7%in SQT,and 74.9%and 78.6%in STT,*** RR for eradication of HP with SQT compared with STT was 1.14(95%CI:1.09-1.18)for ITT analysis and 1.14(95%CI:1.10-1.19)for PP *** was significant heterogeneity between trial results(I=72%,Pment.

关键词： Eradication Helicobacter pylori Meta-analysis Triple therapy Sequential therapy

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Circulating Nogo-B are correlated with liver cirrhosis

Circulating Nogo-B are correlated with liver cirrhosis

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第十七届西南地区消化病学术会议暨2014贵州省消化病及消化内镜学术年会

作者： Maoyao Wen ruoting men Yongjun Zhu Xuelian Dan Wenchao Wu Xiaojing Liu Li Yang Division of Digestive Diseases West China HospitalSichuan University Laboratory of Cardiovascular Diseases Regenerative Medicine Research CenterWest China HospitalSichuan University

Aim:To evaluate the significance of plasma Nogo-B levels in patients with liver ***:Plasma Nogo-B levels were determined by enzyme linked immunosorbent assay(ELISA)in 301patients with liver cirrhosis and 130 healthy *** parameters were analyzed for the possible relationship with plasma ***:Plasma Nogo-B levels were significantly higher in liver cirrhotic patients(429.84±226.66 pg/mL)than in healthy controls(218.08±77.02 pg/mL,P0.05).Nogo-B levels were the highest in Child-Pugh class C patients among all the Child-Pugh class.(Child-Pugh class A:328.44±141.17 pg/mL,Child-Pugh class B:402.51±179.33 pg/mL,Child-Pugh class C:625.79±273.36 pg/mL,P<0.05).Plasma Nogo-B levels were positively correlated with INR(r=0.523,P=0.000)and negatively with albumin(r=-0.530,P=0.000).Plasma Nogo-B levels were significantly increased in patients with grade 3 ascites(533.25±236.58 pg/mL)than those with grade 1 ascites(351.53±198.88pg/mL)and without ascites(342.73±158.10 pg/mL)(P<0.05).Receiver operating characteristic analysis revealed that a plasma NogoB reading of 291.78 pg/mL provided a sensitivity of 61.8%and a specificity of89.6%).The area under the ROC curve of NogoB in discriminating patients with hepatic cirrhosis from healthy people was 0.815(95%confidence interval:0.771-0.858,P<0.,001).Conclusions:Plasma Nogo-B levels are increased in patients with hepatic cirrhosis while there is no significant difference among patients with different etiologies of ***,the concentrations of Nogo-B are correlated with some clinical parameters of hepatic cirrhosis.

关键词： Plasma Nogo-B hepatic cirrhosis the severity of liver diseases

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肝功能异常的少见原因:谷固醇血症1例

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中华肝脏病杂志 2021年第5期29卷 477-479页

作者：沈怡倪萍门若庭杨丽四川大学华西医院消化内科成都610041

报道1例以鼻衄、脾大起病,后因肝功能异常而最终诊断为谷固醇血症的病案。文中患者的诊治过程曲折,期间经历了两次肝脏穿刺组织学检查、脾脏切除手术,但病因一直未能明确。最终,通过基因检测等检查确诊并予以治疗,此后患者肝功能改善、... 详细信息

报道1例以鼻衄、脾大起病,后因肝功能异常而最终诊断为谷固醇血症的病案。文中患者的诊治过程曲折,期间经历了两次肝脏穿刺组织学检查、脾脏切除手术,但病因一直未能明确。最终,通过基因检测等检查确诊并予以治疗,此后患者肝功能改善、未再出现鼻衄。该例病案提醒临床医生,遇到反复肝功能异常的患者,若经常规实验室、影像学及组织学检查后仍未明确病因,则应重视遗传代谢性肝病相关基因的筛查,利于及时诊断、尽早治疗。

关键词：肝功能异常谷固醇血症 ABCG8

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Pharmacokinetics,Safety,and Tolerability of Vonoprazan-or Esomeprazole-Based Bismuth Containing Quadruple Therapy:A Phase 1,Double-Blind,Parallel-Group Study in Adults with Helicobacter pylori Infection in China

Pharmacokinetics,Safety,and Tolerability of Vonoprazan-or Es...

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2023年度全国临床药理学学术论坛

作者：苗佳 Chao Hu Jie Tang Wenyan Wang Ying Wang ruoting men Li Yang Liqun Gu Naoki Yoshida Richard Czerniak 四川大学华西医院临床试验中心 Clinical Trial Center West China HospitalSichuan University Department of Critical Care Medicine West China HospitalSichuan University Department of Gastroenterology and Hepatology West China HospitalSichuan University

Quadruple therapy comprising 2 antibiotics,a proton pump inhibitor,and bismuth,is recommended for Helicobacter pylori eradication in *** Phase 1,double-blind,parallel-group study aimed to evaluate the pharmacokinetics,safety,and tolerability of bismuth-containing vonoprazan-or esomeprazole-based quadruple therapy in ***–positive healthy subjects at a single site in *** therapy comprising vonoprazan 20 mg or esomeprazole 20 mg with bismuth potassium citrate 600 mg(equivalent to bismuth 220 mg),clarithromycin 500 mg,and amoxicillin 1000 mg was administered twice daily for 2 ***-four subjects were enrolled,22 each in the vonoprazan(mean age,34.5 years;men,63.6%) and esomeprazole(mean age,31.6 years;men,59.1%) *** 14 bismuth plasma pharmacokinetic parameters area under the plasma concentration–time curve during a dosing interval(geometric mean ratio,1.07 [90% confidence interval,0.82–1.40]) and maximum observed plasma concentration(geometric mean ratio,1.30 [90% confidence interval,0.94–1.81]) were similar between the treatment *** Day 42 follow-up,100% and 94.4% of subjects were *** negative in the vonoprazan and esomeprazole groups,*** incidence of treatment-emergent adverse events was similar between the groups,with no serious adverse *** new safety concerns were *** conclusion,vonoprazan had no significant effect on plasma bismuth exposure compared with esomeprazole.

关键词： bismuth esomeprazole Helicobacter pylori pharmacokinetics vonoprazan

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原发性胆汁性胆管炎治疗应答的影响因素及预后预测作用研究

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四川大学学报（医学版） 2023年第5期54卷 930-936页

作者：刘一锋凡小丽沈怡门若庭郭雨欣杨丽四川大学华西医院消化内科成都610041

目的探索血脂异常的原发性胆汁性胆管炎(primary biliary cholangitis,PBC)患者对熊去氧胆酸(ursodeoxycholic acid,UDCA)治疗应答不佳的影响因素、预后特点。方法回顾性收集2009年1月-2022年3月在四川大学华西医院治疗的512例确诊为PB... 详细信息

目的探索血脂异常的原发性胆汁性胆管炎(primary biliary cholangitis,PBC)患者对熊去氧胆酸(ursodeoxycholic acid,UDCA)治疗应答不佳的影响因素、预后特点。方法回顾性收集2009年1月-2022年3月在四川大学华西医院治疗的512例确诊为PBC的患者。根据UDCA治疗应答情况分为完全应答组(n=305)和UDCA应答不佳组(n=207),对比两组患者的资料,预测影响应答的不利因素。受试者工作特征(receiver operating characteristic,ROC)曲线下面积(area under the curve,AUC)确定血清总胆固醇(total cholesterol,TC)的临界值,分析患者基线实验室检查指标、治疗后应答的差异。根据临界值将患者分为TC≥5.415 mmol/L组与TC<5.415 mmol/L组,并使用UK-PBC、GLOBE评分评估两组预后的差异。结果UDCA应答不佳组的基线谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、总胆红素(total bilirubin,TB)、碱性磷酸酶(alkaline phosphatase,ALP)、γ-谷氨酰转肽酶(gammaglutamyl transferase,GGT)、甘油三酯(triglyceride,TG)、TC、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)和低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)较完全应答组升高(P均<0.05),白蛋白水平下降(P=0.012)。logistic回归模型多因素分析提示TC[比值比(odds ratio,OR)=1.501,95%置信区间(confidence interval,CI):1.275~1.767,P<0.01]和ALP(OR=1.005,95%CI:1.003~1.006,P<0.01)是影响应答的独立风险因素。ROC曲线分析提示TC≥5.415 mmol/L的PBC患者预后更差(AUC:0.727,95%CI:0.680~0.775,敏感性63.8%,特异性76.4%)。另外,高TC组(TC≥5.415 mmol/L)治疗1年时的UK-PBC风险评分高于低TC组(TC<5.415 mmol/L),差异有统计学意义(P<0.01)。结论高胆固醇血症是PBC患者对UDCA应答不佳的一个独立风险因素。当基线血清TC≥5.415 mmol/L时,PBC患者对UDCA治疗的应答及预后较差。

关键词：原发性胆汁性胆管炎熊去氧胆酸生化应答高胆固醇血症

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慢性萎缩性胃炎防治若干问题及对策

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中国中医药现代远程教育 2013年第13期11卷 105-106页

作者：刘柏宏邱作成李志钢闫宏宇门若庭乐德行新疆维吾尔自治区中医院新疆医科大学附属中医院乌鲁木齐830002 四川大学华西医院消化内科 2011级研究生成都610042

目的探讨慢性萎缩性胃炎诊治问题及策略方法。方法结合现代医学病因治疗研究进展,应用中医因机证治,整体和微观辨证结合研究方法,治疗慢性萎缩性胃炎。结果中医整体和微观辨论证结合方法,能阻断或逆转部分肠上皮化生和异型增生,使药物... 详细信息

目的探讨慢性萎缩性胃炎诊治问题及策略方法。方法结合现代医学病因治疗研究进展,应用中医因机证治,整体和微观辨证结合研究方法,治疗慢性萎缩性胃炎。结果中医整体和微观辨论证结合方法,能阻断或逆转部分肠上皮化生和异型增生,使药物预防胃癌成为可能。结论中西医结合治疗慢性萎缩性胃为有效治疗方法。

关键词：慢性萎缩性胃炎防治对策

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