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Current therapies and novel approaches for biliary diseases 预览
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作者 Indu G Rajapaksha Peter W Angus Chandana B Herath 《世界胃肠病理生理学杂志:英文版(电子版)》 2019年第1期1-10,共10页
Chronic liver diseases that inevitably lead to hepatic fibrosis, cirrhosis and/or hepatocellular carcinoma have become a major cause of illness and death worldwide. Among them, cholangiopathies or cholestatic liver di... Chronic liver diseases that inevitably lead to hepatic fibrosis, cirrhosis and/or hepatocellular carcinoma have become a major cause of illness and death worldwide. Among them, cholangiopathies or cholestatic liver diseases comprise a large group of conditions in which injury is primarily focused on the biliary system. These include congenital diseases (such as biliary atresia and cystic fibrosis), acquired diseases (such as primary sclerosing cholangitis and primary biliary cirrhosis), and those that arise from secondary damage to the biliary tree from obstruction, cholangitis or ischaemia. These conditions are associated with a specific pattern of chronic liver injury centered on damaged bile ducts that drive the development of peribiliary fibrosis and, ultimately, biliary cirrhosis and liver failure. For most, there is no established medical therapy and, hence, these diseases remain one of the most important indications for liver transplantation. As a result, there is a major need to develop new therapies that can prevent the development of chronic biliary injury and fibrosis. This mini-review briefly discusses the pathophysiology of liver fibrosis and its progression to cirrhosis. We make a special emphasis on biliary fibrosis and current therapeutic options, such as angiotensin converting enzyme-2 (known as ACE2) over-expression in the diseased liver as a novel potential therapy to treat this condition. 展开更多
关键词 Chronic liver disease BILIARY FIBROSIS CURRENT THERAPIES for BILIARY FIBROSIS ANGIOTENSIN CONVERTING enzyme-2 Gene therapy
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Novel non-invasive score to predict cirrhosis in the era of hepatitis C elimination:A population study of ex-substance users in Singapore 预览
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作者 Yue Zhao Prem Harichander Thurairajah +3 位作者 Rahul Kumar Jessica Tan Eng Kiong Teo John Chen Hsiang 《国际肝胆胰疾病杂志:英文版》 SCIE CAS CSCD 2019年第2期143-148,共6页
Background:Chronic hepatitis C infection is common among people with history of substance use.Liver fibrosis assessment is a barrier to linkage to care,particularly among those with history of substance users.The use ... Background:Chronic hepatitis C infection is common among people with history of substance use.Liver fibrosis assessment is a barrier to linkage to care,particularly among those with history of substance users.The use of non-invasive scores can be helpful in predicting liver cirrhosis in the era of HCV elimination,especially in countries where transient elastography(TE)is not available.We compared the commonly used non-invasive scores with a novel non-invasive score in predicting liver cirrhosis in this population.Methods:HCV patients with history of substance use between 2011 and 2016 were analyzed.All patients had TE for liver fibrosis assessment.Clinical performance of established non-invasive scores for fibrosis assessment and novel score were compared.Youden’s index was used to determine optimal cut-off of the novel score.Results:A total of 579 patients were included.In multivariate logistic regression,cirrhosis on TE was associated with age(P=0.002),aspartate aminotransferase(AST)(P=0.004),and platelet count(P<0.001),but not alanine aminotransferase(ALT)(P=0.896).These form the components of modified AST-toplatelet ratio index(APRI)score.Modified APRI was superior to APRI in predicting cirrhosis(AUROC,0.796 vs.0.770,P=0.007),but not fibrosis-4 score(FIB-4)(P=1.00).Modified APRI at cut-off of 4 has sensitivity,specificity and negative predictive value(NPV)of 94.4%,26.9%and 92.6%,respectively,and at 19,has sensitivity,specificity and positive predictive value(PPV)of 33.3%,96.2%and 77.1%,respectively.FIB-4 has a NPV and PPV of 88.6%,41.8%and 78.5%,77.6%,at cut-off of 1.45 and 3.25,respectively.Using the cut-off of 4 and 14 for modified APRI,32.5%of patients can be correctly classified and misses out only 5.6%of cirrhosis patients.Conclusions:Modified APRI score is superior in predicting cirrhosis in HCV population,with 32.5%of the population being correctly classified using cut-off of 4 and 14.Further studies are required to validate the findings. 展开更多
关键词 Hepatitis C Cirrhosis Fibrosis assessment AST-to-platelet ratio index Modified APRI Fibrosis-4 SCORE
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Iron and liver fibrosis:Mechanistic and clinical aspects 预览
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作者 Kosha J Mehta Sebastien Je Farnaud Paul A Sharp 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第5期521-538,共18页
Liver fibrosis is characterised by excessive deposition of extracellular matrix that interrupts normal liver functionality.It is a pathological stage in several untreated chronic liver diseases such as the iron overlo... Liver fibrosis is characterised by excessive deposition of extracellular matrix that interrupts normal liver functionality.It is a pathological stage in several untreated chronic liver diseases such as the iron overload syndrome hereditary haemochromatosis,viral hepatitis,alcoholic liver disease,non-alcoholic fatty liver disease,non-alcoholic steatohepatitis and diabetes.Interestingly,regardless of the aetiology,iron-loading is frequently observed in chronic liver diseases.Excess iron can feed the Fenton reaction to generate unquenchable amounts of free radicals that cause grave cellular and tissue damage and thereby contribute to fibrosis.Moreover,excess iron can induce fibrosis-promoting signals in the parenchymal and non-parenchymal cells,which accelerate disease progression and exacerbate liver pathology.Fibrosis regression is achievable following treatment,but if untreated or unsuccessful,it can progress to the irreversible cirrhotic stage leading to organ failure and hepatocellular carcinoma,where resection or transplantation remain the only curative options.Therefore,understanding the role of iron in liver fibrosis is extremely essential as it can help in formulating iron-related diagnostic,prognostic and treatment strategies.These can be implemented in isolation or in combination with the current approaches to prepone detection,and halt or decelerate fibrosis progression before it reaches the irreparable stage.Thus,this review narrates the role of iron in liver fibrosis.It examines the underlying mechanisms by which excess iron can facilitate fibrotic responses.It describes the role of iron in various clinical pathologies and lastly,highlights the significance and potential of iron-related proteins in the diagnosis and therapeutics of liver fibrosis. 展开更多
关键词 IRON LIVER PATHOLOGIES LIVER FIBROSIS Hepatic stellate cells Cirrhosis
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microRNA在心脏重塑中的研究进展 预览
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作者 陈阳 王婧 马丽杰 《基础医学与临床》 CSCD 2019年第4期589-593,共5页
microRNAs(miRNAs)通过对其靶基因的转录后调控参与胚胎发育、细胞增殖、分化及凋亡等过程,与心血管疾病的发生发展密切相关。心脏重塑目前缺乏有效的治疗靶点和有效的诊疗标志物,并且心脏重塑的机制研究还不够深入。目前发现miRNAs可... microRNAs(miRNAs)通过对其靶基因的转录后调控参与胚胎发育、细胞增殖、分化及凋亡等过程,与心血管疾病的发生发展密切相关。心脏重塑目前缺乏有效的治疗靶点和有效的诊疗标志物,并且心脏重塑的机制研究还不够深入。目前发现miRNAs可通过不同的分子机制调节心肌纤维化、心肌肥大以及能量代谢调节重塑。 展开更多
关键词 MICRORNAS 心脏重塑 纤维化 肥大
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Persistent elevation of fibrosis biomarker cartilage oligomeric matrix protein following hepatitis C virus eradication 预览
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作者 Kristofer Andréasson Goran Jonsson +1 位作者 Roger Hesselstrand Hans Norrgren 《世界肝病学杂志:英文版(电子版)》 2019年第3期330-334,共5页
Serum levels of cartilage oligomeric matrix protein (COMP) has been presented as a biomarker of liver fibrosis in several cross-sectional studies. COMP is also an essential mediator in carcinoma development and has al... Serum levels of cartilage oligomeric matrix protein (COMP) has been presented as a biomarker of liver fibrosis in several cross-sectional studies. COMP is also an essential mediator in carcinoma development and has also been associated with hepatocellular carcinoma. We present a prospective analysis of this biomarker in 38 patients with chronic hepatitis C who were subject to eradication therapy with direct acting antivirals. We confirm previous studies associating COMP elevation with liver cirrhosis. We also show how viral levels are correlated with COMP at baseline. In our prospective analysis, we report that successful eradication of hepatitis C results in improvement in liver stiffness and laboratory liver function tests at 1 year follow-up. In contrast, median COMP-levels remain unchanged during the study period. We conclude that the biomarker potential of COMP in the prospective evaluation of liver diseases, remains to be elucidated. 展开更多
关键词 Hepatitis C Chronic CARTILAGE oligomeric matrix protein FIBROSIS
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六味地黄丸通过调控NF-κB及TGF-β/Smad双信号通路减轻糖尿病肾病炎症及纤维化
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作者 陶鹏宇 张悦 《广州中医药大学学报》 CAS 2019年第2期245-250,共6页
【目的】基于核因子kappa B(NF-κB)及转化生长因子β(TGF-β)/Smad双信号通路,观察六味地黄丸对糖尿病肾病炎症及纤维化的影响,探讨其对肾保护作用机制。【方法】将30只SD大鼠随机分为正常组、模型组、中药组,每组10只。采用一次性腹... 【目的】基于核因子kappa B(NF-κB)及转化生长因子β(TGF-β)/Smad双信号通路,观察六味地黄丸对糖尿病肾病炎症及纤维化的影响,探讨其对肾保护作用机制。【方法】将30只SD大鼠随机分为正常组、模型组、中药组,每组10只。采用一次性腹腔注射链脲佐菌素法复制糖尿病大鼠模型。中药组给予大鼠六味地黄丸(剂量为6.75 g·kg-1·d-1)灌胃,正常组、模型组给予大鼠等体积生理盐水灌胃。给药12周后取材,检测各组大鼠空腹血糖(FBG)、尿素氮(BUN)、血肌酐(SCr)、24h尿蛋白量(24h-Pro),采用苏木素-伊红(HE)与Masson染色观察肾组织病理变化,蛋白免疫印迹(Western blot)法检测肾组织NF-κB、单核细胞趋化蛋白1(MCP-1)、TGF-β、alpha平滑肌抗体(α-SMA)、Smad2、Smad3、Smad7的表达。【结果】生化指标结果显示:与正常组比较,模型组大鼠FBG、BUN、SCr、24h-Pro升高(P<0.01);六味地黄丸治疗后上述指标均有所改善(P<0.05)。HE与Masson染色结果显示,模型组肾小球官腔变窄、系膜基质增生及炎症细胞浸润,而中药组有所改善。Western blot结果显示:与正常组比较,模型组的NF-κB、MCP-1、TGF-β、α-SMA、Smad2、Smad3表达均呈明显上调,而Smad7表达降低(P<0.01);中药组NF-κB、MCP-1、TGF-β、α-SMA、Smad2、Smad3表达下调,Smad7表达上调(P<0.05)。【结论】六味地黄丸具有肾脏保护作用,其机制可能与通过调控NF-κB及TGF-β/Smad双信号通路,从而减轻糖尿病肾病炎症损伤和纤维化有关。 展开更多
关键词 六味地黄丸 糖尿病肾病 炎症 纤维化 NF-ΚB信号通路 TGF-Β SMAD信号通路 疾病模型 动物 大鼠
虫草素抗肾纤维化研究进展 预览
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作者 代丽娟 宋立群 +3 位作者 贠捷 张德欣 于思明 马艳春 《中国临床保健杂志》 CAS 2019年第1期115-119,共5页
虫草素是从蛹虫草中分离出的一种核苷类抗生素,具有明显的抗肾纤维化作用。通过对肾纤维化病理机制的研究,阐述虫草素可从细胞分子学水平调控多种细胞因子,从而介导七大信号通路,阻碍其信号传导。七种通路相互关联,从而延缓肾纤维化及... 虫草素是从蛹虫草中分离出的一种核苷类抗生素,具有明显的抗肾纤维化作用。通过对肾纤维化病理机制的研究,阐述虫草素可从细胞分子学水平调控多种细胞因子,从而介导七大信号通路,阻碍其信号传导。七种通路相互关联,从而延缓肾纤维化及慢性肾脏病的进展。 展开更多
关键词 虫草素 肾纤维化 肾功能衰竭 慢性 信号传导
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血管紧张素II受体-脑啡肽酶双重阻滞对雌性高血压大鼠生殖道氧化应激以及纤维化的影响 预览
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作者 喻晓荣 马瑞新 +3 位作者 赵洋 张盼盼 韩学芳 余静 《海南医学院学报》 CAS 2019年第6期414-418,423共6页
目的:探讨沙库巴曲缬沙坦(LCZ696)对雌性高血压大鼠生殖道氧化应激的影响。方法:使用16周龄的SPF级别的自发性高血压大鼠,随机分为LCZ696组、缬沙坦组、氯噻酮组、SHR组、正常WKY组,每组10只。进行为期3个月的给药时期,药物通过灌胃的... 目的:探讨沙库巴曲缬沙坦(LCZ696)对雌性高血压大鼠生殖道氧化应激的影响。方法:使用16周龄的SPF级别的自发性高血压大鼠,随机分为LCZ696组、缬沙坦组、氯噻酮组、SHR组、正常WKY组,每组10只。进行为期3个月的给药时期,药物通过灌胃的方式给予。12周后,对所有大鼠在无菌的操作间进行手术取材,取其阴道组织用于实验研究,Western印迹法测其氧化应激指标(eNOS、nNOS蛋白表达),以及通过HE染色观察阴道组织纤维化程度。结果:⑴大鼠血压的改变:和自发性高血压大鼠相比,LCZ696组、缬沙坦组和氯噻酮组均能明显降低血压,包括收缩压、舒张压和平均动脉压;且和缬沙坦、氯噻酮组相比,LCZ696组降低收缩压的幅度更显著。⑵Western印迹法结果:与SHR组相比,LCZ696组和缬沙坦组eNOS、 nNOS蛋白表达明显上调(P<0.01),氯噻酮组变化无统计学意义。⑶HE染色结果:WKY组结果显示阴道上皮层形态基本正常,胶原纤维没有增加,排列整齐,没有发生明显病理改变;SHR组大鼠阴道上皮层显著增厚,角化明显,胶原纤维明显增加,排列紊乱,病理改变明显;LCZ696组和缬沙坦组均能降低阴道上皮增生,阴道胶原纤维增加,但程度有稍许差别,LCZ696组和缬沙坦组相比,阴道上皮增加稍有减轻,胶原纤维增加有所减少,纤维化程度有所减轻;而氯噻酮组对降低阴道纤维化程度不明显。结论:SHR雌性大鼠生殖道发生纤维化的原因与氧化应激有关,LCZ696在一定程度上可以抑制氧化应激的发生,改善生殖道血管内皮损伤,降低纤维化程度,从而改善SHR雌性大鼠生殖道重塑。 展开更多
关键词 高血压 雌性 LCZ696 氧化应激 纤维化
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同源性磷酸酶-张力蛋白经PI3K/AKT通路调控关节纤维化肌成纤维细胞增殖 预览
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作者 庄泽 余东杰 +4 位作者 易小友 肖大海 江诗海 何容涵 王昆 《中国组织工程研究》 CAS 北大核心 2019年第5期767-772,共6页
背景:研究显示大鼠关节纤维化中相关调控肌成纤维细胞表达的基因目前报导较少,对抑癌基因同源性磷酸酶-张力蛋白(phosphatase and tensin homolog,PTEN)在关节纤维化组织的表达目前尚未见报道。目的:探讨关节纤维化大鼠关节囊组织中PTE... 背景:研究显示大鼠关节纤维化中相关调控肌成纤维细胞表达的基因目前报导较少,对抑癌基因同源性磷酸酶-张力蛋白(phosphatase and tensin homolog,PTEN)在关节纤维化组织的表达目前尚未见报道。目的:探讨关节纤维化大鼠关节囊组织中PTEN基因的表达变化及下游PI3K/AKT信号通路在大鼠关节纤维化中的作用。方法:膝关节固定法建立大鼠膝关节纤维化模型,取膝关节后关节囊,组织块培养法分离培养肌成纤维细胞。采用定量实时PCR检测PTENmRNA的表达,采用蛋白质印迹Western Blot方法检测肌成纤维细胞中胶原蛋白1-A1、PTEN蛋白的表达情况及下游PI3K,AKT通路的信号分子改变情况。再使用PI3K/AKT通路阻滞剂LY294002对肌成纤维细胞进行处理,观察肌成纤维细胞的增殖改变情况。结果与结论:关节纤维化中PTENmRNA及蛋白表达水平较对照侧下调(P<0.05)。PTEN表达下调后,下游PI3K/AKT通路的信号分子PI3K,p-AKT的表达水平出现上调(P<0.05),肌成纤维细胞的细胞增殖活跃,使用PI3K/AKT通路阻滞剂LY294002后细胞增殖受到抑制。提示纤维化关节中PTEN表达发生下调,并经由PI3K/AKT通路调控关节纤维化的发展。 展开更多
关键词 肌成纤维细胞 关节 纤维化 PTEN PI3K/AKT通路 关节挛缩 固定 增殖 组织构建 成纤维细胞 组织工程
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不用b=0图像的活体组织体素内不相干运动分析:应用在肝脏纤维化评估的一个例子
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作者 王毅翔 《新发传染病电子杂志》 2019年第1期8-14,共7页
体素内不相干运动(intravoxel incoherent motion,IVIM)成像系列的组成一般由开始没有弥散成像梯度磁场的成像(b=0s/mm^2)及一系列不同强度(或不同持续时间)的弥散成像梯度磁场的成像。在人体的许多器官,比如肝脏,b值与成像信号的关系... 体素内不相干运动(intravoxel incoherent motion,IVIM)成像系列的组成一般由开始没有弥散成像梯度磁场的成像(b=0s/mm^2)及一系列不同强度(或不同持续时间)的弥散成像梯度磁场的成像。在人体的许多器官,比如肝脏,b值与成像信号的关系一般分为两部分:①低b值时信号快速下降与组织内的血液灌注导致的快速水分子移位有关;②高b值时信号相对较为缓慢下降与组织内的水分子弥散相关。这些关系大致表现为b值系列与信号的双指数衰减下降关系,并由三个参数来表示即Dslow(D)、Dfast(D^*)、PF(f)。Dslow反映水分子弥散移位的快慢,Dfast反映血液灌注的水分子移位的快慢,PF反映灌注占的百分比。IVIM成像虽然理论上有许多优越性,但是以前常规描述的方式在临床医学中没有实际应用起来,其原因是公式拟合困难,测量结果不稳定。肝脏为富血供器官,适合IVIM观察,但是肝脏同时受到一些生理性运动的影响,比如呼吸运动以及心脏的跳动,左肝还受到胃内容物引起的磁敏感伪影的影响。最近我们发表了两个小型临床研究,第一个研究中有16位健康志愿者及33位乙型肝炎性肝纤维化患者(其中15例为1期肝纤维化);第二个研究中有26位健康志愿者及12位乙型肝炎性肝纤维化患者(其中4例为1期肝纤维化)。这两个研究中所有的健康人与肝纤维化患者均可以通过IVIM区别。而且,第二个研究中有4例活检病理无肝纤维化的患者,其IVIM结果与正常人类似。虽然迄今为止我们的IVIM扫描参数以及数据处理方式尚未最优化,我们推想,优良的结果是基于我们采取了下面的方法:①IVIM数据分析去除b=0的图像;②仔细选择b值分布及合理选择分段拟阀值b;③去除质量不好的图像;④将所有的IVIM参数考虑进临床判断。本文描述的IVIM评估肝脏纤维化的图像采集及图像后处理分析尚未最优化。可以预期,优化后的 展开更多
关键词 体素内不相干运动 弥散成像 肝脏 纤维化
超声弹性成像联合血清标志物评估慢性乙肝纤维化的价值评价 预览
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作者 周海萍 黄岩花 +1 位作者 涂晓波 谢丽丹 《中国现代医生》 2019年第10期119-122,I0002共5页
目的观察超声弹性成像联合血清标志物评估慢性乙肝纤维化的价值。方法随机选择2015年1月~2017年12月至我院进行慢性乙型肝炎肝纤维化诊治患者100例,所有患者均给予肝脏组织病理学检查、血清学检查以及超声弹性成像检查。以肝脏组织活检... 目的观察超声弹性成像联合血清标志物评估慢性乙肝纤维化的价值。方法随机选择2015年1月~2017年12月至我院进行慢性乙型肝炎肝纤维化诊治患者100例,所有患者均给予肝脏组织病理学检查、血清学检查以及超声弹性成像检查。以肝脏组织活检结果为最终诊断结果,观察超声弹性成像和血清标志物联合诊断对乙肝纤维化分级的准确性。结果以组织学检查为最终检查结果,联合检查的总准确率为91.00%,两种检查结果无统计学差异(P>0.05)。乙肝纤维化分级F1~F4患者的超声弹性成像评分和FIB4评分随分级增加而增加,且具有统计学差异(P<0.05)。结论超声弹性成像联合血清标志物在评估慢性乙肝纤维化程度方面具有重要的临床应用价值,具有无创伤、操作简便、准确性高的特点,能够为疾病的诊断和分期提供可靠依据。 展开更多
关键词 超声弹性成像 血清标志物 慢性乙肝 纤维化
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Human immunodeficiency virus and hepatotropic viruses comorbidities as the inducers of liver injury progression 预览
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作者 Murali Ganesan Larisa Y Poluektova +1 位作者 Kusum K Kharbanda Natalia A Osna 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第4期398-410,共13页
Hepatotropic viruses induced hepatitis progresses much faster and causes more liver-related health problems in people co-infected with human immunodeficiency virus(HIV).Although treatment with antiretroviral therapy h... Hepatotropic viruses induced hepatitis progresses much faster and causes more liver-related health problems in people co-infected with human immunodeficiency virus(HIV).Although treatment with antiretroviral therapy has extended the life expectancy of people with HIV,liver disease induced by hepatitis B virus(HBV)and hepatitis C virus(HCV)causes significant numbers of non-acquired immune deficiency syndrome(AIDS)-related deaths in coinfected patients.In recent years,new insights into the mechanisms of accelerated fibrosis and liver disease progression in HIV/HCV and HIV/HBV co-infections have been reported.In this paper,we review recent studies examining the natural history and pathogenesis of liver disease in HIV-HCV/HBV co-infection in the era of direct acting antivirals(DAA)and antiretroviral therapy(ART).We also review the novel therapeutics for management of HIV/HCV and HIV/HBV coinfected individuals. 展开更多
关键词 Human IMMUNODEFICIENCY VIRUS HEPATITIS C VIRUS HEPATITIS B VIRUS FIBROSIS Stiffness Treatment
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多回声T2^*加权序列和核磁共振扩散加权成像对肝纤维化和肝硬化的量化对比初步实验 预览
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作者 顾均玉 赵虹 +3 位作者 张晶 林锦仕 林晓瑞 贝金玲 《中国医学创新》 CAS 2019年第4期14-18,共5页
目的:比较多回声T2^*加权序列与扩散加权成像(DWI)鉴别慢性肝病病患纤维化阶段的效力。方法:选取慢性肝病肝纤维化患者42例为试验组,24名健康成人志愿者为对照组。均进行MRI检查,比较肝纤维化各阶段的肝T2^*值与ADC值,分析T2^*值和ADC值... 目的:比较多回声T2^*加权序列与扩散加权成像(DWI)鉴别慢性肝病病患纤维化阶段的效力。方法:选取慢性肝病肝纤维化患者42例为试验组,24名健康成人志愿者为对照组。均进行MRI检查,比较肝纤维化各阶段的肝T2^*值与ADC值,分析T2^*值和ADC值对S1~4期纤维化分期的诊断效果,以及T2^*值和ADC值在预测纤维化0期患者出现纤维化1期或更高阶段(≥S1),纤维化1期和以下患者出现2期或更高阶段(≥S2),纤维化2期或以下患者出现3期或更高阶段(≥S3)的效力。结果:每个纤维化阶段的T2^*值和ADC值在2~4期均有明显的重叠,纤维化期和T2^*及ADC值均呈显著正相关(r=0.389、0.665,P<0.001),T2^*值和ADC值在不同纤维化阶段比较差异均有统计学意义(H=19.904、28.954,P<0.001);ROC分析显示,T2^*值和ADC值的AUC分别为0.814和0.762,比较差异有统计学意义(P<0.001),且与ADC值比较,T2^*值在区分≥S1、≥S2、≥S3时的AUC值均有更好的表现(P<0.05),另外在识别≥S1期时,T2^*值和ADC值的AUC、敏感性和特异性为0.988、100%和89.7%。结论:多回声呼吸控制T2^*加权梯度回波序列对肝纤维化期的快速、无创和准确评估有重要意义,可以作为一种技术用于判定抗病毒治疗和监测慢性肝炎患者的治疗反应,并替代部分患者的肝活检。 展开更多
关键词 慢性肝炎 纤维化 肝脏 多回声T2^*加权序列 扩散加权成像
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长期静脉注射羧基化单壁碳纳米管对大鼠肾脏的毒性作用研究 预览
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作者 谢雪平 成晓静 +3 位作者 秦悦 李苏宁 刘华钢 赖泽锋 《广西医科大学学报》 CAS 2019年第4期501-506,共6页
目的:评价静脉注射羧基化单壁碳纳米管(c-SWNTs)对大鼠肾脏的毒性作用。方法:将64只SD大鼠随机分为空白对照组(Control组)和实验组(c-SWNTs组),每组32只,Control组经尾静脉注射5%葡萄糖溶液,c-SWNTs组经尾静脉注射c-SWNTS葡萄糖溶液。... 目的:评价静脉注射羧基化单壁碳纳米管(c-SWNTs)对大鼠肾脏的毒性作用。方法:将64只SD大鼠随机分为空白对照组(Control组)和实验组(c-SWNTs组),每组32只,Control组经尾静脉注射5%葡萄糖溶液,c-SWNTs组经尾静脉注射c-SWNTS葡萄糖溶液。分别在干预30d、60d、90d及c-SWNTs组停止染毒30d后(共120d),每组随机取8只大鼠,麻醉处死后采集肾脏标本,透射电子显微镜(TEM)观察肾组织超微结构,苏木精—伊红(HE)染色和Masson染色观察肾组织病理学改变,Western blotting法检测Ⅲ型胶原(Col Ⅲ)蛋白的表达。结果: TEM结果显示,与Control组比较,30d后c-SWNTs组大鼠肾小球体积明显缩小,细胞核固缩,线粒体增大。HE和Masson染色结果显示,与Control组相比,c-SWNTs组大鼠肾脏血管壁局部增厚,肾小球毛细血管襻与球囊壁发生黏连,毛细血管襻内发生炎症细胞浸润,并随着染毒时间延长而向肾小球旁的间质扩散,肾小管管腔明显扩张,肾小球旁和肾髓质间质纤维组织增生;90d后c-SWNTs组大鼠肾脏炎症和纤维化程度最严重,但停止染毒30d后,炎症反应和纤维化程度有所减轻。与Control组比较,c-SWNTs组在连续染毒90 d后肾组织Col Ⅲ蛋白表达显著上调(P<0.05),而停止染毒30d后下调,与Control组相比差异无统计学意义(P>0.05)。结论:长期静脉注射c-SWNTs会损伤大鼠肾脏肾皮质、肾髓质和肾血管,引起可逆性的炎性反应和肾纤维化。 展开更多
关键词 单壁碳纳米管 静脉注射 肾脏 炎性反应 纤维化
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Noninvasive evaluation of nonalcoholic fatty liver disease: Current evidence and practice 预览
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作者 Jiang-Hua Zhou Jing-Jing Cai +1 位作者 Zhi-Gang She Hong-Liang Li 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第11期1307-1326,共20页
With the increasing number of individuals with diabetes and obesity,nonalcoholic fatty liver disease(NAFLD) is becoming increasingly prevalent,affecting one-quarter of adults worldwide. The spectrum of NAFLD ranges fr... With the increasing number of individuals with diabetes and obesity,nonalcoholic fatty liver disease(NAFLD) is becoming increasingly prevalent,affecting one-quarter of adults worldwide. The spectrum of NAFLD ranges from simple steatosis or nonalcoholic fatty liver(NAFL) to nonalcoholic steatohepatitis(NASH). NAFLD, especially NASH, may progress to fibrosis, leading to cirrhosis and hepatocellular carcinoma. NAFLD can impose a severe economic burden,and patients with NAFLD-related terminal or deteriorative liver diseases have become one of the main groups receiving liver transplantation. The increasing prevalence of NAFLD and the severe outcomes of NASH make it necessary to use effective methods to identify NAFLD. Although recognized as the gold standard, biopsy is limited by its sampling bias, poor acceptability, and severe complications, such as mortality, bleeding, and pain. Therefore, noninvasive methods are urgently needed to avoid biopsy for diagnosing NAFLD. This review discusses the current noninvasive methods for assessing NAFLD,including steatosis, NASH, and NAFLD-related fibrosis, and explores the advantages and disadvantages of measurement tools. In addition, we analyze potential noninvasive biomarkers for tracking disease processes and monitoring treatment effects, and explore effective algorithms consisting of imaging and nonimaging biomarkers for diagnosing advanced fibrosis and reducing unnecessary biopsies in clinical practice. 展开更多
关键词 NONALCOHOLIC fatty liver disease NONALCOHOLIC STEATOHEPATITIS STEATOSIS FIBROSIS NONINVASIVE EVALUATION
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Diffusion-weighted magnetic resonance imaging and micro-RNA in the diagnosis of hepatic fibrosis in chronic hepatitis C virus 预览
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作者 Tarek Besheer Hatem Elalfy +11 位作者 Mohamed Abd El-Maksoud Ahmed Abd El-Razek Saher Taman Khaled Zalata Wagdy Elkashef Hossam Zaghloul Heba Elshahawy Doaa Raafat Wafaa Elemshaty Eman Elsayed Abdel-Hady El-Gilany Mahmoud El-Bendary 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第11期1366-1377,共12页
BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important r... BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important roles in the regulation of biological processes such as cell proliferation and hepatic fibrosis.AIM To assess diffusion-weighted magnetic resonance imaging and miRs in diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.METHODS This prospective study included 208 patients and 82 age-and sex-matched controls who underwent diffusion-weighted magnetic resonance imaging of the abdomen, miR profiling, and liver biopsy. Pathological scoring was classified according to the METAVIR scoring system. The apparent diffusion coefficient (ADC) and miR were calculated and correlated with pathological scoring.RESULTS The ADC value decreased significantly with the progression of fibrosis, from controls(F0) to patients with early fibrosis(F1 and F2) to those with late fibrosis(F3 and F4)(median 1.92, 1.53, and 1.25 × 10-3 mm2/s, respectively)(P = 0.001).The cut-off ADC value used to differentiate patients from controls was 1.83 × 10-3 mm2/s with an area under the curve(AUC) of 0.992. Combining ADC and miR-200 b revealed the highest AUC(0.995) for differentiating patients from controls with an accuracy of 96.9%. The cut-off ADC used to differentiate early fibrosis from late fibrosis was 1.54 × 10-3 mm2/s with an AUC of 0.866. The combination of ADC and miR-200 b revealed the best AUC(0.925) for differentiating early fibrosis from late fibrosis with an accuracy of 80.2%. The ADC correlated with miR-200 b(r =-0.61, P = 0.001), miR-21(r =-0.62, P = 0.001), and miR-29(r = 0.52,P = 0.001).CONCLUSION Combining ADC and miRs offers an alternative surrogate non-invasive diagnostic tool for diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C. 展开更多
关键词 DIFFUSION Magnetic RESONANCE imaging FIBROSIS Liver HEPATITIS C VIRUS MICRO-RNA
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Serum Mac-2 binding protein glycosylation isomer level predicts hepatocellular carcinoma development in E-negative chronic hepatitis B patients 预览
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作者 Lung-Yi Mak Wai-Pan To +5 位作者 Danny Ka-Ho Wong James Fung Fen Liu Wai-Kay Seto Ching-Lung Lai Man-Fung Yuen 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第11期1398-1408,共11页
BACKGROUND Liver cirrhosis is a major risk factor for hepatocellular carcinoma(HCC)development in chronic hepatitis B(CHB). Serum Mac-2 binding protein glycosylation isomer(M2 BPGi) is a novel serological marker for f... BACKGROUND Liver cirrhosis is a major risk factor for hepatocellular carcinoma(HCC)development in chronic hepatitis B(CHB). Serum Mac-2 binding protein glycosylation isomer(M2 BPGi) is a novel serological marker for fibrosis. The role of M2 BPGi in prediction of HCC is unknown.AIM To examine the role of serum M2 BPGi in predicting HCC development in hepatitis B e antigen(HBeAg)-negative patients.METHODS Treatment-naive CHB patients with documented spontaneous HBeAg seroconversion were recruited. Serum M2 BPGi was measured at baseline(within3 years from HBeAg seroconversion), at 5 years and 10 years after HBeAg seroconversion and expressed as cut-off index(COI). Multivariate cox regression was performed to identify predictors for HCC development. ROC analysis was used to determine the cut-off value of M2 BPGi.RESULTS Among 207 patients(57% male, median age at HBeAg seroconversion 40 years old) with median follow-up of 13.1(11.8-15.5) years, the cumulative incidence of HCC at 15 years was 7%. Median M2 BPGi levels were significantly higher in patients with HCC compared to those without HCC(baseline: 1.39 COI vs 0.38 COI, P < 0.001;5-year: 1.45 COI vs 0.47 COI, P < 0.001;10-year: 1.20 COI vs 0.55 COI, P = 0.001). Multivariate analysis revealed age at HBeAg seroconversion[odds ratio(OR) = 1.196, 95% confidence interval(CI): 1.034-1.382, P = 0.016] and baseline M2 BPGi(OR = 4.666, 95%CI: 1.296-16.802, P = 0.018) were significant factors predictive of HCC. Using a cut-off value of 0.68 COI, baseline M2 BPGi yielded AUROC of 0.883 with 91.7% sensitivity and 80.8% specificity.CONCLUSION High serum M2 BPGi within 3 years after HBeAg seroconversion was a strong predictor for subsequent HCC development in treatment-naive HBeAg-negative CHB patients. 展开更多
关键词 Hepatocellular carcinoma Hepatitis B Liver FIBROSIS Mac-2 binding protein GLYCOSYLATION ISOMER BIOMARKER
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转化生长因子-β1对肺成纤维细胞中lncRNA-ATB和纤维化因子mRNA水平的影响
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作者 孙林清 王发选 +1 位作者 周倩文 李玲 《环境与职业医学》 CSCD 北大核心 2019年第3期261-265,共5页
[目的]研究转化生长因子(TGF)-β1刺激肺成纤维细胞MRC-5后被TGF-β活化的长链非编码RNA(lncRNA-ATB)和I型胶原蛋白(Col Ⅰ)、Ⅲ型胶原蛋白(Col Ⅲ)以及纤连蛋白(FN)等纤维化因子基因mRNA水平的变化及其相关性。[方法]将成纤维细胞株MR... [目的]研究转化生长因子(TGF)-β1刺激肺成纤维细胞MRC-5后被TGF-β活化的长链非编码RNA(lncRNA-ATB)和I型胶原蛋白(Col Ⅰ)、Ⅲ型胶原蛋白(Col Ⅲ)以及纤连蛋白(FN)等纤维化因子基因mRNA水平的变化及其相关性。[方法]将成纤维细胞株MRC-5以5×103个/孔的密度种于96孔板中,分别经浓度为0、2.5、5.0、10.0 ng/mL的TGF-β1刺激24 h后,通过MTT法测定细胞增殖活性,采用实时荧光定量PCR法检测MRC-5细胞中lncRNA-ATB、Col Ⅰ、Col Ⅲ、FN的mRNA相对水平。采用Spearman秩相关检验分析lncRNA-ATB与Col Ⅰ、Col Ⅲ、FN 3个基因mRNA相对水平之间的相关性。[结果]随着TGF-β1刺激浓度的增加,MRC-5细胞增殖活性增高,5.0、10.0 ng/mL组的细胞增殖活性分别是0 ng/mL组的1.07倍和1.12倍(P <0.05)。随TGF-β1浓度的增加,2.5、5.0、10.0 ng/mL组中FN的mRNA水平分别是0 ng/mL组的2.11倍(P=0.018)、3.58倍(P=0.03)和6.51倍(P <0.01);2.5、5.0、10.0 ng/mL组中Col Ⅰ的mRNA水平分别是0 ng/mL组的1.28倍(P=0.324)、4.64倍(P <0.01)和3.97倍(P <0.01);2.5、5.0、10.0 ng/mL组中Col Ⅲ的mRNA水平分别是0 ng/mL组的1.21倍(P=0.400)、1.42倍(P=0.120)和4.23倍(P <0.01)。2.5、5.0、10.0 ng/mL组中lncRNA-ATB的mRNA水平分别是0 ng/mL组的1.80倍(P=0.073)、3.57倍(P <0.01)和4.55倍(P <0.01)。此外,相关性分析结果显示,lncRNA-ATB与FN(r=0.86)、Col Ⅰ(r=0.85)和Col Ⅱ(Ir=0.82)的mRNA相对水平呈正相关关系(均P <0.05)。[结论] TGF-β1可刺激成纤维细胞增殖,升高lncRNA-ATB、Col Ⅰ、Col Ⅲ、FN的mRNA相对水平。lncRNA-ATB与纤维化因子的表达呈正相关,提示其可能与肺纤维化的发生有关。 展开更多
关键词 长链非编码RNA 转化生长因子-Β1 纤维化 Ⅰ型胶原蛋白 Ⅲ型胶原蛋白 纤连蛋白
内耳局部给药抑制人工耳蜗植入术后炎性反应和纤维化的研究进展
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作者 于浩然 贾欢 杨军 《中华耳鼻咽喉头颈外科杂志》 CAS CSCD 北大核心 2019年第1期69-72,共4页
目前全球已有超过30万人植入人工耳蜗,随着植入适应证的放宽,植入时、植入后如何良好保留患者的残余听力和内耳原有微结构及功能,如何安全有效地借助药物减轻术后炎性反应和纤维化、保留残余听力、减少毛细胞和螺旋神经节细胞的凋亡等... 目前全球已有超过30万人植入人工耳蜗,随着植入适应证的放宽,植入时、植入后如何良好保留患者的残余听力和内耳原有微结构及功能,如何安全有效地借助药物减轻术后炎性反应和纤维化、保留残余听力、减少毛细胞和螺旋神经节细胞的凋亡等已成为该领域的研究热点。由于血-迷路屏障的存在,人工耳蜗植入围手术期静脉应用激素类药物难以在内耳达到足够的药物浓度,而过度提高静脉给药剂量又会造成更严重的全身不良反应,而且部分患者因自身基础疾病限制了激素类药物的使用。因此,内耳局部给药的研究在近年受到国内外学者的重视。本文将内耳局部给药方法分为鼓室内直接给药、鼓室内缓释载体给药、耳蜗内给药和人工耳蜗植入电极的修饰四大类,并分别就其研究结果及前沿进展做一综述。 展开更多
关键词 耳蜗植入术 投药 局部 炎症 纤维化
灯盏乙素对小鼠糖尿病心肌病的保护作用研究
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作者 陈荣昌 马晓玉 +2 位作者 徐丽娇 孙桂波 孙晓波 《药学学报》 CAS CSCD 北大核心 2019年第2期294-300,共7页
探讨灯盏乙素对小鼠糖尿病心肌病的改善作用。采用高脂饲料喂养,并一次性腹腔注射50 mg?kg-1链脲佐菌素(streptozotocin, STZ)制备小鼠2型糖尿病模型,灯盏乙素腹腔注射给药, 8周后进行空腹血糖测定、血清中相关生化指标检测,并对心肌组... 探讨灯盏乙素对小鼠糖尿病心肌病的改善作用。采用高脂饲料喂养,并一次性腹腔注射50 mg?kg-1链脲佐菌素(streptozotocin, STZ)制备小鼠2型糖尿病模型,灯盏乙素腹腔注射给药, 8周后进行空腹血糖测定、血清中相关生化指标检测,并对心肌组织进行Masson染色。通过Western blot观察小鼠心肌组织中Nrf2、NFκB、AKT、p-AKT表达水平。实验过程均符合北京协和医学院动物保护委员会的相关规定。结果显示,灯盏乙素显著降低糖尿病小鼠心体比,提高心肌收缩功能,明显降低小鼠心肌纤维化水平及心肌组织collagenⅠ和collagenⅢ的表达。灯盏乙素有效降低糖尿病小鼠血清中乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)、丙二醛(MDA)水平,升高血清中抗氧化酶水平,并抑制炎性因子的释放。进一步研究发现,灯盏乙素显著升高Nrf2核转位,抑制NFκB核转位,提高AKT磷酸化水平。以上结果表明,灯盏乙素对小鼠糖尿病心肌病具有显著改善作用。 展开更多
关键词 灯盏乙素 糖尿病心肌病 纤维化 炎性反应 氧化应激
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