sp600125对乙醛刺激的HSC-T6细胞株的影响

肝星状细胞(HSC)的增殖与凋亡在肝纤维化的形成缮中起作十分重要的作用.乙醛刺激的HSC增殖是导致酒精性肝纤维化发生的关键因素 [1-2].丝裂原激活蛋白激酶(MAPK)包括细胞外调节蛋白激酶、c-Jun氨基末端激酶和p38,是HSC激活、增殖并导致肝纤维化发生的主要信号传导通路之一,其中,JNK信号传导通路参与了细胞增殖、分化以及凋亡的调控.我们既往对肝纤维化发病机制的研究结果证实,乙醛刺激的HSC中,p-JNK水平随JNK信号传导通路特异阻断剂sp600 125浓度增加而减少[3].     

阻断细胞外信号调节激酶活性对乙醛刺激的大鼠肝星状细胞功能的影响

细胞外信号调节激酶（ERK）信号通路参与调控细胞增殖与分化，其在乙醛刺激的肝星状细胞（HSC）活化中的意义鲜见报道。我们观察了特异性阻断剂PD98059阻断ERK活性后对乙醛刺激的HSC增殖、Ⅰ型胶原分泌、转化生长因子β1（TGFβ1）mRNA及Na^＋／Ca^2＋交换蛋白表达的影响，以探讨ERK在调控乙醛刺激HSC激活及其活化后功能改变中的作用，为肝纤维化的防治提供理论依据。     

IL-1β促肝星状细胞增殖与JNK/AP-1信号转导通路的关系

目的探讨JNK/AP-1信号转导通路在白细胞介素-1β（IL-1β）介导的促肝星状细胞（HSC）增殖中的作用。方法应用W estern印记检测JNK的活化程度。应用活细胞计数试剂盒-CCK-8检测HSC增殖并观察JNK特异性阻断剂SP600125对IL-1β促HSC增殖的影响。应用凝胶电泳移动抑制法测定AP-1的活性。结果IL-1β有明显促大鼠HSC增殖作用,JNK特异性阻断剂SP600125可抑制此作用。IL-1β刺激大鼠HSC首先引起JNK活化,并呈现出一定的时效变化。IL-1β作用HSC后可使AP-1活性增强,并呈现出一定的时效变化,而SP600125可抑制此作用。结论IL-1β可刺激HSC增殖,细胞内JNK/AP-1信号转导通路参与了IL-1β促HSC增殖作用。     

酒精性肝纤维化中主要信号转导通路的研究

在酒精性肝病的进展过程中,乙醇在体内代谢通过多个环节诱导肝星状细胞(HSC)活化增殖,导致肝纤维化的发生,这个过程是向酒精性肝硬化进展的病理阶段,早期具有可逆转的特点。了解参与HSC活化增殖的相关细胞因子介导的信号转导通路可为逆转酒精性肝纤维化提供有效的靶向。目前研究较多的信号途径包括TGF-β/Smads通路、Wnt/β-catenin通路和NF-κB通路等。     

肝星状细胞主要信号转导通路与肝纤维化的关系

肝纤维化是肝脏对各种急慢性炎症刺激损伤修复反应的结果,以胶原为主的细胞外基质(ECM)生成与降解之间失衡,在肝内大量沉积的病理过程。活化的肝星状细胞(HSC)是肝纤维化时产生ECM的主要细胞,是肝纤维化发生的核心环节。控制HSC的激活和增殖以逆转肝纤维化的进程是抗肝纤维化研究的重点之一。因此,了解影响HSC活化增殖的有关信号转导通路的作用机制有助于从根本上治疗肝纤维化,为肝纤维化的治疗提供更多更有效的思路和方法。目前研究较多的信号途径有TGF-β/Smad通路、MAPK通路、PPARγ通路、Leptin通路I、ntegrin通路、NF-κB通路等。     

转化生长因子-β信号通路与肝纤维化分子治疗研究进展

肝星状细胞（HSC）是肝纤维化发生的关键细胞，转化生长因子-β（TGF-β）在肝纤维化发生、发展过程中具有活化HSC、促进细胞外基质（ECM）合成和沉积等作用。TGF-β-Smad信号通路是TGF-β发挥生物学效应的主要通路，其分子组成和分子调节复杂，与其他信号通路存在广泛交互影响。深入研究TGF-β-Smad信号通路可进一步阐述肝纤维化的发病机制，为肝纤维化的防治提供新的有效途径。     

肝星状细胞增殖过程中的信号转导及可能的抗肝纤维化治疗靶点

如何逆转肝纤维化是临床面临的重要问题，其发病机制是一个复杂的级联反应，包括肝星状细胞（HSC）活化、增殖、表达各种信号分子及产生大量以胶原为主的细胞外间质（ECM）成分。活化HSC的增殖受一系列细胞信息分子和细胞内信号传导的调控，作用于这些信号及其转导过程或阻断这些信号转导级联反应的重要环节正成为防治肝纤维化的重要策略。本文就活化肝星状细胞增殖过程中所涉及的主要细胞内信号转导及可能的抗肝纤维化治疗靶点作一综述。     

阻断Wnt/β-catenin信号通路对活化肝星状细胞凋亡的影响

HSC的活化是肝纤维化的中心环节,参与HSC活化的多种因素如生长因子、细胞因子、氧化应激产物等,需通过HSC细胞内的信号转导才能发挥作用。Wnt／β-catenin信号通路是调控细胞生长、增殖和凋亡的关键通路,在胚胎发育和肿瘤发生中起着重要作用。近年来发现该信号通路与肺及肾纤维化的形成密切相关。     

肝纤维化中肝星状细胞内主要信号转导通路

肝纤维化是肝脏对各种慢性刺激进行损伤修复反应时,以胶原为主的细胞外基质(ECM)在肝内大量沉积的病理过程.活化的肝星状细胞(HSC)是肝纤维化时产生ECM的主要细胞.细胞因子、氧化应激以及ECM的改变等外部因素通过一定的细胞内信号转导通路激活HSC.了解HSC活化的信号转导通路能从根本上为治疗肝纤维化提供更多更有效的思路和方法.目前研究较多的信号途径有TGF-β/Smad通路、MAPK通路、PI3K通路、JAK/STAT通路、NF-κB通路、过氧化物酶体增殖物激活受体通路等.本文简要综述了肝纤维化时HSC中主要的细胞内信号转导通路.     

细胞外信号调节激酶调控乙醛对肝星状细胞的影响

目的 观察PD98059(特异性丝裂原细胞外信号反应激酶阻断剂)调控乙醛刺激大鼠肝星状细胞(HSC)周期，影响细胞增殖、Ⅰ型胶原蛋白分泌及转化生长因子(TGF)β1 mRNA表达。方法 不同浓度PD98059对乙醛刺激的HSC进行处理；流式细胞仪检测细胞周期，MTT法检测细胞增殖变化，ELISA法检测HSC内Ⅰ型胶原蛋白分泌，RT-PCR法检测HSC内TGFβ1 mRNA表达。结果 PD98059能剂量依赖性地影响乙醛刺激的HSC周期，使G0／G1期细胞百分比增高，S期细胞减少，从而抑制乙醛刺激的HSC增殖、HSC内Ⅰ型胶原蛋白分泌及TGFβ2mRNA表达。结论 细胞外信号调节激酶信号通路影响乙醛刺激的大鼠HSC增殖Ⅰ型胶原蛋白分泌及TGFβ1mRNA表达。     

妊娠时间与肺结核复发的相关性研究及诊治对策

目的 分析肺结核史患者妊娠时间和肺结核复发间相关性.方法 选取我院收治的有肺结核史的妊娠妇女576例作为研究对象,对其妊娠前肺结核治疗、治愈后妊娠时间、妊娠后复发肺结核等进行分析,总结有肺结核史育龄女性的妊娠时间和肺结核复发之间的关系.结果 肺结核治愈后不同时间段妊娠者的结核复发率比较,差异具有显著性（P＜0.05）,停药后间隔时间越久妊娠,肺结核复发的几率越小.结论 加强孕期痰菌检查,及早发现复发肺结核,提高母婴安全.     

我国骨关节结核诊治的回顾与展望

骨关节结核是危害人们健康的严重感染性疾病,近95％由他处结核病继发而来.罹患骨关节结核疾病后几乎均将致残,严重影响人们的健康、工作和生活.建国以来在党和国家的关心和支持下,骨关节结核的诊治水平取得了长足进步.时至今日,由于多种原因,学科发展和被重视程度受到一定的制约,同整个医疗行业的发展不相适应.回顾过去,展望未来,我们需要重新审视骨关节结核的诊治方法,努力推进骨关节结核诊疗技术的科学发展.     

Effect of phosphorylation of MAPK and Stat3 and expression of c-fos and c-jun proteins on hepatocarcinogenesis and their clinical significance

AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto detect the expression of p42/44~(MAPK), p-Stat3,c-fos and c-jun proteins in 55 hepatocellularcarcinomas (HCC) and their surrounding livertissues.RESULTS The positive rates and expressionlevels of p42/44~(MAPK), p-Stat3, c-fos and c-junproteins in HCCs were significantly higher thanthose in pericarcinomatous liver tissues (PCLT).A positive correlation was observed between theexpression of p42/44~(MAPK) and c-fos proteins, andbetween p-Stat3 and c-jun, but there was nosignificant correlation between P42/44~(MAPK) and p-Stat3 in HCCs and their surrounding livertissues.CONCLUSION The abnormalities of Ras/Raf/MAPK and JAKs/ Stat3 cascade reaction maycontribute to malignant transformation ofhepatocytes. Hepatocytes which are positive forp42/ 44~(MAPK), c-fos or c-jun proteins may bepotential malignant pre-cancerous cells.Activation of MAPK and Stat3 proteins may be anearly event in hepatocellular carcinogenesis.     

Replication and Inhibitors of Enteroviruses and Parechoviruses

The Enterovirus (EV) and Parechovirus genera of the picornavirus family include many important human pathogens, including poliovirus, rhinovirus, EV-A71, EV-D68, and human parechoviruses (HPeV). They cause a wide variety of diseases, ranging from a simple common cold to life-threatening diseases such as encephalitis and myocarditis. At the moment, no antiviral therapy is available against these viruses and it is not feasible to develop vaccines against all EVs and HPeVs due to the great number of serotypes. Therefore, a lot of effort is being invested in the development of antiviral drugs. Both viral proteins and host proteins essential for virus replication can be used as targets for virus inhibitors. As such, a good understanding of the complex process of virus replication is pivotal in the design of antiviral strategies goes hand in hand with a good understanding of the complex process of virus replication. In this review, we will give an overview of the current state of knowledge of EV and HPeV replication and how this can be inhibited by small-molecule inhibitors.     

Effect of phosphorylation of MAPK and Stat3 and expression of c-fas and c-jun proteins on hepatocarcinogenesis and their clinical significance

AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto detect the expression of p42/44MAPK, p-Stat3,c-fos and c-jun proteins in 55 hepatocellularcarcinomas (HCC) and their surrounding livertissues.RESULTS The positive rates and expressionlevels of p42/44MAPK, p-Stat3, c-fos and c-junproteins in HCCs were significantly higher thanthose in pericarcinomatous liver tissues (PCLT).A positive correlation was observed between theexpression of p42/44MAPK and c-fos proteins, andbetween p-Stat3 and c-jun, but there was nosignificant correlation between p42/44MAPK and p-Stat3 in HCCs and their surrounding livertissues.CONCLUSION The abnormalities of Ras/Rat/MAPK and JAKs/ Stat3 cascade reaction maycontribute to malignant transformation ofhepatocytes. Hepatocytes which are positive forp42/ 44MAPK, c-fos or c-jun proteins may bepotential malignant pre-cancerous cells.Activation of MAPK and Stat3 proteins may be anearly event in hepatocellular carcinogenesis.     

心电图、心电向量图与冠状动脉造影结果对比分析

目的:通过分析心电图(Electrocardiogram,ECG)和心电向量图(Vectorcardiogram,VCG)的改变与冠脉造影（CAG）结果进行对比,探讨ECG、VCG在冠状动脉病变中的诊断价值。方法: 选择2008年1月~2009年12月临床拟诊断为冠心病患者108例,行常规ECG、VCG检查,并于1周内进行CAG,对检查结果依据各自的诊断标准进行判定,以CAG为标准诊断法,利用四格表法,计算相关评价真实性的指标并进行比较。结果: ①VCG检测的灵敏度、特异度、准确度显著高于ECG(P<0.05,P<0．01)。②ECG、VCG阳性率与冠脉病变支数组间比较:在单支病变、双支病变中,VCG阳性率明显高于ECG(P<0.05),左主干或三支病变无统计学意义;组内比较:ECG组左主干或三支病变组较单支病变、双支病变阳性率高(P<0.05,P<0.01);VCG组左主干或三支病变组较单支病变阳性率高(P<0.05);与双支病变阳性率比较无统计学意义;③ECG、VCG阳性率与冠脉病变程度组间比较:冠脉病变狭窄50%～69%的VCG阳性率明显高于ECG (P<0.05),其他两组阳性率比较无统计学意义;组内比较:ECG组冠脉病变狭窄≥90%较50%～69%、70%～89%的阳性率高(P<0.05,P<0.01); VCG组狭窄≥90%较50%～69%阳性率高（P<0.01),其他无统计学意义。结论: VCG对冠心病检测价值显著高于ECG。     

Detection and characterization of the product of hydroethidine and intracellular superoxide by HPLC and limitations of fluorescence

Here we report the structural characterization of the product formed from the reaction between hydroethidine (HE) and superoxide (O(2)(.-)). By using mass spectral and NMR techniques, the chemical structure of this product was determined as 2-hydroxyethidium (2-OH-E(+)). By using an authentic standard, we developed an HPLC approach to detect and quantitate the reaction product of HE and O(2)(.-) formed in bovine aortic endothelial cells after treatment with menadione or antimycin A to induce intracellular reactive oxygen species. Concomitantly, we used a spin trap, 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO), to detect and identify the structure of reactive oxygen species formed. BMPO trapped the O(2)(.-) that formed extracellularly and was detected as the BMPO-OH adduct during use of the EPR technique. BMPO, being cell-permeable, inhibited the intracellular formation of 2-OH-E(+). However, the intracellular BMPO spin adduct was not detected. The definitive characterization of the reaction product of O(2)(.-) with HE described here forms the basis of an unambiguous assay for intracellular detection and quantitation of O(2)(.-). Analysis of the fluorescence characteristics of ethidium (E(+)) and 2-OH-E(+) strongly suggests that the currently available fluorescence methodology is not suitable for quantitating intracellular O(2)(.-). We conclude that the HPLC/fluorescence assay using HE as a probe is more suitable [corrected] for detecting intracellular O(2)(.-).     

大鼠骨髓间充质干细胞的分离培养和外源基因的导入

目的探讨绿色荧光蛋白基因转染骨髓间质干细胞的可行性。方法采用F icoll-PaqueTMP lus淋巴细胞分离液,根据细胞密度梯度原理,分离大鼠骨髓间充质干细胞(rM SC s)并进行体外原代培养和传代扩增,倒置相差显微镜观察细胞生长情况,免疫细胞化学法对其初步鉴定。流式细胞仪分析转染效率。结果原代和传代培养的细胞呈现梭形外观,具有较强的生长增殖能力;细胞均一表达CD44、CD54、CD106、CD29抗原。电穿孔法转染rM SC s转染率为32.8%±3%。结论采用比重为1.077 g/L的F icoll-PaqueTMP lus能分离获得大鼠骨髓间充质干细胞,经原代培养和传代培养能够迅速扩增。电穿孔法具有较高的介导外源基因表达于rM SC s的效率。     

Overweight and Obesity and Progression of ADPKD

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医源性消化道出血常见病因及其防治

目的分析医源性消化道出血的常见病因,并探讨防治措施。方法就临床所见的69例医源性消化道出血进行分析。结果医源性消化道出血分布于临床各科室,病因各不相同,但以外科手术、外伤、脑血管意外、。肾功能衰竭、呼吸功能衰竭、激素治疗、阿司匹林治疗等为主,临床上多以黑便为主要症状;对于已发生的医源性消化道出血,及时予制酸剂和胃黏膜保护剂治疗,能及时止血,大出血时经积极止血及抗休克治疗,甚至内镜治疗效果良好。结论医源性消化道出血各个临床科室均常见,病因各异,经积极、合理的治疗多预后良好。