慢性乙型肝炎肝星状细胞形态改变与肝脏微循环障碍的关系

目的研究慢性乙型肝炎肝星状细胞形态改变与肝脏微循环障碍的关系。方法采用光镜观察肝星状细胞内脂滴数和体密度的变化,同时采用透射电镜观察肝星状细胞超微结构的变化和肝窦微循环结构的改变。结果慢性乙型肝炎肝星状内脂滴数减少,典型肝星状细胞数量减少,过渡型肝星状细胞数量增多,超微结构显示核被膜表面不规则,胞质内粗面内质网明显增多,多扩张,内有中等电子密度的絮状物质,高尔基复合体发达,细胞周围胶原原纤维量明显增多。肝窦内皮细胞窗孔减少变小,有的肝窦内皮细胞内出现WP（Weibel—Paladebody）小体。狄氏腔中胶原纤维沉积增多,肝窦内皮细胞下有基底膜形成。结论肝星状细胞激活后形态改变是肝脏微循环障碍的重要促进因素。     

蛇毒所致微循环障碍的处理

地球上有蛇类２７００余种，其中毒蛇５７０余种；我国有蛇类２０３种，其中毒蛇４７种，包括陆生剧毒蛇３１种和海蛇１６种。对人类危害较大的有陆生剧毒蛇９种和海蛇２种，即蝰蛇科的五步蛇（ＡｇｋｉｓｔｒｏｄｏｎａｃｕｔｕｓＧｕｅｎｔｈｅｒ）、蝮蛇（Ａｇｋｉｓｔ...     

高复制型慢性乙型肝炎血清HBV复制指标与肝脏病变关系的探讨

本文报道５５例高复制型慢性乙型肝炎患者血清ＨＢＶ复制指标与肝脏病变的关系。５５例均为血清ＨＢｓＡｇ、ＨＢｅＡｇ及抗－ＨＢｃ阳性,部分病例血清ＨＢｃＡｇ、ＤＮＡＰ、ＨＢＶ－ＤＮＡ阳性,均作肝穿活检,病理报告ＣＡＨ５例、ＣＬＨ９例、ＣＰＨ４１例,前二者组成Ａ组,代表病变活动组;ＣＰＨ称Ｂ组,代表病变稳定组。结果显示Ａ组各项肝脏病变在ＨＢＶ复制情况下检出率普遍高于Ｂ组;ＡＬＴ异常时肝脏各项病变检出率达８０％以上者Ａ组也多于Ｂ组,而且Ａ组出现４例碎片状坏死、Ｂ组则无,显示乙肝病毒复制程度与肝脏病变活动性、广泛程度、肝功能受损等情况密切相关,因而提示抗病毒治疗的必要性。     

慢性乙型肝炎患者肠道菌群与肝脏生化指标的相关性

乙型肝炎病毒感染引起的慢性乙型肝炎(Chronic hepatitis B,CHB)是一种全球性流行疾病,严重时可引起肝功能衰竭,甚至发展成肝硬化和肝癌.也已发现CHB的发生和发展与肠道菌群的组成和结构的变化密切相关.为进一步探究肠道菌群结构与肝脏生化指标之间的联系,文中随机纳入14名CHB患者和11名健康对照者(Co...     

细胞凋亡及API5与糖尿病性勃起功能障碍的相关性研究

为探讨糖尿病(DM)大鼠阴茎海绵体凋亡情况,以及与API5表达的相关性,采用链脲佐菌素(STZ)诱导建立糖尿病大鼠模型,并使用APO阴茎勃起实验筛选DMED大鼠并检测各组大鼠阴茎海绵体压力(ICP).10周后取大鼠阴茎海绵体组织,通过原位末端标记法(TUNEL)和免疫组织化学法分别检测阴茎海绵体细胞凋亡及API5的表达情况.在该实验中,动物模型血糖浓度:观察组显著高于对照组(P<0.05);体重变化:观察组明显低于对照组(P<0.05);观察组ICP和ICP/MAP均明显低于对照组(P<0.05);观察组大鼠阴茎海绵体组织的细胞凋亡较对照组显著升高(P<0.05);观察组大鼠阴茎海绵体组织中API5蛋白表达较对照组明显减少.通过实验,可了解DM大鼠阴茎海绵体细胞凋亡率增加,这可能是糖尿病性勃起功能障碍的发病机制之一,而API5可能参与了DM大鼠阴茎海绵体细胞凋亡的基因调控.     

慢性乙型肝炎的基因治疗研究

近年来 ,慢性乙型肝炎的治疗 (主要是抗病毒治疗 )已取得较大进展。尤其是α 干扰素 (ＩＦＮ α)的合理应用及核苷类似物药物的开发与应用 ,对慢性乙型肝炎的治疗有了较大进步 ,但其疗效还不理想。如ＩＦＮ α在有选择的病例中对乙肝的长期疗效仅为 30 %～ 40 %。新近开发的抗病毒药物核苷类似物如拉咪呋啶 (ｌａｍｉｖｕｄｉｎｅ)及华米可维 (ｆａｍｉ ｃｌｏｖｉｒ)等 ,也由于其抗病毒作用短暂及易于诱发ＤＮＡ多聚酶的突变而形成耐药性和停药后易于复发等缺点 ,使其应用受到一定限制。因此 ,抗乙肝病毒的基因治疗被寄于新的希望。本文就…     

慢性乙型肝炎基因治疗若干进展

基因治疗是极具潜力的慢性乙型肝炎治疗策略。具体包括：DNA疫苗、核酶、RNA干扰等。     

冠状动脉微循环障碍及微血管型心绞痛的治疗现状

10%到30%的胸痛患者并无明显的冠状动脉病变(coronary artery disease,CAD),但50%到65%患者的细小冠状动脉血管舒张功能受损,发生冠状动脉微循环障碍(coronary microvascular dysfunction,CMD),即微血管型心绞痛(microvascular angina,MA),目前尚无针对MA的最佳治疗方案。本文综述了既往7篇微血管型心绞痛的治疗方案的临床研究结果,提示西地那非,喹那普利,雌激素和经皮脊髓电刺激对本病有一定的治疗效果,但并未发现L-精氨酸,多沙唑嗪,普伐他丁和地尔硫卓对本病有明确疗效。然而,这7篇研究对冠状动脉微循环障碍的定义不同、采用的治疗方案和效果评价指标存在较大差异,纳入的样本量较小,这些都严重影响了临床研究结果的可靠性。在将来的相关临床试验中需统一冠脉微循环障碍的定义,评估无阻塞性冠脉病变所致胸痛的冠脉微循环障碍以及相应的治疗效果。     

慢性乙型肝炎的中医治疗思路

慢性乙型肝炎是我国比较常见的慢性传染病之一,全球携带慢性乙型肝炎病毒者达到约三点五亿人,对于如何有效的治疗给医务工作者带来了较大的难题。本文作者通过中医疗法治疗慢性乙型肝炎,作出以下几点总结。     

肠道病毒与细胞凋亡的关系

肠道病毒可导致多种疾病,严重损害机体健康。为抵抗病毒侵染,宿主会利用细胞凋亡清除被感染的细胞和病毒。肠道病毒在与宿主细胞的斗争中,进化出了平衡细胞凋亡的策略以利于自身的复制和传播。本文讨论了几种肠道病毒调节细胞凋亡的途径,为进一步阐明肠道病毒急性感染相关机制和抗病毒药物的研发提供了理论基础。     

血清铁蛋白含量与HBV相关慢性肝病的临床相关性

目的 研究HBV相关慢性肝病患者血清铁蛋白（SF）含量及其与肝功能血清学指标的相关性,进一步探讨铁蛋白在诊断HBV相关慢性肝病中的价值。方法 选取2016年1~6月于安徽医科大学第二附属医院就诊的慢性乙型肝炎患者（CHB）27例、肝硬化代偿期患者（LC）17例、肝硬化失代偿期患者（DLC）30例及健康对照者30例。采用免疫比浊法分析患者SF含量,采用Spearman秩相关分析SF含量与血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、白蛋白（ALB）、前白蛋白（PALB）、总胆红素水平（TBIL）的相关性,运用受试者工作特征（ROC）曲线评价SF能否作为鉴别诊断LC与DLC的临床指标。结果 与对照组相比,CHB患者与LC患者的SF水平明显升高,DLC患者SF水平明显低于CHB患者。与LC患者相比,DLC患者SF水平明显降低。CHB患者与LC患者间SF水平差异无统计学意义。ROC曲线显示,采用SF诊断LC与DLC的曲线下面积为0.816,敏感性为56.67%,特异性为94.12%,界值为66.3。Spearman分析显示,CHB患者SF水平与ALT、AST、TBIL水平呈显著正相关,与ALB、PALB水平呈显著负相关;LC患者SF水平与ALT、AST、TBIL水平呈显著正相关;DLC患者SF水平与ALB、PALB、TBIL水平呈显著正相关。结论 SF水平与HBV相关慢性肝病的进展具有相关性,可作为临床鉴别诊断LC与DLC的血清学指标和判断HBV相关肝病损伤的潜在指标。     

Parasites mediate the relationship between host diversity and disturbance frequency

Patterns of community and population diversity are likely to be dependent on interactions between ecological variables. Here we address how two important ecological variables – extrinsic periodic mortality events (disturbances) and the presence of obligate‐killing parasites – interact to affect the diversity of niche‐specialist genotypes in laboratory populations of the bacterium Pseudomonas fluorescens. Consistent with previous studies, diversity was maximized at intermediate frequencies of disturbance in the absence of parasitic bacteriophages (phages). By contrast, no relationship was found between diversity and disturbance frequency in the presence of phage. The results can be explained in part by differential effects of phage on bacterial densities, and hence resource competition, under different disturbance regimes.     

慢加急性乙型肝炎肝衰竭并发症与预后的关系研究

目的探讨慢加急性乙型肝炎肝衰竭并发症与预后的关系,为临床上预后判断和有效治疗提供重要依据。方法回顾性分析2002年7月至2004年12月北京地坛医院收治的206例慢加急性乙型肝炎肝衰竭患者。结果慢加急性乙型肝炎肝衰竭最常见的并发症是肝性脑病(HE)、肝肾综合征(HRS)、消化道出血(GB)和继发细菌感染(SBI),HE组与无HE组好转率分别是6.9%和55.5%,HRS组与无HRS组好转率分别是0和58.9%,GB组与无GB组好转率分别是9.7%和40%,SBI组与无SBI组好转率分别是27.6%和54.1%,以上各组比较P值均≤0.001,差异有统计学意义。结论慢加急性乙型肝炎肝衰竭并发症的出现预后差,临床上预防、早期诊断和有效治疗并发症,能有效改善预后,应引起临床工作者更大重视和关注。     

Detection of elevated caspase activation and early apoptosis in liver diseases

Apoptosis has been implicated in the pathogenesis of many diseases including various forms of liver failure. The apoptotic process is essentially regulated by intracellular proteases, called caspases, which cleave several vital proteins. Despite the rapid elucidation of apoptotic signaling cascades, however, almost no information exists about the activation of caspases in situ. In the present study, a monoclonal antibody was employed which selectively recognized cleavage site-specific fragments of the caspase substrate cytokeratin-18. We demonstrate that this antibody labeled apoptotic hepatocytes in culture and, in addition, could be used to monitor caspase activation in formalin-fixed tissue biopsies. In liver sections of different liver diseases an increased number of early apoptotic cells was detected which were not found in normal tissue. Our data reveal that hepatobiliary diseases are characterized by elevated caspase activation and apoptosis, which can be specifically detected in situ by a cleavage site-specific antibody against cytokeratin-18.     

慢性乙肝肝硬化患者肝性脑病不同分级与肝脏储备功能的相关性

回顾性研究分析慢性乙肝肝硬化并发不同分级的肝性脑病（HE）患者的临床特点,探究影响HE患者预后的因素。

将380例HE患者根据临床症状进行分级,分为1～4级。分析各级HE患者的性别、年龄、实验室检查情况、终末期肝病模型（MELD）、谷草转氨酶与血小板计数比值（APRI）及白蛋白与总胆红素比值（ALBI）。采用Spearman相关性分析轻、重型HE的影响因素,并使用多因素Logistic回归法分析HE预后的影响因素,最后选用ROC曲线来评估各种独立变量对HE预后的预测价值。

1～4级HE患者组间性别、年龄差异均无统计学意义（均P＞0.05）,而血氨、MELD、APRI和ALB差异均有统计学差异（均P＜0.05）。轻、重型HE患者中性粒细胞计数和淋巴细胞计数的比值（NLR）、血氨、总胆红素（TBil）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、肿瘤坏死因子（TNF-α）、MELD、APRI及ALBI差异有统计学意义（均P＜0.05）。相关性分析显示,NLR、PLR、血氨、TBIL、ALT、AST及TNF-α是重型HE的独立影响因素。血氨及MELD评分与肝脏储备功能的相关性最高。NLR、血氨、TBil、TNF-α、高MELD评分及合并电解质紊乱均为HE预后的独立影响因素。ROC曲线分析显示,NLR的曲线下面积最大,其灵敏度最高、特异度也最大。

MELD、APRI和ALBI可用来评估不同分级HE患者的肝脏储备功能。在轻、重型HE中,血氨及MELD评分影响最大。在评估预后影响因素中,NLR水平可作为HE患者预后不良的危险因素。

     

Abrogation of hepatocyte apoptosis and early appearance of liver dysplasia in ethanol-fed p53-deficient mice

Ethanol consumption represents a major risk factor for cancer development, and a significant fraction of hepatocarcinomas arises in alcoholic liver cirrhosis. Increasing evidence indicates that ethanol acts as a tumor promoter on genetically initiated cells, by increasing the intracellular concentration of reactive oxygen species and promoting tissue necrosis/regeneration and cell proliferation. The tumor suppressor p53 restrains the expansion of carcinogen-initiated cells by inducing cell cycle arrest and apoptosis; accordingly, p53-deficient mice develop spontaneous and chemically induced neoplasms at a much higher frequency than normal mice. In normal mice exposed to a subacute (3 weeks) ethanol intoxication, a significant increase in the number of apoptotic hepatocytes was observed in concomitance with the up-regulation of the mitochondrial superoxide scavenger MnSOD, a reliable indicator of oxidative stress. Cell death occurred in the absence of liver inflammation and necrosis. Ethanol-induced hepatocyte apoptosis was completely abrogated in the p53 null background, suggesting that the tumor suppressor is necessary for hepatocyte death by ethanol. Accordingly, p53 -/- MEF were, unlike wild type cells, completely insensitive up to 0.5M ethanol in the culture medium. Strikingly, marked and widespread signs of dysplasia, with nuclear pleomorphisms and initial loss of normal architecture, heralding malignant transformation, were scored in all the mutant mice exposed to ethanol, but not in the control-fed littermates nor in ethanol-fed normal mice. These observations suggest that p53-dependent apoptosis restrains the tumorigenic effect of ethanol on liver cells, in agreement with the frequent loss of p53 function in HCC, and reveal an unexpected carcinogenic potential of alcohol which appears to be independent from the induction of cirrhosis and hepatocyte regeneration.     

Reciprocal relationships and potential feedbacks between biodiversity and disturbance

Two major foci of ecological research involve reciprocal views of the relationship between biodiversity and disturbance: disturbance determines community diversity or diversity determines realized disturbance severity. Here, we present an initial attempt to synthesize these two approaches in order to understand whether feedbacks occur, and what their effects on patterns of diversity might be. Our review of published experiments shows that (i) disturbance severity can be both a cause and a consequence of local diversity in a wide range of ecosystems and (ii) shapes of the unidirectional relationships between diversity and disturbance can be quite variable. To explore how feedbacks between diversity and disturbance might operate to alter expected patterns of diversity in nature, we develop and then evaluate a conceptual model that decomposes the relationships into component parts, considering sequentially the effect of diversity on disturbance severity, and the effect of realized disturbance on diversity loss, subsequent recruitment, and competitive exclusion. Our model suggests that feedbacks can increase mean values of richness, decrease variability, and alter the patterns of correlation between diversity and disturbance in nature. We close by offering ideas for future research to help fill gaps in our understanding of reciprocal relationships among ecological variables like diversity and disturbance.     

细胞凋亡与疾病的相关性

细胞凋亡是一种由基因控制的细胞自主性死亡过程。细胞凋亡在维持机体内环境的稳定方面起着重要作用。在细胞代谢过程中,一旦出现细胞凋亡失衡,将会导致许多疾病的发生。简单介绍细胞凋亡的基本情况及与疾病的关系。