超声造影在肝硬化合并肝内局灶性小病灶中的诊断价值

目的:探讨超声造影(CEUS)在肝硬化合并肝内局灶性小病灶(≤3.0 cm)中的诊断价值。方法:选择我院自2010年4月至2014年8月患有肝硬化合并肝内局灶性小病灶的患者100例,采用MRI、CT及病理确定病灶良恶性,同时对比影像结果,计算常规超声和CEUS的准确性。结果:MRI、CT及病理确定病灶105个,其中恶性组45例,良性组60例,超声造影技术能清晰的显示出血流灌注的情况以及动脉相、门脉相及延迟相的特点。数据统计结果显示常规超声和CEUS的准确性、特异性和敏感性分别为59.05%、77.78%、45.00%和95.24%、95.56%、95.00%,两者之间的差异具有统计学意义(P0.05)。结论:相对于常规超声,CEUS对患有肝硬化合并肝内局灶性小病灶的患者具有更高的诊断价值。     

血清胱抑素C 与乙型肝炎性肝硬化肝功能损害程度的相关性分析

目的:探讨血清胱抑素C(Cys C)与乙型肝炎性肝硬化患者肝功能损伤程度的相关性分析。方法:将98例乙型肝炎性肝硬化患者按照肝功能分级的Child-Pugh评分将分为A组(Child A级,n=45例)、B组(Child B级,n=33例)、C组(Child C级,n=20例),同期选取本院门诊正常健康体检者为对照组,检测所有受试者的血清Cys C水平,比较各种之间相关指标的差异。结果:A组、B组、C组、对照组丙氨酸氨基转移酶(ALT)、天门冬氨酸转移酶(AST)、血清白蛋白(ALB)、血清Cys C及血清Cys C阳性率均有统计学差异(P0.05),C组血清Cys C、血清Cys C阳性率高于对照组(P0.05)、A组、B组,而B组高于对照组、A组(P0.05);血清Cys C阳性组与阴性组中含有Child A级、Child B级、Child C级患者的构成比具有统计学意义(P0.05),Cys C阳性组中的Child C级患者比例高于阴性组(P0.05);血清Cys C与Child-Pugh评分呈正相关(P0.05);Child-Pugh评分、ALT、AST与患者血清Cys C阳性呈正相关(P0.05);而ALB则与其呈负相关(P0.05);结论:乙型肝炎性肝硬化患者血清Cys C水平与肝功能损伤程度呈一定相关性,早期检测血清Cys C水平对于评估乙型肝炎性肝硬化患者的肝功能损害具有一定的临床意义。     

Hydroxyproline reaction with free radicals generated during benzoyl peroxide catalytic decomposition of carbon tetrachloride Structure of reaction products formed

Summary Benzoyl peroxide catalytic decomposition of carbon tetrachloride in a model system produces trichloromethyl and trichloromethylperoxyl free radicals. These radicals are also produced by CCl₄ bioactivation in liver and are considered to be responsible for the deleterious effects of this hepatotoxin. In this study, it is attempted to learn about how the .CCl₃ and CCl₃O₂. tend to react with hydroxyproline in a model system. Hydroxyproline was selected because of its role in collagen metabolism. During the interaction of both radicals with hydroxyproline a total of 16 reaction products were isolated and identified by gas chromatographic-mass spectrometric analysis. All of them were hydroxyproline analogs, no single one contained C from CCl₄ and only three contained chlorine. Consequently, most adducts would be missed in experiments where formation of reaction products are studied by formation of¹⁴C or³⁶Cl labeled adducts (e.g. covalent binding studies used by toxicologists). If similar hydroxyproline analog reaction products were observed during CCl₄ intoxication it might be reasonably expected that they interfered with collagen metabolism and participate in cirrhogenic effects of CCl₄ on the liver.     

基于Bcl-2/CytC探究槲皮素对肝硬化大鼠微循环及肝脏病变的影响

摘要 目的：基于Bcl-2/CytC调控网络探讨槲皮素对肝硬化大鼠微循环及肝脏病变的影响。方法：选取清洁级SD大鼠45 只,随机数字表法分为A组、LC组、QUE low group、QUE high group,ETV组,10 只/组,除10只健康大鼠外其余均建立肝硬化模型,QUE low group采用槲皮素50 mg/kg灌胃,QUE high group采用槲皮素100 mg/kg灌胃,ETV组采用恩替卡韦分散片0.5 mg/次灌胃,A组与LC组均用生理盐水灌胃,均1 次/d,共计14 d。采用ELISA检测大鼠血清中丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST)、总胆固醇（TC）、甘油三酯（TG）水平及血栓素A2（TXA2）、血管紧张素II（AngⅡ）、前列环素（PGI2）含量,HE染色比较各组肝组织形态,免疫印迹检测大鼠肝组织中Bcl-2、Bax、细胞色素C(CytC)蛋白表达。结果：与A group相比,LC group的ALT、AST、TC、TG、TXA2、AngII表达均较高,PGI2、CytC、Bax较低（P<0.05）;与LC组比较,QUE low group的ALT、AST、TC、TG、TXA2、AngII均降低,PGI2、CytC、Bax升高（P<0.05）;与QUE low group比较,ETV group的ALT、AST、TC、TG、TXA2、AngII均降低,PGI2、CytC、Bax升高（P<0.05）;与ETV group比较,QUE high group的ALT、AST、TC、TG、TXA2、AngII均降低,PGI2、CytC、Bax升高（P<0.05）。A组大鼠肝脏组织完好;LC group大鼠肝组织损伤严重;QUE low group大鼠肝间质仍有纤维组织增生及炎症浸润现象;ETV组仍有肝细胞变性及炎性因子;QUE high group大鼠肝组织变性反应及汇管区炎症降低。与A group比较,LC group有明显肝纤维化、肝细胞变性坏死及炎细胞浸润（P＜0.05）;与LC group比较,QUE low group大鼠肝脏纤维化等有所缓解（P＜0.05）;与QUE low group比较,ETV group大鼠肝脏纤维化、变性坏死及炎细胞浸润缓解（P＜0.05）;与ETV group比较,QUE high group大鼠肝脏纤维化、变性坏死及炎细胞浸润改善（P＜0.05）。结论：槲皮素对肝硬化大鼠的肝组织具有一定保护作用,改善肝功能和肝脏微循环、肝脏病变,其机制可能调节Bcl-2、Bax和CytC等相关蛋白有关。     

心得安预防门脉高压引起初次消化道出血的疗效观察

目的:观察心得安预防门脉高压症消化道出血的疗效、不良反应及临床应用的注意事项。方法选择本院102例肝硬化食道胃底静脉曲张患者,随机分为心得安组(52例)和安慰剂组(25例)。对出血发作的病情、持续的时间、输血量的多少、对止血药物的反应、生存期以及副反应进行观察。结果随访12个月,治疗组出血发生率为19.2%,安慰剂组为28%,两组差异无显著意义。随访20个月,治疗组出血发生率28.8%,安慰剂组48%,两组比较有显著性差异(P<0.05),但生存时间无显著差异。结论心得安对预防门脉高压症消化道初次出血有明显疗效,但不能延长肝硬化病人的生存期。     

A computational model of the hepatic circulation applied to analyze the sensitivity of hepatic venous pressure gradient (HVPG) in liver cirrhosis

Measurement of hepatic venous pressure gradient (HVPG) is currently widely adopted to provide an estimate of portal pressure gradient (PPG) in the diagnosis and treatment of portal hypertension associated with liver cirrhosis. Despite the well-documented clinical utility of HVPG, it remains poorly understood how the relationship between HVPG and PPG is affected by factors involved in the pathogenesis and progression of cirrhosis. In the study, a computational model of the hepatic circulation calibrated to in vivo data was developed to simulate the procedure of HVPG measurement and quantitatively investigate the error of HVPG relative to PPG under various pathophysiological conditions. Obtained results confirmed the clinical consensus that HVPG is applicable to the assessment of portal hypertension caused by increased vascular resistance located primarily at the sinusoidal and postsinusoidal sites rather than at the presinusoidal site. On the other hand, our study demonstrated that the accuracy of HVPG measurement was influenced by many factors related to hepatic hemodynamics even in the case of sinusoidal portal hypertension. For instance, varying presinusoidal portal vascular resistance significantly altered the difference between HVPG and PPG, while an enhancement in portosystemic collateral flow tended to improve the accuracy of HVPG measurement. Moreover, it was found that presinusoidal and postsinusoidal vascular resistances interfered with each other with respect to their influence on HVPG measurement. These findings suggest that one should take into account patient-specific pathological conditions in order to achieve a better understanding and utilization of HVPG in the clinical practice.     

肝纤维化发病机制中细胞和分子机制的研究进展

关于肝纤维化形成的复杂的细胞和分子联系已经有了相当多的研究进展。最近的数据表明,纤维化进程的终止和纤维分解途径的恢复可以逆转晚期肝纤维化甚至肝硬化。因此,需要更好地阐明参与肝纤维化的细胞和分子机制。HSC(肝星状细胞)的激活是肝纤维化发生的中心事件,此外还有产生基质的其他细胞来源,包括肝门区的成纤维细胞,纤维细胞和骨髓来源的肌纤维母细胞。这些细胞与其邻近细胞通过多种联系聚集产生纤维疤痕并造成持续性损伤。阐明不同类型的细胞的相互作用,揭示细胞因子对这些细胞的影响,理清活化HSC基因表达的调控,将有助于我们探索新的肝纤维化治疗靶点。此外,不同的病因有不同的致病途径,弄清这一点有助于针对特异性疾病治疗方法的发现。本文概述了肝纤维化的细胞和分子机制的最新研究进展,可能为未来治疗方法带来新的突破。     

Circulating mortalin autoantibody—a new serological marker of liver cirrhosis

Mortalin is a stress chaperone belonging to the Hsp70 family of proteins. Frequently enriched in cancers, it is a multifunctional protein and regulates cell proliferation, apoptosis, mitochondrial functions, and the activity of tumor suppressor protein p53. In the present study, we investigated circulating mortalin and its autoantibody in normal, cirrhosis, and cancerous liver. We found that although mortalin is enriched in liver cancer cells and tumors, it is not detected in the serum of either the liver cirrhosis or cancer patients. In contrast, mortalin autoantibody was detected in patients’ sera and showed significant correlation with the occurrence of cirrhosis. It is suggested as a potential noninvasive marker for liver cirrhosis.     

维生素K2对肝脏的保护作用

急慢性肝损伤、肝硬化和肝癌等肝脏疾病是严重影响人类健康的重大疾病。肝脏是人体内最大的消化腺,是体内新陈代谢的中心站,也是肠道内容物及细菌代谢产物进入体内循环的必经之路。虽然由肠道吸收的很多细菌代谢产物对肝脏有伤害作用,然而越来越多的研究表明细菌产生的维生素K2对于肝脏具有保护作用。本文综述近几年来维生素K2在肝癌、肝硬化、肝再生等方面的研究进展,简要总结了维生素K2可能的作用机制,使我们看到了维生素K2防治肝脏疾病的潜力。