A serum metabonomics study on the difference between alcohol- and HBV-induced liver cirrhosis by UPLC coupled with Q-TOF mass spectrometry

Background Liver cirrhosis is the fatal sequel of chronic hepatitis, making early diagnosis of liver cirrhosis critical. Liver biopsy is still the standard diagnostic method for liver cirrhosis, although its use in a wide population with alcoholism or HBV infection remains difficult. In this study, we used the metabonomic approach to detect potential biomarkers for early diagnosis of liver cirrhosis. Methods Serums were collected prospectively from normal control subjects (n=22) and patients with alcoholic cirrhosis (n=18) or hepatitis B virus (HBV)-induced cirrhosis (n=19). The serum metabonome was analyzed using ultraperformance liquid chromatography (LC)/time-of-flight mass spectrometry (MS) integrated with chemometrics. The acquired LC-MS data were normalized and processed using principal component analysis and partial least squares discrimination analysis. Results Significant differences in the metabonome among the three groups were observed. Lysophosphatidyl cholines (LPCs) (LPC C16:0, LPC C18:0, LPC C18:2, LPC C18:3, LPC C20:3, LPC C20:5) decreased in the serum of patients with hepatic cirrhosis, whereas bile acids (glycocholic acid, glycochenodeoxycholic acid), hypoxanthine, and stearamide increased in the serum of patients with liver cirrhosis. These metabolites are considered “common” biomarkers for hepatic cirrhosis. Oleamide and myristamide increased in the serum of patients with alcoholic cirrhosis but decreased in those with HBV-induced cirrhosis. These could be specific biomarkers for differential diagnosis between alcohol- and HBV-induced hepatic cirrhosis. Conclusions There are significance metabonomic differences between alcohol- and HBV-induced liver cirrhosis. This study demonstrates that metabonomics is a top-down system biology tool for conducting research on clinical problems.     

重型乙型病毒性肝炎的临床治疗现状及进展

重型病毒性肝炎是病毒性肝炎中最严重的类型,因肝细胞广泛、大量坏死,导致肝脏合成、解毒、排泄和生物转化等功能发生严重障碍或失代偿,表现为极度乏力、短期内肝功能急剧恶化、肝性脑病、凝血功能障碍、凝血酶原活动度（PTA）小于40％、腹水等;病情进展迅速,治疗难度大,尽管目前临床治疗技术得到了很大提高,但重型肝炎的病死率仍然很高。     

非生物型人工肝治疗应对血浆和白蛋白来源困难的策略

近年来人工肝技术尤其是非生物型人工肝治疗在临床上逐渐普及,明显降低了肝衰竭患者的病死率[1-2].但由于我国血浆、白蛋白供给日益紧张,在一定程度上限制了临床上人工肝治疗的开展.现针对非生物型人工肝治疗中如何应对血浆、白蛋白等来源困难的策略进行探讨.应对目前血浆、白蛋白等来源困难可以从两大方面努力,其一是大力宣传、推广义务献血及加快人造血制品的研究,以增加临床上血浆和白蛋白供应量,其二是改进临床上人工肝治疗方法、治疗技术,以节约血浆和白蛋白应用量,现主要讲述第二方面内容.     

非生物型人工肝治疗肝衰竭的现状

肝衰竭（重型肝炎）的主要治疗目标是通过支持治疗使肝脏再生以达到有效的重建肝脏基本功能,或者等到肝移植。肝移植作为改善肝衰竭患者的生存率最有效治疗手段存在着供肝来源困难的问题。而人工肝支持技术能明显改善肝衰竭患者的临床症状和生化学指标,并为肝移植起到了良好的桥梁作用。人工肝可分为非生物型人工肝和生物型人工肝。非生物型人工肝以去除体内蛋白结合毒素及水溶性毒素、补充一些体内缺乏的但必需的有益物质为目的,通过为肝脏的自我修复创造时间和机会来达到治疗肝衰竭的目的。生物型人工肝可以较好的替代肝脏解毒、生物合成和分泌代谢等功能,是国内外研究的热点。     

淫羊藿苷对缺糖缺氧条件下间充质干细胞活性及旁分泌功能的影响

目的:研究淫羊藿苷对缺糖缺氧(OGD)环境下移植的间充质干细胞(MSCs)活性和促血管生成相关细胞因子、microRNA等旁分泌功能的影响。方法:MTT法检测OGD时间、淫羊藿苷浓度对MSCs增殖活性的影响,流式细胞仪分析细胞凋亡水平,Hoechst 33342染色观察凋亡细胞形态;ELISA评估VEGF、bFGF的细胞分泌水平;实时荧光定量PCR测定MSCs及外泌体中5种促血管生成相关microRNA的表达水平。结果:高、低浓度的淫羊藿苷对OGD处理6h的MSCs表现出明显的促细胞增殖活性(P<0.05),淫羊藿苷孵育显著抑制OGD诱导的MSCs早、晚期凋亡,增加细胞上清中VEGF、bFGF的分泌水平。除了miR_103_3p,淫羊藿苷显著上调mi R_126a_5p、miR_210_3p、miR_378a_5p和miR_322_5p在MSCs的表达(P<0.05),外泌体中的表达水平低于细胞内。结论:淫羊藿苷可显著提高OGD条件下M SCs的增殖活性和旁分泌功能。     

X连锁先天性肾上腺发育不良一家系

先证者(Ⅳ2) 男,3岁1月.因"发热咳嗽20余天,腹痛呕吐10余天"入院.患儿入院前20余天无明显诱因出现发热,体温最高39.4℃,服退热药后体温能降至正常,5～6h后体温复升.伴咳嗽,阵发性3～4声连声咳,有痰难以咳出,咳嗽无明显日夜差异,无气喘气促,无畏寒寒战,无呕吐,无腹痛、腹胀、腹泻,无皮疹.当地医院予"头孢曲松+阿奇霉素"抗感染治疗5天后体温正常,咳嗽改善.10余天前出现呕吐,非喷射性,为胃内容物,同时有腹痛,阵发性,较剧烈,脐周明显,无放射痛,腹痛及呕吐与进食无明显关系,无发热、头痛,无咳嗽加重,无腹泻,无尿频、尿急、尿痛.于当地医院查血常规、超敏C反应蛋白基本正常.肝功能谷丙转氨酶330 U/L(正常参考值5～50 U/L).腹部B超提示腹腔多发淋巴结肿大,脑电图提示轻度异常.