目的 分析不明原因的慢性血生化异常(NCALBT)患者病因诊断及其肝组织学表现.方法 回顾性分析我院诊治的248 例NCALBT患者的临床资料.所有患者接受肝活检,采用改良Scheuer评分评估.常规检测血生化、血清学和病毒学指标.结果 在248 例NCALBT患者中,诊断药物性肝损伤(DILI)89 例(35.9%),自身免疫性肝病(AILD)67例(27.0%),非酒精性脂肪性肝病(NAFLD)39 例(15.7%),遗传代谢性肝病(IMLD)30 例(12.1%),特发性非硬化性门静脉高压(INCPH)20 例(8.1%)和其他肝病 3 例(1.2%);DILI和AILD患者血生化指标显著高于其他肝病患者(P<0.05);本组168 例(67.8%)NCALBT患者肝组织处于 G2-4/S2-4 状态,即有明显的炎症和纤维化损伤,DILI(61.8%)、AILD(95.5%)、NAFLD(56.4%)、INCPH(65.0%)和其他肝病(100.0%)均以G2-4/S2-4 为主,而IMLD患者肝组织G2-4/S2-4 只占36.7%.结论 NACLBT患者病因以常见病为主,综合血清和组织学检查往往可以明确诊断.

Objective: To analyze the correlation between indocyanine green retention rate at 15 minutes (ICG-R15) and modified Scheuer score in liver tissues of patients with hepatitis B e antigen-positive/negative chronic hepatitis B (CHB), and further explore the indocyanine green clearance test (ICGCT) applied value in judging the progress of CHB-related liver disease. Methods: 407 HBeAg (+) / HBeAg (-) CHB inpatients with normal or slightly elevated serum alanine aminotransferase (ALT) [< 2 times the upper limit of normal (ULN)] and modified Scheuer score were collected, and divided into mild liver disease group (M group, 131 cases, modified Scheuer score < G2S2) and progressive liver disease group (A group, 276 cases, modified Scheuer score≥G2 and / or S2). Furthermore, the groups were sub-divided into HBeAg (+) - M group, HBeAg (-) - M group, HBeAg (+) - A group and HBeAg (-) - A group. The correlation between ICG-R15 and modified Scheuer score was analyzed retrospectively. The data were analyzed by SPSS 24.0 software. Results: Basic clinical characteristics: Among the 407 CHB cases with normal or mildly elevated serum ALT, 171 were HBeAg(+) CHB and 236 were HBeAg(-) CHB. The baseline mean serum HBV DNA was higher in HBeAg(+) CHB patients [(6.06 ± 1.95) log10IU/ml] than HBeAg(-) CHB patients [(3.60±1.37)log10IU/ml (P = 0.000)]. Included patients ICG-R15 detection characteristics: (1) The baseline mean value of ICG-R15 was not statistically significant between the two groups of HBeAg(+) CHB and HBeAg(-) CHB, and was basically within the normal range (< 10%); (2) Comparison of ICG-R15 baseline mean value among the subgroups showed that the patients in the HBeAg(+)-A group/HBeAg(-)-A group were higher than the HBeAg(+)-M group/HBeAg(-)-M group patients, and the difference was statistically significant (P = 0.013/P = 0.000). Included patients' correlation analysis between ICG-R15 and modified Scheuer score: (1) ICG-R15 and modified Scheuer score had shown weak positive correlation with inflammatory activity grade (g) in HBeAg (+) / HBeAg (-) CHB (r = 0.237, P = 0.002); r = 0.244, P = 0.000); (2) There was a weak positive correlation between ICG-R15 and fibrosis stage (s) in HBeAg (+) / HBeAg (-) CHB (r = 0. 254, P = 0; r = 0.225, P = 0.001). Included patients ICG-R15 predictive value for the severity of liver histological progression: when the cut-off value of ICG-R15 was 5.1%, the area under the receiver operating characteristic curve from M group to A group was 0.601 (P = 0.001) for predicting HBeAg (+) / HBeAg (-) CHB patients. Conclusion: ICG-R15 is positively correlated with the modified Scheuer score of liver tissue in HBeAg (+)/HBeAg (-) CHB patients with normal or slightly elevated ALT. In addition, when the cut-off value of ICG-R15 was 10%, it could not accurately reflect the effective hepatocyte reserve function of HBeAg (+) / HBeAg (-) CHB patients with normal or slightly elevated ALT. Importantly, when the cut-off value of ICG-R15 is 4.0% ~ 5.0%, it may have predictive value for liver disease progression to modified Scheuer score ≥ G2 and / or ≥S2 in HBeAg (+) / HBeAg (-) CHB patients with normal or slightly elevated ALT.

目的 :乙型肝炎病毒(hepatitis B virus,HBV)相关肝细胞癌(hepatocellular carcinoma,HCC)关键microRNA的鉴定及其对HCC细胞增殖和迁移能力的影响.方法:①利用GEO2R工具分析GEO数据库中GSE69580和GSE67882数据集,筛选HBV相关HCC组织与正常肝脏组织之间的差异表达miRNAs(DEMs);②利用miRTarBase数据库预测miRNAs的靶基因,并通过DAVID数据库对DEMs的靶基因进行基因本体论(GO)功能注释分析与京都基因和基因组百科全书(KEGG)通路富集分析;③利用蛋白-蛋白互作(PPI)网络分析确定DEMs的关键miRNAs,并利用miRNACancerMAP数据库分析miRNAs可能参与的信号通路;④使用Kaplan-Meier Plotter数据库分析关键miRNAs与HCC临床预后的关系;⑤使用MTT法和划痕实验验证DEMs对HCC细胞增殖和迁移能力的影响.结果:通过生物信息学分析共鉴定出12个上调DEMs和1个下调DEMs,并通过GO和KEGG功能富集分析表明,miR-93和miR-125b参与MAPK、PI3K-AKT和P53等肿瘤相关信号通路.通过Kaplan-Meier plotter生存分析发现,miR-93表达水平与HBV相关HCC患者的预后负相关(P=0.036),而miR-125b表达水平与HBV相关HCC患者的预后呈正相关关系(P=0.032).在HBsAg阳性的肝癌细胞系MHCC-97H中,过表达miR-93或抑制miR-125b均可增强MHCC-97H细胞的增殖和迁移能力(均P<0.05),而过表达miR-125b或抑制miR-93可降低MHCC-97H细胞增殖和迁移能力(均P<0.05).结论:miR-93和miR-125b是HBV相关HCC的关键miRNAs,且上调miR-125b或下调miR-93可抑制肝癌细胞系MHCC-97H的增殖和迁移能力.

肝细胞癌(hepatocellular carcinoma,HCC)是最常见的原发性肝脏恶性肿瘤,其侵袭性强,死亡率高,而治疗手段有限.HCC发病率的不断上升促使人们深入研究其细胞、遗传和分子生物学机制,以期开发更有效的治疗方法.约95％的HCC患者存在Wnt/β-catenin信号通路的异常激活,靶向Wnt/β-catenin信号通路为HCC的治疗提供了一条新的途径,针对该通路的抑制剂在HCC的治疗中具有良好的应用前景.本文概述了Wnt/β-catenin信号通路的作用机制和Wnt/β-catenin信号通路抑制剂在HCC中的研究.

对新型冠状病毒感染的迅速、有效干预是一项重大挑战.治疗严重急性呼吸综合征和中东呼吸综合征的经验可为新型冠状病毒感染的治疗提供新的思路,已经批准用于治疗艾滋病、乙型肝炎和丙型肝炎等疾病的核苷(酸)类似物、蛋白酶抑制剂、干扰素等抗病毒药物也是潜在的有效药物.本文对潜在抑制新型冠状病毒的抗病毒药物进行简要概述.