[摘 要] 目的：探究银杏内酯B（GKB）调控蛋白激酶R样内质网激酶（PERK）/转录激活子4（ATF4）/C/EBP同源蛋白（CHOP）信号通路对肝癌细胞增殖、迁移、凋亡和上皮间质转化（EMT）的影响。方法：将人肝癌细胞MHCC-97H随机分为对照组、GKB组、GSK2656157（PERK抑制剂）组和GKB + GSK2656157组，以GKB和GSK2656157分别干预后，采用MTT法和EdU染色检测各组细胞的增殖活性及增殖率，划痕愈合实验、流式细胞术分别检测各组细胞的迁移及凋亡水平，WB法检测各组细胞中EMT和PERK/ATF4/CHOP信号通路相关蛋白的表达水平。构建MHCC-97H细胞裸鼠移植瘤模型，以同法分组及药物干预后测定各组移植瘤体积，采用免疫组化、TUNEL染色分别检测各组肿瘤细胞增殖、凋亡水平，WB法检测各组移植瘤组织中EMT和PERK/ATF4/CHOP信号通路相关蛋白的表达水平。结果：与对照组比较，GKB组细胞活性、增殖率、迁移率、移植瘤体积、Ki-67阳性细胞率、MMP2、N-cadherin与MMP9蛋白表达均显著降低（均P < 0.05），细胞凋亡率、TUNEL阳性细胞率、p-PERK/PERK与E-cadherin、ATF4、CHOP蛋白表达均显著升高（均P < 0.05）；GSK2656157组各指标变化与GKB组相反（均P < 0.05）。与GKB组比较，GKB + GSK2656157组细胞活性、增殖率、迁移率、移植瘤体积、Ki-67阳性细胞率、MMP2、N-cadherin与MMP9蛋白表达均显著升高（均P < 0.05），细胞凋亡率、TUNEL阳性细胞率、p-PERK/PERK与E-cadherin、ATF4、CHOP蛋白表达均显著降低（均P < 0.05）。结论：GKB可通过激活PERK/ATF4/CHOP信号通路抑制肝癌MHCC-97H细胞增殖、迁移和EMT并促进其凋亡。

[摘 要] 目的：采用生物信息学方法分析E3泛素连接酶（HECW2）在胃腺癌组织中的表达及其临床意义，为寻找胃腺癌诊断和预后生物标志物提供新的线索。方法：用R语言分析HECW2在泛癌中的表达及其与泛癌预后的关系。借助UCSC Xena、HPA、Kaplan-Meier Plotter等数据库分析HECW2在胃腺癌组织中的表达及其与临床病理特征之间的关系。采用WB法检测中国人胃腺癌组织及其癌旁组织中HECW2蛋白水平以验证数据库中的分析结果。借助TIMER和Cibersort数据库分析HECW2与胃腺癌免疫浸润的关系。通过LinkedOmics数据库对胃腺癌中HECW2进行GO功能分析和KEGG信号通路富集分析及相关性基因分析。结果：生物信息学分析结果表明，33种不同类型肿瘤中，包括胃腺癌在内的12种肿瘤中HECW2呈显著高表达（均P<0.05），WB法结果显示，中国人胃腺癌组织中HECW2也呈显著高表达（P<0.05）。HECW2表达水平越高，胃腺癌患者OS越短，包括CD4+ T细胞、巨噬细胞、中性粒细胞和树突状细胞在内的免疫细胞浸润丰度越高（均P˂0.01）。此外，HECW2相关信号通路主要富集于细胞外基质受体相互作用、黏着斑、细胞黏附和氧化磷酸化等生理病理过程（均P˂0.01）。结论：HECW2在胃腺癌组织中呈显著高表达且其与胃腺癌预后不良和免疫细胞浸润密切相关，有成为胃腺癌预后标志物和治疗靶点的潜力。

ObjectiveTo investigate the effect of the expression level of diacylglycerol kinase gamma (DGKγ) in paracancerous tissue on the postoperative prognosis of patients with hepatocellular carcinoma (HCC) and its clinical value. MethodsRelated clinical data were collected from 78 HCC patients who were admitted and underwent surgical resection from December 2008 to August 2012 in the Affiliated Cancer Hospital of Zhengzhou University. Quantitative real-time PCR was used to measure the mRNA expression level of DGKγ in paracancerous tissue, and then the 78 patients were divided into low expression group (DGKγ ＜0.086 2, LEP group) and high expression group (DGKγ ≥0.086 2, HEP group). Basic data and clinical features were compared between the two groups. The t-test and the Mann-Whitney U test were used for comparison of continuous data, and the chi-square test and the corrected chi-square test were used for comparison of categorical data. Univariate and multivariate Cox regression analyses were used to investigate independent influencing factors for survival and prognosis, and the Kaplan-Meier method was used to analyze the overall survival trends of all patients and the LEP and HEP groups in each subgroup of Barcelona Clinic Liver Cancer (BCLC) stages. ResultsThe multivariate Cox regression analysis showed that the expression level of DGKγ (HR=1.913，95%CI： 1.111-3.296，P=0.019), HBsAg (HR=2.645，95%CI：1.264-5.537，P=0.010), Alb (HR=0.952，95%CI：0.916-0.990，P=0.013), BCLC stage (HR=1.702，95%CI：1267-2.286，P＜0001) and tumor size (HR=1.083，95%CI：1.019-1.152，P=0011) were independent influencing factors for long-term survival of HCC patients； the LEP group had a significantly longer median survival time than the HEP group (45.0 months vs 22.9 months, P=0002 5). The stratified analysis showed that for BCLC stage A HCC, the LEP group had significantly better long-term survival than the HEP group (P=0.034 5); for BCLC stage B/C HCC, the LEP group had a longer median survival time than the HEP group (16.5 months vs 10.8 months), but there was no significant difference in short- and long-term survival between the two groups (P＞0.05). ConclusionThe expression level of DGKγ in paracancerous tissue may be a new index for predicting and evaluating the long-term survival risk of HCC patients after surgery and has certain value in clinical application.

ObjectiveTo investigate the influencing factors for the clinical effect of emergency endoscopic therapy in the treatment of patients with acute-on-chronic liver failure and gastroesophageal variceal bleeding. MethodsA total of 51 patients with acute-on-chronic liver failure and gastroesophageal variceal bleeding who underwent emergency endoscopic therapy in Beijing Shijitan Hospital and The Fifth Medical Center of Chinese PLA General Hospital from January 2016 to December 2018 were enrolled, among whom 26 had successful hemostasis and 25 had failed hemostasis. The two groups were compared in terms of general information, varices grade and bleeding manifestations under endoscope, blood biochemical parameters, ultrasound findings, Child-Pugh class, and Model for End-Stage Liver Disease (MELD) score, and the influencing factors for the outcome of hemostasis were analyzed. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; the logistic regression model was used to perform the multivariate analysis. ResultsOf all patients, 26 achieved successful hemostasis, with a success rate of hemostasis of 51%. There were no significant differences between the two groups in sex, age, etiology of liver cirrhosis, presence or absence of liver cancer, presence or absence of portal vein thrombosis, bleeding for the first time or not, white blood cell count, hemoglobin, platelet count, prothrombin time activity, alanine aminotransferase, total bilirubin, albumin, cholinesterase, MELD score, and bleeding site and bleeding manifestations under gastroscope (all P＞0.05). Compared with the failed hemostasis group, the successful hemostasis group had a significantly longer course of disease (t=2.760, P=0.008) and significantly larger portal vein diameter and diameter of varicose veins under endoscope (t=-4.847, χ2=-6.590, both P＜0.05), and the failed hemostasis group had a significantly higher proportion of patients with Child-Pugh class C disease than the successful hemostasis group (χ2=5.684, P=0.017). Course of liver cirrhosis (odds ratio ［OR］=0.913, 95% confidence interval ［CI］: 0.838-0.994, P＜0.05), portal vein diameter (OR=1.925,95%CI: 1.516-2.443, P＜0.05), and diameter of varicose veins (OR=23.254, 95%CI: 2.250-240.352, P＜0.05) were independent influencing factors for the clinical effect of endoscopic hemostasis. ConclusionThere is a relatively low success rate of emergency endoscopic hemostasis in patients with acute-on-chronic liver failure, and course of liver cirrhosis, portal vein diameter, and diameter of varicose veins are independent influencing factors for the clinical effect of endoscopic hemostasis.