Aberrant alternative splicing is one of the important causes of cancer. Polypyrimidine tract binding protein 1 (PTBP1) has been found to be involved in splicing regulation in a variety of tumors. Here, we observed significant up-regulation of PTBP1 in primary hepatocellular carcinoma (HCC) tissues. High levels of PTBP1 expression were associated with poor prognosis and increased metastatic potential in HCC. In vitro studies demonstrated that elevated PTBP1 promoted both migration and invasion by HCC cells. In contrast, knockdown of PTBP1 significantly inhibited the migration and invasion of HCC cells in vitro. Further, up-regulation of PTBP1 markedly accumulated the expression of oncogenic isoform of NUMB, NUMB-PRRL. We observed two isoforms of NUMB, NUMB-PRRL and NUMB-PRRS exhibit opposite function in HCC cells, which partially explain PTBP1 plays the tumor promoting roles in a NUMB splicing-dependent manner. In summary, our study indicates that PTBP1 may serve as an oncogene in HCC patients by regulating the alternative splicing of NUMB exon 9 and could potentially serve as a prognostic indicator.

本研究旨在观察肝癌大鼠模型经射频消融术后乏氧微环境中缺氧诱导因子(HIF)-1α、基质金属蛋白酶(MMP)-9、血管内皮生长因子(VEGF)、转化生长因子-β1(TGF-β1)表达的影响，现报道如下。

Background:Hepatocellular carcinoma (HCC) is one of the most common carcinomas all over the world, with high mortality and low survival rate. Notably, many studies have showed that a variety of molecules play vital roles in the progression of HCC. Therefore, it is urgent to find reliable biomarkers to diagnose HCC and developing novel strategies are required for the effective treatment of patients with HCC.Methods:This study obtained an HCC cohort from The Cancer Genome Atlas (TCGA). For prognostic analysis, the TCGA cohort was grouped according to different median boundaries. The key module associated with HCC was adopted by Weighted Gene Co-expression Network analysis (WGCNA). We also analyzed the survival ability, functional enrichment, and potential binding proteins of key lncRNAs. The expression of hub lncRNAs in HCC tissues and cell lines was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8) and flow cytometry were applied to detect the cell proliferation, apoptosis, and cell cycle. The interaction between NIFK-AS1 and SRSF1 was examined using an RNA pull-down assay.Results:The green module is the key module in HCC. NIFK-AS1 was highly expressed in HCC tissues and correlated with a poor prognosis in HCC patients (P=0.008). NIFK-AS1 was also significantly associated with cell mitosis, the cell cycle, and other biological processes. NIFK-AS1 deletion prevented cell proliferation, induced apoptosis, caused G2/M arrest, and affected cell cycle progression. RNA pull-down validated the NIFK-AS1/SRSF10 interaction. The overexpression of NIFK-AS1 was sufficient to rescue the growth of SRSF10 knockdown HepG2 cells.Conclusions:This study suggested that NIFK-AS1 promotes HCC cell cycle progression through interaction with SRSF10 and its findings provide new insights into therapeutic targets for HCC.

目的 探讨基于思维导图的以案例为基础(Case-based learning,CBL)教学法对内分泌见习生教学效果以及可行性的分析.方法 选取2016级临床医学专业五年制在本院内分泌科见习的42名学生作为观察组,2015级临床医学专业五年制42名学生作为对照组,以内分泌典型病例甲状腺功能亢进症和2型糖尿病为例,对照组见习生接受CBL教学法,观察组见习生接受思维导图基础上的CBL教学法.对两组学生见习结束后进行见习测试考核以及见习可行性评价.结果 观察组见习生的理论内容测试成绩[(86.50±6.45分)]以及病例分析测试成绩[(88.15±6.59分)]均高于对照组[(分别为(75.58±6.17)分和(76.96±6.33)分];观察组见习生对学习兴趣满意度[(4.43±0.32)分]、临床思维培养满意度[(4.31±0.30)分]以及理论联系实际满意度[(4.27±0.29)分等见习可行性评分均高于对照组[分别为(3.75±0.47)分,(3.64±0.46)分和(3.50±0.44)分],差异有统计性意义(P<0.05).结论 基于思维导图的CBL教学法可提高内分泌学科的临床见习教学质量,见习可行性的应用效果较好,同时对于其他临床学科的教学改革也起到抛砖引玉的作用.

目的 研究射频消融(RFA)对局部晚期胰腺癌的临床疗效.方法 对20例局部晚期胰腺癌患者行术中超声引导下射频消融治疗,并给予胆肠及胃肠吻合术,观察术后并发症、生理生化改变,比较治疗前与治疗3个月后血清CA19-9、影像学的变化、近期疗效、术后生存状况及时间.结果 发生胰瘘6例,逆行胆道感染3例,消化道出血1例,肺部感染3例,胆肠吻合口瘘、胃瘫、膈下感染各1例,2例患者发生急性胰腺炎(均经保守治疗后痊愈).随访3~18个月,术后1个月彩超示肿瘤均有不同程度的缩小,瘤内及周边未见明显血流信号,肿瘤标志物CA19-9均较术前降低.13例患者腹痛较前明显缓解.随访18个月,死亡3例,17例带瘤存活.结论 RFA可以延长晚期胰腺癌患者的生存期并提高生存质量.