Comprehensive analysis of key lncRNAs in HCV-positive hepatocellular carcinoma

IntroductionHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Despite the therapeutic advances in HCC in the past few decades, the mortality rate of HCC is still high. Hepatitis C (HCV) infection is one of the major etiological risk factors of HCCs. However, the underlying mechanisms of HCV-induced hepatocarcinogenesis remain largely unclear.Material and methodsOur study represented the comprehensive analysis of differentially expressed lncRNAs in HCV-positive HCC for the first time by analyzing the public dataset {"type":"entrez-geo","attrs":{"text":"GSE17856","term_id":"17856"}}GSE17856. Co-expression network and gene ontology (GO) analysis revealed the functions of those differentially expressed lncRNAs.ResultsWe identified 256 upregulated lncRNAs and 198 downregulated lncRNAs in HCV- positive HCC compared to the normal liver tissues. Co-expression network and GO analysis showed that these lncRNAs were involved in regulating metabolism, energy pathways, proliferation and the immune response. Seven lncRNAs (LOC341056, CCT6P1, PTTG3P, LOC643387, LOC100133920, C3P1 and C22orf45) were identified as key lncRNAs and co-expressed with more than 100 differentially expressed genes (DEGs) in HCV-related HCC. Kaplan-Meier analysis showed that higher expression levels of LOC643387, PTTG3P, LOC341056, CCT6P1 and lower expression levels of C3P1 and C22orf45 were associated with shorter survival time in the TCGA dataset.ConclusionsWe believe that this study can provide novel potential therapeutic and prognostic biomarkers for HCV-positive HCC.     

传统炎性标志物对妊娠期肝内胆汁淤积症的诊断及预后预测价值

目的探讨传统炎性标志物对妊娠期肝内胆汁淤积症(ICP)的诊断及预后预测价值。 方法选择2009年1月至2019年1月,于厦门大学附属中山医院消化内科和妇产科确诊的130例ICP患者为研究对象,并纳入ICP组,其中,初产妇为86例,经产妇为44例。根据ICP严重程度,进一步将其分为重度ICP亚组(n＝29)和轻度ICP亚组(n＝101)。选择同期在本院就诊的80例健康孕妇纳入对照组。按照86例初产妇的分娩孕龄,进一步分为ICP早产亚组(n＝37)和ICP足月亚组(n＝49)。采集受试者一般临床资料(年龄、孕龄等),天冬氨酸氨基转氨酶(AST)、丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)、γ-谷氨酰转肽酶(GGT)、白细胞计数、中性粒细胞计数、淋巴细胞计数、血小板计数、红细胞分布宽度(RDW)、血红蛋白(Hb)、平均血小板体积(MPV)、血细胞比容(HCT)、中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)和血清总胆汁酸(sTBA)等。本研究经过厦门大学附属中山医院伦理委员会批准(审批文号：2019076),与所有患者签署临床研究知情同意书。 结果①ICP组和对照组孕妇年龄、中性粒细胞计数、淋巴细胞计数、血小板计数、MPV、ALP、AST、NLR和sTBA比较,差异均有统计学意义(P<0.05)。2组孕妇孕龄、白细胞计数、HCT、Hb、GGT、ALT和PLR比较,差异无统计学意义(P>0.05)。②轻度ICP亚组患者的孕龄大于重度ICP亚组,而轻度ICP亚组患者sTBA浓度低于重度ICP亚组,2组比较,差异均有统计学意义(P<0.05)。此外,2组患者年龄、白细胞计数、中性粒细胞计数、淋巴细胞计数、MPV、HCT、血小板计数、Hb、GGT、ALP、ALT、AST、NLR和PLR比较,差异均无统计学意义(P>0.05)。③NLR、血小板计数和MPV诊断ICP的受试者工作特征曲线(ROC)分析结果：NLR、血小板计数和MPV诊断ICP的曲线下面积(AUC)分别为0.802(95%CI：0.737～0.867,P<0.001), 0.642(95%CI：0.560～0.724,P<0.001)和0.947(95%CI：0.920～0.974,P<0.001);根据约登指数最大原则,NLR、血小板计数和MPV诊断ICP的最佳临界值分别为2.831、254×10⁹/L和9.662 fL,此时其诊断ICP的敏感度分别为71.4%、64.7%和72.2%,特异度分别为81.3%、71.2%和82.5%。④ICP早产亚组与ICP足月分娩亚组孕妇ALT、AST和sTBA水平比较,差异均有统计学意义(P<0.05);而2组孕妇年龄、白细胞计数、中性粒细胞计数、淋巴细胞计数、血小板计数、MPV、PDW、NLR和PLR比较,差异均无统计学意义(P>0.05)。⑤sTBA、ALT、AST预测ICP所致早产的ROC分析结果：sTBA、ALT和AST预测ICP所致早产的AUC分别为0.634(95%CI：0.513～0.751,P<0.05),0.672(95%CI：0.563～0.784,P<0.001)和0.692(95%CI：0.544～0.793,P<0.001);根据约登指数最大原则,sTBA、ALT和AST预测ICP所致早产的最佳临界值分别为48 μmol/L、56 U/L和37 U/L,此时其预测ICP所致早产的敏感度分别为67.2%、62.2%和63.2%,特异度分别为59.6%、41.3%和49.6%。 结论传统炎性标志物NLR、血小板计数、MPV对诊断ICP具有良好准确度,而目前发现的传统炎性标志物对ICP严重程度评估均无价值,sTBA、ALT和AST水平可能对ICP所致早产具有一定预测价值。     

Cultural relevance in medication adherence interventions with underrepresented adults: Systematic review and meta-analysis of outcomes

ObjectiveThis meta-analysis systematically compiles intervention research designed to increase medication adherence among underrepresented adults.MethodComprehensive searching located published and unpublished studies with medication adherence behavior outcomes. Studies were included if samples were adults living in North America who had any of the following backgrounds or identities: African American, Native American, Latino, Latino American, Asian, Asian American, Pacific Islander, Native Alaskan, or Native Hawaiian. Random-effect analyses synthesized data to calculate effect sizes as a standardized mean difference and variability measures. Exploratory moderator analyses examined the association between specific efforts to increase the cultural relevance of medication adherence studies and behavior outcomes.ResultsData were synthesized across 5559 subjects in 55 eligible samples. Interventions significantly improved medication adherence behavior of treatment subjects compared to control subjects (standardized mean difference = 0.211). Primary studies infrequently reported strategies to enhance cultural relevance. Exploratory moderator analyses found no evidence that associated cultural relevance strategies with better medication adherence outcomes.ConclusionThe modest magnitude of improvements in medication adherence behavior documents the need for further research with clear testing of cultural relevance features.