Bayesian consensus clustering for multivariate longitudinal data

In clinical and epidemiological studies, there is a growing interest in studying the heterogeneity among patients based on longitudinal characteristics to identify subtypes of the study population. Compared to clustering a single longitudinal marker, simultaneously clustering multiple longitudinal markers allow additional information to be incorporated into the clustering process, which reveals co-existing longitudinal patterns and generates deeper biological insight. In the current study, we propose a Bayesian consensus clustering (BCC) model for multivariate longitudinal data. Instead of arriving at a single overall clustering, the proposed model allows each marker to follow marker-specific local clustering and these local clusterings are aggregated to find a global (consensus) clustering. To estimate the posterior distribution of model parameters, a Gibbs sampling algorithm is proposed. We apply our proposed model to the primary biliary cirrhosis study to identify patient subtypes that may be associated with their prognosis. We also perform simulation studies to compare the clustering performance between the proposed model and existing models under several scenarios. The results demonstrate that the proposed BCC model serves as a useful tool for clustering multivariate longitudinal data.     

Sinensetin attenuates oxygen–glucose deprivation/reperfusion-induced neurotoxicity by MAPK pathway in human cerebral microvascular endothelial cells

Sinensetin is a polymethoxylated flavone with anti-inflammatory and anti-oxidative activities. This work aimed to explore the function and mechanism of sinensetin in oxygen and glucose deprivation/reperfusion (OGD/R)-induced neurotoxicity. The overlapping target genes of cerebral stroke and sinensetin were determined according to GeneCards and ParmMapper tools and were subjected to Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Human cerebral microvascular endothelial cells (HCMECs) were stimulated with OGD/R. Neurotoxicity was investigated by Cell Counting Kit-8, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) level, qRT-PCR, and TUNEL analysis. The proteins (p38, JNK, and ERK) in mitogen-activated protein kinase (MAPK) signaling were measured using Western blotting. Total of 50 overlapping target genes of cerebral stroke and sinensetin were predicted. Pathway analysis showed they might be involved in the MAPK pathway. Sinensetin attenuated OGD/R-induced neurotoxicity by mitigating viability reduction, LDH release, ROS generation, inflammatory response, and apoptosis in HCMECs. Sinensetin weakened OGD/R-induced activation of the MAPK pathway via decreasing the phosphorylation of p38, JNK, and ERK. The pathway inhibitors mitigated the activation of the MAPK signaling, and sinensetin exacerbated this effect. The inhibitors reversed OGD/R-induced neurotoxicity in HCMECs, and sinensetin contributed to this role. Overall, sinensetin prevents OGD/R-induced neurotoxicity through decreasing the activation of MAPK pathway.     

血清维生素D水平对维持性血液透析患者下肢肌力减退的预测作用

目的探讨维持性血液透析(MHD)患者血清维生素D水平对下肢肌力减退的预测作用。 方法横断面研究设计，选择2018年9月至10月于战略支援部队特色医学中心血液净化中心的95例MHD患者，检测其血清25-羟维生素D₃[25(OH)D₃]水平，采用5次站立-坐下实验(5-STS)评价其下肢肌力。根据5-STS完成时间将MHD患者分为下肢肌力正常组(n＝85)与减退组(n＝10)，比较两组患者人口学特征、实验室指标。采用多因素Logistic回归分析下肢肌力减退的影响因素，绘制受试者工作特征(ROC)曲线分析上述因素预测MHD患者发生下肢肌力减退的特异度和敏感度。 结果95例MHD患者血清25(OH)D₃水平为11.00~99.50 nmol/L，中位数31.23(19.90~43.30)nmol/L；5-STS完成时间为3.55 s~18.71 s，中位数9.81(7.12，12.43)s，下肢肌力减退者10例(10.53%)。多因素Logistic回归分析显示，血清25(OH)D₃是MHD患者下肢肌力减退的保护性因素[OR＝0.761，95%CI(0.592~0.978)，P＝0.033]。进一步ROC曲线分析显示，25(OH)D₃对应的ROC曲线下面积为0.815，其预测MHD患者发生下肢肌力减退的敏感度为80.00%，特异度为80.00%。 结论MHD患者血清25(OH)D₃水平普遍较低，下肢肌力减退者更为明显；血清维生素D水平对MHD患者是否存在下肢肌力减退具有较好的预测价值。     

血清miR-208在慢性心力衰竭中的表达及临床意义

目的 探讨血清miR-208在慢性心力衰竭中的表达及其临床意义.方法 选取2018年6月至2021年1月期间榆林市第二医院急诊科收治的慢性心力衰竭(CHF)患者150例,根据美国纽约心脏病协会心功能(NYHA)分级分为A组(NYHAⅠ～Ⅱ级)46例,B组(NYHAⅢ级)55例和C组(NYHAⅣ级)49例,同时选择同期体检的无CHF患者46例为对照组,Real-time PCR检测血清miR-208水平,收集患者N端前脑钠素(NT-proBNP),左心室射血分数(LVEF),左心房(LA)直径和心胸比率等临床病理资料.使用Pearson检验评价患者临床病理参数与血清miR-208表达之间的相关性.结果 四组受检者的年龄,性别,血压,高血压病史或糖尿病病史,BMI比较差异均无统计学意义(P>0.05);四组受检者的血清空腹血糖、总胆固醇(TC)、甘油三酯(TG)和肌酐(Cr)水平比较差异亦均无统计学意义(P>0.05);A、B、C组患者miR-208相对表达均较对照组明显提高,且miR-208表达水平随心功能NYHA分级升高而升高,差异均有统计学意义(P<0.05);四组受检者的NT-proBNP、LVEF、LA直径和心胸比率比较差异均有统计学意义(P<0.05),其中三组患者的NT-proBNP水平较对照组升高,LVEF水平降低,LA直径升高以及心胸比率增加,差异均有统计学意义(P<0.05);此外,患者NT-proBNP水平随心功能NYHA分级升高而升高,LVEF随心功能NYHA分级升高而降低,LA直径随心功能NYHA分级升高而升高,差异均有统计学意义(P<0.05);血清miR-208相对表达与患者NT-proBNP,LA直径正相关(r=0.784,0.524,P<0.05),与LVEF负相关(r=-0.375,P<0.05).结论 CHF患者的血清miR-208水平可作为评估其严重程度的潜在生物标志物.     

基于CiteSpace可视化分析代谢组学在中医药领域的研究现状及趋势＊

目的 应用可视化方法分析代谢组学在中医药领域的现状及趋势。方法 检索中国知网数据库（CNKI）和Web of Science 核心合集数据库2021年3月15日之前收录的中医药领域代谢组学研究的相关文献，应用CiteSpace软件对纳入的文献进行关键词、作者、研究机构等内容进行可视化分析。结果 共纳入中文文献247篇，英文文献350篇。文献数量在波动中迅速上升。中、英文文献作者合作网络显示，张爱华是中医药领域代谢组学研究发文量最多的作者，并形成了核心研究团队。发文机构显示，中国医学科学院是该领域的重要研究机构，机构间合作紧密。中、英文文献关键词分析显示，研究内容主要集中在核磁共振、代谢标记物、冠心病、质谱技术、代谢通路等相关领域。结论 中医药领域代谢组学研究的热点主要为中医药治疗代谢性疾病的机制研究。研究趋势为卵泡代谢组学研究及中药有效成分的研究。     

乙肝相关性肝癌临床病理学特征与高敏C反应蛋白和溶血磷脂酸表达的相关性

目的探讨乙肝相关性肝癌临床病理学特征与溶血磷脂酸(LPA)和高敏C反应蛋白(hs-CRP)表达的相关性。方法选取2019年1月至2020年1月间河南省驻马店市中心医院收治的198例乙肝相关性肝癌患者作为乙肝组,198例酒精相关性肝癌患者作为酒精组。两组患者都进行血清hs-CRP和LPA表达检测,调查患者的病理学特征并进行相关性分析。结果乙肝组患者血清hs-CRP和LPA含量均高于酒精组,差异均有统计学意义(均P <0.05)。两组患者血清ALP、AFP、ALT、AST和GGT含量比较,差异均无统计学意义(P> 0.05)。乙肝组不同临床分期和组织学分化患者的血清hs-CRP和LPA含量比较,差异均有统计学意义(均P <0.05)。乙肝组患者的临床分期和组织学分化与血清hs-CRP和LPA表达均存在相关性,差异均有统计学意义(均P <0.05)。患者的临床分期和组织学分化均为影响hs-CRP和LPA表达的重要因素,差异均有统计学意义(均P <0.05)。结论相对于酒精相关性肝癌,乙肝相关性肝癌的血清hs-CRP和LPA呈现高表达,与患者的临床病理学特征存在相关性。     

Neoadjuvant chemotherapy increases the 5-year overall survival of patients with resectable cervical cancer: A systematic review and meta-analysis

Cervical cancer is a global health challenge in women. Neoadjuvant chemotherapy (NACT) is a recent prospect for alternative cervical cancer treatments. This study investigated the efficacy of NACT against resectable cervical cancer based on the medium and long-term survival of patients with the disease. We searched through PubMed, Web of Science, EBSCO and Cochrane Library for relevant reports published by June 2020. The primary outcomes were 3-year and 5-year progression-free survival (PFS) and overall survival (OS) of patients with resectable cervical cancer. Overall, 22 publications encompassing 5627 patients fulfilled the inclusion criteria. We found NACT not to affect both 3-year PFS and OS as well as 5-year PFS of patients with resectable cervical cancer. However, NACT significantly improves the 5-year OS of patients with resectable cervical cancer (HR = 0.83, 95% CI: 0.73–0.94, p = 0.013). Subgroup analysis (RCTs, non-RCTs, NACT + surgery + AT vs. surgery + AT, NACT + surgery + AT vs. CCRT/RT/CRT) further revealed NACT had no significant effect on 5-year PFS of patients with resectable cervical cancer, converse to the 5-year OS subgroup analysis, which validated the beneficial effect of NACT in patients with resectable cervical cancer. In addition, the effect of NACT was most significant in the non-RCTs subgroup (p = 0.012). NACT may improve the long-term prognosis of patients with resectable cervical cancer. However, further large-scale multicenter studies are needed to validate this finding.