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.     

川陈皮素对糖尿病肾病大鼠AMPK和eNOS表达的影响研究

【摘要】目的 观察川陈皮素对糖尿病肾病大鼠的治疗作用，并从腺苷酸蛋白活化激酶（AMPK）和内皮型一氧化氮酶（eNOS）途径探讨其作用机理。方法 采用高脂高糖饲料喂养+链脲佐菌素（STZ）腹腔注射复制2型糖尿病肾脏损害大鼠模型，模型构建成功后，将其随机分为正常组、模型组、贝那普利干预组以及川陈皮素低、中和高剂量治疗组（n=20）。实验中密切监测大鼠一般情况，治疗期结束后收集尿液检测24h蛋白尿，收集血液检测肾功能指标、抗氧化指标，收集肾脏观察肾脏病理学，同时检测肾脏组织中AMPK及eNOS蛋白和mRNA的表达结果。结果 正常组肾小球正常，无明显病理特征；模型组出现肾小球增大，系膜和肾间质纤维组织增生；贝那普利组和川陈皮素三个剂量组相较于模型组明显减轻。与正常组相比，模型组24h尿蛋白定量、UREA、CREA和MDA明显升高(P＜005)；SOD和GSH明显降低(P＜005)，与模型组相比，贝那普利和川陈皮素三个剂量组24h尿蛋白定量、UREA、CREA和MDA明显降低(P＜005)，SOD和GSH明显升高(P＜005)。与正常组相比，模型组p AMPK、AMPK和eNOS蛋白和mRNA表达均明显降低(P＜005)；与模型组相比，贝那普利组和川陈皮素低、中和高剂量组AMPK和eNOS蛋白和mRNA表达明显升高(P＜005)。结论 川陈皮素可保护肾功能，提高血清和肾脏抗氧化指标，同时增加AMPK和eNOS蛋白和mRNA表达，最终保护糖尿病肾脏损害。     

社区“5+1”糖尿病分阶段达标管理对2型糖尿病患者生存质量干预效果分析

目的 分析社区"5+1"糖尿病分阶段达标管理对2型糖尿病患者生存质量的干预效果及其影响因素，为提高患者生存质量提供依据。方法 采用分层整群抽样的方法在山西省、江苏省和宁夏回族自治区选择12个社区卫生服务中心，分别作为干预组（管理方式：社区"5+1"糖尿病分阶段达标管理）、对照组[管理方式：依据《国家基本公共卫生服务规范（2011年版）》的相关要求]，进行为期2年的随访观察。采用面对面问卷调查的方式，收集患者的人口学信息等基本信息；采用健康调查简表（SF-36）对患者在干预前后测量生存质量。采用SAS 9.4软件进行双重差分法以及多重线性回归模型分析。结果 基线时共纳入2 467名研究对象，终末时共1 924人接受了为期2年完整的随访管理。干预后，干预组、对照组患者生理健康维度（PCS）、心理健康维度（MCS）评分变化净差值分别为13.6分、29.8分。多重线性回归分析结果显示，影响患者PCS得分的主要因素有年龄、医保类型、基线PCS得分以及所在地区，影响患者MCS得分的主要因素有年龄、医保类型、基线MCS得分、是否合并高血压以及所在地区。结论 社区"5+1"糖尿病分阶段达标管理对2型糖尿病患者生存质量的干预效果较好。     

Racial differences in characteristics and prognoses between Asian and white patients with nonsmall cell lung cancer receiving atezolizumab: An ancillary analysis of the POPLAR and OAK studies

This study aimed to compare the differences in characteristics and prognoses between Asian and white patients receiving immunotherapy for nonsmall cell lung cancer (NSCLC). We studied 390 patients who received atezolizumab as part of the POPLAR or OAK trial, and analyzed the differences in baseline characteristics, outcomes and genetic mutations in blood samples between Asian and white patients. Overall survival (OS) was longer in Asian compared to white patients (median OS: 18.7 vs. 11.1 months; p = 0.005). Race was identified as an independent prognostic factor for OS (Asian vs. white: hazard ratio 0.647, 95% confidence interval 0.447–0.936, p = 0.021), together with performance status, histology, baseline sum of the longest tumor diameters (BLSLD) and number of metastatic sites. The two groups also differed in terms of characteristics including smoking history, BLSLD, epidermal growth factor receptor (EGFR) mutation frequency, programmed death-ligand 1 expression and blood-based tumor-mutation burden. Blood mutations of STK11, EGFR, KEAP1, POLE, GRM3, ATM and STAG2 were associated with treatment response, and TP53, KEAP1, APC, RB1, CREBBP, EPHA5 and STAG2 mutations were associated with OS. The blood-based mutation profiles differentiated between Asian and white patients, especially in relation to EGFR (23.8 vs. 8.5%), TP53 (30.2 vs. 46.9%) and STK11 (1.6 vs. 12.3%) mutations (all p < 0.05). The different clinicopathological features and mutation profiles in Asian and white patients may explain the superior outcome following atezolizumab treatment in Asian patients with NSCLC. The results of this study have important implications for further studies on racial disparities in relation to immunotherapy.     

创伤性膈疝21例临床分析

我院自１９８９年３月至１９９５年１０月手术治疗２１例创伤性膈疝，２１例疝愈。 发病机理与胸腹腔压力差、腹腔脏器冲击膈肌及胸腔负压有关。同时简要介绍了创伤性膈疝的诊断和治疗。     

中国已婚育龄妇女分娩保健服务的状况与变化研究

目的:分析我国已婚育龄妇女分娩保健服务状况及其变化。方法:对全国31个省(直辖市、自治区)抽取的调查前三年有生育史的1962名已婚育龄妇女进行问卷调查,结合1997年全国人口与生殖健康调查资料,对两次调查前三年有生育史妇女最近一次活产的分娩保健服务状况进行比较分析。结果:①与1997年调查前三年相比,2001年调查前三年育龄妇女的入院分娩率增加,家庭分娩的比例明显减少;②农村妇女家庭分娩比例明显降低,由1997年调查时的61·41%降为2001年调查时的40·78%,1998~2000年间,92·54%城镇妇女接受分娩保健服务,农村妇女家庭分娩比例高出城镇7·4倍,为40·78%;③分娩保健服务在各地区发展不平衡,东部和中部地区发展快,西部地区,尤其是西南地区发展相对较慢,1998~2000年间,西部地区妇女中,一半以上在家分娩,西部地区农村家庭分娩妇女一半以上由家人接生,约为东部和中部地区的6倍;④少数民族妇女家庭分娩和由家人接生的比例明显高于汉族妇女;⑤随着文化程度和经济收入的增加育龄妇女对分娩保健服务的利用增加,文盲、经济收入低的妇女家庭分娩比例和由家人接生的比例非常高。结论:我国分娩保健服务状况在改善,但发展极不平衡,西部地区农村的分娩保健服务急待提高。应加强对西部地区分娩保健服务的支持力度,研究制定应对策略,加强对西部农村接生人员的专业技术培训。     

持续正压通气辅助治疗高血压并发睡眠呼吸暂停综合征的临床研究

目的探讨持续正压通气辅助治疗高血压并发睡眠呼吸暂停综合征（SAS）对血压的影响。方法41例高血压并发睡眠呼吸暂停综合征病人,随机分为常规组（21例）和持续正压通气治疗组（20例）均给予常规降压药物治疗4周,治疗在常规治疗基础上加用气道持续正压通气治疗,观察两组治疗前后24 h血压变化。结果治疗组治疗后24 h平均收缩压、舒张压进一步降低,夜间收缩压及舒张压则显著降低（P〈0.01）。结论高血压并发睡眠呼吸暂停综合征病人,在常规应用降压药物同时应用持续正压通气辅助治疗血压下降更理想。