肺腺癌竞争内源性RNA网络的综合分析:基于肿瘤基因组图谱数据库

目的:基于肿瘤基因组图谱数据库（TCGA）架构肺腺癌（LUAD）竞争内源性RNA（ceRNA）网络，鉴定潜在的生存关联性生物标志物，并确定特异性治疗的小分子药物。方法:依据纳入研究标准，利用Edger软件筛选LUAD组织与正常组织(mRNA、lncRNA和miRNA)差异表达的基因。通过miRcode、miRDB、TargetScan和miRanda数据库对差异表达的RNA之间的关系进行分析，构建ceRNA网络。采用Kaplan-Meier方法分析ceRNA网络中的RNA表达量与生存预后的关系，通过富集分析对网络中的mRNA基因功能和调控通路进行分析。通过Cmap数据库筛选治疗LUAD的特异性小分子药物。利用D-lnc软件确定与关键的lncRNA相关的特异性小分子药物。结果:mRNAs(ELAVL2和PBK)、miRNAs(miR-13和miR-210)和lncRNAs(AP002478.1、DSCAM-AS1、LINC00269、LINC00470和LINC00483)与总生存期(OS)关系密切。喜树碱和甲萘醌有可能逆转LUAD的状态。卡铂、多西紫杉醇、帕比司他被确定为与关键lncRNA密切相关的药物。结论:ceRNA网络在LUAD中发挥重要作用，多种差异表达RNA与LUAD预后相关，可能成为潜在的肿瘤诊断标志物和治疗靶点。     

基于网络药理学探讨“黄芪-当归-大枣”角药补气养血的分子机制＊

目的 运用网络药理学探讨“黄芪-当归-大枣”角药补气养血的分子机制。方法 利用中药系统药理学TCMSP数据库收集黄芪、当归和大枣的化学成分，并预测作用靶点。通过STRING数据库和Cytoscape软件构建蛋白互作PPI网络，获得关键靶点。借助DAVID数据库对筛选靶点进行GO功能和KEGG通路富集分析。进一步构建气血两虚小鼠模型，灌胃“黄芪-当归-大枣”水煎剂，检测各组PTGS₂ mRNA表达水平与肿瘤坏死因子-α(TNF-α)含量，完成验证实验。结果 筛选得到“黄芪-当归-大枣”角药化学成分47个，预测作用靶点43个，关键靶点10个，生物功能主要定位在内质网膜和线粒体，通过介导癌症信号通路，TNF、P53、Foxo、HIF-1信号通路，钙信号通路等发挥补气养血作用。动物实验显示“黄芪-当归-大枣”角药可调控气血两虚小鼠中PTGS₂ mRNA表达，降低TNF-α释放，进而抑制TNF信号通路的激活，进一步证实了预测的可靠性。结论 本研究深入诠释“黄芪-当归-大枣”角药补气养血作用多成分、多靶点和多通路的复杂机制，为其进一步临床应用和功能食品开发提供科学依据。     

云南省七个民族学生月经初潮、首次遗精与形态发育的关系

目的 了解云南省7个民族学生月经初潮和首次遗精与形态发育之间的关系,为研究学生生长发育规律和开展青春期性教育提供依据。方法 利用2014年全国学生体质健康调研数据,分析云南省7个民族学生月经初潮和首次遗精对身高、体重、胸围和维尔维克指数的影响。结果 男生性成熟年龄晚于女生,2014年云南省7个民族女生月经初潮半数年龄最小为汉族(12.28岁)、傣族(12.40岁),最大为哈尼族(13.06岁)、傈僳族(13.04岁),男生首次遗精半数年龄最小为佤族(13.43岁)、纳西族(14.01)岁,最大为傈僳族(15.29岁)、哈尼族(14.60岁);女生来潮组的形态发育状况好于未来潮组(P值均<0.05),男生已遗精组与未遗精组的差异,只有部分项目有统计学意义。结论 应针对不同性别、种族、地域特点,适时适量进行青春期性教育,加强少数民族学生的膳食营养,改变不合理膳食结构和饮食习惯,强化体育锻炼,更好地促进学生的生长发育。     

Score confidence intervals and sample sizes for stratified comparisons of binomial proportions

In a series of articles, Gart and Nam construct the efficient score tests and confidence intervals with or without skewness correction for stratified comparisons of binomial proportions on the risk difference, relative risk, and odds ratio effect metrics. However, the stratified score methods and their properties are not well understood. We rederive the efficient score tests, which reveals their theoretical relationship with the contrast-based score tests, and provides a basis for adapting the method by using other weighting schemes. The inverse variance weight is optimal for a common treatment effect in large samples. We explore the behavior of the score approach in the presence of extreme outcomes when either no or all subjects in some strata are responders, and provide guidance on the choice of weights in the analysis of rare events. The score method is recommended for studies with a small number of moderate or large sized strata. A general framework is proposed to calculate the asymptotic power and sample size for the score test in superiority, noninferiority and equivalence clinical trials, or case-control studies. We also describe a nearly exact procedure that underestimates the exact power, but the degree of underestimation can be controlled to a negligible level. The proposed methods are illustrated by numerical examples.     

兰州市1 026名高一新生体重控制行为及其与真实和感知到的体重状态之间的关系

目的 利用青少年体重控制行为量表对兰州市高一新生体重控制行为采用状况进行调查,并考察其与学生真实和感知到的体重状态之间的关联,为制定科学的预防和干预方案提供依据。方法 2018年9月在兰州市抽取1 038名高一新生,对其测查青少年体重控制行为量表及感知到体重状态。回收有效数据1 026份,计算健康体重控制行为和不健康体重控制行为的采用率和平均分。结果 参与调查的高一新生中有364名(76.15%)女生和387名(70.62%)男生采用体重控制行为;男女生采用最频繁的两种健康体重控制行为是 “做运动”[男生416例(75.91%),女生318例(66.53%)]和“多吃水果和蔬菜”[(男生412例(75.18%),女生395例(83.51%)];采用最频繁的两种不健康体重控制行为是“减少吃饭的顿数”[(男生93例(16.97%)],女生82例(17.15%)]和“不吃肉”[(男生37例(6.75%),女生77例(16.11%)]。实际超重的男女生比例分别为21.63%和9.79%。与之形成鲜明的对比,高达52.83%的女生自认为超重。自认为超重的被试比自认为不超重的被试更可能采用不健康体重控制行为(χ²=38.94,P<0.01)。结论 兰州地区高一新生体重控制行为的状况非常普遍,这和他们对于体重认知的偏差有关,需从心理层面进行预防和干预。     

儿童室管膜瘤的临床研究进展

室管膜瘤是一种原发于神经上皮的中枢神经系统肿瘤，病变累及脑和脊髓，多发于儿童。基因分型的新分类方法，为室管膜瘤的治疗和预后评估提供了更为可靠的依据。室管膜瘤对辅助治疗的敏感性低是造成患儿预后较差的重要原因之一。该文对近年来儿童室管膜瘤的分型、诊断、治疗策略等进行综述。     

Impact of state weights on national vaccination coverage estimates from household surveys in Nigeria

National vaccination coverage estimates from household surveys are widely used in monitoring and planning of immunization programs. In Nigeria, survey-reported national coverage estimates have shown large fluctuations in the past few years. In this paper, we examine the impact of state-level survey weighting on Nigeria’s national vaccination coverage estimation. In particular, we focus three vaccination-related outcomes among children aged 12–23 months: the coverage of the third dose of diphtheria, pertussis, and tetanus vaccine (DPT3); the coverage of the first dose of measles-containing vaccine (MCV1); and the availability rate of home-based vaccination record (HBR). We compare the sample selection and weight assignment of three major survey programs in Nigeria, and show that considerable portions of the changes in survey-reported national coverage estimates can be explained by shifts in state-level weights. Our analysis demonstrates the importance of state weighting method in estimating aggregated national coverage figures and provides important context for interpreting changes in coverage estimates between surveys in the future.     

The role of oxytocin in regulation of appetitive behaviour,body weight and glucose homeostasis

Obesity and its associated complications have reached epidemic proportions in the USA and also worldwide, highlighting the need for new and more effective treatments. Although the neuropeptide oxytocin (OXT) is well recognised for its peripheral effects on reproductive behaviour, the release of OXT from somatodendrites and axonal terminals within the central nervous system (CNS) is also implicated in the control of energy balance. In this review, we summarise historical data highlighting the effects of exogenous OXT as a short‐term regulator of food intake in a context‐specific manner and the receptor populations that may mediate these effects. We also describe what is known about the physiological role of endogenous OXT in the control of energy balance and whether serum and brain levels of OXT relate to obesity on a consistent basis across animal models and humans with obesity. We describe recent data on the effectiveness of chronic CNS administration of OXT to decrease food intake and weight gain or to elicit weight loss in diet‐induced obese (DIO) and genetically obese mice and rats. Of clinical importance is the finding that chronic central and peripheral OXT treatments both evoke weight loss in obese animal models with impaired leptin signalling at doses that are not associated with visceral illness, tachyphylaxis or adverse cardiovascular effects. Moreover, these results have been largely recapitulated following chronic s.c. or intranasal treatment in DIO non‐human primates (rhesus monkeys) and obese humans, respectively. We also identify plausible mechanisms that contribute to the effects of OXT on body weight and glucose homeostasis in rodents, non‐human primates and humans. We conclude by describing the ongoing challenges that remain before OXT‐based therapeutics can be used as a long‐term strategy to treat obesity in humans.     

The individual and joint effects of maternal 25(OH)D deficiency and gestational diabetes on infant birth size

Background and aimsTo examine the independent effect of maternal serum 25-hydroxyvitamin D [25(OH)D] deficiency and its joint effect with gestational diabetes mellitus (GDM) on infant birth size.Methods and resultsThis retrospective cohort study was conducted in 15,724 mother-offspring dyads in Beijing, China between 2016 and 2017. Outcomes included infant birth weight Z-score (adjusted for gestational age and sex) and large for gestational age (LGA). Exposures were maternal 25(OH)D concentrations. Linear and logistic regression models were used to assess the associations of exposures with continuous and binary outcomes, respectively. Exposure-outcome associations were not observed when analyzing 25(OH)D concentrations continuously or in quartiles (P > 0.05); however, mothers with severely deficient 25(OH)D concentrations (n = 307) had a decreased risk of LGA compared with those with sufficient 25(OH)D concentrations (≥30.0 ng/mL; n = 5400) (adjusted odds ratio (OR): 0.63; 95% confidence interval (CI): 0.42, 0.93). Compared to mothers with no 25(OH)D deficiency (≥20.0 ng/mL) and no GDM (n = 7975), those with both 25(OH)D deficiency and GDM (n = 1090) had 0.15 (95% CI: 0.09, 0.21) higher infant birth weight Z-score and a higher risk of LGA (OR: 1.29; 95% CI: 1.09, 1.52). Maternal 25(OH)D deficiency and GDM had additive interaction on the risk of LGA (relative risk due to interaction: 0.18).ConclusionMothers with severely deficient 25(OH)D might have a decreased risk of LGA. However, the joint effect of maternal 25(OH)D deficiency and GDM might increase the risk of LGA. Our findings have clinical and public health implications and provide potential directions for future studies.