三种统计分析方法在基因表达谱数据中的比较研究

目的比较SCAD-支持向量机、支持向量机和弹性网三种方法对基因表达谱数据的变量筛选和预测判别能力。方法根据设置的参数生成不同条件的基因表达谱模拟数据和实际数据,利用FDR、一致性错误率和ROC曲线下面积(AUC值)从三个方面评价三种方法的变量筛选和预测判别能力。结果模拟实验显示在差异变量数不变的情况下,随着差异变量间相关系数的增加,三种方法建立模型的变量筛选和预测判别能力均提高;当差异变量间相关系数不变时,随着差异变量数目的增加,SCAD-支持向量机和弹性网方法的变量筛选和预测判别能力均呈下降趋势,而支持向量机呈现提高趋势。结论 SCAD-支持向量机不仅改善了支持向量机不能直接进行变量筛选的不足同时提高了模型的精度以及判别的准确性。综合来看SCAD-支持向量机的变量筛选和预测判别能力更优,处理变量间有高度相关性的基因表达谱数据时可以获得更高的预测精度和更稳定的模型估计。     

低出生体重儿追赶性生长跨度与儿童期超重肥胖的相关性研究

目的 分析低出生体重儿生长早期体重指数(BMI)增幅跨度与儿童期生长水平及发生超重肥胖的关联度,为指导低出生体重儿适度追赶生长提供科学依据。方法 回顾性收集温州市2011年10月-2012年9月期间出生的儿童,将其分为低出生体重组和正常出生体重组进行研究。采集两组儿童满月、1周岁及5周岁时的体重、身长,并分别计算BMI。根据WHO《学龄前儿童生长发育标准》BMI界值点划分BMI分布区间,获取满月至1周岁BMI增幅跨度。分析不同BMI增幅跨度其5周岁时生长水平及超重肥胖发生概率。结果 低出生体重组BMI增幅在3个及以上跨度的较正常出生体重组高出近1/4;低出生体重组BMI增幅0个跨度与1~2个跨度之间超重肥胖发生率差异无统计学意义(P>0.05),正常体重组各增幅跨度之间差异均存在统计学意义(P均<0.05);低出生体重儿BMI增幅与生长水平表现出一定的关联性,满月至周岁BMI处于同一区间的其5周岁体重、身高及BMI均未能达到WHO参考中位数,当BMI增幅达到5个及以上跨度时,体重和BMI高出WHO参考中位数,且差异有统计学意义(P均<0.05)。结论 大多数低出生体重儿较正常出生体重儿生长关键期BMI增幅跨度更大,BMI增幅跨度在1~2个区间的对今后生长及超重肥胖的控制较为有利。     

国外仿制药参比制剂选择简介及对我国的启示

目的：为完善我国仿制药一致性评价中参比制剂选择机制和程序提供参考,为仿制药企业在应用选择参比制剂时提供思路。方法：详细介绍了美国FDA有关参比制剂选择指南草案的最新描述,以及欧盟、日本和WHO对于参比制剂的相关要求。结合我国现阶段仿制药一致性评价工作实际,为完善参比制剂选择程序提出建议。结果与结论：美国详细规定了仿制药参比制剂的选择思路和实际操作程序,为我国仿制药参比制剂的选择提供了新的思路。我国正处于仿制药一致性评价参比制剂遴选的关键时期,制定全面、完善的参比制剂遴选体系和机制,有助于规范参比制剂的选择程序,加快一致性评价工作进程,提升我国仿制药一致性评价参比制剂选择的科学性和完整性。     

Modeling individualized coefficient alpha to measure quality of test score data

Individualized coefficient alpha is defined. It is item and subject specific and is used to measure the quality of test score data with heterogenicity among the subjects and items. A regression model is developed based on 3 sets of generalized estimating equations. The first set of generalized estimating equation models the expectation of the responses, the second set models the response's variance, and the third set is proposed to estimate the individualized coefficient alpha, defined and used to measure individualized internal consistency of the responses. We also use different techniques to extend our method to handle missing data. Asymptotic property of the estimators is discussed, based on which inference on the coefficient alpha is derived. Performance of our method is evaluated through simulation study and real data analysis. The real data application is from a health literacy study in Hunan province of China.     

Type I error probability spending for post–market drug and vaccine safety surveillance with binomial data

Type I error probability spending functions are commonly used for designing sequential analysis of binomial data in clinical trials, but it is also quickly emerging for near–continuous sequential analysis of post–market drug and vaccine safety surveillance. It is well known that, for clinical trials, when the null hypothesis is not rejected, it is still important to minimize the sample size. Unlike in post–market drug and vaccine safety surveillance, that is not important. In post–market safety surveillance, specially when the surveillance involves identification of potential signals, the meaningful statistical performance measure to be minimized is the expected sample size when the null hypothesis is rejected. The present paper shows that, instead of the convex Type I error spending shape conventionally used in clinical trials, a concave shape is more indicated for post–market drug and vaccine safety surveillance. This is shown for both, continuous and group sequential analysis.     

Spatiotemporal incidence rate data analysis by nonparametric regression

To monitor the incidence rates of cancers, AIDS, cardiovascular diseases, and other chronic or infectious diseases, some global, national, and regional reporting systems have been built to collect/provide population‐based data about the disease incidence. Such databases usually report daily, monthly, or yearly disease incidence numbers at the city, county, state, or country level, and the disease incidence numbers collected at different places and different times are often correlated, with the ones closer in place or time being more correlated. The correlation reflects the impact of various confounding risk factors, such as weather, demographic factors, lifestyles, and other cultural and environmental factors. Because such impact is complicated and challenging to describe, the spatiotemporal (ST) correlation in the observed disease incidence data has complicated ST structure as well. Furthermore, the ST correlation is hidden in the observed data and cannot be observed directly. In the literature, there has been some discussion about ST data modeling. But, the existing methods either impose various restrictive assumptions on the ST correlation that are hard to justify, or ignore partially or entirely the ST correlation. This paper aims to develop a flexible and effective method for ST disease incidence data modeling, using nonparametric local smoothing methods. This method can properly accommodate the ST data correlation. Theoretical justifications and numerical studies show that it works well in practice.     

市场导向下的药企间仿制药一致性评价横向合作的现状分析及对策

中国仿制药占上市化学药品的绝大部分,由于仿制药的质量参差不齐,直接影响到人民群众用药的安全性和有效性。现阶段,我国提出要全面提高仿制药质量,将仿制药分期分批与被仿制药进行质量一致性评价,对于整个医药行业是一次重要的战略机遇。在市场导向下,以企业作为主体通过横向合作的方式,引导企业参与生物等效性(BE)研究平台的建设,通过企业联合建立仿制药一致性评价的参比制剂及研究信息共享机制;同时通过政府引导资源配置,适度倾斜照顾中西部地区企业,解决中西部地区药企面临的实际问题,实现医药行业的区域均衡发展,使之成为促进医药行业的供给侧结构改革的重要抓手。     

Assessment of ultra-structure,viability and function of lipopolysaccharides-stimulated human dermal fibroblasts treated with chrysin and exosomes (in vitro study)

BackgroundLipopolysaccharides (LPS) stimulate production of inflammatory cytokines. Chrysin is flavonoid beneficial for treatment of inflammatory conditions. Bone marrow mesenchymal stem cell (BM-MSC) exosomes have regenerative ability in different tissues.ObjectiveTo assess potential role of chrysin and BM-MSC exosomes on ultra-structure, viability and function of human dermal fibroblasts-adult (HDFa) stimulated by LPS.MethodsHDFa cells were divided into: Group I: Cells received no treatment. Group II: Cells were stimulated with LPS. Group III: LPS stimulated cells were treated with chrysin. Group IV: LPS stimulated cells were treated with exosomes.ResultsAfter 48 h, ultrastructural examination of HDFa cells in Group I revealed intact plasma membrane and numerous cytoplasmic organelles. Group II displayed destructed plasma membrane and apoptotic bodies. Group III showed intact plasma membrane with loss of its integrity at some areas. Group IV demonstrated intact plasma membrane that showed fusion with exosomes at some areas. Statistical analysis of MTT represented highest mean value of cell viability% in Group IV followed by Groups III, I and II respectively. Statistical analysis of enzyme-linked immunosorbent assay (ELISA) showed the highest mean value of interleukin-1β (IL-1β) was in Group II followed by Groups III, IV and I, while highest mean values of interleukin-10 (IL-10), nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins were in Group I, followed by Groups IV, III and II respectively.ConclusionsLPS have harmful consequences on ultra-structure, viability and function of HDFa cells. BM-MSC exosomes have better regenerative action on inflamed fibroblasts in comparison to chrysin.     

Assessment of bone marrow-derived mesenchymal stem cells capacity for odontogenic differentiation and dentin regeneration in methimazole-treated albino rats (Light microscopic Study)

BackgroundMethimazole is an antithyroid drug. It has side effects on many tissues. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are promising in the field of tissue regeneration.ObjectiveTo investigate the capacity of BM-MSCs on odontogenic differentiation and dentin regeneration at different time intervals in methimazole treated rats.MethodsTwenty-eight male albino rats were classified as: Group I: got distilled water. Group II: obtained therapeutic dosage of methimazole as pro-drug “Neo-Mercazole®”. Group III: received methimazole then solitary injection of BM-MSCs at day 21. Group IV: obtained methimazole and single injection of BM-MSCs at the beginning of the experiment. Light microscope was used to examine specimens. Recently formed collagen and β-catenin-immunoreactivity area% were appraised histomorphometrically and statistically.ResultsHistological examination of odontoblasts and dentin illustrated normal structure in Group I and nearly normal features in Group IV. Group II demonstrated discontinuation of odontoblastic layer and areas of different stainability in dentin. Group III showed an evidently wide layer of odontoblast-like cells and distinct dentinal tubules. Masson's trichrome results of dentin in Groups I &IV showed apparently equal areas of new and old collagen. Group II illustrated old collagen mainly. Group III explored new collagen only. β-catenin-immunoreactivity was strong in Groups I & IV, mild in Group II and moderate in Group III. Statistical results revealed that the highest mean of newly formed collagen area% was in Group III, followed by Group I, Group IV then Group II respectively. Regarding β-catenin-immunoreactivity area%, the highest mean was recorded in Group I, subsequently Group IV, next Group III then Group II.ConclusionsMethimazole has destructive consequences. BM-MSCs have a time-based increased capacity for odontogenic differentiation and regeneration of dentin.     

A longitudinal study of early childhood caries in 9- to 18-month-old Thai infants

Abstract – Objective: To examine the rate and pattern of early childhood caries (ECC) development and to investigate the transitional changes of the carious lesions during a follow‐up period of 3–9 months. Methods: A longitudinal observational community‐based survey of 599 children, 9–18 months old. The children's dental examinations were first carried out at the age of 9 months with re‐examination at 12 and 18 months by five dentists using standardized methods. The affected rates of dental caries were determined for prevalence, incidence density for risk of caries per person (ID_p) and risk by surface (ID_s). Changes in dental status over time were explored from unerupted (U) to sound (S), including enamel caries (D1), dentine caries (D2) and caries involving pulp (D3) by computing transitional probabilities. Results: The prevalence of caries was 2.0%, 22.8% and 68.1% among 9‐, 12‐ and 18‐month olds, respectively. The ID_p observed for newly affected children 9–12 and 12–18 months old was 10.32 and 15.70 persons/100 person‐months, respectively. The ID_s for children 9–12 months old was 2.17 newly affected surfaces/100 surface‐months whereas it was 2.22 surfaces/100 surface‐months for children 12–18 months old. The buccal surface of maxillary incisors was the most affected (44.9%) followed by lingual, mesial and distal surfaces, respectively. The transitional probability of caries progression ranged between 1.79% and 15.38% during the follow‐up period from 9 to 12 months old. It was 3.43–39.60% from 12 to 18 months old. Conclusions: An extremely high caries‐affected rate was found among the study children even before the age of 18 months. The buccal surface of the maxillary incisors was the most affected. The teeth acquired caries at 3–6 months after initial eruption and carious lesions developed continuously over time.