Genetic Analysis Workshop II: pedigree analysis of a binary trait without assuming an underlying liability

A model for concordance in a binary measure that does not rely on the assumption of an underlying latent liability dichotomized about a threshold has been demonstrated for twin pairs [Hannah et al, 1983]. It is extended here to pedigrees of arbitrary structure by making an assumption that is, for small incidence rates, almost equivalent to postulating that relative risks are multiplicative. The model is applied to the workshop data to determine the extent to which the known structure of the simulated models can be recovered.     

Dissolution test for felodipine tablets using chemical oxidation in situ to maintain 'sink conditions'

A test model is described for the determination of the dissolution rate of the vasodilator, felodipine, a derivative of dihydropyridine that is practically insoluble in water. ‘Sink conditions’ are maintained by means of an oxidizing agent, ceric sulphate, which reacts rapidly with dissolved drug molecules in the dissolution fluid. A pyridine derivative is formed quantitatively in the oxidation reaction. The amount of dissolved felodipine is calculated from the concentration of the pyridine derivative, as determined by reversed-phase liquid chromatography. Dissolution rates depend on the concentration of the oxidizing agent so that high concentrations accelerate dissolution. The dissolution test suggested for 25-mg felodipine tablets is performed in 500 ml fluid that contains 5 mM ceric sulphate in 0.12 M sulphuric acid. The test is performed on single tablets with USP paddle equipment. Dissolution rates for nine different tablet compositions are correlated to such bioavailability parameters as maximum plasma concentration and total area under the plasma concentration—time curve. Interferences and limitations of the method are discussed.     

社区呼吸康复治疗在慢性呼吸系统 疾病患者干预管理中的应用*

摘 要： 目的：探究中老年人颈动脉斑块与血清25羟维生素D （25-OH-D） 的相关性。 方法：选取2019年1月—2020 年 12 月自愿参与该研究的上海市浦东新区北蔡社区常住居民 412 人为研究对象,测定及记录其一般临床资料及血清 25-OH-D 等实验室检测结果。依据血管 B 超结果将研究对象分为有斑块组 268 人和无斑块组 144 人,比较两组人群血清 25-OH-D水平差异,用Pearson相关性分析各变量的关系,采用logistic回归分析颈动脉斑块形成的危险因素。结果：有斑块 组血清 25-OH-D 为 （45.18±18.71） nmol/L,无斑块组为 （56.12±19.54） nmol/L,两组差异有统计学意义 （χ2=5.573,P＜ 0.05）。相关性分析显示颈动脉斑块与收缩压、HbA1c、年龄呈正相关 （r值分别为0.388、0.119和0.128,P值均＜0.05）;与 血清 25-OH-D 呈负相关 （r=-0.365,P＜0.01）。血清 25-OH-D 是颈动脉斑块形成的独立相关因素 （OR=0.973,95%CI： 0.960,0.985,P＜0.05）。结论：低水平血清25-OH-D是颈动脉斑块形成的独立危险因素。     

妊娠期糖尿病孕妇和糖耐量正常孕妇妊娠压力与社会支持的相关性研究

目的 分析妊娠期糖尿病（GDM）孕妇和糖耐量正常孕妇妊娠压力与社会支持的相关性,对比该相关性在两组间是否存在差异。方法 选取495名GDM孕妇和352名糖耐量正常孕妇,采用一般情况调查表、妊娠压力量表（PPS）和社会支持评定量表（SSRS）进行问卷调查,并运用典型相关分析来研究妊娠压力和社会支持的相关性。结果 GDM组与正常组孕妇都处于轻度压力状态（0.38±0.32分vs.0.38±0.31分, t =0.061, P> 0.05）,且社会支持度均相对较高（40.68±6.88分vs.40.66±6.71分, t=0.042 , P> 0.05）,组间比较显示差异无统计学意义。GDM组和正常组孕妇妊娠压力与社会支持均存在典型相关关系（ λGDM =0.291, F=4.282 ,P<0.01; λ正常 =0.271, F=2.900 ,P<0.01）。GDM组孕妇妊娠压力主要由“确保母子健康和安全”引起,且主观支持的影响较大;而正常组孕妇妊娠压力主要来自于“认同父母角色”,且客观支持的影响较大。结论 应重视孕妇的妊娠压力状态,根据妊娠压力来源的不同可提供有针对性的社会支持,减缓孕期压力,促进母婴健康。     

耳穴特异性与生物分子活性的关系

目的　研究耳穴特异性与机体生物分子活性之间的关系。方法　通过 18例SLE患者和 17位健康者的同体双盲试验及统计和相关分析 ,并结合抗体基因结构与功能的研究。结果　证实耳穴电特性具有反应SLE病理变化的特异性 ;7项抗体指标 (含DNA、补体、类风湿因子、免疫球蛋白等 )与耳穴电特性存在不同程度的相关性。结论　耳穴特异性与机体生物分子活性存在密切的联系 ;耳穴反应病变的特异性可能源于机体内生物分子的活性 ,其中包括基因突变、基因表达及其调控。     

Pseudotumors in Small-Head Metal-on-Metal Total Hip Arthroplasties at a Minimum Follow-Up of 20 Years

BackgroundMetal-on-metal (MOM) surfaces in total hip arthroplasty (THA) have been used widely. Serum cobalt and chromium levels have been the standard investigation for follow-up examinations, but magnetic resonance imaging (MRI) with metal artifact reducing sequences has shown good results in detecting pseudotumors. The aim of this study is to survey a significant correlation among MRI findings, serum metal levels, and clinical scores in patients with small-head MOM implants and if serum cobalt and chromium levels are sufficient in detecting patients with pseudotumors in the long-term follow-up.MethodsAt a minimum follow-up of 20 years, 26 patients (29 THAs) of the original 98 patients (105 THAs) included in this study between November 1992 and May 1994 were available for follow-up examination. Clinical scores, serum metal ion levels, and MRIs were obtained.ResultsWe found mean serum cobalt levels of 1.87 μg/L (±3.44) and chromium levels of 2.23 μg/L (±2.96) and very good clinical and functional results (mean Harris Hip Score 88.6) in the long-term follow-up. Pseudotumors were detected in MRIs of 21 hips. There were no significant differences between patients with or without pseudotumors regarding serum metal levels and the correlation for clinical outcome scores, demographic data, and cup inclination. The cumulative rate of survival was still at 91.4% at 22.8 years.ConclusionThis study presents the first published data on small-head MOM hips, comparing metal ion levels, pseudotumors, clinical, and radiological results in a follow-up period of more than 20 years and reveals that serum metal levels are not significantly higher in patients with pseudotumors.Level of EvidenceTherapeutic Level III     

水提干法制粒的中药配方颗粒溶化性与粉体物理属性相关性研究

目的 为加快实现中药生产过程中对中药配方颗粒的质量控制,从粉体物料属性出发,探究其对水提工艺下干法制粒的中药配方颗粒溶化性影响机制。方法 以60种中药配方颗粒及中间体混合粉为研究对象,通过对各品种混合粉粉体属性进行测定,建立粉体物性参数与颗粒溶化性关联模型。采用二维矩阵热点图对各品种间及物性指标间相似性进行分析,结合系统聚类分析对其进行归类,并运用多元统计方法初步筛选影响水提工艺下中药配方颗粒溶化性的关键因素。结果 各品种间粉体物性参数相关系数在-0.951～1.000,并按照各品种物理属性大致可以分为5类,结合变量投影响应值（variable importance for the projection,VIP）、自变量回归系数与方差膨胀因子（variance inflation factor,VIF）分析,最终筛选出其休止角（α）、含水量（HR）、吸湿性（H）与比表面积（SSA）4个指标为影响中药配方颗粒溶化性的关键物料属性（critical material attributes,CMAs）。结论 基于中药粉体物料属性与数据分析初步探寻影响水提条件下干法制粒的中药配方颗粒的溶化性机...     

基于抗肝纤维化生物活性及近红外谱效相关的鳖甲质量评价研究

目的 从鳖甲临床抗肝纤维化功效出发并结合近红外光谱,探索建立关联抗肝纤维化活性的鳖甲质量生物活性评价方法。方法 建立转化生长因子-β1（transforming growth factor-β1,TGF-β1）诱导的LX-2肝纤维化细胞模型,采用qRT-PCR检测鳖甲对I型胶原（type I collagen,COL1）mRNA表达的影响,计算鳖甲对COL1 mRNA相对表达量的抑制率;采用Western blotting检测鳖甲对COL1蛋白表达的影响,以评价鳖甲在细胞模型上的抗肝纤维化生物活性。采集并处理不同批次鳖甲药材的近红外光谱数据,通过谱-效相关分析探究鳖甲药材近红外光谱数据与其抗肝纤维化活性的相关性,筛选活性波段,建立鳖甲的效应近红外谱,以效应近红外谱下面积评价鳖甲药材的质量。结果 体外实验表明,与模型组比较,鳖甲水提物（water extract of Trionycis Carapax,WECT）处理组细胞中COL1 mRNA与蛋白表达水平显著下调（P＜0.05、0.01）;基于谱-效相关分析,共筛选得到R＞0.6、P＜0.05且波数大于8 cm⁻¹的活性波段3个,分别为5226～5235 cm⁻¹、5943～6071 cm⁻¹与6379～6396 cm⁻¹,以3个活性波段下面积为指标,建立鳖甲药材的效应近红外谱,计算各特征波段下面积和,并分析其与生物活性的相关性,两者相关系数R为0.813 53。结论 WECT可抑制LX-2细胞外基质的产生来治疗肝纤维化;效应波谱下面积和（5226～5235 cm⁻¹、5943～6071 cm⁻¹与6379～6396 cm⁻¹）作为鳖甲药材的质量评价系数,用于评价鳖甲药材的质量,可区分不同批次鳖甲药材的抗肝纤维化活性。     

Cardiac function in adolescents and young adults with 22q11.2 deletion syndrome without congenital heart disease

BackgroundDiagnosis and treatment of 22q11.2 deletion syndrome (22q11.2DS) have led to improved life expectancy and achievement of adulthood. Limited data on long-term outcomes reported an increased risk of premature death for cardiovascular causes, even without congenital heart disease (CHD). The aim of this study was to assess the cardiac function in adolescents and young adults with 22q11.2DS without CHDs.MethodsA total of 32 patients (20M, 12F; mean age 26.00 ± 8.08 years) and a healthy control group underwent transthoracic echocardiography, including Tissue Doppler Imaging (TDI) and 2-dimensional Speckle Tracking Echocardiography (2D-STE).ResultsCompared to controls, 22q11.2DS patients showed a significant increase of the left ventricle (LV) diastolic and systolic diameters (p = 0.029 and p = 0.035 respectively), interventricular septum thickness (p = 0.005), LV mass index (p < 0.001) and aortic root size (p < 0.001). 2D-STE analysis revealed a significant reduction of LV global longitudinal strain (p < 0.001) in 22q11.2DS than controls. Moreover, several LV diastolic parameters were significantly different between groups.ConclusionsOur results suggest that an echocardiographic follow-up in 22q11.2DS patients without CHDs can help to identify subclinical impairment of the LV and evaluate a potential progression of aortic root dilation over time, improving outcomes, reducing long-term complications and allowing for a better prognosis.