Using imputed genotype data in the joint score tests for genetic association and gene–environment interactions in case‐control studies

Genome‐wide association studies (GWAS) are now routinely imputed for untyped single nucleotide polymorphisms (SNPs) based on various powerful statistical algorithms for imputation trained on reference datasets. The use of predicted allele counts for imputed SNPs as the dosage variable is known to produce valid score test for genetic association. In this paper, we investigate how to best handle imputed SNPs in various modern complex tests for genetic associations incorporating gene–environment interactions. We focus on case‐control association studies where inference for an underlying logistic regression model can be performed using alternative methods that rely on varying degree on an assumption of gene–environment independence in the underlying population. As increasingly large‐scale GWAS are being performed through consortia effort where it is preferable to share only summary‐level information across studies, we also describe simple mechanisms for implementing score tests based on standard meta‐analysis of “one‐step” maximum‐likelihood estimates across studies. Applications of the methods in simulation studies and a dataset from GWAS of lung cancer illustrate ability of the proposed methods to maintain type‐I error rates for the underlying testing procedures. For analysis of imputed SNPs, similar to typed SNPs, the retrospective methods can lead to considerable efficiency gain for modeling of gene–environment interactions under the assumption of gene–environment independence. Methods are made available for public use through CGEN R software package.     

鲍温样丘疹病患者HPV E6/E7 mRNA与血清L1-IgG和存活素表达关系

目的 分析人乳头瘤病毒（HPV）感染所致鲍温样丘疹病（BP）患者 L1-IgG抗体、存活素（Survivin）表达水平,为鲍温样丘疹病有效防治提供科学依据。方法 选取2019年1月—2022年1月秦皇岛市第一医院收治的HPV感染致BP患者150例。根据HPV分型分为高危型组112例和非高危型组38例。采用酶联免疫吸附法检测血清HPV L1-IgG抗体、Survivin、免疫球蛋白IgA、IgG、IgM、白介素6（IL-6）、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）水平;采用流式细胞术检测患者外周血CD3⁺、CD4⁺、CD8⁺和CD4⁺/CD8⁺水平;使用杂交信号方法核酸检测技术,检测标本中HPV E6/E7 mRNA数量;Spearman相关性分析HPV E6/E7 mRNA和L1-IgG抗体、Survivin阳性表达水平关系。结果 高危型组和非高危型组患者L1-IgG和Survivin阳性表达分别为73.21%（82/112）、67.86%(76/112）和26.32%（10/38）、31.58%（12/38）,差异均有统计学意义（χ²=26.314,15.400,P<0.01）。高危型组患者HPV E6/E7 mRNA 为（1 125.64±113.42）copies/mL,且L1-IgG、Survivin阳性表达HPV E6/E7 mRNA水平较高,呈正相关（P<0.05）。高危型组和非高危型组患者IgA、IgG、IgM分别为（1.23±0.13）、（8.89±0.91）、（1.13±0.12）g/L和（1.60±0.17） 、（11.42±1.15） 、（1.53±0.16）g/L,高危型组较低,差异均有统计学意义（t=13.971,13.814,16.246,P<0.05）。高危型组和非高危型组患者患者CD3⁺、CD4⁺分别为（58.78±5.91）%、（29.96±3.12）%和（65.48±6.61）%、（65.48±6.61）%,高危型组较低,差异均有统计学意义（t=5.858,8.249,P<0.01）。两组患者CD8⁺和CD4⁺/CD8⁺水平比较,差异无统计学意义（P>0.05）。高危型组患者TNF-α、IFN-γ和IL-6水平分别为（2.64±0.30） 、（4.36±0.53）和（3.11±0.32） pg/mL,高于非高危型组患者（1.67±0.18）、（2.44±0.25） 和（2.21±0.25）pg/mL,差异均有统计学意义（t=8.792,21.499,15.769,P<0.05）。结论 BP患者感染HPV可影响患者免疫调节功能和炎症反应,且HPV高危型患者L1-IgG抗体和Survivin阳性表达水平高于非高危型组患者。     

从元整体发生学观点探讨“天人相应”的本质内涵

中医"天人相应"理论包括天人相副、人天依存、天人相合等不同认识。西医学整体观包含着"人的可分解性",即合整体观;中医学整体观的核心是人与环境、人体自身的"不可分割性",即元整体观。从元整体观探讨天人相应的理论内涵可知,天人相应包含天人本一、以人应天、天人合一在内的逻辑递进的多层次概念。其具体表现在:从宇宙本体论来看,天人相应首先是天人本一;从宇宙发生的过程看,人的健康疾病与自然环境息息相关;从宇宙生态平衡角度看,养生防病上需要天人合一。阐明"天人相应"理论深层次内涵,有助于从根本上理解健康与疾病及其防治,有益于中医"天人相应"理论的继承和发展。     

呼吸减痛法配合一对一陪伴分娩临床研究

目的探讨呼吸减痛法配合一对一陪伴分娩的临床效果。方法选取在孕期接受呼吸减痛法培训的初产妇50例做为观察组,选取未接受呼吸减痛法培训的初产妇50例作为对照组,临产时观察组由一名专职助产士有针对性地进行呼吸减痛法的指导,对照组不做呼吸减痛法的指导,仅采用传统的方法进行待产。两组孕妇均按常规一对一陪伴分娩,按正常方法观察产程,收集相关资料后进行统计学分析。结果观察组中出现Ⅰ级与Ⅱ级分娩疼痛的产妇较对照组增加,而Ⅲ级分娩疼痛者明显少于对照组;第一产程、第二产程和总产程时间明显短于对照组,产后出血率、新生儿窒息率明显少于对照组,差异均有统计学意义(P<0.05)。结论呼吸减痛分娩法是一种安全、有效的减痛分娩方法,可以缩短总产程,减少产后出血及新生儿窒息的发生。     

肠造瘘术后一次性造口袋拆除方法的改进

介绍一种肠造瘘术后一次性造口袋拆除的方法。将2000—2008年的108例肠造瘘术后使用一次性造口袋患者按时间顺序分为对照组和观察组,每组各54例。对照组采用传统方法拆除一次性造口袋,观察组采用改进方法拆除。对照组发生局部皮肤破损14例（25.93%）,观察组1例（1.85%）,2组比较有显著性差异（P＜0.01）。观察组患者主观感受及局部皮肤破损具体情况优于对照组。改进后的拆除一次性造口袋的方法安全、科学,可减轻患者痛苦。     

A Pilot Study Investigating the Dynamics of Pigeon Circovirus Recombination in Domesticated Pigeons Housed in a Single Loft

Pigeon circovirus (PiCV) infects pigeon populations worldwide and has been associated with immunosuppression in younger pigeons. Recombination is a common mechanism of evolution that has previously been shown in various members of the Circoviridae family, including PiCV. In this study, three groups of pigeons acquired from separate lofts were screened for PiCV, and their genome sequence was determined. Following this, they were housed in a single loft for 22 days, during which blood and cloacal swab samples were taken. From these blood and cloacal swabs, PiCV genomes were determined with the aim to study the spread and recombination dynamics of PiCV in the birds. Genome sequences of PiCV were determined from seven pigeons (seven tested PiCV positive) before they were housed together in a loft (n = 58 sequences) and thereafter from the ten pigeons from blood and cloacal swabs (n = 120). These 178 PiCV genome sequences represent seven genotypes (98% pairwise identity genotype demarcation), and they share >88% genome-wide pairwise identity. Recombination analysis revealed 13 recombination events, and a recombination hotspot spanning the 3′ prime region, the replication-associated protein (rep) gene and the intergenic region. A cold spot in the capsid protein-coding region of the genome was also identified. The majority of the recombinant regions were identified in the rep coding region. This study provides insights into the evolutionary dynamics of PiCV in pigeons kept under closed rearing systems.     

High prevalence of airway obstruction and pulmonary emphysema in urothelial (renal pelvis,ureter, and bladder) cancer patients

BackgroundCigarette smoking is a major cause of COPD, with patients also presenting complications that stem from other smoking-related diseases, including urothelial cancer. However, the prevalence of COPD or airflow obstruction in urothelial cancer patients has not been well studied.MethodsWe investigated the prevalence of airflow obstruction (FEV1/FVC < 70%) in newly diagnosed urothelial cancer patients and identified the risk factors for airflow obstruction in existing urothelial cancer patients. Additionally, we compared the characteristics of subjects who had been diagnosed with both airflow obstruction and urothelial cancer, and subjects whose airflow obstruction was discovered during health screenings.ResultsA total of 217 patients were newly diagnosed with urothelial cancer during the study period at our institution. Among all patients, 210 (96.8%) underwent an evaluable lung function test, in which 38.6% (81 patients) displayed airflow obstruction defined as FEV1/FVC < 70%. In urothelial cancer patients, age, smoking index (pack-years), and BMI proved to be significant risk factors for airflow obstruction in multivariate logistic regression (p = 0.007, p < 0.0001, and p = 0.035, respectively). Gender, cancer stage, and cancer location were not significant risk factors. Patients with both airflow obstruction and urothelial cancer showed a more advanced emphysematous change than subjects presenting with airflow obstruction alone (unpaired t-test, p = 0.0003).ConclusionsAirflow obstruction was identified in 38.6% of urothelial cancer patients. Age, smoking index (pack-years), and BMI were significant risk factors. A significantly higher emphysematous score was observed in subjects with urothelial cancer than in subjects with airway obstruction alone.     

Treatment of therapy-induced preleukemic syndrome

Summary Two young adult patients with therapy-induced preleukemic syndrome and Hodgkin's disease as primary malignancy were treated with aggressive antileukemic regimens before the establishment of leukemic conversion. Pretreatment clinical staging procedures did not reveal recurrence of Hodgkin's disease. One of the regimens consisted of an HLA-identical allogeneic bone marrow transplant and the other of high dose cytosine arabinoside. Both therapeutic approaches have proved successful in restoring normal hematopoiesis with reversal to normal karyotypes and unmaintained remiisions 556 and 192 days post-treatment. The rationale for such a therapeutic approach in the preleukemic stage of therapy-induced leukemogenesis is discussed.     

慢性阻塞性肺疾病患者血清肺表面活性蛋白D水平变化及其临床意义

目的探讨慢性阻塞性肺疾病患者血清肺表面活性蛋白D水平变化及其临床意义。方法选取COPD急性加重期患者30例、COPD稳定期患者30例及对照者30例,分别测定其血清SP-D水平,并与COPD患者严重程度进行相关分析。结果 COPD急性加重、稳定期患者血清SP-D水平均高于对照组(P0.05);COPD急性加重组患者血清SP-D水平明显高于稳定期组(P0.05)。相关性分析结果显示:COPD急性加重、稳定期患者血清SP-D水平与一秒钟用力呼气容积占预计值百分比(FEVl%pred)均呈负相关(P0.05)。结论 COPD急性加重、稳定期患者血清SP-D水平均高于对照组,血清SP-D水平变化可作为判定COPD病情严重程度的指标之一。