发育性协调障碍儿童动作能力干预研究系统评价

目的 探讨不同干预方法对发育性协调障碍(DCD)儿童动作能力的影响,为DCD儿童干预方案的选择提供理论依据。方法 搜集1995年1月-2015年3月关于针对改善DCD儿童动作能力的中英文干预研究,并对文献进行筛选、资料提取分析、文献质量评价、结果讨论和结论报告。41篇文献最终被纳入系统评价,本文将纳入文献中提及的干预方式分为“以任务为导向”的方法、“以过程为导向”的方法和药物治疗3类,并采用PEDro量表和牛津中心证据水平评价纳入文献的质量,进而对每类方法的治疗效果进行评价。结果 PEDro量表文献质量评价平均得分为6.3,为中等水平;采用牛津中心证据水平对文献质量评价,证据水平均在中等(Ⅱb)及以上。不同类型干预方式对DCD儿童动作能力改善程度为:“以任务为导向”的方法对DCD儿童动作能力的提高最有效,其效果高于“以过程为导向”的方法。药物治疗对DCD和ADHD共病儿童具有一定的疗效。结论 以“任务为导向”的DCD儿童动作能力发展干预方法优于以“过程为导向”的方法,药物治疗对DCD和ADHD共病儿童有较好的干预。     

承德市健康体检女性“两癌”筛查意愿及影响因素分析

目的 探讨承德市普通体检女性“两癌”筛查意愿及影响因素。方法 以2020年7月至2021年6月在承德市某医院进行普通体检的成年女性作为调查对象进行“两癌”筛查意愿问卷调查,采用描述性分析方法对“两癌”筛查意愿进行分析,并对其影响因素进行分析。结果 最终有效调查承德市健康女性3 150人,30~60岁1 752人,占55.62%,已婚2 159人,占68.54%,有筛查意愿970人,占30.79%。个人月收入>8 000元（OR=3.025）、居住地为城市（OR=3.154）、31~60岁（OR=1.335）、文化程度为硕士及以上（OR=2.331）的健康体检女性“两癌”筛查意愿较高。结论 承德市普通体检女性“两癌”筛查意愿较低,需引起重视,需要加强“两癌”筛查相关认知宣传,需制定综合措施增加女性“两癌”筛查积极性。     

深圳市流感指数的制定及应用

目的 探索疾病监测数据的应用新模式,提升疾病监测质量。方法 采用综合评分法,对流感样病例百分比的基线值和平均值、每周流感病毒检测阳性率和每周流感样病例暴发疫情起数的高低程度评分和计算权重系数,建立“流感指数”判定方程。结果 “流感指数”分为4个等级,分别为极易发生（Ⅰ级,指数值3.6~4）、易发生（Ⅱ级,指数值2.6~3.5）、较易发生（Ⅲ级,指数值1.6~2.5）和较少发生（Ⅳ级,指数值1~1.5）。结论 “流感指数”是将疾病监测数据转化为实际应用的新尝试,具有良好的社会效益。     

德阳地区妇女“两癌”防治知识知晓现状及影响因素分析

目的 调查德阳地区妇女乳腺癌和宫颈癌（简称“两癌”）防治知识的掌握情况,探讨影响女性“两癌”防治知识认知的相关因素,为更好地开展 “两癌”筛查工作提供参考依据。方法 采用分层整群抽样方法于2019年6—9月抽取德阳市妇女作为研究对象进行“两癌”防治知识知晓情况现场问卷调查,采用描述流行病学分析方法进行分析,并采用单、多因素分析方法对“两癌”防治知识知晓影响因素进行分析。结果 共对1 835名德阳市女性居民进行分析,年龄20~69岁,平均（42.36±5.22）岁。文化程度以初中（653人,35.59%）和高中（634人,34.55%）为主。城镇居民占60.60%。职业以企事业职工为主（594人,32.37%）。“两癌”防治知识的总均分为（23.6±5.3）分,总知晓率为49.30%。答对“两癌”防治知识问卷60%以上题的有878人,了解率为47.85%。年龄越大（OR=0.730）的女性居民“两癌”防治知识了解的可能性较小,文化程度越高（OR=2.787）、居住地在城镇（OR=5.512）、职业为企事业单位职工或个体户（OR=5.124、1.713）、家庭人均月收入越高（OR=2.298）、乳腺疾病史（OR=1.775）和妇科疾病史（OR=1.320）是女性“两癌”防治知识了解率的促进因素。结论 德阳市适龄妇女“两癌”防治知识的掌握情况不佳,应重点针对高龄、文化程度低、农村地区的低收入女性人群加强“两癌”健康知识宣传教育工作。     

TGF-β1基因多态性与肝纤维化易感性关系的Meta分析

目的 系统评价转化生长因子β₁ (TGF-β₁) 基因-509C>T、Leu10Pro(T>C)、Arg25Pro(G>C)位点单核苷酸多态性与肝纤维化遗传易感性的关系。方法 以“liver cirrhosis”和“Transforming Growth Factor beta1”为主题词,辅以“liver Fibrosis”、“ TGF-β1”、“肝硬化”等关键词,在PubMed 、CNKI等中英文数据库检索相关文献。要求入选文献均为非相关研究,以OR或RR为效应指标,利用Review Manager5.2和Stata12软件进行合并分析、亚组分析、异质性检验、敏感性分析,最后用漏斗图和Egger检验对发表偏倚进行评估。结果 最终选定17篇文献,均为病例对照研究,累计病例2043例,对照2316例。合并分析显示： TGF-β₁基因-509C>T位点单核苷酸多态性与肝纤维化患病风险有关（等位基因比较：OR=0.820,95%CI:0.728-0.923, P=0.001;显性模型：OR=0.826,95%CI: 0.689 -0.990, P=0.039;隐性模型：OR=0.731,95%CI: 0.600 -0.891, P=0.002;纯合子比较：OR=0.711,95%CI: 0.567 -0.893, P=0.003）。Leu10Pro(T>C)位点单核苷酸多态性与肝纤维化患病风险无关联(P>0.05)。Arg25Pro( G>C)位点单核苷酸多态性与肝纤维化患病风险有关（等位基因比较：OR=0.063,95%CI:0.049-0.080, P=0.000; 隐性模型：OR=0.600,95%CI: 0.441 -0.816, P=0.001）。结论 TGF-β₁基因变异与肝纤维化遗传易感性有关联,其中-509C>T位点的C等位基因、Arg25Pro (G>C)位点的G等位基因与肝纤维化的易感性呈负相关,提示该等位基因可能是个体肝纤维化的保护因素。     

我国甲型H1N1流感疫苗免疫效果评估系统综述*

目的 通过对甲型H1N1流感疫苗免疫学效果和保护效果的系统回顾,为完善甲型流感免疫策略提供依据。方法 采用系统评价方法,“甲型H1N1流感疫苗”或“甲型流感疫苗”“评估”或“效果”或“效果评估”为检索词,全面检索中国知识资源总库期刊全文数据库（2009~2014年6月）和万方学术期刊数据库（2009~2014年6月）,对纳入文献进行系统分析。结果 符合纳入标准的文献12篇,免疫学效果和保护效果系统评价显示：抗体阳转率为61％~100％,GMT为1:200~1:736.23,甲流发病率<8.5%,疫苗的保护率为 45.15%~100%。结论 甲流疫苗具有较好的免疫保护作用。     

重视全科医学教育加大力度培养居民健康守门人

全科医学是一门综合性学科,在临床、预防、康复与健康管理方面具有一体化指导作用。全科医生遵循“以人为本,以人的健康为中心”的服务理念,在疾病预防与健康管理方面具有重要作用,是居民健康的“守门人”。随着全科医学教育培训的实施,可以有效培养满足社会需求的综合医学人才,有利于疾病的预防、早期发现及健康保障,有利于缓解就医压力,促进我国医疗服务体系的完善,提高初级卫生保健服务水平,加快推进健康中国2030建设。     

海南省“营养改善计划”某试点地区中小学生贫血状况及影响因素分析

目的 分析海南省“农村义务教育学生营养改善计划”（简称“计划”）某试点地区中小学生贫血的变化趋势及影响因素。方法 2014—2017年采用分层整群随机抽样法,在实施“计划”的重点监测县抽取中小学生进行血红蛋白等生化指标检测及问卷调查。多组均值间比较采用方差分析,率的比较采用χ²检验,贫血影响因素分析采用二分类Logistic回归。结果 2014—2017年共抽取学生2 590人,各年血红蛋白平均水平分别为（138.1±12.0）、（136.4±13.4）、（138.1±12.4）、（138.1±15.4）g/L,差异无统计学意义（P>0.05）。4年来各年贫血率分别为5.4%、5.4%、4.5%、6.7%,变化趋势无统计学意义（P>0.05）;其中2015年初中生贫血率高于小学生（P<0.05）,其余年度小学、初中生间,男、女生间贫血率差异均无统计学意义（均P>0.05）。Logistic回归分析结果显示,少数民族学生（OR=6.947）和维生素A亚临床缺乏/缺乏学生（OR=2.030）发生贫血的风险更高。结论 该地区中小学生贫血状况改善不明显,少数民族和维生素A亚临床缺乏/缺乏学生是需改善贫血的重点人群。     

深圳市龙华区校园传染病防控能力评价指标体系构建及应用

目的 建立深圳市龙华区中小学校及幼儿园传染病防控能力评价指标体系,并对学校及幼儿园传染病防控能力进行初步评价。方法 通过查阅文献、参考相关的工作规范和专家咨询的方法,拟定龙华区校园传染病防控能力评价的基础指标,采用2轮专家评分法对基础指标进行筛选、增、减得到最终评价指标体系及其权重,最后利用问卷调查法对校园传染病的防控能力进行评价。结果 邀请13名具有医学背景、熟悉传染病防控业务且具有丰富实践经验的专家进行咨询,建立的校园传染病防控能力评价指标体系由4个一级指标、15个二级指标、33个三级指标组成。应用该评价体系对龙华区245所中小学校和幼儿园进行初步评分,10.61%（26/245）评价对象的传染病防控能力“很强”（90.00~100.00分）,50.61%（124/245）为“强”（80.00~89.99分）,23.27%（57/245）为“一般”（70.00~79.99分）,13.06%（32/245）为“差”（60.00~69.99分）,2.45%（6/245）为“很差”（0~59.99分）。结论 通过校园传染病防控能力评价指标体系,对学校及幼儿园进行综合评价,找出传染病防控的薄弱环节,为进一步提高传染病防控能力提供科学依据。     

流动人口中已婚育龄妇女保健知识认知情况及其影响因素探析

目的调查流动人口中已婚育龄妇女保健知识认知情况,并对影响因素进行分析。方法对宁波市北仑区2013年1月~2013年12月的586名已婚育龄妇女,通过自制的“基本情况调查问卷”以及“妇女保健知识调查问卷”进行调查。结果所有研究对象的保健知识总分为30~72分,平均（54.2±7.6）分,其中生殖卫生得分平均（9.5±2.8）、妇科保健得分平均（8.0±2.1）、计划生育得分平均（7.9±2.2）、优生优育得分平均（9.9±2.4）、孕期保健得分平均（9.8±3.7）和产褥期保健得分平均（8.2±2.6）。其中年龄在21~30岁、年收入在10000元以上、文化程度为高中及以上者、对于婚姻满意,且生育1个孩子的妇女保健知识认知情况,各维度得分在各组间均最高(P<0.05)。结论应针对流动人口已婚育龄妇女中年龄在40岁以上、年收入及文化程度较低、婚姻状况不佳,且生育多个子女的妇女重点进行健康教育知识宣教,以提高其保健知识。     

Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate

Nonsyndromic cleft palate (CP) is a common birth defect with a complex and heterogeneous etiology involving both genetic and environmental risk factors. We conducted a genome-wide association study (GWAS) using 550 case-parent trios, ascertained through a CP case collected in an international consortium. Family-based association tests of single nucleotide polymorphisms (SNP) and three common maternal exposures (maternal smoking, alcohol consumption, and multivitamin supplementation) were used in a combined 2 df test for gene (G) and gene-environment (G × E) interaction simultaneously, plus a separate 1 df test for G × E interaction alone. Conditional logistic regression models were used to estimate effects on risk to exposed and unexposed children. While no SNP achieved genome-wide significance when considered alone, markers in several genes attained or approached genome-wide significance when G × E interaction was included. Among these, MLLT3 and SMC2 on chromosome 9 showed multiple SNPs resulting in an increased risk if the mother consumed alcohol during the peri-conceptual period (3 months prior to conception through the first trimester). TBK1 on chr. 12 and ZNF236 on chr. 18 showed multiple SNPs associated with higher risk of CP in the presence of maternal smoking. Additional evidence of reduced risk due to G × E interaction in the presence of multivitamin supplementation was observed for SNPs in BAALC on chr. 8. These results emphasize the need to consider G × E interaction when searching for genes influencing risk to complex and heterogeneous disorders, such as nonsyndromic CP.     

Genetic polymorphisms in alcohol-metabolizing enzymes and chronic pancreatitis

AIMS: Alcohol misuse is now regarded as an important risk factor for development of chronic pancreatitis (CP). However, not every alcohol misuser develops CP and it therefore might be suggested that susceptibility could be further influenced by inter-individual variations in the activities of alcohol-metabolizing enzymes. Several genetic polymorphisms that may affect the activities of alcohol-metabolizing enzymes have been described. Therefore we determined whether polymorphisms in the genes for alcohol dehydrogenase 3 (ADH3) or cytochrome p450 2E1 (CYP2E1) predispose to the development of CP. METHODS: DNA samples were obtained from 142 adult CP patients with hereditary (n = 21), alcoholic (n = 82) or idiopathic (n = 39) CP. DNA from 128 healthy controls and from 93 alcoholic controls was analysed for comparison. Patients and controls were all of Caucasian origin. Genetic polymorphisms in ADH3 and CYP2E1 were determined by PCR, followed by restriction-fragment-length-polymorphism analyses in all subjects. RESULTS: The frequencies of ADH3 and CYP2E1 c1c2 genotypes did not differ between CP patients and alcoholic and healthy controls. However, a trend for a higher frequency of the CYP2E1 intron 6 D allele was demonstrated in patients with alcohol-induced CP, compared to that of healthy controls (OR = 3.03, 95%CI = 1.0-9.1) or alcoholic controls (OR = 2.76, 95%CI = 0.9-8.7). CONCLUSIONS: These data suggest that the presence of the CYP2E1 intron 6 DD genotype might confer a higher risk of alcoholic CP.     

Evaluation of two putative susceptibility loci for oral clefts in the Danish population

Previous studies suggest that the risk of nonsyndromic cleft lip with or without cleft palate (CL+/-P) and isolated cleft palate (CP) is influenced by genetic variation at several loci and that the relation between specific genetic variants and disease risk may be modified by environmental factors. The present study evaluated potential associations between CL+/-P and CP and two putative clefting susceptibility loci, MSX1 and TGFB3, using data from a nationwide case-control study conducted in Denmark from 1991 to 1994. The potential effects of interactions between these genes and two common environmental exposures, first trimester exposure to maternal cigarette smoke and alcohol intake, were also examined. Analyses of these data provide evidence of an association between the risk of CP and variation at the TGFB3 locus. However, there is no evidence that the risk of CL+/-P or CP is influenced by gene-environment interactions involving MSX1 or TGFB3 and either first trimester exposure to maternal cigarette smoke or alcohol consumption.     

中国人群寻常型银屑病易感基因研究进展

银屑病是一种常见的多因子遗传模式的复杂疾病,复杂疾病的发病机制在不同人群中存在种族差异性和遗传异质性。随着全基因组关联分析(GWAS)技术的推广应用,中国人群寻常型银屑病易感基因与其他国家人群的种族差异性逐渐被揭示,LCE、MHC等银屑病易感基因在中国人群的遗传异质性均被论证,PSORS9则被证实为汉族人群银屑病患者所特有的易感位点。     

How much are we missing in SNP-by-SNP analyses of genome-wide association studies?

Genome-wide association studies have discovered common genetic variants associated with susceptibility for several complex diseases, but they have been unfruitful for many others. Typically, analysis is done "agnostically," by considering one single nucleotide polymorphism (SNP) at a time and controlling the overall type I error rate by correcting for multiple testing. Such one-at-a-time analyses may be inadequate for screening genes under realistic causal models. We use oral clefting as a disease model to develop a range of toy example scenarios: risk might involve only genes, or genes and exposure, or genes, exposure, and their supermultiplicative interaction. These examples illustrate how dramatically important genetic variants can be obscured by a one-SNP-at-a-time analysis when multiple biologic pathways and multiple genes jointly influence etiology. These examples highlight the need for better methods for gene-by-environment and gene-by-gene analyses.     

Genetic susceptibility to occupational exposures

Because of their high prevalence in the general population, genetic variants that determine susceptibility to environmental exposures may contribute greatly to the development of occupational diseases in the setting of specific exposures occurring in the workplace. Studies investigating genetic susceptibilities in the workplace may: (1) provide mechanistic insight into the aetiology of disease, in particular the determination of environmentally responsive genes; (2) identify susceptible subpopulations with respect to exposure; and (3) provide valuable input in setting occupational exposure limits by taking genetic susceptibility into account. Polymorphisms in the NAT2 and the HLA-DPB1(G)(lu69) genes provide classic examples of how genetic susceptibility markers have a clear role in identifying disease risk in bladder cancer and chronic beryllium disease, respectively. For diseases with more complex and multifactorial aetiology such as occupational asthma and chronic airways disease, susceptibility studies for selected genetic polymorphisms provide additional insight into the biological mechanisms of disease. Even when polymorphisms for genetic susceptibility have a clear role in identifying disease risk, the value of wide scale genetic screening in occupational settings remains limited due to primarily ethical and social concerns. Thus, large scale genetic screening in the workplace is not currently recommended.     

The New Obesity Genes

Individual susceptibility to obesity is recognized to be influenced significantly by genetic inheritance. Recently, candidate obesity genes have been identified that may contribute to the inheritance of body fat mass and the partitioning of fat between central and peripheral fat depots. In studies of animal models of obesity, the genetic basis for obesity in the obese (Ob/Ob) mouse, the Fat mouse, and the Yellow (V^vy) mouse has been identified. Further research is needed to determine whether abnormalities in these genes contribute to human obesity as well. In studies of humans, sequence variation in at least six genes has been linked to increased body fatness and/ or susceptibility to obesity. In addition, five other encoding genes have been linked to a disproportionate storage of fat in the abdominal region. These genes identified in studies of humans are currently thought to be modifying or background genes, each separately conferring a modest increase in susceptibility to fatness. Further research is needed to identify additional candidate genes that confer susceptibility to obesity and to determine the relative importance of each one in a range of human populations with distinct environments.     

A Clustered Multiclass Likelihood‐Ratio Ensemble Method for Family‐Based Association Analysis Accounting for Phenotypic Heterogeneity

Although compelling evidence suggests that the genetic etiology of complex diseases could be heterogeneous in subphenotype groups, little attention has been paid to phenotypic heterogeneity in genetic association analysis of complex diseases. Simply ignoring phenotypic heterogeneity in association analysis could result in attenuated estimates of genetic effects and low power of association tests if subphenotypes with similar clinical manifestations have heterogeneous underlying genetic etiologies. To facilitate the family‐based association analysis allowing for phenotypic heterogeneity, we propose a clustered multiclass likelihood‐ratio ensemble (CMLRE) method. The proposed method provides an alternative way to model the complex relationship between disease outcomes and genetic variants. It allows for heterogeneous genetic causes of disease subphenotypes and can be applied to various pedigree structures. Through simulations, we found CMLRE outperformed the commonly adopted strategies in a variety of underlying disease scenarios. We further applied CMLRE to a family‐based dataset from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts (ICOC) to investigate the genetic variants and interactions predisposing to subphenotypes of oral clefts. The analysis suggested that two subphenotypes, nonsyndromic cleft lip without palate (CL) and cleft lip with palate (CLP), shared similar genetic etiologies, while cleft palate only (CP) had its own genetic mechanism. The analysis further revealed that rs10863790 (IRF6), rs7017252 (8q24), and rs7078160 (VAX1) were jointly associated with CL/CLP, while rs7969932 (TBK1), rs227731 (17q22), and rs2141765 (TBK1) jointly contributed to CP.     

蛋白酪氨酸磷酸酶非受体型22与类风湿性关节炎的关系

类风湿性关节炎（RA）是以对称性的多关节炎为主要临床表现的异质性、系统性和自身免疫性疾病。近年来，除主要组织相容性位点（MHC位点）以外，与 RA 发病有关的易感基因不断被发现，其中蛋白酪氨酸磷酸酶非受体型22（PTPN22）单核苷酸多态性（SNP）作为 RA的一个易感基因是目前公认的除 MHC 之外与自身免疫性疾病发病相关的最重要的危险因子。本文总结PTPN22基因与 RA 的相关研究结果与观点，主要阐述两者的作用关系，旨在为检测PTPN22基因变异位点诊断 RA提供有价值的信息。     

Gene-environment interaction: a central concept in multifactorial diseases

Unlike the rare and severe genetic defects that cause monogenic diseases, the genetic factors that modulate the individual susceptibility to multifactorial diseases (cardiovascular diseases, cancers, diabetes, etc.) are common, functionally different, forms of genes (polymorphisms), which generally have a modest effect at an individual level but, because of their high frequency in the population, can be associated with a high attributable risk. Environmental factors can reveal or facilitate the phenotypic expression of such susceptibility genes. Indeed, in common diseases genetic effects can be considerably amplified in the presence of triggering factors. There is now accumulating evidence that most of the susceptibility genes for common diseases do not have a primary aetiological role in predisposition to disease, but rather act as response modifiers to exogenous factors such as stress, environment, disease, drug intake. A better characterisation of the interactions between environmental and genetic factors constitute a key issue in the understanding of the pathogenesis of multifactorial diseases. The present paper will review three examples of gene-environment interactions in the field of CHD.