云浮市呼吸道和消化道传染病发生与气象因素的关系探讨

目的研究云浮市气温、相对湿度、气压等气象因素对传染病发生的影响。方法监测、收集2006-2007年云浮市呼吸道和消化道两类传染病的发病情况，结合两年云浮市气温、相对湿度、降水量、气压、日照时数等5个气象因素变化，分析疾病发生与气象因素两者的关系。结果两类传染病发生受气象因素的影响较大，气候发生变化时，疾病的发生和流行亦产生很大的变化。结论气象因素是影响传染病发生和流行的重要因素，两者关系较密切。     

淄博市张店区手足口病流行与气象因素的关系研究

目的 探讨淄博市张店区手足口病发病与气象因素之间的关系,为预测淄博市张店区手足口病发病情况提供依据。方法 收集2007-2009年淄博市张店区月度手足口病发病资料和气象资料（气温、气压、湿度、降水天数、降水量）,使用SPSS13.0对手足口病和气象因素资料进行相关和回归分析。结果 手足口病受气象因素影响较大,经逐步回归方法分析,发现气温、气压、平均降水量、相对湿度、降水天数5个参数均进入方程。结论 气象因素与手足口病发病关系密切。     

原发性肥厚型心肌病与HLA-DQ的相关性研究

本文用PCR/SSO方法对41例原发性肥厚型心肌病患者和52例正常人HLA-DQA1和DQB1基因的多态性进行分析.发现,在肥厚型心肌病患者中,DQA1＊0201,DQB1＊0504,0502等位基因频率明显较低,其相对风险值分别为9.51、5.87和11.60;而DQA1*0501,DQB1＊03031的频率明显地高,相对风险值分别为2.93和6.65.初步认为,原发性肥厚型心肌病与某些HLA-DQ基因相关联.     

Tests of Association Between Quantitative Traits and Haplotypes In A Reduced-Dimensional Space

Candidate gene association tests are currently performed using several intragenic SNPs simultaneously, by testing SNP haplotype or genotype effects in multifactorial diseases or traits. The number of haplotypes drastically increases with an increase in the number of typed SNPs. As a result, large numbers of haplotypes will introduce large degrees of freedom in haplotype‐based tests, and thus limit the power of the tests. In this study we propose using the principal component method to reduce the dimension, and then construct association tests on the lower‐dimensional space to test the association between haplotypes and a quantitative trait using population‐based samples. The proposed method allows ambiguous haplotypes. We use simulation studies to evaluate the type I error rate of the tests, and compare the power of the proposed tests with that of the tests without dimension reduction, and the tests with dimension reduction by merging rare haplotypes. The simulation results show that the proposed tests have correct type I error rates and are more powerful than other tests in most cases considered in our simulation studies.     

成纤维细胞生长因子受体2基因与肿瘤的相关性研究

成纤维细胞生长因子受体2(fibroblast growth factor receptor 2,FGFR2)是人成纤维细胞生长因子受体(FGFRs)家族中的一员,FGFRs在细胞的增殖、分化、血管生成、骨骼发育中起着十分重要的作用.研究表明成纤维细胞生长因子受体2(FGFR2)与肿瘤的发生存在一定相关性.本文就其特点作如下总结.     

A Comparison Between Different Designs and Tests to Detect QTLs in Association Studies

The availability of different designs and tests to detect QTLs in association studies raises questions about the relative merits of the various approaches. We therefore compared the power of quantitative versus categorical tests, the power in population samples versus samples with subjects selected on the basis of their trait scores, and the power of tests that control for population stratification using parental genotypes versus tests that do not control for stratification. In case–control samples the power of quantitative tests was clearly better than that of categorical tests especially when the control group was a population sample. In samples of genotyped trios of cases and their parents, the power of quantitative tests was much poorer. Compared to population samples, selection always improved the power in case–control samples where the controls were sampled from the opposite end of the continuum and frequently deteriorated the power when the controls were a population sample. Mainly because subjects with at least one heterozygous parent need to be selected, the use of tests that control for stratification resulted in a substantial decrease of power. In the final section our power calculations were integrated into a more general discussion about optimizing designs in association studies.     

转录因子FOXA2与肺发育相关研究

在肺发育过程中,需要多种转录因子、生长因子以及其他的信号分子协调作用,共同促进细胞的增殖和分化,实现肺正常发育,其中翼螺旋转录因子Foxa2可参与促进肺上皮细胞增殖分化、表面活性物质合成等过程,在建立正常肺形态和功能上发挥重要作用,其表达异常可致肺发育异常。     

中国人动脉血栓性疾病与活化蛋白C裂解FV和FVIII基因位点突变的相关性研究

目的 :检测脑血栓 (CT)和急性心肌梗死 (AMI)患者活化蛋白C(APC)抵抗 (APCR)及APC裂解凝血因子V (FV )和凝血因子VIII(FVIII)肽链的基因位点突变。方法 :用单链构象多态性分析 (SSCP)方法 ,检测 10 2例CT、46例AMI和 10 5例健康人的APC裂解FV肽链 (Arg3 0 6、Arg 5 0 6、Arg 679和结合部位 1865～ 1875 )、裂解FVIII肽链 (Arg3 3 6、Arg 5 62和结合部位 2 0 0 5～ 2 0 18)的基因位点。结果 :对照组和患者组均未检出FV的突变基因。结论 :中国人动脉血栓性疾病患者无APC裂解FV和FVIII肽链的基因突变 ,患者的APC敏感性的降低可能由其他因素所致     

Lack of Association Between Genetic Variation in 9 Innate Immunity Genes and Baseline CRP Levels

It is well‐known that baseline levels of C‐reactive protein (CRP) are an independent cardiovascular risk factor. We hypothesized that genetic variation with significant influence on CRP levels might be found in genes of the innate immunity system. We performed a candidate gene association study examining common single nucleotide polymorphisms in 9 innate immunity genes (CARD15, IRAK1, IRAK4, LBP, LY86, MEFV, TLR2, TLR4 and NFKB1) in relation to CRP levels. Seven hundred and seventeen subjects from the Women's Health Study population were studied: 359 and 358 samples with extremely low (<0.2 mg/liter) and high (>5 mg/liter) CRP levels, respectively. SNPs were identified from publicly available resequencing data, using a minor allele frequency threshold of >5% and a linkage disequilibrium (LD)‐based strategy (r² > 0.8) to select 63 LD‐independent markers. One non‐synonymous SNP in TLR4 and two non‐synonymous SNPs in CARD15, previously associated with atherosclerosis and Crohn's disease, respectively, were also studied. Univariate, haplotype and gene‐gene interaction analyses all indicated no significant association with CRP levels. Although this work excludes a significant association of common SNPs in these nine genes with CRP levels, it is possible that rarer alleles in these genes, or variation in other innate immunity genes, could be associated with variation in CRP.     

Investigating Association of Three Polymorphisms of Coagulation Factor XIII and Recurrent Pregnancy Loss

Citation Jeddi‐Tehrani M, Torabi R, Mohammadzadeh A, Arefi S, Keramatipour M, Zeraati H, Zarnani AH, Akhondi MM, Mahmoudian J, Mahmoudi AR, Zarei S. Investigating association of three polymorphisms of coagulation factor XIII and recurrent pregnancy loss. Am J Reprod Immunol 2010; 64: 212–217 Problem Among important suspected causes of thrombophilia in women with recurrent pregnancy loss (RPL) are the polymorphisms of coagulation factor XIII (FXIII) gene. We performed a case–control study on the association between three polymorphisms of factor XIII (FXIII G103T, FXIII A614T and FXIII C1694T) and RPL in Iranian women. Method of study DNA samples from peripheral blood of 100 female patients with at least two recurrent abortions, as case group, and 100 healthy women with history of at least two successful deliveries were subjected to PCR‐RFLP, and the frequencies of the polymorphisms were calculated and compared between the two groups. Results The prevalence of FXIII G103T polymorphism was 29% in the case group and 17% in the control group (P = 0.158). The frequencies of FXIII A614T and FXIII C1694T were 84% and 66% in the case group and 48% and 31% in the control group (P < 0.001 and P < 0.001), respectively. The two latter polymorphisms are associated with RPL in Iranian women and increase the risk of RPL. A correlation was also found between FXIII A614T and FXIII C1694T polymorphisms (P < 0.001). Conclusion We suggest the evaluation of FXIII A614T and FXIII C1694T polymorphisms in women with RPL.     

Relation Between the Heavy Chain Complementarity Region 3 Characteristics and Rheumatoid Factor Binding Properties

Among the rheumatoid factors (RFs), monospecific and polyspecific types can be distinguished. However the molecular basis responsible for their different specificity is not well understood. In a previous report, we have shown that the binding of the majority of the polyspecific antibodies is salt-sensitive. No binding to IgG was observed under high ionic strength (0.3-0.5 M NaCl). This salt-sensitivity was only observed for 18% of the monospecific RFs. Here, we have analyzed 14 RFs representing the 3 different groups (6 salt-insensitive monospecific, 4 salt-sensitive monospecific and 4 salt-sensitive polyspecific RFs). By analysis of the amino acid composition and the distribution of polar and non-polar residues of their heavy chain complementarity-determining region 3 (H-CDR3) in relation to mono/polyspecifieity, salt-sensitivity and reactivity against human IgG subclasses, we have identified common structural features responsible for their different binding properties. Salt-sensitive RFs (mono as well as polyspecific antibodies) were characterized by long H-CDR3′s (15.3 ± 2.7) that contained large numbers of hydrophilic residues such as arginine and serine, while salt-insensitive RFs had more hydrophobic H-CDR3′s of smaller length (11.3 ± 2.4). In addition, for the monospecific RFs, remarkably similar hydrophilicity H-CDR3 profiles were found that were correlated with their specificity for IgG subclasses. These observations confirm the importance of the H-CDR3 for the binding of RFs to IgG. Furthermore, on the basis of their shorter H-CDR3′s and their rather unique H-CDR3 hydrophilicity profiles, it is likely that the majority of the monospecific RFs should be considered as a group of RFs that is independent of the polyspecific RF repertoire.     

The Association between Genetic Variation in Wnt Transcription Factor TCF7L2 (TCF4) and Alopecia Areata

Background: Alopecia areata (AA) is a non-scarring hair loss with a polymorphous presentation ranging from patchy lesions to involvement of the entire scalp. The disease is the consequence of an autoimmune attack on hair bulbs that results in a premature transition of hair follicles to catagen and telogen. Thus the Wnt/β-catenin signaling pathway that regulates the hair cycling might be involved in the pathogenesis of AA. Genetic variations in the components of Wnt/β-catenin could greatly alter their adaptive mechanisms against an immunologic attack.

Objectives: Our aim was to investigate the association between AA and genetic polymorphisms in the TCF7L2 gene, one of the most important components of the Wnt/β-catenin pathway.

Methods: This is a case-control study of 145 patients with AA and 152 healthy controls. Genotyping of the TCF7L2 gene (rs7903146) was performed via the ARMS—PCR method (amplification refractory mutation system- polymerase chain reaction). The allele and genotype distribution was compared between the two groups.

Results: The frequency of the T allele (0.38 vs. 0.28, odds ratio = 1.56, 95% CI = 1.09–2.17, p = 0.013) and TT + CT genotypes (0.68 vs. 0.53, odds ratio = 1.88, 95% CI = 1.17–3.02, p = 0.008) were significantly higher in AA patients.

Conclusions: This study indicates that the TCF7L2 gene variant is associated with AA. Its contribution to disease pathogenesis could either be through a hair cycling defect or dendritic cell dysregulation.     

No Association Between General Cognitive Ability and the A1 Allele of the D2 Dopamine Receptor Gene

Berman and Noble (1995) reported significantly reduced visuospatial performance in children with the TAQI A1 allele of the D2 dopamine receptor (DRD2) gene. Given that visuospatial performance loads highly on an unrotated principal component indexing general cognitive ability, we tested the association between DRJD2 and WISC-R IQ comparing 51 high-IQ, 51 average-IQ, and 35 low-IQ children in the IQ Quantitative Trait Loci (QTL) Project. No statistically significant association between the TAQI A DRD2 alleles and IQ was found. Given that a statistically significant portion of genetic variance for specific cognitive abilities is independent of general cognitive ability, it is possible that the TAQI DRD2 association is specific to visuospatial performance and independent of general cognitive ability.     

糖尿病视网膜病变与血管性血友病因子和纤维蛋白原的关系

目的 :探讨糖尿病视网膜病变 (DR)与纤维蛋白原 (FIB)及vonWillebrand因子 (vWF)水平的关系及其临床意义。方法 :2型糖尿病人 10 4例根据病史及是否合并糖尿病微血管病变进行如下分组 :无并发症组 5 3例 (男 2 6例 ,女 2 7例 ) ,合并糖尿病视网膜病变组 5 1例(男 2 5例 ,女 2 7例 ) ,正常对照组 5 6例 (男 2 8例 ,女 2 8例 )。三组分别采用硫酸胺比浊法及双抗酶联免疫吸附法 (EUA)分别进行FIB、vWF的测定 ,并测定血压、糖化血红蛋白等指标。结果 :糖尿病患者血浆vWF、FIB水平较正常对照组明显升高 (P <0 .0 1) ,合并糖尿病视网膜病变组较无并发症组显著升高 (P <0 .0 1)。结论 :血浆FIB及vWF水平的升高与糖尿病视网膜病变的发生发展有关。     

C9ORF72 Intermediate Repeat Copies Are a Significant Risk Factor for Parkinson Disease

We set out to determine whether expansions in the C9ORF72 repeat found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) families are associated with Parkinson disease (PD). We determined the repeat size in a total of 889 clinically ascertained patients (including PD and essential tremor plus Parkinsonism (ETP)) and 1144 controls using a repeat‐primed PCR assay. We found that large C9ORF72 repeat expansions (>30 repeats) were not contributing to PD risk. However, PD and ETP cases had a significant increase in intermediate (>20 to 30+) repeat copies compared to controls. Overall, 14 cases (13 PD, 1 ETP) and three controls had >20 repeat copies (Fisher's exact test p = 0.002). Further, seven cases and no controls had >23 repeat copies (p = 0.003). Our results suggest that intermediate copy numbers of the C9ORF72 repeat contribute to risk for PD and ETP. This also suggests that PD, ALS and FTD share some pathophysiological mechanisms of disease. Further studies are needed to elucidate the contribution of the C9ORF72 repeat in the overall PD population and to determine whether other common genetic risk factors exist between these neurodegenerative disorders.     

内隐联想测验(IAT)在临床心理学中的应用

本文介绍了内隐联想测验 (IAT)及其在临床心理学研究中的应用。内隐联想测验是比传统自我报告测验更好的一种研究不合理信念的新工具 ,现已在社交焦虑、抑郁与成瘾行为等研究中得到了应用。最后 ,本文讨论了内隐联想测验的局限性与其在临床心理学应用中的前景     

Reduced Vascular Endothelial Growth Factor and Capillary Density in the Occipital Cortex in Dementia with Lewy Bodies

In dementia with Lewy bodies (DLB), blood flow tends to be reduced in the occipital cortex. We previously showed elevated activity of the endothelin and angiotensin pathways in Alzheimer's disease (AD). We have measured endothelin‐1 (ET‐1) level and angiotensin‐converting enzyme (ACE) activity in the occipital cortex in DLB and control brains. We also measured vascular endothelial growth factor (VEGF); factor VIII‐related antigen (FVIIIRA) to indicate microvessel density; myelin‐associated glycoprotein (MAG), a marker of ante‐mortem hypoperfusion; total α‐synuclein (α‐syn) and α‐synuclein phosphorylated at Ser129 (α‐syn‐p129). In contrast to findings in AD, ACE activity and ET‐1 level were unchanged in DLB compared with controls. VEGF and FVIIIRA levels were, however, significantly lower in DLB. VEGF correlated positively with MAG concentration (in keeping with a relationship between reduction in VEGF and hypoperfusion), and negatively with α‐syn and α‐syn‐p129 levels. Both α‐syn and α‐syn‐p129 levels increased in human SH‐SY5Y neuroblastoma cells after oxygen‐glucose deprivation (OGD), and VEGF level was reduced in SH‐SY5Y cells overexpressing α‐syn. Taken together, our findings suggest that reduced microvessel density rather than vasoconstriction is responsible for lower occipital blood flow in DLB, and that the loss of microvessels may result from VEGF deficiency, possible secondary to the accumulation of α‐syn.     

血管内皮生长因子与缺血性脑血管疾病关系的研究进展

血管内皮细胞生长因子是近年来发现的新生血管形成的主要调控因子,它与缺血性脑血管疾病的关系已经成为目前竞相研究的领域。本文从血管内皮生长因子在缺血性脑血管疾病中的表达,生物学作用,以及用于脑缺血病情的判断和治疗等不同侧面阐述了它与缺血性脑血管疾病的关系。