维生素D受体基因多态性与妊娠期糖尿病关系的病例对照研究

目的 探讨维生素D受体（VDR）基因多态性与妊娠期糖尿病（GDM）之间的关系,为GDM的机制研究提供线索与依据。方法 采用病例对照研究设计,以2012年3月1日至2014年7月30日在山西医科大学第一医院产科分娩的孕妇为研究对象,其中334例被诊断为GDM,按年龄、妊娠时间及居住地1∶1匹配相应健康对照。对研究对象进行DNA基因分型,剔除基因分型缺失率>10%者,最终323例病例和320例对照纳入研究。在共显性、显性、隐性和等位基因遗传模型下,通过非条件logistic回归分析VDR基因位点多态性和GDM之间的关系,并采用Haploview软件分析单倍型与GDM之间的关系。结果 在基因水平上,VDR基因与GDM发病风险有关（P<0.05）。在调整孕前BMI、糖尿病家族史后,rs7967152位点在共显性（AC vs. AA,OR=1.58,95%CI：1.13~2.21）、显性（AC+CC vs. AA,OR=1.58,95%CI：1.15~2.18）和等位基因（C vs. A,OR=1.41,95%CI：1.10~1.82）遗传模型下与GDM风险升高有关;rs2238140位点在共显性（AA vs. GG,OR=2.24,95%CI：1.19~4.20）、显性（GA+AA vs. GG,OR=1.48,95%CI：1.07~2.03）和等位基因（A vs. G,OR=1.43,95%CI：1.11~1.83）遗传模型下与GDM风险升高有关。在共显性和显性遗传模型下,孕妇携带rs2853564位点AG基因型、AG+GG基因型（OR=1.46,95%CI：1.04~2.05;OR=1.45,95%CI：1.05~2.00）与携带AA基因型相比,是GDM的危险因素;孕妇携带rs2853566位点AG基因型、AG+GG基因型（OR=1.43,95%CI：1.03~2.00;OR=1.41,95%CI：1.02~1.94）与携带AA基因型相比,是GDM的危险因素。在VDR基因内由rs1544410、rs7967152组成的单倍型区块,其GC单倍型与是GDM的危险因素（OR=1.50,95%CI：1.15~1.97）。结论 VDR基因rs7967152、rs2238140、rs2853564、rs2853566位点多态性和区块（rs1544410、rs7967152）GC单倍型与GDM的发病风险升高有关。     

Long-term persistent immunogenicity after successful standard and triple-dosed hepatitis B vaccine in hemodialysis patients: A 3-year follow-up study in China

BackgroundAlthough the efficacy of hepatitis B vaccines among hemodialysis patients has been documented, the long-term persistence of immunogenicity in this population remains largely unknown. We explored the long-term persistence of immunogenicity induced by different hepatitis B vaccine regimens in hemodialysis patients.MethodsIn initial study, we conducted a randomized, multicenter, double-blind, parallel-controlled trial among hemodialysis patients in 13 hospitals in Shanxi Province, China. A total of 352 hemodialysis patients were allocated to receive 3-dose 20 μg (IM20 group) and 3-dose 60 μg (IM60 group) recombinant hepatitis B vaccine at months 0, 1, and 6. Vaccine-induced immune responses were measured at month 7. In this study, the responders (anti-HBs ≥ 10 mIU/mL) were followed up at months 18, 24, 30, 36 and 42, respectively. We used the generalized log-rank test and generalized estimating equations (GEE) to analyze the long-term durability of responses and the kinetics of anti-HBs levels, respectively.ResultsA total of 284 patients were involved in the extended follow-up period. The duration of vaccine-induced response with 75% of patients maintained protective antibody were 12 months and 18 months in the IM20 group and IM60 group, respectively (P = 0.291). The long-term persistent immunogenicity induced by 3-dose 60 μg was more satisfactory than that by 3-dose 20 μg hepatitis B vaccine in patients with hemodialysis duration ≥ five years (P = 0.023). The peak anti-HBs levels in 100–1000 mIU/mL or ≥ 1000 mIU/mL were more likely to maintain long-term protective antibody compared to anti-HBs levels in 10–100 mIU/mL (P ＜ 0.05). The kinetic profile was similar between the two groups (P = 0.334).ConclusionHigh-dose 60 μg hepatitis B vaccine could lead a satisfactory long-term durability of immunogenicity among patients with hemodialysis duration of five years or more. Peak anti-HBs level after vaccination was associated with the long-term persistence of immunogenicity.     

Magnetocardiography for the Diagnosis of Coronary Artery Disease—A Systematic Review and Meta‐Analysis

Background: Coronary artery disease (CAD) has a significant disease burden making early diagnosis and management imperative. Magnetocardiography (MCG) is a relatively new noninvasive technique that allows diagnosis of CAD by recording the magnetic fields generated by the electrical activity of the heart. Methods: We searched MEDLINE and the Cochrane Central Register of Controlled Trials for prospective studies that evaluated the test characteristics (e.g., sensitivity, specificity, likelihood ratios) of MCG for detection of CAD. Studies were included if they evaluated either patients with stable CAD documented by angiogram or patients presenting initially with acute coronary syndrome and subsequently diagnosed with CAD. The quality of included studies was assessed using an adaptation of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. We performed meta‐analyses of sensitivity, specificity and positive and negative likelihood ratios using Meta‐DiSc software. Results: Screening of titles and abstracts followed by full‐text review yielded seven studies that met our inclusion criteria. Meta‐analyses yielded a pooled sensitivity of 83% (95% confidence interval [CI] 80% to 86%) and a specificity of 77% (95% CI 73% to 81%). The pooled positive likelihood ratio was 3.92 (95% CI 2.30 to 6.66) and negative likelihood ratio was 0.20 (95% CI 0.12 to 0.35). Significant heterogeneity was present in all meta‐analyses. Conclusions: The pooled test characteristics for MCG are similar to those of existing noninvasive modalities for diagnosing CAD. Our results suggest that MCG is a potential complementary or alternative tool for noninvasive detection of CAD.     

Advanced but not mild liver disease is a predictor of decreased survival in children with cystic fibrosis,with far greater impact in females: A 27-year real-life cohort study

BackgroundImproved survival of children with CF has increased our need to understand the relevance of cystic fibrosis-associated liver disease (CFLD). We assessed the impact of liver disease and disease severity on the survival of children with cystic fibrosis.MethodsA real life, single center cohort study with 27 years follow up was conducted. Mild CFLD was diagnosed as children with abnormal serum liver function tests and abnormal ultrasound. Advanced CFLD was established by detection of cirrhosis or portal hypertension. A directed acyclic graph, Kaplan-Meier (KM) and Cox regression analysis were used to model survival.Results290 patients were enrolled, 48 (16.5%) had mild CFLD and 55 (19%) had advanced CFLD. Ten children with advanced CFLD and 1 with mild CFLD died. Based on the KM analysis, the mean (SE) overall survival age of all CF children was 29.1 years (0.50). The mean (SE) survival among females with advanced CFLD was 24.7 years (1.58) compared to 30.4 years (0.66) for females without advanced CFLD (p = 0.0027). Advanced CFLD was a predictor of decreased survival when adjusted for sex and diabetes (HR 2.54, 95%CI 1.05–6.15, p = 0.039). Mild CFLD was not associated with decreased survival. The effect of advanced CFLD on survival was mainly borne by females (HR = 6.37, 95%CI 1.62–25.06 vs. males, HR = 1.00, 95%CI 0.25–4.01).ConclusionAdvanced but not mild CFLD was associated with an increased risk of death when adjusted for sex and diabetes, and resulted in premature death in females with cystic fibrosis by approximately 6 years.     

Cognitive interventions for mild cognitive impairment and dementia: An overview of systematic reviews

PurposeConducting an overview of systematic reviews (SRs)/Meta analyses (MAs) to assess the effectiveness of cognitive interventions on participants with mild cognitive impairment (MCI) or dementia and evaluate the methodological quality of SRs/MAs.MethodsPubMed, EMBASE, Cochrane library, Web of science, China National Knowledge Infrastructure (CNKI) and Chinese Biomedical Databases (CBM) were systematically searched from inception to January 1, 2019 to identify SRs/MAs. Three reviewers independently screened the articles, extracted data and assessed the quality of the included studies according to the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), the Grading of Recommendations Assessment Development and Evaluation (GRADE) was used to evaluate the quality of evidence.ResultsA total of 22 reviews were included. New meta-analyses (36 RCTs) showed that cognitive interventions were more effective than routine therapies for the alleviation of MCI and dementia symptoms (SMD: 0.62; 95%CI: 0.47, 0.78; I² = 53.9%). The results of AMSTAR-2 showed that the methodological quality of most included studies was critically low, and two reviews were low quality. The lowest score was item 10, none of reviews reported on the sources of funding for the included studies. Followed by the “provide a list of excluded studies and justify the exclusions” item with only one (4.5%) reviews conforming to this item. Results of GRADE manifested that moderate quality evidence was provided in 11 reviews (39.3%), 12 (42.9%) were low quality and 5 (17.8%) were very low.ConclusionThe present SRs/MAs indicated that persons with MCI or dementia could benefit from cognitive interventions. Future trial designs should focus on measuring changes in individual specific cognitive functions. More high-quality evidence is needed to further determine the effectiveness of cognitive interventions.     

Gender differences in the impact of metabolic syndrome components on mortality in older people: A systematic review and meta-analysis

Background and aimsThe influence of metabolic syndrome (MetS) on mortality may be influenced by age- and gender-related changes affecting the impact of individual MetS components. We investigated gender differences in the association between MetS components and mortality in community-dwelling older adults.Methods and resultsProspective studies were identified through a systematic literature review up to June 2019. Random-effect meta-analyses were run to estimate the pooled relative risk (RR) and 95% confidence intervals (95% CI) of all-cause and cardiovascular (CV) mortality associated with the presence of MetS components (abdominal obesity, high triglycerides, low HDL cholesterol, high fasting glycemia, and high blood pressure) in older men and women. Meta-analyses considering all-cause (103,859 individuals, 48,830 men, 55,029 women; 10 studies) and CV mortality (94,965 individuals, 44,699 men, 50,266 women; 8 studies) did not reveal any significant association for abdominal obesity and high triglycerides in either gender. Low HDL was associated with increased all-cause (RR = 1.16, 95% CI: 1.02–1.32) and CV mortality (RR = 1.34, 95% CI: 1.03–1.74) among women, while weaker results were found for men. High fasting glycemia was associated with higher all-cause mortality in older women (RR = 1.35, 95% CI: 1.22–1.50) more than in older men (RR = 1.21, 95% CI: 1.13–1.30), and CV mortality only in the former (RR = 1.36, 95% CI: 1.04–1.78). Elevated blood pressure was associated with increased all-cause mortality (RR = 1.16, 95% CI: 1.03–1.32) and showed marginal significant results for CV death only among women.ConclusionsThe impact of MetS components on mortality in older people present some gender differences, with low HDL cholesterol, hyperglycemia, and elevated blood pressure being more strongly associated to all-cause and CV mortality in women.