糖尿病前期成年人综合健康生活方式与糖尿病、心血管疾病、癌症和死亡的关联--来自中、美、英三个国家的四个队列研究

在糖尿病前期人群中,采取健康的生活方式可以有效预防糖尿病的发生。然而,健康生活方式与心血管疾病(cardiovascular disease,CVD)、癌症和死亡的长期风险之间的关联尚未阐明。本文旨在探究糖尿病前期人群中综合健康生活方式与上述多种健康结局之间的关联。本研究纳入的121254名糖尿病前期参与者来自以下4个前瞻性队列,包括中国的东风-同济队列(Dongfeng-Tongji,DFTJ)和开滦研究,英国生物银行(UK Biobank,UKB)和美国的国家健康与营养调查(National Health and Nutrition Examination Survey,NHANES;仅用于死亡分析)。随访期间,共诊断了18333例新发糖尿病病例、10829例新发心血管疾病病例、6926例新发癌症病例和9877例全因死亡。本文基于5个因素(从不吸烟或戒烟超过10年、适量饮酒、充足的体力活动、健康膳食和理想的腰围)构建综合健康生活方式评分。各因素均被分为健康水平(赋1分)和不健康水平(赋0分),评分的加和为综合健康生活方式评分(0~5分)。首先,采用Cox比例风险回归模型计算每个队列中综合健康生活方式评分与健康结局之间的关联;然后,通过随机效应模型的荟萃分析合并各独立队列结果的多变量校正的风险比(hazard ratio,HR)和95%置信区间(confidence interval,CI)。与生活方式最不健康(评分为0~1分)的研究对象相比,生活方式最健康(评分为4~5分)的研究对象具有更低的糖尿病、心血管疾病、癌症和死亡风险,合并的HR(95%CI)分别为0.57(0.48~0.69)、0.67(0.62~0.73)、0.80(0.73~0.88)和0.54(0.42~0.70)。根据研究对象的基线人口学特征和代谢健康状况进行亚组分析的结果也与主要分析的结果一致。总而言之,本研究对来自三个国家的4个队列的合并分析表明,在糖尿病前期人群中,坚持更健康的生活方式与糖尿病及主要并发症的发生风险降低有关。本研究的发现为临床指南和公共卫生政策提供了可靠证据。

Association of colorectal cancer susceptibility variants with esophageal cancer in a Chinese population

AIM: To investigate the association between colorectal cancer(CRC) genetic susceptibility variants and esophageal cancer in a Chinese Han population.METHODS: A case-control study was conducted including 360 esophageal cancer patients and310 healthy controls. Thirty-one single-nucleotide polymorphisms(SNPs) associated with CRC risk from previous genome-wide association studies were analyzed. SNPs were genotyped using Sequenom Mass-ARRAY technology, and genotypic frequencies in controls were tested for departure from HardyWeinberg equilibrium using a Fisher's exact test. The allelic frequencies were compared between cases and controls using a χ 2 test. Associations between the SNPs and the risk of esophageal cancer were tested using various genetic models(codominant, dominant,recessive, overdominant, and additive). ORs and95%CIs were calculated by unconditional logistic regression with adjustments for age and sex.RESULTS: The minor alleles of rs1321311 and rs4444235 were associated with a 1.53-fold(95%CI:1.15-2.06; P = 0.004) and 1.28-fold(95%CI: 1.03-1.60;P = 0.028) increased risk of esophageal cancer in the allelic model analysis, respectively. In the genetic model analysis, the C/C genotype of rs3802842 was associated with a reduced risk of esophageal cancer in the codominant model(OR = 0.52, 95%CI:0.31-0.88; P = 0.033) and recessive model(OR =0.55, 95%CI: 0.34-0.87; P = 0.010). The rs4939827C/T-T/T genotype was associated with a 0.67-fold(95%CI: 0.46-0.98; P = 0.038) decreased esophageal cancer risk under the dominant model. In addition,rs6687758, rs1321311, and rs4444235 were associated with an increased risk. In particular, the T/T genotype of rs1321311 was associated with an 8.06-fold(95%CI: 1.96-33.07; P = 0.004) increased risk in the codominant model.CONCLUSION: These results provide evidence that known genetic variants associated with CRC risk confer risk for esophageal cancer, and may bring risk for other digestive system tumors.

Differential roles of RIG-Ⅰ like receptors in SARS-CoV-2 infection

Retinoic acid-inducible gene Ⅰ (RIG-Ⅰ) and melanoma differentiation-associated protein 5 (MDA5) sense viral RNA and activate antiviral immune responses.Herein we investigate their functions in human epithelial cells,the primary and initial target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).A deficiency in MDA5,RIG-Ⅰ or mitochondrial antiviral signaling protein (MAVS) enhanced viral replication.The expression of the type I/III interferon(IFN) during infection was impaired in MDA5;and MAVS;,but not in RIG-Ⅰ;,when compared to wild type (WT) cells.The mRNA level of full-length angiotensin-converting enzyme 2 (ACE2),the cellular entry receptor for SARS-CoV-2,was approximately 2.5-fold higher in RIG-Ⅰ;than WT cells.These data demonstrate MDA5 as the predominant SARS-CoV-2 sensor,IFN-independent induction of ACE2 and anti-SARS-CoV-2 role of RIG-Ⅰ in epithelial cells.