端粒长度与食管癌发生风险的孟德尔随机化研究

目的：采用孟德尔随机化方法,探索端粒长度与食管癌发生风险的关系,为食管癌防治提供理论依据。方法：利用中国人群食管癌的全基因组关联研究（genome?wide association studies,GWAS）中1 877例食管癌病例和2 084例无肿瘤独立对照样本,使用与白细胞端粒长度具有显著相关性的9个单核苷酸多态性（single nucleotide polymorphisms,SNP）位点作为工具变量,通过遗传风险得分法（genetic risk score,GRS）和逆方差加权法（the inverse?variance weighting method,IVW）估计端粒长度与食管癌发生风险之间的关联。此外,根据年龄、性别做分层分析,探讨是否存在分层因素与暴露因素之间的交互作用。结果：孟德尔随机化分析结果显示端粒长度与食管癌发生风险无统计学上的显著关联,无论是基于基因型个体数据（individual?level data）的GRS法还是基于汇总数据（summarized data）的IVW法均得出一致的结果（GRS：OR=1.19,95%CI：0.81~1.77,P=0.380;IVW：OR=1.22,95%CI：0.81~1.84,P=0.380）。分层分析发现性别之间有层间异质性,但进一步分析各性别人群中端粒长度与食管癌的关系都没有得到显著性关联（女性：OR=0.83,95%CI：0.43~1.6,P=0.582;男性：OR=1.49,95%CI：0.91~2.44,P=0.115）。结论：研究尚未发现端粒长度与食管癌发生风险之间有显著性关联。     

Polycystic Ovary Syndrome is not Associated with Offspring Birth Weight: A Mendelian Randomization Study

Polycystic ovary syndrome(PCOS) is a common metabolic and hormonal disorder afflicting approximately 5%–20% of all women of reproductive age~([1]). PCOS is characterized with hyperandrogenism,oligo-anovulation, and a polycystic ovarian morphology. The syndrome features heterogeneous manifestations, such as hirsutism, menstrual dysfunction, and obesity. Women with PCOS are at higher risk of developing multiple metabolic comorbidities and subsequent cardiovascular complications even beyond childbearing age.     

实时定量PCR分析外周血白细胞的端粒长度

目的 采用一种新的简便的测定端粒DNA相对长度的方法一实时荧光定量PCR法,研究其可行性.方法 分别取40～49岁和60～69岁的健康男性外周静脉血各12例,提取DNA后,采用实时荧光定量PCK对两组受试者外周血白细胞的端粒长度进行检测.结果 40～49岁组的受检者外周血白细胞端拉(1.5±0.87)长于60～69岁组(0.8±0.16)(t=11.37,P<0.05).结论 随着年龄增加健康人外周血白细胞的端拉长度缩短,实时荧光定量PCK洲定端拉长度的方法可行.     

Association between 25 Hydroxyvitamin D Concentrations and the Risk of COVID-19: A Mendelian Randomization Study

Coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic[1]. Primary prevention, which is aimed at delaying disease onset by modulating modifiable risk factors, has been proposed to address the global challenge posed by COVID-19. Vitamin D plays a critical role in the immune system, and vitamin D deficiency is a risk factor for several adverse health outcomes, such as cancer, cardiovascular diseases, metabolic disorders, infectious diseases, and autoimmune diseases. Some studies have shown that low 25 hydroxyvitamin D (25OHD) concentrations are associated with a high risk of COVID-19[2], but other studies have found no association[3]. Therefore, the association between 25OHD concentrations and the risk of COVID-19 has not been established. The above studies were observational, and traditional epidemiological studies are vulnerable to reverse causality and residual confounding.     

Association of C-reactive Protein with Cardiovascular Outcomes: A Mendelian Randomization Study in the Japanese Population

Objective Traditional epidemiological studies have shown that C-reactive protein(CRP) is associated with the risk of cardiovascular diseases(CVDs). However, whether this association is causal remains unclear. Therefore, Mendelian randomization(MR) was used to explore the causal relationship of CRP with cardiovascular outcomes including ischemic stroke, atrial fibrillation, arrhythmia and congestive heart failure.Methods We performed two-sample MR by using summary-level data obtained from Japanes...     

91种炎症蛋白与5种心血管疾病之间的因果关系：双样本孟德尔随机化研究

摘要 目的：通过采用孟德尔随机化(MR)方法和反向孟德尔随机化方法评估91种炎症蛋白与5种心血管疾病（动脉夹层、动脉瘤、冠心病、非风湿性瓣膜病和风湿性瓣膜病）之间的因果关系。 方法：使用来自欧洲人群的全基因组关联研究（GWAS）数据,利用孟德尔随机化（MR）方法和反向孟德尔随机化方法对 91 种炎症蛋白与5种心血管疾病之间的双向因果关系进行评估分析。MR分析方法包括inverse variance weighted (IVW)、Weighted median、MR-Egger、Simple Mode和Weighted mode。敏感性分析包括 Cochran''s Q 检验、MR-Egger 截距检验、MR-PRESSO 方法和 leave-one-out 方法。 结果：共有16种炎症蛋白可能与心血管疾病风险存在相关性,包括CCL20、CD5、CCL28、IL20RA、LAP-TGF-β1、TSLP、CST5、LIF、EIF4EBP1、CCL4、IL22RA1、IL-10、IL-17C、MCP-2/CCL8、NRTN和MCP-3/CCL7。此外,心血管疾病的进展可能会导致总共 10 种炎症蛋白水平的变化,包括 CCL11、IL-8、TNF-β、FGF19、IL10RA、FGF-21、IL10RB、β-NGF、CD5 和 MCP-1/CCL2。 结论：本研究结果表明,多种炎症蛋白与5种心血管疾病之间存在双向因果关系,证明了进一步研究各种炎症蛋白与上述心血管疾病之间的相关性存在更深入的研究空间。     

Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis: A Systematic Review

Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD) from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR) using genetic variant depression(n = 113,154) and MDD(n = 208,811) from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was...     

生物素标记探针检测外周血白细胞端粒长度的应用研究

目的建立生物素标记测定端粒DNA长度的方法,探讨其法医学应用价值．方法基因组DNA经RsaⅠ和HinfⅠ限制性内切酶消化,0.8％琼脂糖凝胶电泳,Southern印迹转移,以5′末端生物素标记寡核苷酸（TFAGGG）3为探针进行杂交,化学发光检测DNA谱带,与DNA标准分子量比较计算端粒长度．结果通过严格控制印迹转移条件、探针的工作浓度、杂交温度等主要影响因素,获得了比较好的杂交条带．结论生物素标记探针检测端粒DNA长度方法稳定、可靠,无放射污染,杂交信号明显．     

Association between Physical Activity and Telomere Length in a North Chinese Population: A China Suboptimal Health Cohort Study

Several studies have demonstrated an association between physical activity and telomere length:however,the association remains inconsistent.A cross-sectional study consisting of 588 participants(375 females,median age of 33.8 years) was carried out to investigate the association between telomere length and physical activity in a general population from North China.The results show that relative telomere length is not significantly different in participants in the northern Chinese population with different levels of physical activity,either in the model only adjusted for age(F = 2.127,P = 0.120) or in the model adjusted for demographics and lifestyle(F = 1.227,P = 0.294).The gender-stratified analysis also produced insignificant results.Our study confirmed a non-significant association between physical activity and telomere length in the northern Chinese population,which adds to the inconsistent association between physical activity and telomere length across different ethnic populations.     

基于两样本孟德尔随机化方法探讨睡眠与痛风的关联

[目的] 通过两样本孟德尔随机化设计,探讨睡眠与痛风之间的关联。[方法] 从一项包含763 813名参与者的全基因组关联研究(genome-wide association study,GWAS)中获取痛风遗传关联数据。以与打鼾、睡眠时间、睡眠类型、失眠及白日困倦程度等睡眠表型相关的单核苷酸多态性(single nucleotide polymorphism,SNP)作为工具变量,采用逆方差加权(inverse variance weighted,IVW)评估遗传学预测的不同睡眠表型与痛风发生风险的关系。采用MR-Egger回归和孟德尔随机多态性残差和离群值(MR pleiotropy residual sum and outlier,MR-PRESSO)检验进行敏感性分析,以评估工具变量的多效性。进一步采用加权中位数法、简单中位数法、最大似然比法等分析方法检验结果的稳健性与可靠性。[结果] IVW结果显示,遗传学预测的打鼾[优势比(odds ratio,OR)=3.12,95%置信区间(confidence interval,CI)(1.21～8.05),PFDR=0.045]和失眠[OR=1.09,95%CI(1.04～1.15),PFDR=0.005]与痛风发生风险呈正相关,而睡眠时间、睡眠类型及白日困倦程度与痛风发生之间不存在统计学关联。MR-Egger回归提示上述因果关联未受到水平多效性影响,加权中位数法、简单中位数法、最大似然比法得出与IVW相似的结果。[结论] 打鼾、失眠与痛风发生风险呈正相关,纠正打鼾和失眠可能对痛风有一定的预防作用。     

不同癌细胞株放射敏感性与端粒长度的关系

目的:研究人类不同癌细胞株放射敏感性与端粒长度的关系,寻求放射敏感性预测的可行指标。方法:以不同层次的人类癌细胞株为实验对象,既包括鳞癌(Hep-2)、腺癌(ZR-75-30、MCF-7、MDA-MB-435S、T-47-D、F539-1590)、胶质瘤U251,又含有同一病理类型的不同亚株(5种不同的乳腺癌细胞株),还包括辐射诱导建立的放射抗拒细胞株(Hep-2R),用克隆形成实验拟合细胞存活曲线测定8株细胞的放射生物学参数,Southernblotting法测量各细胞株的端粒限制片断长度(TRF),分析放射敏感性与端粒限制片断长度的关系。结果:8株细胞的放射敏感性各不相同,Hep-2(人喉鳞癌细胞株)的SF2=0.4148,U251(人恶性胶质瘤细胞株)的SF2=0.7520,腺癌细胞株介于二者之间;端粒长度在放射抗拒细胞株Hep-2R中达11.12kb,数倍长于鳞癌亲本株或腺癌细胞株。端粒长度与放射敏感性参数SF2(r=0.786,P<0.05)、D0(r=0.905,P<0.01)均成正相关关系。结论:端粒长度与人癌细胞株的放射敏感性描述参数SF2、D0成正相关关系,故端粒长度与人癌细胞株的放射敏感性成负相关关系,它可以作为放射敏感性预测指标之一。     

Relationship between TERT Polymorphism and Telomere Length in Workers Exposed to Omethoate

Omethoate is a highly toxic organophosphorus pesticide that is widely used in agricultural production because of its high efficiency, broad spectrum, and low residue. Organophosphorus pesticides, such as omethoate, can inhibit acetylcholinesterase activity, leading to the accumulation of the neurotransmitter acetylcholine at cholinergic synapses. Accumulation of acetylcholine continues to stimulate cholinergic receptors, causing central nervous effects. Studies have shown that organophosphorus pesticides can cause genotoxicity in a variety of organisms, resulting in chromosomal DNA damage[1].     

Mendelian Randomization Analysis to Analyze the Effect of Emergency Caesarean Section on Different Allergic Diseases and Related Blood Markers

<正>Caesarean section is a well-established surgical procedure that allows for maximum fetal rescue under special circumstances, such as intrauterine distress and intrauterine hypoxia, and minimizes injuries to pregnant women who cannot tolerate vaginal delivery. Emergency caesarean section is a special type of caesarean section that plays an important role in protecting the lives of pregnant mothers and fetuses^[1].     

缺血性中风与血小板颗粒膜蛋白(GMP—140)关系的临床研究

近年来,在缺血性中风的血液学检测方面,发现了血小板颗粒膜蛋白(GMP—140)在血小板活化、凝集过程中起着重要作用.缺血性中风的主要病机是与动脉粥样硬化和血小板异常凝集形成血栓有关.祖国医学认为缺血性中风是由于各种原因最终导致气滞血瘀而发病.两者在发病机理的认识上有相似之处.本文通过对30例缺血性中风患者及30例健康者的GMP—140含量的测定,发现缺血性中风者的含量明显高于健康者.认为缺血性中风病中血小板CMP—140含量增高可作为该病的客现血液学检测指标之一。     

冰毒成瘾者外周血白细胞端粒长度与中医证素关系的研究

目的探讨冰毒成瘾者外周血白细胞端粒长度与中医证素的关系,从而在基因水平上揭示冰毒对人体健康影响的可能中医内在机制。方法研究对象均为年龄在20~49岁的汉族人,试验组为冰毒吸食者136例;对照组为200例健康受试者,规范采集四诊信息,应用证素辨证方法提取中医证素特征和运用QPCR基础技术来测量外周血白细胞的端粒长度。结果①校正年龄和性别后,冰毒组的端粒长度比健康组的短（P<0.05）。②冰毒成瘾者的中医证素分布：病位以肝、脾、肾为主,尤以肝最为多见;病性上,实证以气滞最为多见;虚证以气虚最为多见。③校正年龄和性别后,形成肝、湿、热等证素的冰毒组端粒长度与健康组的端粒长度之间均具有明显差异（P<0.05）,且端粒长度比健康组的端粒长度短。结论①吸食冰毒会造成端粒损伤,使端粒长度缩短。②冰毒对人体的损伤是多脏腑功能失调共同所致,肝是冰毒成瘾者最主要的病位因素,气滞和气虚是冰毒成瘾者最主要的病性因素。③冰毒成瘾者端粒长度的缩短主要体现在中医肝、湿、热证素的形成上,在基因水平上揭示了冰毒对人体健康影响的可能中医内在机制。     

缺血性脑卒中患者入院时白细胞水平与卒中类型及其神经功能缺损关系的研究

目的研究缺血性脑卒中患者入院时白细胞水平在不同卒中类型中的变化规律及白细胞水平与入院神经功能缺损程度的关系。方法收集急性缺血性脑卒中患者910例,按照国际TOAST卒中分型标准将其分为大动脉粥样硬化性脑卒中（large artery arteriosclerosis,LAA）425例、小动脉闭塞性脑卒中（small artery occlusion,SAO）370例、心源性栓塞性脑卒中（cardiac embolism,CE）88例、其他病因明确性脑卒中（other certain,OC）及原因不明性脑卒中（undetermined etiology,UE）27例,对所有患者进行入院神经功能缺损评定,并与入院白细胞水平进行对照分析。结果心源性栓塞性脑卒中组白细胞水平最高,神经功能缺损最严重;大动脉粥样硬化性脑卒中组次之;小动脉闭塞性脑卒中组白细胞水平大致正常,神经功能缺损较轻或无缺损。结论缺血性脑卒中患者入院时的白细胞水平可能与其神经功能缺损程度相关,且白细胞水平随卒中类型的不同而变化。     

MRI对腔隙性脑梗死患者的临床诊断价值分析

目的对比分析CT和MRI对腔隙性脑梗死(lacunar infarction,LAC)的诊断价值。方法选择2012年1月至2014年7月在我院神经内科接受治疗的LAC病患178例。将MRI检查结果记为观察组,相应的CT检查记为对照组。对比两组检查的病灶部位、大小情况,并对1个月后复检病患进行MRI检查同时记录病灶情况。结果MRI共检出1770个病灶,CT组共检出420个病灶。MRI检出的总数是CT检出总数的4.2倍。并且MRI组对于病灶≤5mm的检出率明显高于CT组而6-15mm的检出率相对更低。最后对复检病患根据首次检查大小分组发现病灶呈现明显的缩小,其中最为显著的是≥11mm的病患,差异均有统计学意义(P0.05)。结论 LAC病患在首次检查病灶出现的频率很高,多为≤5mm。其中MRI检出病灶的总数明显高于CT检出总数,且MRI对≤5mm病灶检出有明显的优势。而在发病初期出现水肿情况,需要准确、及时的诊断保证后期治疗。因此,MRI更具有临床应用价值。     

伴腔隙性脑梗死的脑白质疏松症与糖尿病的相关性

目的:研究伴腔隙性脑梗死患者脑白质疏松症的严重程度与糖尿病的相关性。方法:选择2013年8月-2015年8月在本院神经内科住院患者,经头颅核磁确诊为腔隙性脑梗死合并脑白质疏松患者200例为研究对象,伴腔隙性脑梗死的脑白质疏松症合并糖尿病患者为试验组,伴腔隙性脑梗死的脑白质疏松症非糖尿病患者为对照组,研究两组脑白质疏松的严重程度与糖尿病的相关性。结果:试验组的白质疏松严重程度明显高于对照组,差异有统计学意义(P<0.001)。脑白质疏松Fazekas评分分值与糖尿病患者血糖升高呈正相关。结论:伴腔隙性脑梗死的脑白质疏松的发生与糖尿病有一定相关性。     

Association between Long Interspersed Nuclear Element-1 Methylation and Relative Telomere Length in Wilms Tumor

Background:

DNA hypomethylation of long interspersed nuclear elements-1 (LINEs-1) occurs during carcinogenesis, whereas information addressing LINE-1 methylation in Wilms tumor (WT) is limited. The main purpose of our study was to quantify LINE-1 methylation levels and evaluate their relationship with relative telomere length (TL) in WT.

Methods:

We investigated LINE-1 methylation and relative TL using bisulfite-polymerase chain reaction (PCR) pyrosequencing and quantitative PCR, respectively, in 20 WT tissues, 10 normal kidney tissues and a WT cell line. Significant changes were analyzed by t-tests.

Results:

LINE-1 methylation levels were significantly lower (P < 0.05) and relative TLs were significantly shorter (P < 0.05) in WT compared with normal kidney. There was a significant positive relationship between LINE-1 methylation and relative TL in WT (r = 0.671, P = 0.001). LINE-1 Methylation levels were significantly associated with global DNA methylation (r = 0.332, P < 0.01). In addition, relative TL was shortened and LINE-1 methylation was decreased in a WT cell line treated with the hypomethylating agent 5-aza-2′-deoxycytidine compared with untreated WT cell line.

Conclusion:

These results suggest that LINE-1 hypomethylation is common and may be linked to telomere shortening in WT.