Discovery of novel non-synonymous SNP variants in 988 candidate genes from 6 centenarians by target capture and next-generation sequencing

Despite evidence of a substantial genetic component, the genetic factors that underlie longevity in humans remain to be identified. Previous genome-wide linkage and association studies have not found strong evidence for the contribution of common variants besides the APOE gene, suggesting the role of rare variants in human longevity. To discover rare variants that might contribute to longevity, we selected 988 candidate genes and performed a pilot study to identify novel non-synonymous variants in 6 Ashkenazi Jewish centenarians older than 105. Our candidate genes act in pathways implicated in aging and longevity, including neurodegeneration, cognitive function, lipid metabolism, DNA repair, and genome maintenance. By implementing custom-designed Agilent SureSelect target capture and next-generation sequencing, we discovered a total of 89 novel non-synonymous SNPs (nsSNPs) and validated 51 nsSNPs by iPLEX MassArray assays. Genotyping analysis of these novel SNPs in 410 Ashkenazi Jewish controls and 390 centenarians showed significant enrichment (5.3 fold, p = 0.02) of the p.Y318C variant in PMS2 and significant depletion (7.5 fold, p = 0.04) of the p.V465A variant in GABRR3 in centenarians compared to controls. Our study presents the potential of targeted next-generation sequencing for discovery of rare but functional genetic variation which may lead to exceptional longevity in humans.     

吉非替尼治疗转移性乳腺癌个案报道及文献复习

【摘要】〓我国乳腺癌的发病率在女性恶性肿瘤里发病率居于第1位。分子靶向治疗药物成为近年来肿瘤治疗中的一大热点,表皮生长因子受体酪氨酸激酶抑制剂吉非替尼是EGFR敏感突变型非小细胞肺癌的标准一线治疗。近几年国外有临床研究显示吉非替尼对乳腺癌有一定治疗效果,但目前国内此类相关临床研究较少。现将我科诊治的一例吉非替尼治疗转移性乳腺癌的病例报告如下并做文献复习。     

目标血糖管理对脓毒症患者 CD69及 HLA －DR 表达的影响及其临床意义

目的：探讨早期目标血糖管理对脓毒症患者T淋巴细胞CD69、CD 14＋单核细胞（ HLA－DR）表达的影响及其临床意义。方法90例脓毒症患者按随机数字表法分为三组：血糖控制A组（4．4～6．1 mmol／L）30例、血糖控制B组（6．2～8．3 mmol／L）30例、血糖控制C 组（8．4～10．0 mmol／L）30例。入住ICU时就给予早期目标血糖管理,分别在入院时（0 d）及治疗后第1、3、7天采集静脉血,应用流式细胞仪检测T淋巴细胞CD69、CD14＋单核细胞HLA－DR的表达水平。相同时间点观察APACHEⅡ评分,并计算28 d病死率、MODS发生率及低血糖发生率。结果 A组第1、3、7天CD69和HLA－DR表达水平均较入院时明显升高,差异有统计学意义（ P均＜0.05）;B组第1、7天CD69表达水平较入院时明显升高,差异有统计学意义（P均＜0．05）,第3、7天HLA－DR表达水平与入院时比较差异有统计学意义（ P＜0．05）;C组CD69和HLA－DR表达呈先降低后升高的趋势,第3、7天CD69表达水平与入院时比较差异均有统计学意义（ P均＜0.05）,第1、7天HLA－DR表达水平与入院时比较差异有统计学意义（P＜0．05）。三组APACHEⅡ评分第1、3、7天较入院时均降低,差异有统计学意义（ P＜0．05）;第7天A组与B、C组比较显著降低,差异有统计学意义（P＜0．05）。三组28 d死亡率、MODS发生率及低血糖发生率均无统计学意义（ P均＞0．05）。结论目标血糖管理水平（4．4～6．1 mmol／L）能够促进CD69、HLA－DR的表达,有利于免疫稳态的恢复,可能对终止脓毒症患者免疫紊乱和免疫麻痹的恶性进程有利。     

~(99m)Tc-MIBI SPECT/CT同机融合亲肿瘤显像辅助勾画肺癌放疗靶区及预测放疗疗效的临床价值研究

背景近年来,肺癌的发病率逐年升高,放疗是治疗肺癌的重要手段,如何精确界定放疗靶区及预测放疗疗效日益受到广大医师的重视。目的探讨99mTc-MIBI SPECT/CT同机融合亲肿瘤显像辅助勾画肺癌放疗靶区及预测放疗疗效的临床价值。方法选择2012年5月—2014年3月在承德医学院附属医院肿瘤科住院治疗的肺癌患者36例,在放疗前行99mTc-MIBI SPECT/CT同机融合亲肿瘤显像,并对所摄取比值行半定量分析,采用99mTc-MIBI SPECT/CT同机融合亲肿瘤显像辅助勾画肺癌放疗靶区。并根据患者放疗疗效将其分为有效组和无效组,并比较两组早期相肿瘤/正常肺组织摄取比值(EUR)、延迟相肿瘤/正常肺组织摄取比值(DUR)及滞留指数(RI)。结果 36例患者中13例(36.1%)修改了基于CT图像的靶区,其中10例(22.8%)明确区分了肺癌组织和肺不张、3例(8.3%)排除了纵隔淋巴结转移。有效组26例,EUR为(1.95±0.56)、DUR为(1.71±0.31),均高于无效组的(1.31±0.14)、(1.12±0.11)(P0.05),两组RI比较〔(-4.19±2.01)比(-4.56±2.25)〕,差异无统计学意义(P0.05)。结论99mTc-MIBI SPECT/CT同机融合亲肿瘤显像可以优化肺癌三维适形放疗靶区,在预测肺癌放疗疗效方面亦具有重要的临床价值。     

miR-221/222与肿瘤发生发展关系的研究进展

微小RNA-221/222(miR-221/222)是一类与肿瘤发生密切相关的微小RNA,异常表达存在于机体多系统、多步骤、多位点肿瘤的分化发展进程中。miR-221/222通过靶向不同靶基因的信号转导途径发挥着抑癌基因或促癌基因的作用,有望成为恶性肿瘤的生物学标志物和新型治疗靶点。该文就miR-221/222与肿瘤发生发展关系的研究进展作一综述。     

白大衣高血压患者血压变异性对靶器官损害的影响

目的探讨血压变异性对白大衣高血压患者靶器官损害的影响。方法门诊患者119例,根据24 h动态血压和诊室血压分为正常血压组(NT)和白大衣高血压组(WCH)。其中白大衣高血压组根据24 h收缩压变异程度分为:白大衣高血压血压变异性低组(WCH-L),白大衣高血压血压变异性高组(WCH-H)。心脏和颈动脉超声检查:计算二尖瓣环心肌舒张早期峰值运动速度(Em)与舒张晚期峰值运动速度(Am)比值(Em/Am),评价左心室舒张功能及颈动脉损害的发生率。结果 (1)NT组左心室舒张功能减退发生率(21.87%,7例/32例)、颈动脉损害的检出率(18.75%,6例/32例)与WCH-L组(31.11%,14例/45例;22.22%,10例/45例)相近,组间差异无统计学意义(P=0.370、0.711);(2)WCH-H组左心室舒张功能减退发生率(52.38%,22例/42例)、颈动脉损害的检出率(42.85%,18例/42例)明显高于NT组(P=0.008、0.028)和WCH-L组(P=0.044、0.040),差异均有统计学意义。结论血压变异性较大的白大衣高血压患者具有较高的靶器官损害发生率。     

隐匿性高血压与靶器官损害的研究进展

<正>临床上,医生通过非诊室血压(包括动态血压监测、家庭血压监测)和诊室血压这两种不同的检测方法来识别4种类型的血压状态:(1)诊室血压和动态血压均正常为血压正常;(2)诊室血压和动态血压均高于正常为持续性高血压;(3)诊室血压高于正常,动态血压正常为白大衣高血压;(4)诊室血压正常,动态血压高于正常为隐匿性高血压(Masked hypertension,MH)。而隐匿性高血压最早是在1991年由Devereux和Pickering提出的"白大衣正常血压",并定义为诊室血压正常而24 h动态血压监测异常的高血压。目前,     

Metabolic syndrome in hypertensive patients:An unholy alliance

For many years, it has been recognized that hypertension tends to cluster with various anthropometric and metabolic abnormalities including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, glucose intolerance, insulin resistance and hyperuricemia. This constellation of various conditions has been transformed from a pathophysiological concept to a clinical entity, which has been defined metabolic syndrome(MetS). The consequences of the MetS have been difficult to assess without commonly accepted criteria to diagnose it. For this reason, on 2009 the International Diabetes Federation, the American Heart Association and other scientific organizations proposed a unified MetS definition. The incidence of the MetS has been increasing worldwide in parallel with an increase in overweight and obesity. The epidemic proportion reached by the MetS represents a major public health challenge, because several lines of evidence showed that the MetS, even without type 2 diabetes, confers an increased risk of cardiovascular morbidity and mortality in different populations including also hypertensive patients. It is likely that the enhanced cardiovascular risk associated with MetS in patients with high blood pressure may be largely mediated through an increased prevalence of preclinical cardiovascular and renal changes, such as left ventricular hypertrophy, early carotid atherosclerosis, impaired aortic elasticity, hypertensive retinopathy and microalbuminuria. Indeed, many reports support this notion, showing that hypertensive patients with MetS exhibit, more often than those without it, these early signs of end organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular outcomes.     

目标责任制在ICU护理管理中的应用观察

目的探讨目标责任制在ICU护理管理中的应用效果。方法选取2017年12月~2018年12月于我院ICU住院治疗的92例患者作为分析对象,按照随机数字表法将其分为观察组与对照组各46例。对照组患者予以常规护理,观察组患者予以目标责任制护理。出院时,评估两组ICU护理质量(基础护理、护理技能、病房管理、健康教育、护理流程);观察两组患者在ICU住院时间、院内感染发生率、病死率差异。比较两组患者出院4周后生活质量[健康状况调查问卷(SF-36)]评分差异。结果出院时,观察组ICU护理质量明显高于对照组(P均<0.05);观察组患者ICU住院时间明显低于对照组(P<0.05),两组患者院内感染发生率、病死率比较差异无统计学意义(P均>0.05)。出院4周后,观察组患者生活质量明显高于对照组(P均<0.05)。结论目标责任制护理能提高ICU护理质量,能缩短患者ICU住院时间,降低院内感染发生率及病死率,提高患者生活质量。