中国成年人吸烟与心血管疾病发病风险的关联及其性别差异分析

目的 分析中国成年人吸烟与不同心血管疾病发病风险的关联及其性别差异。方法 研究对象来自中国慢性病前瞻性研究,基线调查开展于2004年6月至2008年7月,剔除基线自报患有恶性肿瘤、冠心病、脑卒中的个体,最终纳入487 373名研究对象。随访人年数的计算从研究对象完成基线调查时开始,至最早出现以下任一事件的时间为止：心血管疾病（CVD）发病、死亡、失访或2015年12月31日。使用Cox比例风险模型计算吸烟行为特征和心血管疾病发病风险的关联。结果 研究对象平均随访8.9年。随访期间新发缺血性心脏病33 947人,急性冠心病事件6 048人,脑内出血7 794人,脑梗死31 722人。男性吸烟率（67.9%）远高于女性（2.7%）。与非吸烟者相比,吸烟能增加各类CVD结局的发病风险,风险效应值HR值 （95%CI）由大到小依次为急性冠心病事件1.54 （1.43～1.66）、缺血性心脏病1.28 （1.24～1.32）、脑梗死1.18 （1.14～1.22）、脑内出血1.07 （1.00～1.15）。当前吸烟者中,每天吸烟量和开始吸烟年龄与急性冠心病事件风险间的关联存在性别差异（性别交互作用P值分别为0.006、0.011）,主要表现为女性吸烟者风险高于男性。每天吸烟量和开始吸烟年龄与缺血性心脏病、脑内出血和脑梗死之间的关联均未见性别差异（性别交互作用P>0.05）。结论 吸烟能够增加各类CVD的发病风险,而女性吸烟者发生急性冠心病事件的风险远高于男性。     

国家慢性病综合防控示范区建设总体实施现状研究

目的 了解国家慢性病综合防控示范区（示范区）自创建以来各项活动总体开展情况,为进一步开展示范区建设活动提供参考。方法 采用依据实施方案设计的问卷,调查全国参与示范区创建的机构各项目活动开展情况,每个示范区选取8个机构部门共完成12份问卷调查。结果 示范区实施情况实际得分占总分的71.8%。示范区要求开展的7项活动中,百分制得分较高的为监测（88.0%）、保障措施（75.0%）、健康教育和健康促进（75.0%）;得分相对较低的是全民健康生活方式行动（67.7%）、社区诊断（66.7%）、高危人群发现和干预（64.7%）、患者管理（60.9%）。东、中、西三个地区在保障措施、健康教育和健康促进及高危人群发现和干预专项得分的差异有统计学意义。总体来讲,东部示范区实施情况优于中部和西部。示范区慢性病防控工作指标体系中的23项活动开展情况中,百分制得分最高的5项分别为政策保障、死因监测、肿瘤登记、心脑血管事件报告和烟草控制;得分最低的5项为平衡膳食、患者自我管理、口腔卫生、示范创建和基本公共卫生服务均等化。23项活动总体得分结果为东部地区得分高于中部和西部地区,中部和西部地区得分基本一致。结论 国家慢性病示范区创建各项工作总体实施情况良好,高危人群发现和干预,以及患者管理是示范区今后工作重点。     

哈尔滨市人群饥荒暴露对中老年期慢性病患病风险的影响

目的 研究哈尔滨市人群的饥荒暴露对中老年期糖尿病、肥胖、高血压、冠心病和脑卒中等慢性病患病风险的影响。方法 以中国慢性病前瞻性研究（China Kadoorie Biobank,CKB）项目哈尔滨市的基线调查人群为研究对象,采用回顾性队列研究设计,应用logistic分析比较饥荒暴露人群与非饥荒暴露人群中老年期糖尿病、肥胖、高血压、冠心病和脑卒中等慢性病患病风险的差异。结果 调整影响因素后,饥荒暴露人群的肥胖（OR=1.204,95% CI：1.104~1.313,P<0.01）、高血压（OR=1.315,95% CI：1.210~1.429,P<0.01）和冠心病（OR=1.495,95% CI：1.369~1.632,P<0.01）的危险性高于非饥荒暴露人群。饥荒暴露年龄越小,中老年期各种慢性病发生风险越大。结论 饥荒暴露是肥胖、高血压和冠心病的危险因素。保证生命全过程,尤其是生命早期和青少年期的营养充足对预防中老年期肥胖、高血压和冠心病具有重要意义。     

Gamma-secretase complex-dependent intramembrane proteolysis of CD147 regulates the Notch1 signaling pathway in hepatocellular carcinoma

The γ-secretase complex is a presenilin-dependent aspartyl protease involved in the intramembranous cleavage of various type I transmembrane proteins. As a type I transmembrane protein, CD147 is highly expressed in hepatoma cells and promotes cell proliferation, migration, and invasion. However, the direct underlying mechanism of how CD147 promotes cancer cell proliferation is unknown. Here, we demonstrated that CD147 undergoes an intramembranous cleavage by the γ-secretase at lysine 231 to release its intracellular domains (ICDs). The nuclear translocation of the CD147ICD regulated Notch1 expression by directly binding to the NOTCH1 promoter and promoted the activation of the Notch signaling pathway. Simultaneously, overexpression of CD147ICD promoted cancer cell proliferation via Notch1 signaling. In 102 cases of human hepatocellular carcinoma (HCC) tissues, patients with a high positive rate of nuclear CD147ICD expression had a significantly poor overall survival compared with patients with a low positive rate of nuclear CD147ICD expression. We confirmed that nuclear CD147ICD predicted a poor prognosis in human HCC. The combined therapy of the γ-secretase complex inhibitor and CD147-directed antibody showed better efficacy than monotherapy in orthotopic transplantation HCC mouse models. In conclusion, CD147 is cleaved by the γ-secretase and releases CD147ICD to the cell nucleus, promoting Notch1 expression via direct binding to the NOTCH1 promoter. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

ARL4C stabilized by AKT/mTOR pathway promotes the invasion of PTEN-deficient primary human glioblastoma

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) deficiency in primary human glioblastoma (GBM) is associated with increased invasiveness and poor prognosis with unknown mechanisms. Therefore, how loss of PTEN promotes GBM progression remains to be elucidated. Herein, we identified that ADP-ribosylation factor like-4C (ARL4C) was highly expressed in PTEN-deficient human GBM cells and tissues. Mechanistically, loss of PTEN stabilized ARL4C protein due to AKT/mTOR pathway-mediated inhibition of ARL4C ubiquitination. Functionally, ARL4C enhanced the progression of GBM cells in vitro and in vivo. Moreover, microarray profiling and GST pull-down assay identified that ARL4C accelerated tumor progression via RAC1-mediated filopodium formation. Importantly, targeting PTEN potently inhibited GBM tumor progression in vitro and in vivo, whereas overexpression of ARL4C reversed the tumor progression impaired by PTEN overexpression. Clinically, analyses with patients' specimens validated a negative correlation between PTEN and ARL4C expression. Elevated ARL4C expression but PTEN deficiency in tumor was associated with poorer disease-free survival and overall survival of GBM patients. Taken together, ARL4C is critical for PTEN-deficient GBM progression and acts as a novel prognostic biomarker and a potential therapeutic candidate. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

The influence of ICAM1 rs5498 on diabetes mellitus risk: evidence from a meta-analysis

Inflammation Research - Both type 1 diabetes (T1D) and type 2 diabetes (T2D) are classified as forms of diabetes mellitus (DM) and commonly considered inflammatory process. Intercellular adhesion...     

维甲酸对小鼠牙胚冠部形态发生的影响

目的探讨维甲酸对早期牙胚形态发生的影响。方法利用体外鼠磨牙牙胚器官培养模型，观察不同剂量维甲酸对１４天胎龄的小鼠下颌第一磨牙牙胚形态发育的影响。结果培养６天后，在不含维甲酸的培养基中牙胚形成明显的牙乳头尖；当培养基中维甲酸的浓度为１×１０－７ｍｏｌ／Ｌ时，牙胚冠部仍形成明显的牙乳头尖；当培养基中维甲酸的浓度为１×１０－６ｍｏｌ／Ｌ时，牙胚冠部无牙乳头尖形成。结论牙胚冠部形态发生与维甲酸剂量有密切关系，过量的维甲酸可抑制牙胚冠部牙乳头尖的形成。     

A two-year randomized clinical trial of chlorhexidine varnish on dental caries in Chinese preschool children

The objective of this study was to assess the effect of six-monthly professional applications of chlorhexidine varnish on the prevention of dental caries in primary molars in Chinese preschool children. In a double-blinded, randomized, placebo-controlled clinical trial, 334 children aged 4-5 years were randomly divided into two groups. Children in the test group received six-monthly applications of a 40% chlorhexidine varnish, and the control children received a placebo varnish. Caries status of the children was assessed by two calibrated examiners at baseline and after 24 months, according to criteria recommended by the World Health Organization. The two-year mean caries increments in the test and the control group children were 1.0 and 1.6 decayed, missing, or filled molar surfaces (dmfs-molar), respectively, a 37.3% reduction (t test, p = 0.036). No side-effects were found. It was concluded that six-monthly applications of chlorhexidine varnish were effective in reducing the incidence of dental caries in primary molars.     

Effect of biofilm formation on virulence factor secretion via the general secretory pathway in Streptococcus mutans

Objectives

To investigate the role of SecA in protein secretion, and to evaluate the effect of biofilm formation on protein secretion in Streptococcus mutans.

Design

S. mutans strains UA159 and GS-5 were used in this study. Cells grown in biofilm and planktonic conditions were observed using immunogold electron microscopy. The mRNA levels of ftf, gtfB, gtfC, gtfD, Pac and secA were analysed in different growth conditions using real-time quantitative polymerase chain reaction. The levels of wall proteins and whole-cell protein extracts were examined using Western blot analysis.

Results

A microdomain colocalised with SecA and virulence factors such as Pac (AgI/II) and glucosyltransferase (GTF) was observed. The mRNA level of secA was upregulated in the biofilm condition. The level of protein expression of SecA and wall protein levels of GTF, fructosyltransferase (FTF) and Pac (AgI/II) in the biofilm condition were significantly higher than in the planktonic condition.

Conclusions

These data suggest that S. mutans utilises the Sec pathway to secrete virulence factor proteins such as Pac (AgI/II), GTF and FTF, and protein secretion occurred at a distinct microdomain. The level of SecA, the key factor in the Sec pathway, was influenced significantly by biofilm formation in S. mutans.     

变形链球菌葡糖基转移酶缺陷突变株粘了会特征的观察

为了揭示变形链球菌葡糖基转移酶在变链菌粘附中的作用，通过扫描电镜观察了其缺陷突变株对玻片的附粘。结果显示，在蔗糖存在的条件下，变链菌ＭＴ８１４８及其ＧＴａｓｅ缺陷株表面出不贩粘附模式。