基质细胞衰老在子宫内膜蜕膜化及容受性建立中的作用机制

胚胎着床过程复杂而精密。胚胎质量、子宫内膜容受性以及两者的同步发育是决定胚胎着床的关键因素。蜕膜化是子宫内膜基质细胞转变为分泌型的蜕膜基质细胞的过程, 与子宫内膜容受性密切相关。异常蜕膜化可导致胚胎着床失败或不良妊娠结局。最新研究表明子宫内膜蜕膜化中存在子宫内膜基质细胞衰老的现象, 一定程度的基质细胞衰老促进蜕膜化和容受性建立, 而过度或不足的基质细胞衰老则可能导致蜕膜化异常和容受性受损。本文旨在对基质细胞衰老在子宫内膜蜕膜化及容受性建立中的作用进行综述, 以期为容受性相关疾病的发病机制和治疗提供新的启示。     

丝裂原活化蛋白激酶信号通路与胚胎着床

胚胎着床是在诸多因素作用下,细胞内信号通路被激活,调控特定基因的表达,使胚胎滋养层和子宫内膜同步变化,从而使得发育正常的胚泡顺利植入子宫内膜的精密而复杂的过程.丝裂原活化蛋白激酶(MAPK)信号转导通路是真核细胞调节增殖、分化、凋亡及细胞间功能同步化的基本信号通路.最近几年研究发现,MAPK通路在早期胚胎发育、子宫内膜蜕膜化、胚泡黏附、滋养层细胞增殖以及侵入子宫内膜过程中都起着重要作用.     

子宫内膜在胚泡着床过程中的反应

在着床过程中,胚胎与子宫双方都处在生长发育的动态阶段。子宫内膜发生着一系列形态、生理及生化的变化,以迎接和维持胚泡着床。在这些变化中,最明显的变化就是子宫内膜的蜕膜化。在哺乳动物中,由于不同的着床方式其子宫内膜蜕膜化的程度也不相同。根据不同的着床方式可分为三种不同类型的胎盘:①上皮绒毛型。胚泡滋养层直接与子宫内膜上皮接触,滋养层细胞不侵入内膜层,只是与子宫内膜上皮紧紧相邻,内膜细胞不发生蜕膜化。猪、马等家畜属此型。②内皮绒毛型。胚泡滋养层侵入上皮但不深,多数食肉类动物属此型。③血窦绒毛     

促性腺激素释放激素激动剂预处理对人子宫内膜基质细胞蜕膜化的影响

目的探讨促性腺激素释放激素激动剂(GnRH-a)预处理对人子宫内膜基质细胞蜕膜化的影响。方法分离并纯化正常人的原代子宫内膜基质细胞,先以100 n M的GnRH-a预处理人子宫内膜基质细胞不同时间,再用环磷酸腺苷(c AMP)诱导基质细胞蜕膜化,设置诱导蜕膜化同时添加GnRH-a(终浓度100 n M)的共处理组及未经GnRH-a预处理直接诱导蜕膜化的对照组,比较各组间蜕膜标志物的表达水平。结果 GnRH-a预处理人子宫内膜基质细胞一定时间后再诱导蜕膜化能显著提高蜕膜标志物催乳素(PRL)、胰岛素样生长因子结合蛋白-1(IGFBP-1)及层粘连蛋白亚单位1(LAMA-1)的表达水平,而诱导蜕膜化同时添加GnRH-a共处理对基质细胞蜕膜化无显著影响。结论 GnRH-a预处理能促进人子宫内膜基质细胞蜕膜化。     

缝隙连接蛋白43在生殖中的研究进展

摘要：子宫内膜基质细胞靠缝隙连接传递信号,在月经周期不同的激素调解下,协调一致地呈现周期性的变化。缝隙链接蛋白作为子宫内膜基质细胞上缝隙连接的基本单位,缝隙链接蛋白43（connexion43,Cx43）参与了细胞生长、分化、肿瘤化、血管重塑、凋亡等过程,Cx43的正常表达,是发生蜕膜反应的必要条件,直接影响子宫内膜对胚胎的容受性。同时参与了子宫内膜异位症,子宫内膜癌等病理反应。由于目前辅助生殖技术成功率主要受限于较低的胚胎着床率,能够区别容受性与非容受性子宫内膜的生物标志尚不清楚。因此,阐明如何诱导形成容受性子宫内膜,以及如何维持容受性变得尤为重要。本文综述了Cx43如何参与蜕膜反应,与子宫内膜容受性的关系,Cx43的信号调节通路及其与子宫内膜疾病发生的关系,分析了Cx43参与诱导容受性子宫内膜的可能机制     

子宫内膜蜕膜化的研究进展北大核心CSCD

妊娠是一个复杂的生理过程,胎儿在母体内的正常发育是一个在细胞与分子水平上受到严密调控的过程。早期妊娠阶段,子宫内膜基质细胞转变为分泌型蜕膜细胞,为早期妊娠的维持和胎盘形成提供重要的营养物质和免疫环境,这个过程就是蜕膜化。在甾体激素的精确调节下,子宫内膜基质细胞体积增大并快速增殖、小血管生成,同时各类分子也呈现出时间-空间性表达,在蜕膜化过程中发挥它们的独特作用。为了更全面地了解子宫内膜蜕膜化,并探讨早期妊娠失败的潜在原因,本文对蜕膜化的形成及相关调控分子做一综述,以期为未来妊娠相关疾病提供更多的理论依据。     

微小RNA在子宫内膜蜕膜化中的功能

子宫内膜蜕膜化是子宫内膜在排卵期后转化为分泌期至胚胎着床期间发生的持续的形态和功能变化,对妊娠的建立、维持及内膜的周期性变化至关重要。子宫内膜基质细胞的蜕膜化是其中最重要的改变。这一过程由孕酮和环磷酸腺苷信号驱动,伴随着一系列标志性分子的表达改变。微小RNA（miRNA）在基因表达的转录后调控中起着广泛并且非常重要的作用。大量研究显示,miRNA通过调控胰岛素样生长因子结合蛋白1（IGFBP1）、催乳素（PRL）、Krüppel样因子12（KLF12）和同源框基因A10（HOXA10）等基因表达,在子宫内膜蜕膜化及相关疾病发病中发挥重要的作用。现就miRNA合成酶和一些miRNA在蜕膜化中发挥的作用及其分子机制进行综述,以期为蜕膜化及其相关疾病,如反复种植失败、子宫内膜异位症和子痫前期等的诊疗提供更多的理论依据。     

子宫内膜基质细胞的缝隙连接蛋白43及其作用

子宫内膜基质细胞靠缝隙连接传递信号,在月经周期不同的激素调节下,协调一致地呈现周期性变化。缝隙连接蛋白是子宫内膜基质细胞上缝隙连接的基本单位。缝隙连接蛋白43(connexin 43,Cx43)参与了细胞生长、分化、肿瘤化、血管重塑、凋亡等过程,Cx43的正常表达是发生蜕膜反应的必要条件,直接影响子宫内膜对胚胎的容受性;同时参与子宫内膜异位症、子宫内膜癌等病理反应。由于目前辅助生殖技术的成功率主要受限于较低的胚胎着床率,能够区别容受性与非容受性子宫内膜的生物学标记尚不明确。因此,阐明如何诱导形成容受性子宫内膜,以及如何维持容受性变得尤为重要。本文综述了Cx43如何参与蜕膜反应,与子宫内膜容受性的关系,Cx43的信号调节通路及其与子宫内膜疾病发生的关系,分析了Cx43参与诱导容受性子宫内膜的可能机制。     

cAMP对子宫内膜异位症在位子宫内膜基质细胞体外蜕膜化进程的促进作用

目的:研究cAMP对在位子宫内膜基质细胞体外蜕膜化过程中的促进作用,作为子宫内膜异位症(EMs)的体外细胞模型,可用于了解子宫内膜异位症患者在位内膜的蜕膜化能力,进而研究子宫内膜异位症与不孕症的关系。方法:将内异症患者在位内膜细胞随机分为3组,Ⅰ组为未干预组;EP组用E2(10 nM)和P4(1μM)作用24 h、48 h、96 h;EPC组用E2(10 nM)、P4(1μM)和8-溴-cAMP(0.5 mM)作用24 h、48 h、96 h,收集细胞后测定3组PRL(催乳素)和IGFBP1(胰岛素样生长因子结合蛋白1)的mRNA水平。结果:EPC组作用96 h后细胞形态发生明显变化,PRL和IGFBP1明显高于EP组。结论:8-溴-cAMP联合P4、E2能明显促进子宫内膜异位症在位子宫内膜基质细胞体外蜕膜化进程,是目前作为EMs体外蜕膜化细胞模型的最佳方法。     

早孕蜕膜的生长调控

子宫内膜的蜕膜化和蜕膜功能的正常表达，对胚胎着床、妊娠建立与维持，以及分娩发动均起着极为重要的作用。随着细胞凋亡及其调控机制研究的不断深入，人类对于生殖过程中蜕膜细胞增殖与凋亡及调节因素也越来越重视，并且取得了相应进展。但仍有许多鲜为人知的环节，需要更多和更深入的研究，以便为探索生殖奥秘，主动干预和调节人类生殖过程提供理论指导。     

Calcium intake in the elderly: validation of a dietary questionnaire

Epidemiological studies of calcium and osteoporosis have been hampered by the lack of a suitable tool for assessing calcium intake. This report describes a new frequency and amount questionnaire for measuring present and past calcium intake in the elderly. The validity of the questionnaire was tested against two commonly used standards of dietary assessment, five-day duplicate diets and seven-day weighed dietary inventories. The resulting correlation coefficients were, respectively, r = 0.76 and r = 0.69, while that for repeatability was r = 0.84. Furthermore, the questionnaire categorized subjects into thirds of the distribution of intake with almost no gross misclassification. It is suggested that the present findings may be extended to the majority of normal, healthy elderly subjects, implying wide application for the questionnaire in the assessment of calcium intake in the elderly.     

The occurrence of antimicrobial substances in toilet,sink and shower drainpipes of clinical units: A neglected source of antibiotic residues

Antibiotics represent one of the most important drug groups used in the management of bacterial infections in humans and animals. Due to the increasing problem of antibiotic resistance, assurance of the antibacterial effectiveness of these substances has moved into the focus of public health. The reduction in antibiotic residues in wastewater and the environment may play a decisive role in the development of increasing rates of antibiotic resistance. The present study examines the wastewater of 31 patient rooms of various German clinics for possible residues of antibiotics, as well as the wastewater of five private households as a reference.To the best of our knowledge, this study shows for the first time that in hospitals with high antibiotic consumption rates, residues of these drugs can be regularly detected in toilets, sink siphons and shower drains at concentrations ranging from 0.02?μg·L^?1 to a maximum of 79?mg·L^?1. After complete flushing of the wastewater siphons, antibiotics are no longer detectable, but after temporal stagnation, the concentration of the active substances in the water phases of respective siphons increases again, suggesting that antibiotics persist through the washing process in biofilms. This study demonstrates that clinical wastewater systems offer further possibilities for the optimization of antibiotic resistance surveillance.     

Self-reported health problems among Swedish miners one year after unemployment

Unemployment is considered to be a public health concern sincedeterioration in the health of the unemployed is often anticipated.However, for some groups, such as miners, unemployment mightimprove health due to a cessation of potentially harmful occupationalexposures. This study evaluates the health of 79 miners in oneSwedish iron-ore mine, and 226 age-matched controls from thegeneral population, during one year after the closure of themine. The participants received a questionnaire regarding medicalhistory and subjective symptoms at the beginning of the studyperiod, and after one year. Statistically significant negativeeffects on self-reported health attributable to unemploymentwere not found, although neuropsychiatric symptoms were morecommon among the unemployed miners. The miners reported a statisticallysignificant improvement in grip force (p=0.031). They had asignificantly higher prevalence of symptoms associated withmining related exposures when compared with the population controls;pain in the upper extremities [relative risk (RR)=2.27, 95%confidence interval (Cl)=1.44–3.59), back pain (RR=1.84;Cl=1.237–2.75), vasospastic disease of the fingers (RR=2.05;Cl=1.18–3.57) and obstructive respiratory symptoms (attacksof dyspnea and wheezing: RR=3.67; Cl=1.167–11.6).     

Excès de cas humains et animaux de tularémie en France au cours de l’hiver 2007–2008 : émergence ou phénomène isolé ?

Context

Tularemia is a zoonosis affecting humans and hares in France. We describe the results of surveillance in both species, in 2007 and 2008.

Methods

Human tularemia cases are mandatorily notifiable in France since 2003. In hares, surveillance relies on volunteer hunter associations in all districts of the country. Data from mandatory reports and volunteer surveillance in 2007/2008 were analyzed and compared with previous results.

Results

In 2007/2008, 144 cases were reported in humans and 117 cases in hares. This was a 100% increase compared to previous years. Human cases differed from those of previous years only by the frequency of contact with breeding animals. Human cases without any documented risk exposure were also more frequent.

Conclusion

An increase of tularemia cases occurred in 2007/2008 in both species. Complementary studies are needed to identify the species reservoir in France to understand the causes of this peak of cases.     

Occupational health hazards in mining: an overview

This review article outlines the physical, chemical, biological, ergonomic and psychosocial occupational health hazards of mining and associated metallurgical processes. Mining remains an important industrial sector in many parts of the world and although substantial progress has been made in the control of occupational health hazards, there remains room for further risk reduction. This applies particularly to traumatic injury hazards, ergonomic hazards and noise. Vigilance is also required to ensure exposures to coal dust and crystalline silica remain effectively controlled.     

Manufacture and use of nanomaterials: current status in the UK and global trends

This paper provides an overview of the production and use of nanomaterials (NMs), particularly in the UK. Currently, relatively few companies in the UK are identifiable as NM manufacturers, the main emphasis being the bulk markets in metals and metal oxides, and some niche markets such as carbon nanotubes and quantum dots. NM manufacturing in the UK does not reflect the global emphasis on fullerenes, nanotubes and fibres. Some assumptions have been made about the types of NM that are likely to be imported into the UK, which currently include fullerenes, modified fullerenes and other carbon-based NMs including nanotubes. Many university departments, spin-offs and private companies have developed processes for the manufacture of NMs but may only be producing small quantities for research and development (R&D) purposes. However, some have the potential to scale up to produce large quantities. The nanotechnology industry in the UK has strong R&D backup from universities and related institutions. This review has covered R&D trends at such institutions, and appropriate information has been added to a searchable database. While several companies are including NMs in their products, only a few (e.g. manufacturers of paints, coatings, cosmetics, catalysts, polymer composites) are using nanoparticles (NPs) in any significant quantities. However, this situation is likely to change rapidly. There is a need to collect more information about exposure to NPs in both manufacturing and user scenarios. As the market grows, and as manufacturers switch from the micro- to the nanoscale, the potential for exposure will increase. More research is required to quantify any risks to workers and consumers.     

深圳公立医院管理体制改革制度设计

深圳公立医院管理体制改革实行政事分开、管办分开,在理事会架构下按法定机构模式组建市医管中心,落实公立医院运营管理自主权.作者从当前公立医院管理体制的弊端入手,介绍了深圳市进行公立医院管理体制改革的基本思路及改革方案设计的主要举措,深入剖析了的改革方案的特点,并对改革效果进行了预测.     

Effects of nitrogen dioxide on red blood cells of rats: Changes in components of red cell membranes during in vivo exposure to NO2

Red cell membranes, prepared from red blood cells of rats exposed to 4, 10, or 20 ppm nitrogen dioxide (NO₂) for 1 to 10 days, were examined for evidence of changes in membrane components. Appreciable changes were not found in contents of phospholipid and cholesterol during exposure to 10 ppm NO₂. By contrast, protein content altered with the time of exposure. Moreover, changes in protein composition were observed by employing sodium dodecyl sulfate — polyacrylamide gel electrophoresis. Twenty-four-hour exposure to NO₂ at the concentration above 10 ppm resulted in a marked increase in the percentage of lysophosphatidylethanolamine (LysoPE) to the total phospholipids. The prolonged exposure to 10 ppm NO₂ gave rise to a further increase in LysoPE, whereas the percentage of phosphatidylethanolamine (PE) showed a gradual decrease. A 1-day exposure to 4.0 ppm NO₂ also caused an increase in sialic acid content and decreases in those of PE and hexose. In addition to contents of these components the percentage of LysoPE increased 5 days after exposure and the elevated values were maintained up to the end of exposure period. These results demonstrate that red blood cells in circulation exhibit different membrane properties in terms of lipid and carbohydrate composition during 10 days of exposure to 4.0 ppm NO₂.     

Investigating clusters in the workplace and beyond

Clusters of disease are common and occur in the workplace and in the general community. They often arouse considerable concern among the population. Investigations have sometimes lead to exciting new knowledge, but in general the investigation of clusters is difficult and often unrewarding, especially for community clusters. In the workplace, investigations are more likely to find associations and even new causes, but still many clusters remain enigmatic. Despite this, there are many reasons for investigating clusters, including allaying community concern and identifying uncontrolled exposures. A structure for investigating clusters in the workplace is suggested.