组蛋白去乙酰化酶对学习记忆的调控

背景 学习记忆行为是大脑的基本功能,揭示学习记忆的分子生物学机制有重要意义.近年来的研究发现,表观遗传修饰对学习记忆过程具有重要的调控作用,组蛋白乙酰化和去乙酰化是表观遗传修饰中最为常见的调节方式,乙酰化与去乙酰化平衡对学习记忆的正确形成与维持有极为重要的意义.去乙酰化由组蛋白去乙酰化酶(histone deacetylases,HDACs)调控.目的 阐述HDACs对学习记忆的调控作用及相关机制,为明确学习记忆的分子机制提供基础,并为学习记忆障碍治疗提供新思路.内容 HDACs的组织来源、分类、分子生物学功能.HDACs对学习记忆起负调控,使用其抑制剂可增强突触可塑性,改善受损的学习记忆.趋向 深入研究HDACs调控学习记忆的机制,不仅有助于阐明学习记忆及相关疾病的机制,并可为其治疗提供新靶点.     

从环磷酸腺苷通路研究氯胺酮对学习记忆的影响

背景 大量的研究表明,环磷酸腺苷反应元件结合蛋白(cAMP response element binding protein,CREB)直接或间接激活相关基因转录,在学习记忆等方面发挥重要作用.另外,研究证实受环磷酸腺苷(cyclic AMP,cAMP)调节的下游蛋白CREB参与了氯胺酮导致未成年大鼠学习记忆障碍的形成. 目的 研究氯胺酮与cAMP通路及相关调控蛋白细胞外调节激酶(extracellular signal regulating kinase,ERK)对学习记忆的影响. 内容 cAMP激活蛋白激酶A(protein kinase A,PKA)磷酸化并激活CREB,后者是一种重要的核蛋白,其调节启动子中具有环磷酸腺苷反应单元(cAMP response element,CRE)的基因转录,这种核转录因子具有调节包括学习记忆在内的广泛的生物学功能.趋向 希望从cAMP通路和ERK通路中,摸索一条治疗氯胺酮导致的学习记忆障碍的新途径.     

氯胺酮对小鼠海马脑片ERK1、ERK2和CREB磷酸化水平的影响

海马组织神经元细胞外信号调节激酶(ERK)参与调节突触可塑性和记忆的形成[1,2];活化的ERK从胞浆易位到胞核,激活核糖体S6蛋白激酶,然后使转录因子cAMP反应元件结合蛋白(CREB)在133位的丝氨酸磷酸化被激活,活化的CREB参与了长时程增强的维持和记忆形成[3-6].有研究表明,氯胺酮可抑制记忆功能[7,8].ERK和CREB是否与氯胺酮抑制记忆功能的机制有关尚不清楚.本研究拟通过观察氯胺酮对小鼠海马脑片ERK1、ERK2和CREB磷酸化水平的影响,从分子水平探讨其抑制记忆功能的机制.     

环腺苷酸效应元件结合蛋白在学习记忆中的作用及机制

背景 环腺苷酸效应元件结合蛋白(cAMP response-element binding protein,CREB)是新发现的学习记忆正调控因子.近年来的研究提示CREB可能通过多种途径调控学习记忆. 目的 阐述CREB在学习记忆中的作用及机制,为认知障碍相关疾病的防治提供思路. 内容 阐述CREB的来源、结构及其在学习记忆中的作用.分析其调控学习记忆的相关机制. 趋向 CREB的确切上游调控机制及自身的表达调控需要进一步明确,对其深入研究可为多种认知障碍疾病的防治提供新的靶点与思路.     

缺氧诱导因子在肾脏发育及肾脏疾病的机制研究进展

组织内缺氧是癌症、心肌梗死、中风和肾脏疾病等重要的病理特征.在缺氧环境下,细胞通过调控一系列基因的转录活化调节并维持机体的代谢平衡,这些氧感受调节机制包括代谢适应、血管生成、降低能量需求、促进红细胞生成和维持细胞存活等.缺氧诱导因子(hypoxia-inducible factors,HIF)包含一个能够在缺氧环境下调控细胞转录的氧敏感性碱性螺旋-环-螺旋蛋白的家族.研究表明HIF的异常激活与包括肾透明细胞癌的许多恶性肿瘤发生发展密切相关.目前猜测HIF家族在急性和慢性肾脏疾病中的发生和发展中起到关键作用.本文主要讨论肾细胞中的氧感受机制以及生理环境下、肾脏发育中和急慢性肾脏疾病下缺氧及缺氧诱导因子激活所产生的不同作用.     

MyoD肌形成作用机制研究进展

MyoD是成肌调节因子家族四成员之一,具有碱性螺旋-环-螺旋(bHLH)结构域,能把多种类型细胞转化为成肌细胞,能促使成肌细胞融合为肌管.在肌肉特异基因转录调控中,MyoD起着总开关的作用,作用于许多基因的启动子区或增强子区,在其他因子的辅助下,促进它们的转录活性.胰岛素样生长因子-Ⅱ、转录共激活因子p300/CBP、核因子90、核激素受体复合激活子、干扰素相关发育调节因子1等能促进MyoD对基因的转录调控;抑制素2、肌源性生长抑素、组蛋白甲基转移酶Suv39h1、DNA结合抑制因子Id、肿瘤坏死因子-α等可抑制MyoD对基因的转录调控及其活性,使MyoD能适应内环境和生理功能的需要.MyoD主要通过泛素蛋白酶体通路降解,以适应分子通路调节的需要.该文就MyoD肌形成机制的最新进展作一综述.     

Nrf2因子在烫伤脓毒症大鼠免疫脏器中的表达

研究表明,核转录因子Nrf2是脓毒症中调节氧化应激的关键因子[1],对许多细胞因子和炎症介质基因均有特异性调控作用.本研究以烫伤合并金黄色葡萄球菌、铜绿假单胞菌感染大鼠模拟烫伤脓毒症模型,观察Nrf2在烫伤脓毒症大鼠各免疫脏器组织中的表达并分析其可能机制.     

Nrf2因子在烫伤脓毒症大鼠免疫脏器中的表达

研究表明,核转录因子Nrf2是脓毒症中调节氧化应激的关键因子[1],对许多细胞因子和炎症介质基因均有特异性调控作用.本研究以烫伤合并金黄色葡萄球菌、铜绿假单胞菌感染大鼠模拟烫伤脓毒症模型,观察Nrf2在烫伤脓毒症大鼠各免疫脏器组织中的表达并分析其可能机制.     

Nrf2因子在烫伤脓毒症大鼠免疫脏器中的表达

研究表明,核转录因子Nrf2是脓毒症中调节氧化应激的关键因子[1],对许多细胞因子和炎症介质基因均有特异性调控作用.本研究以烫伤合并金黄色葡萄球菌、铜绿假单胞菌感染大鼠模拟烫伤脓毒症模型,观察Nrf2在烫伤脓毒症大鼠各免疫脏器组织中的表达并分析其可能机制.     

HOXA1O,Meis1在构建子宫内膜容受性分子网络中的作用

胚胎着床是哺乳动物生殖的关键环节之一.HOXA10作为雌、孕激素直接调控的多效性核内转录因子,介导胚胎着床的多个环节.HOXA10对胚胎着床的多效性调控作用是通过对其下游基因的调控介导.转录因子Meis1可能与HOXA10结合形成异源二聚体,通过增强HOXA10与下游靶基因结合的特异性,从而在构建子宫内膜容受性独特的分子网络中发挥重要作用.     

Presenteeism and Absenteeism Before and After Total Hip and Knee Arthroplasty

BackgroundAbsenteeism is costly, yet evidence suggests that presenteeism—illness-related reduced productivity at work—is costlier. We quantified employed patients’ presenteeism and absenteeism before and after total joint arthroplasty (TJA).MethodsWe measured presenteeism (0-100 scale, 100 full performance) and absenteeism using the World Health Organization’s Health and Work Performance Questionnaire before and after TJA among a convenience sample of employed patients. We captured detailed information about employment and job characteristics and evaluated how and among whom presenteeism and absenteeism improved.ResultsIn total, 636 primary, unilateral TJA patients responded to an enrollment email, confirmed employment, and completed a preoperative survey (mean age: 62.1 years, 55.3% women). Full at-work performance was reported by 19.7%. Among 520 (81.8%) who responded to a 1-year follow-up, 473 (91.0%) were still employed, and 461 (88.7%) had resumed working. Among patients reporting at baseline and 1 year, average at-work performance improved from 80.7 to 89.4. A Wilcoxon signed-rank test indicated that postoperative performance was significantly higher than preoperative performance (P < .0001). The percentage of patients who reported full at-work performance increased from 20.9% to 36.8% (delta = 15.9%, 95% confidence interval = [10.0%, 21.9%], P < .0001). Presenteeism gains were concentrated among patients who reported declining work performance leading up to surgery. Average changes in absences were relatively small. Combined, the average monthly value lost by employers to presenteeism declined from 15.3% to 8.3% and to absenteeism from 16.9% to 15.5% (ie, mitigated loss of 8.4% of monthly value).ConclusionAmong employed patients before TJA, presenteeism and absenteeism were similarly costly. After, employed patients reported increased performance, concentrated among those with declining performance leading up to surgery.     

The German emergency and disaster medicine and management systemdhistory and present

As well for optimized emergency management in individual cases as for optimized mass medicine in disaster management, the principle of the medical doctors approaching the patient directly and timely, even close to the site of the incident, is a long-standing marker for quality of care and patient survival in Germany. Professional rescue and emergency forces, including medical services, are the “Golden Standard” of emergency management systems. Regulative laws, proper organization of resources, equipment, training and adequate delivery of medical measures are key factors in systematic approaches to manage emergencies and disasters alike and thus save lives. During disasters command, communication, coordination and cooperation are essential to cope with extreme situations, even more so in a globalized world. In this article, we describe the major historical milestones, the current state of the German system in emergency and disaster management and its integration into the broader European approach.     

Differences in Osteocyte Density and Bone Histomorphometry Between Men and Women and Between Healthy and Osteoporotic Subjects

Bone defects related to osteoporosis develop with increasing age and differ between males and females. It is currently thought that the bone remodeling process is supervised by osteocytes in a strain-dependent manner. We have shown an altered response of osteocytes from osteoporotic patients to mechanical loading, and osteocyte density is reduced in osteoporotic patients, which might relate to imperfect bone remodeling, leading to lack of bone mass and strength. Hence, information on osteocyte density will contribute to a better understanding of bone biology in males and females and to the assessment of osteoporosis. Osteocyte density as well as conventional histomorphometric parameters of trabecular bone were determined in cancellous iliac crest bone of healthy postmenopausal women and men and of osteoporotic women and men. Osteocyte density was higher in healthy females than in healthy males and lower in osteoporotic females than in healthy females. Bone mass was reduced in osteoporotic patients, both male and female. In females, trabecular number was reduced, whereas in males, trabecular thickness was reduced and eroded surface was increased. There were no correlations between the parameter groups bone architecture, bone formation, bone resorption, and osteocyte density. These results are consistent with impaired osteoblast function in osteoporotic patients and with a different mechanism of bone loss between men and women, in which osteocyte density might play a role. The reduced osteocyte numbers in female osteoporotic patients might relate to imperfect bone remodeling leading to lack of bone mass and strength. M. G. Mullender and S. D. Tan contributed equally to this work.     

肝内胆管囊腺瘤和囊腺癌的CT、MRI及病理表现

目的探讨肝内胆管囊腺瘤和囊腺癌的CT、MRI和病理特点。方法回顾性分析经手术病理证实的6例肝内胆管囊腺瘤和2例肝内胆管囊腺癌的影像及临床病理资料，将病变的影像表现与其病理大体形态及组织学表现作对照分析。结果6例肝内胆管囊腺瘤，女4例、男2例；2例肝内胆管囊腺癌均为女性病人；8例病人平均年龄55岁。所有病灶均表现为多房囊性肿块，肿瘤囊腔各分房内常为多种液体成分，在CT上可表现为不同密度、在MRI上可表现为不同信号强度。囊内出现多发大小不等的壁结节在胆管囊腺癌内更常见，囊内有分隔但无壁结节只见于胆管囊腺瘤。在7例CT扫描中，4例胆管囊腺瘤和1例胆管囊腺癌可见囊壁或分隔上钙化，囊壁、囊内分隔及囊内结节均为轻、中度延迟增强。肿瘤中出现卵巢样间质见于3例胆管囊腺瘤和1例胆管囊腺癌，且均为女性病人。结论肝内胆管囊腺瘤和囊腺癌是肝脏不常见的囊性肿瘤，影像上多房、囊内有分隔且各分房囊内密度或信号不一致，高度提示肝内胆管囊腺瘤或囊腺癌的诊断，如囊内伴有多发大小不等的结节，则进一步提示囊腺癌的可能。但影像学表现不能区分肿瘤中有无卵巢样间质。