糖皮质激素受体参与阿片耐受机制的研究进展

阿片药物耐受是影响临床应用阿片类药物进行疼痛治疗的主要问题.阿片药物耐受机制复杂,有许多调节因素参与其中.近年的研究提示,糖皮质激素受体在阿片耐受机制的各个环节中均发挥调节作用.如能合理利用糖皮质激素受体的这种调节作用,来找到治疗阿片耐受的突破点,将为难治性疼痛的治疗带来福音.     

CC类趋化因子亚家族在神经病理性疼痛中的作用机制

背景 现有的药物对慢性疼痛的治疗效果不佳且副作用较大,因而需要寻找新的、安全有效的治疗方法.而最近研究发现,趋化因子及其受体在慢性疼痛的发生发展中起着重要的作用. 目的 综述趋化因子在慢性疼痛尤其是神经病理性疼痛中的作用机制. 内容 就趋化因子家族CC类亚家族参与疼痛调控的相关研究进行综述,阐述其在神经病理性疼痛发生发展中的可能作用机制. 趋向 越来越多的学者发现CC类亚家族参与神经病理性疼痛的发生发展,其有望成为临床上治疗慢性疼痛的一个新靶点.     

神经调节蛋白1在慢性疼痛中的研究进展

背景 神经调节蛋白1 (neuregulin 1,NRG1)是一类表皮生长因子家族的成员,其在神经元及胶质细胞的生长发育及迁移等方面起着关键作用,但在成熟的神经系统及慢性疼痛中的作用却不甚清楚. 目的 阐述NRG1介导慢性疼痛的最新研究进展,并对其在疼痛中作用的研究提出展望. 内容 简述NRG1及其受体的功能以及在疼痛领域中作用的研究.趋向 NRG1通过复杂的机制参与了神经病理性疼痛的发生发展,有望为临床提供新的治疗靶点.     

海人藻酸受体功能调节机制在脊髓痛觉敏化中的作用

海人藻酸（kainate, KA）受体在中枢神经系统中广泛分布,通过调节外周和中枢感觉神经元之间的兴奋性信号参与疼痛处理。近年研究发现,多个与KA受体功能相关的蛋白在KA受体功能调节机制中发挥重要作用,从而参与伤害性疼痛信号的传递。文章通过综述KA受体特点、KA受体在疼痛通路中的表达与分布以及KA受体功能调节机制,包括...     

受体附件蛋白参与糖皮质激素受体激活研究进展

受体附件蛋白（RAPs）在糖皮质激素受体（GR）功能发挥中起着重要作用。GR与其配体糖皮质激素（GC）的结合和受体异源复合物的转移需要多种伴侣分子的参与和调节。对GR与RAPs作用模型的进一步认识可能会对与之相关性疾病发病机制和治疗的认识和研究提供更有力的基础。     

兴奋性氨基酸及其受体与阿片耐受

运用阿片类药物治疗疼痛时常产生耐受,而致阿片类药效降低。大量研究表明兴奋性氨基酸及其受体参与影响了阿片类药物的抗伤害性作用及其耐受机制。近年来众多学者通过对兴奋性氨基酸受体进行干预,在增强阿片类药物抗伤害作用的同时抑制其耐受的发展,证明其在阿片耐受的机制中产生了重要影响,并为临床阿片治疗急慢性疼痛提供了新的治疗方案。     

EphrinBs/EphBs信号通路与疼痛研究进展

背景 Ephs受体是人类基因组中受体型酪氨酸蛋白激酶(receptor tyrosine kinase,RTKs)中最大的亚家族,与其配体Ephrins结合参与组织边缘形成、血管再生、轴突导向及突触可塑性等诸多生长发育过程.近年来研究发现EphrinBs/EphBs 信号系统参与调控了疼痛的发生和维持.目的 回顾和总结EphrinBs/EphBs调控疼痛的机制.内容 大量研究证明EphrinBs/EphBs信号系统的激活可能通过上调伤害性脊神经节和脊髓后角的广动力范围型神经元兴奋性,诱导中枢致敏,以及活化下游丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPKs)通路参与了伤害性信息的调制.趋向 明晰EphrinBs/EphBs信号系统参与疼痛过程的下游机制,有助于发现临床上治疗疼痛的新靶点.     

Stargazin调节使君子酸受体亚基转运和突触靶向——疼痛治疗的新靶点

背景 使君子酸(α-amino-3 -hydroxy-5 -methy-4-isoxazole propionate,AMPA)受体是中介中枢神经系统兴奋性突触传递的主要受体,参与疼痛信号传递.Stargazin蛋白是一种AMPA受体调节蛋白,在AMPA受体中介的疼痛信号传递中扮演重要角色.目的 对Stargazin蛋白调节AMPA受体亚基在胞浆胞膜中的转运作用及与疼痛的关系作用进行回顾与总结.内容 Stargazin蛋白可调节AMPA受体不同亚基在胞浆胞膜转运,并通过与突触后膜致密蛋白-95 (postsynaptic density-95,PSD-95)的相互作用,促进AMPA受体亚基突触靶向；Stargazin还通过C末端自身磷酸化修饰改变与PSD-95蛋白相互作用的强度,控制AMPA受体的突触靶向.Stargazin通过调节AMPA受体的转运,间接调控AMPA受体中介的疼痛信号传递.趋向 下调Stargazin的表达或干扰其与兴奋性突触后PSD-95蛋白的相互作用,可间接抑制AMPA受体的功能,是未来疼痛治疗研究的新靶点.     

尼古丁镇痛作用机制的研究进展

背景 烟草危害是当今世界最严重的公共卫生问题之一.目前我国约有吸烟者3.5亿,占全球吸烟总人数的1/3,其中成年男性吸烟率为66.0％,女性为3.08％.吸烟成瘾实质上就是尼古丁依赖,尼古丁依赖患者罹患各种慢性疼痛疾病的比例增高.临床和动物实验发现尼古丁具有镇痛作用. 目的 了解尼古丁具有镇痛作用的神经生物学机制及其研究进展.内容 尼古丁镇痛作用是通过乙酰胆碱受体(nAChRs)介导的,作用于α4β2AChR受体通过脊髓上机制发挥镇痛作用;作用于α7 nAChR通过胆碱能抗炎反射,进而影响小胶质细胞的迁移、增殖和活化等来发挥镇痛作用. 趋向 研究尼古丁镇痛作用和尼古丁依赖戒断后机体疼痛生理的变化机制,为吸烟患者的疼痛治疗研究奠定基础.     

瞬时受体电位通道A1和瞬时受体电位通道M8在冷过敏中的作用

背景 冷过敏是炎性痛和神经病理性疼痛的一个常见症状,其内在机制尚不清楚. 目的 阐明瞬时受体电位通道A1 （transient receptor potential cation channel,subfamily A,member 1,TRPA1）和瞬时受体电位通道M8（transient receptor potential melastatin 8,TRPM8）参与冷过敏的机制. 内容 综述TRPA1和TRPM8的分子结构和门控机制及其在有害的冷、炎性痛和神经病理性疼痛的冷过敏形成、维持中的作用等方面的研究. 趋向 深入研究TRPA1和TRPM8在冷过敏发生中的作用,有助于阐明冷过敏的机制,并为开发拮抗剂提供理论依据.     

2015年乳腺癌辅助化疗进展

【摘要】〓乳腺癌是危害我国女性健康的头号杀手,尽管近年来辅助化疗的研究进展突飞猛进,但临床中仍有不少问题未能明确,如辅助化疗的合适人群、化疗的开始时间、蒽环及紫杉类的地位和用法、强化维持治疗的作用、疗效及预后的生物标志物等。本文结合乳腺癌辅助化疗在临床上的常见问题和2015年各大乳腺癌会议阐述乳腺癌辅助化疗的最新进展。     

Alterations in T-Cell Subset Frequency in Peripheral Blood in Obesity

Background: Obesity affects the regulation of immune and inflammatory responses. This study characterizes differences in peripheral blood lymphocyte phenotype in obese humans. Methods: Frequencies of lymphocyte subsets among peripheral blood mononuclear cells were compared between 10 obese (BMI ≥35) and 10 lean subjects, as determined by antibodies directed against cluster differentiation (CD) markers. Results: Obese patients demonstrated an increased frequency of CD3+CD4+ T-cells (mean difference 12%, P=0.004), a decreased frequency of CD3+CD8+ T-cells (mean difference 9.4%, P=0.016) and an increased frequency of CD3+CD8+CD95+ T-cells (mean difference 13.3%, P=0.032). No other differences among T-cell or monocyte subsets were noted. Conclusions: Obesity is associated with alterations in frequencies of peripheral CD4+ and CD8+ T-cells and aberrations in the expression of CD95 among CD8+ T-cells. These data suggest both CD4+ and CD8+ T-cell compartments, as well as the regulation of CD95 expression on CD8+ T-cells, as targets for further study into obesity's effects on the immune system.     

西宁地区烧伤病人动脉血气分析观察

对高海拔地区的27例烧伤病人动脉血气变化进行了分析和观察。结果证明:无论是存活病人还是死亡病人伤后均存在有低氧血症问题。并且在死亡病人和烧伤合并吸入性损伤病人其低氧血症的发生早于单纯烧伤病人。提示:吸入性损伤病人应立即行气管切开术以保障氧气供给,单纯烧伤病人可常规吸氧以维持正常血 PaO_2,ARDS 均发生在合并吸入性损伤的病人,高频喷射通气技术对纠正低氧血症有一定效果。     

Controversies in Fistula in Ano

Managing a complex fistula in ano can be a daunting task for most surgeons; largely due to the two major dreaded complications—recurrence & fecal incontinence. It is important to understand the anatomy of the anal sphincters & the aetiopathological process of the disease to provide better patient care. There are quite a few controversies associated with fistula in ano & its management, which compound the difficulty in treating fistula in ano. This article attempts to clear some of those major controversies.     

β-半乳糖苷酶在体内外成骨细胞中的表达

目的 研究β—半乳糖苷酶(β—gal)在成骨细胞中的表达状况，为阐明MorquioB综合征的发病机制提供依据。方法 裸鼠各器官和骨组织标本行X-gal染色检测。抽取羊和人骨髓行骨髓基质细胞(BMSCs)培养，分为4组：I：Adv-hBMP-2转染组；Ⅱ：Adv—β—gal转染组；Ⅲ：未转染组；Ⅳ：地塞米松诱导组。分别行X-gal染色和RT-PCR检测β—gal的表达。结果 裸鼠骺板两侧、骨膜内面及松质骨的成骨细胞和破骨细胞可见多量β—gal的表达。未转染BMSCs组有少量β—gal的表达，其他3组细胞的β—gal表达增高。结论成骨细胞和破骨细胞可表达多量β—gal，该两种细胞的β—gal缺乏可能是MorquioB综合征骨骼异常的直接原因。     

Smoking-Attributable mortality in Spain in 2016

IntroductionSmoking-attributable mortality (SAM) is a valuable indicator that can be used to characterize the course and health burden of the smoking epidemic. The aim of this paper was to estimate SAM in Spain in 2016 in the population aged 35 and over, using the best available evidence.MethodsA smoking prevalence-dependent analysis based on the estimation of population-attributable fractions was performed. Smoking prevalence (never, former, and current smokers) was calculated from a combination of the Spanish Health Survey (2016) and the European Health Survey (2014); the relative risk of death among current and former smokers was taken from the follow-up of various cohorts; and mortality rates were obtained from National Center for Statistics data. SAM estimates are presented globally, and by sex, age groups, and major disease categories: cancer, cardiometabolic diseases and respiratory diseases.ResultsIn 2016, 56,124 deaths were attributed to tobacco consumption, 84% in men (47,000), and 50% in the population aged over 74 (27,795). Overall, 50% of SAM was due to cancer (28,281), 65% of which was lung cancer. One in 4 attributable deaths (13,849) occurred before the age of 65.ConclusionsOne in 7 deaths in Spain in 2016 were attributable to smoking. This estimation of SAM clearly highlights the great impact of smoking on mortality in Spain, mainly due to lung cancer and chronic obstructive pulmonary disease.     

MicroRNAs in hepatic pathophysiology in diabetes

MicroRNAs(miRNAs or miRs) are small approximately 22 nucleotide RNA species that are believed to regulate diverse metabolic and physiological processes.In the recent past,several reports have surfaced that demonstrate the role of miRNAs in various biological processes and numerous disease states.For a disease as complex as diabetes,the emergence of miRNAs as key regulators leading to the disease phenotype has added a novel dimension to the area of diabetes research.On the other hand,the liver,a metabolic hub,contributes in a major way towards maintaining normal glucose levels in the body as it can both stimulate and inhibit hepatic glucose output.This equilibrium is frequently disturbed in diabetes and hence,the liver assumes special significance considering the correlation between altered hepatic physiology and diabetes.While the understanding of the mechanisms behind this altered hepatic behavior is not yet completely understood,recent reports on the status and role of miRNAs in the diabetic liver have further added to the complexities of the knowledge of hepatic pathophysiology in diabetes.Here,we bring together the various miRNAs that play a role in the altered hepatic behavior during diabetes.     

Fluid-phase transcytosis in the primate epididymis in vitro and in vivo

Ligated tubules from the corpus epididymidis of men and monkeys were incubated in medium containing horseradish peroxidase (HRP) as a marker for fluid-phase endocytosis. HRP was localized by light and electron microscopy after 0, 15, 30 and 60 min of incubation. Movement between the cells was prevented by tight junctions, but bypass of this barrier was apparently achieved by an intracellular vesicular mechanism leading to a time-dependent appearance of HRP in the lumen. Uptake of HRP into basal cells and capture by the lysosomal apparatus of principal cells were also observed. HRP-filled vesicles also appeared in the basal, mid and apical cytoplasm of epithelial cells in the caput 1 h after injection of the tracer into the epididymal circulation of the monkey, suggesting that this pathway also operates in vivo.