脾切除术对大鼠海马tau表达的影响

目的 评价脾切除术对大鼠海马tau表达的影响.方法 SD大鼠105只,随机分为3组,正常对照组(A组,n=15)不给予任何处理,麻醉组(B组,n=45)仅吸入1.5%异氟醚2 h,手术+麻醉组(C组,n=45)吸入1.5%异氟醚(吸入2 h)麻醉下实施脾切除术.B组和C组分别于麻醉后或术后1、3、7 d时处死15只大鼠,取海马组织,测定海马IL-1β mRNA、TNF-α mRNA、IL-1β、TNF-α、总tau、苏氨酸第205位点磷酸化tau(pT205 tau)、丝氨酸第396位点磷酸化tau(pS396 tau)、总糖原合成酶-3β(GSK-3β)和磷酸化GSK-3β(p-GSK-3β)的表达水平.结果 与A组比较,B组各时点IL-1β mRNA、TNF-α mRNA、IL-1β、TNF-α、总tau、pT205 tau、pS396 tau、GSK-3β和p-GSK-3β的表达水平差异无统计学意义(P＞0.05),C组术后IL-1βmRNA、TNF-α mRNA、IL-1β、pT205 tau和pS396 tau的表达上调,p-GSK-3β表达下调(P＜0.05或0.01).结论 手术创伤可导致大鼠海马tau磷酸化,其机制与手术创伤诱发炎性反应,从而激活GSK-3β有关.     

毒扁豆碱对异氟醚麻醉大鼠炎性反应和认知功能的影响

目的探讨毒扁豆碱对异氟醚麻醉大鼠认知功能的影响及其机制。方法 2月龄SD大鼠80只,随机分为四组,每组20只。对照组(C组)吸入含有30%氧气的空氧混合气体6h;异氟醚组(I组)吸入1.4%的异氟醚6h;毒扁豆碱+异氟醚组(PI组)与毒扁豆碱组(P组)腹腔注射毒扁豆碱100μg/kg,每8小时一次,共3次。首次给药后,PI组吸入1.4%异氟醚6h;P组吸入同浓度载气6h。麻醉结束行动脉血气分析,12h后取海马组织,ELISA法检测TNF-α、IL-1β、IL-6含量,RTPCR法检测capase-3mRNA的表达。光镜下观察海马CA1区锥体细胞形态学变化。麻醉后第2~7天评估认知功能。结果四组大鼠动脉血气指标、血糖和海马TNF-α含量差异均无统计学意义。与C组和P组比较,I组和PI组大鼠海马IL-1β、IL-6含量、capase-3mRNA明显升高,第4~6天逃避潜伏期明显延长,探索时间明显缩短(P0.05)。与I组比较,PI组大鼠海马IL-1β、IL-6含量、caspase-3mRNA表达明显降低,第4~6天逃避潜伏期明显缩短,探索时间明显延长(P0.05)。结论毒扁豆碱改善了异氟醚麻醉引起的大鼠认知功能损害,其机制可能与抑制海马炎性反应及神经元凋亡有关。     

异氟烷对发育期大鼠海马IL-1β mRNA、IL-6 mRNA和TNF-α mRNA表达的影响

目的 探讨异氟烷对发育期大鼠海马IL-1β mRNA、IL-6 mRNA和TNF-α mRNA表达的影响.方法 出生7 d的SD大鼠64只,随机分为2组(n=32):对照组(C组)和异氟烷麻醉组(I组).I组大鼠吸入1.5%异氟烷麻醉6 h,C组吸入空气.I组于麻醉前(T0,基础状态)、麻醉2 h(T1)、4 h(T2)、6 h(T3)、麻醉停止后4 h(L)、6 h(T5)、12 h(T6)、24 h(T7)时,C组在对应时点各取4只大鼠,测定海马IL-1β mRNA、IL-6 mRNA及TNF-α mRNA的表达水平.结果 C组各时点海马IL-1β mRNA、IL-6 mRNA和TNF-α mRNA比较差异无统计学意义(P＞0.05);与C组比较,I组海马T1～5 时IL-1βmRNA表达上调,T2,3 时IL-6 mRNA表达上调,T1～6时TNF-α mRNA表达上调(P＜ 0.05).结论 1.5%异氟烷麻醉可短暂上调发育期大鼠海马IL-1β mRNA、IL-6 mRNA和TNF-α mRNA的表达.     

异氟醚对大鼠海马高级糖基化终末产物受体表达的影响

目的 探讨异氟醚对大鼠海马高级糖基化终末产物受体(RAGE)表达的影响.方法 雄性老龄SD大鼠45只,月龄24月;雄性成年SD大鼠45只,月龄4月,分为老龄组和成年组(n=45),每组再分为3个亚组(n=15):老龄对照组(OC组)和成年对照组(AC组)吸入含30%氧气的空氧混合气体;老龄单次吸入异氟醚组(OS组)和成年单次吸入异氟醚组(AS组)吸入1.5%异氟醚2 h;老龄多次吸入异氟醚组(OR组)和成年多次吸入异氟醚组(AR组)吸入1.5%异氟醚3次,2 h/次,每天1次.吸入异氟醚后1 d各组随机取8只大鼠行Morris水迷宫实验测定认知功能,余大鼠处死取海马,采用RT-PCR法检测RAGE mRNA的表达水平,免疫组织化学法检测RAGE蛋白的表达水平.结果 与OC组比较,OS组和OR组认知功能减退,海马RAGE mRNA及其蛋白的表达上调(P＜0.05);与AC组比较,AS组和AR组认知功能减退,AR组海马RAGE mRNA及其蛋白的表达上调(P＜0.05);与OS组比较,OR组认知功能减退,海马RAGE mRNA表达上调(P＜0.05);与AS组比较,AR组认知功能减退,海马RAGE mRNA及其蛋白的表达上调(P＜0.05).结论 异氟醚可导致老龄和成年大鼠认知功能降低,尤其对老龄大鼠影响明显,可能与其上调海马RAGE表达有关.     

异氟醚麻醉对老龄大鼠海马β淀粉样蛋白生成、c-Jun氨基末端激酶和环磷酸腺苷反应元件结合蛋白磷酸化的影响

目的 探讨异氟醚麻醉对老龄大鼠海马β淀粉样蛋白(Aβ)生成、c-Jun氨基末端激酶(JNK)和环磷酸腺苷反应元件结合蛋白(CREB)磷酸化的影响.方法 雄性SD大鼠96只,18月龄,体重450～500 g,采用随机数字表法,将其分为3组:正常对照组(C组)、1％异氟醚麻醉组(S1组)和2％异氟醚麻醉组(S2组).S1组和S2组分别吸入1％和2％异氟醚4h.每组取12只大鼠,麻醉后1d行Morris水迷宫实验,每组分别于麻醉后1 d(T1)、7 d(T7)取12只大鼠,行旷场反应实验,旷场反应实验结束后,处死大鼠,取海马组织,采用Western blot法测定Aβ、磷酸化JNK(p-JNK)和磷酸化CREB(p-CREB)的表达.结果 与C组比较,S1组和S2组逃避潜伏期延长,原平台象限探索时间比减少,S1组T1时总运动距离、离开边界距离和内环内距离延长,海马组织Aβ表达上调,p-CREB表达下调,T7时离开边界距离和内环内距离延长,海马组织Aβ表达上调,S2组T1时总运动距离、快速运动距离、离开边界距离延长和内环内距离延长,海马组织Aβ表达上调,p-JNK表达上调,p-CREB表达下调,T7时总运动距离、快速运动距离、离开边界距离延长和内环内距离延长,海马组织Aβ表达上调(P＜ 0.05或0.01).结论 异氟醚麻醉导致老龄大鼠认知功能减退的原因与其促进海马Aβ生成、JNK激活和抑制CREB激活有关.     

吸入不同浓度异氟醚对老龄大鼠海马细胞色素c表达的影响

目的 评价吸入不同浓度异氟醚对老龄大鼠海马细胞色素c(Cyt c)表达的影响.方法 健康雄性老龄SD大鼠63只,月龄20月,体重500～600 g,随机分为3组(n=21),对照组(C组):吸入30%氧气2 h;0.75%异氟醚组(L组):吸入0.75%异氟醚和30%氧气的混合气体2 h;1.5%异氟醚组(I2组):吸入1.5%异氟醚和30%氧气的混合气体2 h.分别于麻醉30 min、1和2 h时,各组取5只大鼠,取动脉血样行血气分析.于麻醉结束后24 h时,各组取8只大鼠,测定认知功能;取8只大鼠,分别采用免疫组化法和Western blot法测定海马Cyt c 的表达水平.结果 与C组比较,Ⅰ1组和Ⅰ2组逃避潜伏期延长,原平台象限停留时间缩短,穿越原平台次数减少,海马Cyt c表达上调(P＜0.05);与Ⅰ1组比较,Ⅰ2组逃避潜伏期、原平台象限停留时间缩短和穿越原平台次数差异无统计学意义(P＞0.05),海马Cyt c表达上调(P＜0.05).结论 吸入异氟醚可通过上调海马Cyt c的表达导致老龄大鼠认知功能障碍.     

异氟醚通过上调NMDA受体导致发育期大鼠海马神经元凋亡

目的探讨异氟醚麻醉对新生大鼠海马神经元N-甲基-D-天冬氨酸(NMDA)受体亚基及凋亡的影响。方法新生1d的SD大鼠36只,雌雄不拘,取海马组织进行原代培养。采用随机数字表法将培养海马神经元5d的培养皿随机分为三组:对照组(C组)、异氟醚组(I组)和AP5+异氟醚组(A组),每组12只。I组和A组培养的海马神经元放置在密闭箱中,吸入1.5%异氟醚和纯氧,吸入时间6h,C组不做任何处理。于异氟醚麻醉结束后2、4、6、24h(C组于相应时点),提取海马神经元总mRNA和总蛋白,采用RT-PCR法测定NR2A mRNA、NR2BmRNA和caspase-3mRNA的表达量,采用Westen blot法测定caspase-3蛋白含量。结果与C组比较,异氟醚麻醉结束后2、4和6hI组海马神经元NR2AmRNA和NR2BmRNA的表达量明显上调(P0.05)。与C组和A组比较,I组异氟醚麻醉结束后2、4和6h海马神经元caspase-3mRNA的表达量、异氟醚麻醉后4和6h海马caspase-3蛋白含量明显升高(P0.05)。结论吸入1.5%异氟醚可能通过上调新生大鼠海马神经元NMDA受体导致发育神经元凋亡,阻断NMDA受体可以预防异氟醚导致的发育期海马神经元凋亡。     

异氟醚对老龄和成龄大鼠海马synaptotagmin-Ⅰ蛋白质的影响

目的探讨异氟醚对成龄及老龄大鼠海马synaptotagmin-Ⅰ(Syt-Ⅰ)蛋白表达的影响。方法用蛋白质印迹方法对吸入2h异氟醚的全身麻醉模型和吸氧对照的成龄及老龄大鼠,取24h后的海马组织检测Syt-Ⅰ蛋白的表达水平。结果异氟醚麻醉后24h老龄大鼠海马组织Syt-Ⅰ蛋白质与对照组比较表达量下调(P<0.05),而成龄大鼠海马组织Syt-Ⅰ蛋白质表达量与对照组比较没有明显变化。结论异氟醚麻醉后的老龄大鼠早期海马Syt-Ⅰ蛋白质可能参与异氟醚麻醉后延迟相大鼠的学习和记忆功能改变。     

异氟醚对老龄大鼠海马蛋白质组的影响

目的 探讨异氟醚对老龄大鼠海马蛋白质组的影响.方法 清洁级老龄雌性SD大鼠75只,22月龄,随机分为对照组(C组,n=35)和异氟醚组(I组,n=40).C组吸入含40%氧气的空气2 h,I组通过异氟醚挥发罐的调节使麻醉箱内异氟醚浓度为3%,待翻正反射消失后将异氟醚浓度降至1.2%,维持2 h.I组苏醒后24 h采用Y型迷宫实验检测认知功能,麻醉结束后24 h和72 h分别随机取5只大鼠,取海马行双向凝胶电泳和质谱分析.结果 与c组比较,I组麻醉结束后24 h和48 h正确反应次数和主动回避次数降低,全天总反应时间延长(P＜0.05);学习能力I组低于C组(P＜0.05).2组麻醉结束后24 h差异表达蛋白17种,其中6种蛋白质表达上调,11种蛋白质表达下调;2组麻醉结束后72 h差异表达蛋白16个,其中10种蛋白质表达上调,6种蛋白质表达下调.结论 异氟醚麻醉后早期老龄大鼠认知功能下降具有可逆性,这种现象可能与海马蛋白质组变化有关.     

手术对异氟醚麻醉下老龄大鼠术后认知功能的影响

目的 探讨手术对老龄大鼠异氟醚麻醉下术后认知功能的影响.方法 健康雄性老龄SD大鼠72只,年龄20月,体重500～600 g,随机分为3组(n=24):对照组(C组)、异氟醚麻醉组(I组)和手术组(O组).C组吸入30%氧气2 h,I组吸入1.5%异氟醚和30%氧气的混合气体2 h,O组吸入1.5%异氟醚和30%氧气的混合气体2 h,并实施腹部手术.于麻醉结束后或术后24 h时随机取8只大鼠,取海马组织,采用免疫组织化学法和RT-PCR法分别测定神经元胆碱乙酰转移酶(ChAT)及ChAT mRNA的表达水平,其余大鼠进行Morris水迷宫实验,测定认知功能.结果 与C组比较,I组和O组逃避潜伏期延长,原平台象限停留时间缩短,穿越原平台次数减少,海马神经元ChAT mRNA及其蛋白表达水平降低(P<0.05);与I组比较,O组术后第4、5天逃避潜伏期延长,原平台象限停留时间缩短,海马神经元ChAT mRNA及其蛋白表达水平降低(P<0.05);与麻醉结束后或术后第3天比较,C组第4、5天逃避潜伏期差异无统计学意义(P>0.05),I组和O组逃避潜伏期延长(P<0.05);I组和O组麻醉结束后或术后第4、5天逃避潜伏期差异无统计学意义(P>0.05).结论 手术操作可加重异氟醚引起的老龄大鼠术后认知功能障碍,其机制可能与海马胆碱能神经元受损有关.     

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.