银杏叶提取物预处理对大鼠术后认知功能的影响

目的探讨银杏叶提取物预处理对大鼠术后认知功能的影响及可能机制。方法雄性无特定病原体(SPF)级SD大鼠54只,体重600~700g,月龄12月左右,按随机数字表法分为三组:空白对照组(C组)、手术组(O组)和Egb干预+手术组(E组),每组18只。E组于手术前连续5d腹腔注射Egb 100mg/kg,C组和O组分别腹腔注射等量生理盐水。行肝叶部分切除术建立大鼠术后认知功能障碍(POCD)模型。采用Morris水迷宫测试观察各组大鼠认知功能变化。三组大鼠于术前5d行定位航行实验训练,记录大鼠逃避潜伏期。于术后第3、5、7天行空间探索实验测试,记录目标象限停留时间和穿台次数。应用透射电镜观察大鼠海马CA1区缝隙连接结构,Western blot法测定大鼠海马缝隙连接蛋白Cx36的表达水平。结果大鼠术前定位航行实验第1天到第5天各组逃避潜伏期均逐渐缩短,但三组差异无统计学意义。术后第3、5、7天E组和O组大鼠目标象限停留时间明显短于C组(P0.05),穿台次数明显少于C组(P0.05);E组大鼠目标象限停留时间明显长于O组(P0.05),穿台次数明显多于O组(P0.05)。C组大鼠海马CA1区神经元之间的缝隙连接部分正常;O组大鼠术后3、5、7天海马CA1区神经元之间缝隙连接细胞膜结构不连续,通道间距不规则增宽,中间有空泡状结构。E组海马CA1区神经元之间细胞膜密度较高,至第7天基本恢复正常,与C组相似。术后第3、5、7天O组大鼠海马Cx36蛋白的表达水平明显低于C组(P0.05),E组大鼠海马Cx36蛋白的表达水平明显高于O组(P0.05)。术后第3、5天E组大鼠海马Cx36蛋白的表达水平明显低于C组(P0.05);术后第7天E组大鼠海马Cx36蛋白的表达水平低于C组,但差异无统计学意义。结论银杏叶提取物预处理可改善大鼠术后的认知功能,其机制可能与影响海马缝隙连接结构及Cx36蛋白的表达有关。     

手术创伤对老龄大鼠海马环氧化酶-2和前列腺素E2的影响

目的 探讨手术创伤对老龄大鼠海马环氧化酶-2(COX-2)和前列腺素E2(PGE2)的影响.方法 健康雄性SD大鼠45只,月龄18月,体重500～600 g,随机分为3组(n=15):对照组(C组)腹腔注射生理盐水3 ml;麻醉组(A组)和手术组(S组)腹腔注射1%戊巴比妥钠50 mg/kg(稀释至3 ml)麻醉,S组麻醉下行腹腔探查+阑尾切除术+脾切除术.于麻醉或术后1、3、7 d(T1～3)时测定认知功能、海马COX-2 mRNA表达和PGE2含量.结果 与C组和A组比较,S组中央格时间延长,跨格及站立次数和正确反应次数减少,全天总反应时间延长,海马COX-2 mRNA表达上调,PGE2含量增加(P＜0.05),C组和A组上述指标差异无统计学意义(P＞0.05).结论手术创伤导致老龄大鼠术后认知功能障碍的机制可能与上调海马COX-2 mRNA表达和增加PGE2含量有关.     

老龄术后认知功能障碍大鼠海马炎症反应的变化

目的 观察老龄术后认知功能障碍大鼠海马炎症反应的变化.方法 20个月龄雄性SD大鼠45只,体质量500～650 g,随机分为3组:对照组(C组,n=15)、麻醉组(A组,n=15)和手术组(S组,n=15).采用剖腹探查术建立老龄大鼠术后认知功能障碍模型.C组腹腔注射生理盐水0.8 ml;A组腹腔注射安定2.5 mg/kg和氯胺酮50 mg/kg(稀释至0.8 ml)麻醉,不行剖腹探查术;S组腹腔注射与A组等量的麻醉药物后行剖腹探查术.各组于干预结束后第1、3、7天(T_1、T_2、T_3)随机取5只大鼠采用旷场分析实验和Y迷宫实验测试大鼠认知功能,测试完毕后处死大鼠,取海马组织,采用放射免疫分析法测定白细胞介素(IL)-6和肿瘤坏死因子(TNF)-α的表达水平.结果 T_1时,与C组比较,A组各项行为学指标差异无统计学意义(P>0.05),S组中央格时间延长、跨格和站立次数减少、错误反应次数增加、全天总反应时间增加(P<0.05);与A组比较,S组中央格时间延长、跨格和站立次数减少、错误反应次数增加、全天总反应时间增加(P<0.05).T_2及T_3时点,上述各项指标差异无统计学意义(P>0.05).T_1时,与C组比较,A组IL-6和TNF-α表达水平差异无统计学意义(P>0.05),S组IL-6和TNF-α表达水平增高(P<0.01);与A组比较,S组IL-6和TNF-α表达水平增高(P<0.01).T_2及T_3时点,各组间IL-6和TNF-α表达水平差异无统计学意义(P>0.05).结论 老龄大鼠行剖腹探查术后出现短暂认知功能障碍,可能与海马IL-6和TNF-α表达增多有关.     

参麦注射液预处理对老龄大鼠术后认知功能的影响

目的观察参麦注射液预处理对老龄大鼠术后炎症反应水平和认知功能的影响。方法健康雄性老龄SD大鼠72只,月龄约20个月,体重500~600g。按随机数字表法分为对照组(C组)、参麦注射液组(S组)和布洛芬组(I组),每组24只。S组腹腔注射参麦注射液,I组给予布洛芬悬液灌胃,C组腹腔注射等量生理盐水。七氟醚麻醉下行脾切除术建立老龄大鼠POCD模型。三组大鼠分别于麻醉后即刻、术后即刻和术后1d采集颈静脉血,采用ELISA固相夹心法测定IL~(-1)β、IL-6和TNF-α浓度。于术前、术后1、3和7d进行Morris水迷宫实验和旷场实验,记录大鼠的逃避潜伏期、平台穿越次数、中央格停留时间、修饰次数和直立次数。结果术后即刻,S组和I组IL~(-1)β、IL-6和TNF-α浓度均明显低于C组(P0.01或P0.05);术后1d,I组IL~(-1)β与S组和I组IL-6的浓度均明显低于C组(P0.01或P0.05)。与术前比较,术后1、3dC组和S组的逃避潜伏期明显延长(P0.05),平台穿越次数明显减少(P0.01或P0.05),中央格停留时间明显延长(P0.01或P0.05),修饰和直立次数均明显减少(P0.01或P0.05)。与C组和S组比较,术后1、3dI组逃避潜伏期明显缩短(P0.01或P0.05),平台穿越次数均明显增多(P0.01或P0.05),中央格停留时间明显缩短(P0.01),修饰次数和直立次数均明显增多(P0.01或P0.05)。结论参麦注射液预处理可减轻手术后炎症反应,但对POCD无明显影响。     

海马腺苷酸活化蛋白激酶水平与老龄大鼠脾切除术后认知功能障碍的关系

目的 评价海马腺苷酸活化蛋白激酶(AMPK)水平与老龄大鼠脾切除术后认知功能障碍(POCD)的关系.方法 健康雄性老龄SD大鼠63只,体重480～550 g,采用随机数字表法,将其分为3组(n=21):对照组(C组)、麻醉组(A组)和手术组(S组).S组于术前、术后1、3、7d、A组和C组于相应时点进行Morris水迷宫实验,记录逃避潜伏期和游泳距离.术后1、3、7d水迷宫实验结束后随机取7只大鼠,处死后取海马组织,采用Western blot法测定海马AMPK、磷酸化AMPK(p-AMPK)的表达水平.结果 与术前相比,S组术后1、3d逃避潜伏期和游泳距离延长(P＜0.05);与C组相比,S组术后1、3d逃避潜伏期和游泳距离延长,术后1、3、7d海马AMPK表达上调,术后1、3 d p-AMPK表达上调(P＜0.05),A组上述指标差异无统计学意义(P＞0.05).结论 海马AMPK水平升高是老龄大鼠脾切除术后认知功能障碍形成时机体的适应性调节机制.     

曲马多对东莨菪碱致大鼠认知功能障碍的影响

目的探讨曲马多对东莨菪碱致大鼠认知功能障碍的影响。方法健康雄性SD大鼠40只,随机分为盐水对照组(C组)、东莨菪碱组(S组)、东莨菪碱+曲马多干预组(ST组)和单纯曲马多干预组(T组),每组10只。采用腹腔注射东莨菪碱的方法建立大鼠认知功能障碍模型。S组腹腔注射东莨菪碱1.8 mg/kg,ST组腹腔注射东莨菪碱1. 8 mg/kg和曲马多10 mg/kg, T组腹腔注射等容量曲马多10 mg/kg,C组腹腔注射等容量生理盐水。4组大鼠于注药后第7天行Y型电迷宫实验,观察大鼠认知功能变化。Y型电迷宫实验完毕即刻处死大鼠,取海马组织,采用ELISA法检测大鼠血清和海马组织中5-HT浓度,采用HE染色法观察海马神经元细胞形态学。结果与C组比较,S组和ST组Y型迷宫实验正确反应次数明显减少,达标时间明显延长,血清和海马组织中5-HT浓度明显降低(P0.05); T组血清和海马组织中5-HT浓度明显升高(P0.05)。与S组比较,ST组Y型迷宫实验正确反应次数明显增多,达标时间明显缩短,血清和海马组织中5-HT浓度明显升高(P0.05)。光镜下,C组与T组海马神经元细胞排列整齐,层次清晰,核大而圆,形态完整。S组海马神经元细胞排列紊乱,层次不清,出现细胞膜断裂,细胞质减少,细胞核固缩,甚至空泡变性。ST组海马神经元细胞上述形态学改变较S组明显减轻。结论腹腔注射曲马多10 mg/kg可改善东莨菪碱所致大鼠认知功能,使大鼠海马神经元细胞形态学改变减轻,海马组织和血清中5-HT浓度升高。提示东莨胆碱致大鼠认知功能障碍可能与大鼠体内乙酰胆碱及5-HT这两种神经递质之间的均衡性失调有关。     

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.     

异丙酚对氯胺酮致老龄大鼠认知功能障碍的影响

目的 探讨异丙酚对氯胺酮致老龄大鼠认知功能障碍的影响.方法 健康雄性SD老龄大鼠32只,月龄18～24月龄,体重380～470 g,随机分为4组(n=8):对照组(C组)、异丙酚组(P组)、氯胺酮组(K组)和异丙酚+氯胺酮组(PK组).P组静脉输注异丙酚30 mg·kg-1·h-1,K组静脉输注氯胺酮40 mg·kg-1·b-1,PK组静脉输注异丙酚30 mg·kg-1·h-1+氯胺酮40 mg·kg-1·h-1,C组给予等容量生理盐水,每天2 h,连续7 d.给药结束后测定大鼠认知功能,记录逃避潜伏期和穿越平台次数.认知功能测试完毕后,处死大鼠,取海马组织,检测CA1区神经元凋亡情况,计算神经元凋亡率;测定CA1区caspase-3的表达水平.结果 与C组比较,P组逃避潜伏期、穿越平台次数、海马CA1区神经元凋亡率和caspase-3表达差异无统计学意义(P＞0.05),K组和PK组逃避潜伏期延长,穿越平台次数减少,海马CA1区神经元凋亡率升高,caspase-3表达上调(P＜0.05);与K组比较,PK组逃避潜伏期缩短,穿越平台次数增加,海马CA1区神经元凋亡率降低,caspase-3表达下调(P＜0.05).结论 异丙酚可减轻氯胺酮致老龄大鼠认知功能障碍,其机制可能与异丙酚可在一定程度上抑制氯胺酮所致caspase-3表达上调,从而抑制氯胺酮诱发的神经元凋亡有关.     

老龄大鼠行心肺转流术建立长期术后认知功能障碍模型

目的通过在老龄大鼠行脾切除术或心肺转流(CPB)术建立术后认知功能障碍(postoperative cognitive dysfunction,POCD)模型。方法健康雄性SPF级SD大鼠60只,18月龄,随机分为脾切除术组(A组)、CPB术组(B组)及空白对照组(C组),每组20只,术后第31~35天进行Morris水迷宫、穿梭箱实验及旷场实验,评估大鼠认知功能。结果与C组比较,B组穿越原平台次数明显减少[(5.2±2.2)次vs.(8.6±3.2)次],主动回避反应次数明显减少[(12.3±2.7)次vs.(15.2±1.8)次],主动回避反应潜伏期明显延长[(9.50±2.31)s vs.(5.14±1.43)s],修饰次数[(13.8±2.6)次vs.(19.5±2.2)次]、直立次数明显减少[(6.8±1.5)次vs.(10.2±1.7)次],中央格停留时间明显延长[(7.78±1.51)s vs.(5.34±0.72)s],术后第33~35天逃避潜伏期明显延长(P0.05);与A组比较,B组中央格停留时间明显延长[(7.78±1.51)s vs.(6.06±1.67)s,P0.05]。结论行心肺转流术的老龄大鼠术后长期认知功能损害明显,可作为心血管麻醉后长期术后认知功能障碍研究的动物模型。     

NLRP3炎症小体在姜黄素减轻七氟烷麻醉大鼠术后认知功能障碍中的作用

目的评价NOD样受体蛋白3(NLRP3)炎症小体在姜黄素减轻七氟烷麻醉大鼠术后认知功能障碍中的作用。方法 SPF级健康雄性SD大鼠40只, 17～18月龄, 体质量580～600 g, 采用随机数字表法分为4组(n=10):对照组(C组)、术后认知功能障碍组(P组)、姜黄素组(CU组)和姜黄素+NLRP3炎症小体激活剂组(CN组)。采用吸入1.5%七氟烷探查腹腔的方法制备大鼠术后认知功能障碍模型。CU组和CN组大鼠姜黄素混悬液300 mg/kg灌胃, CN组大鼠尼日菌素钠盐5 mg/kg同时灌胃, 1次/d, 连续6 d, C组和P组大鼠等量生理盐水灌胃。随后采用水迷宫实验测定大鼠穿越原平台位置次数和目标象限停留时间, HE染色法观察海马组织病理学结果, TUNEL染色法检测神经元凋亡情况, Western blot法检测NLRP3、Bcl-2和Bax表达。结果与C组比较, P组大鼠穿越原平台位置次数减少, 目标象限停留时间缩短, 神经元凋亡率升高, NLRP3和Bax表达上调, Bcl-2表达下调(P<0.05);与P组比较, CU组大鼠穿越原平台位置次数增加, 目标象限停留时...     

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.