曲马多预先给药对切口痛大鼠背根神经节神经生长因子表达的影响

目的 探讨曲马多预先给药对切口痛大鼠背根神经节神经生长因子(NGF)表达的影响.方法 雄性SD大鼠24只,体重200～250 g,随机分为4组(n=6),对照组(C组)仅给予麻醉及腹腔注射生理盐水5 ml;切口痛组(I组)于术前30 min腹腔注射生理盐水5 ml;曲马多1 mg/kg预先给药组(T1组)和曲马多10 mg/kg预先给药组(T10组)分别于术前30 min腹腔注射曲马多1、10 mg/kg.制备大鼠右后爪切口痛模型,T1组和T10组大鼠苏醒后采用累积疼痛评分法评定痛行为学,于术前30 min和术后2 h测定大鼠机械痛阈、热痛阈及右侧背根神经节NGF的表达水平.结果 与C组比较,I组、T1组术后2 h机械痛阈和热痛阈降低,累积疼痛评分升高,背根神经节NGF表达上调,T10组背根神经节NGF表达上调(P＜0.05或0.01);与I组比较,T1组和T10组术后2 h机械痛阈和热痛阈升高,累积疼痛评分降低,背根神经节NGF表达下调(P＜0.05);与T1组比较,T10组术后2 h机械痛阚和热痛阈升高,累积疼痛评分降低(P＜0.05或0.01),背根神经节NGF表达差异无统计学意义(P＞0.05).结论 曲马多1、10 mg/kg腹腔内预先给药均可下调切口痛大鼠背根神经节NGF表达水平.     

对乙酰氨基酚联合曲马多腹腔注射对神经病理性疼痛大鼠的协同治疗作用

目的观察腹腔注射对乙酰氨基酚加曲马多对脊神经部分结扎大鼠神经病理性疼痛的作用。方法雄性SD大鼠建立脊神经部分结扎神经病理性疼痛后,随机分为十组(n=8):对乙酰氨基酚40mg/kg(Ⅰ组)、80mg/kg(Ⅱ组)和160mg/kg(Ⅲ组),曲马多5mg/kg(Ⅳ组)、10mg/kg(Ⅴ组)和20mg/kg(Ⅵ组),对乙酰氨基酚40mg/kg加曲马多5mg/kg(Ⅶ组),对乙酰氨基酚80mg/kg加曲马多10mg/kg(Ⅷ组),对乙酰氨基酚160mg/kg加曲马多20mg/kg(Ⅸ组),生理盐水对照组(Ⅹ组)。采用热辐射法和vonFrey细丝法分别测定大鼠热刺激缩足反射潜伏期(TWL)和机械刺激缩足反射痛阈值(MWT)。结果与Ⅹ组相比,除Ⅰ、Ⅱ、Ⅲ、Ⅳ组大鼠TWL和MWT差异无统计学意义外,其余各组的TWL和MWT均显著延长或增大(P<0.05或P<0.01);与Ⅳ、Ⅴ、Ⅵ组相比,Ⅶ、Ⅷ、Ⅸ组的TWL和MWT均显著延长或增大(P<0.05或P<0.01)。结论腹腔注射对乙酰氨基酚加曲马多对脊神经部分结扎大鼠机械性痛觉过敏和热痛觉过敏具有协同的抗伤害感受性作用,对临床上神经病理性疼痛的治疗具有指导意义。     

曲马多对致痛小鼠血清核因子-κB及白细胞介素-2的影响

目的 研究曲马多对致痛小鼠血清核因子-κB(NF-κB)和白细胞介素-2(IL-2)的影响.方法 112只BALB/c雄性小鼠.体重25～30 g,随机均分为网组:曲马多组(T组,50 mg/kg曲马多)、吗啡组(M组,5 mg/kg吗啡)和假给药组(S组,生理盐水)、空白对照组(C组).各组在给药后1 h(T_1)、3 h(T_2)、12 h(T_3)、24 h(T_4)时眶静脉采血,用酶联免疫吸附法(ELISA)测定血清NF-κB及IL-2的含量,热板法测痛阈.结果 与S组比较,T组和M组的各时点痛阈增高(P<0.05).NF-κB:与C组比较,T_4时T组升高(P<0.05),T_3、T_4时M组和S组降低(P<0.05);与S组比较,T_2～T_4时T组升高;与M组比较,T_2～T_4时T组升高(P<0.05).T_1～T_3时T组IL-2含量高于M组(P<0.05).结论 吗啡对福尔马林致痛小鼠血清NF-κB和IL-2有抑制作用.曲马多对其具有增强作用,提示曲马多可能对疼痛所致的免疫抑制有改善作用.     

鞘内注射PSD-93反义寡核苷酸对大鼠神经病理性痛的疗效

目的 探讨鞘内注射PSD-93反义寡核苷酸对大鼠神经病理性痛的疗效.方法 雄性SD大鼠60只,随机分为5组(n=12):假手术组(S组)、C7脊神经压迫组(N组)、C7脊神经压迫+鞘内注射PSD-93误义寡核苷酸10 μg组(M组)、C7脊神经压迫+鞘内注射PSD-93反义寡核苷酸5 μg组(AJ组)和C7脊神经压迫+鞘内注射PSD-93反义寡核苷酸10 μg组(A2 组).N组、M组、A1组和A2组用60 g无创微血管夹压迫大鼠右侧C7脊神经15 min,制备神经病理性痛模型,经枕骨大孔鞘内置管,术毕当日开始给药,每日1次,连续4 d.于术前2 d(T0)和术后1、3、5、7 d(T1-4)测定机械痛阈和、热痛阈;T2和T4时分别处死6只大鼠,取C7脊髓,免疫组化法测定脊髓背角PSD-93蛋白表达.结果 与S组比较,N组、M组和A1组T1-4时机械痛阈及热痛阈降低,N组和M组T2,4时脊髓背角PSD-93蛋白表达上调(P＜0.05);与N组和M组比较,A1组T1,2时、A2组T1～4时机械痛阈及热痛阈升高,A1组T2时、A2组T2,4时脊髓背角PSD-93蛋白表达下调(P＜0.05);与A1组比较,A2组T1-4时机械痛阈及热痛阈升高,T2,4时脊髓背角PSD-93蛋白表达下调(P＜0.05).结论 鞘内注射PSD-93反义寡核苷酸可减轻大鼠神经病理性痛.     

鞘内注射氯胺酮对慢性神经痛大鼠脊髓背角一氧化氮合酶的影响

目的 探讨鞘内注射(IT)氯胺酮对慢性坐骨神经挤压损伤大鼠(CCI)脊髓背角一氧化氮合酶(NOS)活性的影响。方法 雄性SD大鼠36只,随机分为6组(n=6):假手术组(组Ⅰ);CCI组(组Ⅱ);氯胺酮组:于术前30min、术后1、2、3d分别IT氯胺酮12.5μg(组Ⅲ)、50μg(组Ⅳ)、100μg(组Ⅴ)、300μg(组Ⅵ)。按Bennett法制作CCI模型,以von-Frey filaments测定触痛及冷刺激反应,术后14d断头取腰段脊髓,以紫外分光光度计测定脊髓背角NOS活性。结果 与组Ⅰ相比,术后第7、14天组Ⅱ、组Ⅲ痛阈下降,冷刺激反应升高(P<0.05或0.01),组Ⅳ、Ⅴ、Ⅵ痛阈及冷刺激反应无显著性变化(P>0.05);与组Ⅱ比较,组Ⅳ、Ⅴ、Ⅵ的痛阈升高,冷刺激反应下降(P<0.05或0.01)。与组Ⅰ相比,组Ⅱ、Ⅲ脊髓背角NOS活性升高(P<0.01),而组Ⅳ、Ⅴ、Ⅵ则无显著性变化(P>0.05);与组Ⅱ比较,组Ⅳ、Ⅴ、Ⅵ髓背角NOS活性明显下降(P<0.01)。组Ⅲ、Ⅳ、Ⅴ、Ⅵ痛阈、冷刺激反应和NOS活性组间比较差异无显著性(P>0.05)。结论 N0/NOS系统参与了CCI大鼠痛敏的形成,此过程与NMDA受体有关。     

等效剂量曲马多、吗啡或芬太尼用于老年病人术后静脉镇痛的临床研究

目的　研究等效剂量曲马多、吗啡或芬太尼用于老年病人术后静脉镇痛的临床疗效。方法　 12 0例老年病人 ,随机分为三组 ,每组 4 0例。术后病人第 1次感到疼痛时 ,给予等效初始量曲马多 1 5mg/kg(T组 )、吗啡 0 15mg/kg(M组 )、芬太尼 1 5 μg/kg(F组 )静注 ,然后分别持续静注曲马多 10mg·2ml-1·h-1、吗啡 1mg·2ml-1·h-1或芬太尼 10 μg·2ml-1·h-148小时。记录镇痛期间 1、2、3、4、6、12、2 4、4 8小时静息及活动时疼痛VAS值 ;监测用药前及用药后 10、2 0、30分钟、用药后 1、2小时的RR、SaO2 变化及各种不良反应。结果　三组病人静息时镇痛效果无明显差异 (P >0 0 5 )。前 4小时活动时M组、F组镇痛效果较T组优 (P <0 0 5 ) ;用药后 10、2 0分钟M组、F组RR明显减慢 ,与用药前相比差异显著 (P <0 0 5 ) ,所有病例用药前与用药后SaO2 均保持正常 ;恶心、呕吐的发生率T组明显高于M组、F组 (P <0 0 5 )。结论　连续静注等效剂量曲马多、吗啡或芬太尼用于老年病人术后镇痛均能取得满意的镇痛效果 ,但活动时吗啡和芬太尼的镇痛效果优于曲马多 ;吗啡和芬太尼于首次用药后能引起短暂的呼吸抑制 ,但在持续给氧时SaO2 仍保持正常     

曲马多对致痛小鼠血清β-内啡肽、白细胞介素-4和白细胞介素-10的影响

目的 研究曲马多对福尔马林致痛小鼠血清β-内啡肽(β-EP)、IL-4、IL-10的影响,进一步探讨曲马多对疼痛所致应激及炎症反应的作用.方法 91只昆明清洁级小鼠,体重25～30 g,分为假给药组(S组,n=28)、曲马多组(T组,n=28)、吗啡组(M组,n=28)和空白对照组(C组,n=7).S、T、M三组小鼠制作疼痛模型并记录60 min内疼痛评分,疼痛模型制备后分别给予皮下注射生理盐水0.3 ml、曲马多50mg/kg和吗啡5mg/kg,并于制模后1、3、12、24 h时采集四组小鼠眶静脉血,应用ELISA测定血清β-EP、IL-4、IL-10浓度,热板法测痛阈.结果 与S组比较,M、T组时相Ⅱ疼痛评分明显升高(P＜0.05);T组制模后24 h IL-4浓度和制模后3、12、24 h的IL-10浓度明显升高(P＜0.05).与M组比较,制模后各时点T组和制模后3、12、24hS组β-EP浓度明显降低(P＜0.05);制模后3hT组和S组IL-4浓度明显降低(P＜0.05);制模后3、12、24 hT组的IL-10浓度明显升高(P＜0.05).结论 曲马多和吗啡均可产生良好的镇痛效果,曲马多能有效降低手术、疼痛引起的应激反应,降低β-EP和IL-4的浓度.     

细胞色素P450 2D6*10基因多态性对曲马多术后病人自控镇痛效果的影响

目的 探讨细胞色素P450 2D6* 10(CYP2D6* 10)基因多态性对曲马多术后病人自控镇痛(PCA)效果的影响.方法 全麻病人212例,年龄20～64岁,ASA Ⅰ或Ⅱ级.按基因型分为野生型纯合子(w/w)组,杂合子(m/w)组和突变型纯合子(m/m)组.手术结束前30 min静脉注射曲马多1.5mg/kg.清醒时VAS评分＞4分则静脉注射曲马多,若用量超过3 mg/kg则静脉注射芬太尼,至VAS评分≤4分后开始PCA,记录曲马多负荷量.曲马多PCA背景输注速率18 mg/h、16 h后降为12 mg/h、32h后降为9mg/h,PCA剂量22.5mg.记录术后6、12、24及48 h(T1～4)时曲马多累积用量.分别于T1、T3和T4时采用视觉模拟评分法(VAS)评价疼痛程度.于T4后行PCA镇痛效果评价.结果 与w/w组相比,m/m组曲马多负荷量、T1～3时曲马多累积用量均升高,清醒和T1时VAS评分升高(P＜0.05);与m/w组相比,m/m组曲马多负荷量、T3时曲马多累积用量均升高,T1时VAS评分升高(P＜0.05).结论 C YP2D6* 10基因多态性为曲马多术后镇痛药效学个体差异的因素之一.     

鞘内注射新斯的明对术后疼痛大鼠脊髓背角NOS表达的影响

目的：观察大鼠术前或术后鞘内注射新斯的明(NEO)对脊髓背角一氧化氮合成酶(NOS)表达的影响。方法：16只SD大鼠在鞘内置管成功5天后，随机分为四组。每组4只。I组为假手术组；Ⅱ组在术前30min鞘内注射0．9％NaCl；Ⅲ和Ⅳ组分别于术后或术前30min鞘内注射NEO10μg.用累积疼痛评分法测定疼痛程度；用NADPH-d酶组织化学法显示脊髓NOS阳性神经元。结果：Ⅲ组和Ⅳ组的累积疼痛评分均显著低于Ⅱ组。但Ⅲ组与Ⅳ组组同比较无明显差异。Ⅱ组手术侧脊髓背角浅表面NOS阳性神经元明显多于对侧及I组。与Ⅱ组比较。Ⅲ组和Ⅳ组相同部位的NOS阳性神经元均明显减少。尤以Ⅳ组减少为显著。而NEO用药组(Ⅲ组和Ⅳ组)比较也存在显著性差异。结论：在大鼠切口疼痛模型中，术前或术后鞘内注射NEO均具有明显的镇痛作用，同时脊髓背角NOS的表达明显减少，尤以术前用药组为显著。提示鞘内NEO的抗伤害作用可能与NO有关。     

鞘内注射艾司洛尔对福尔马林疼痛大鼠脊髓背角c-fos蛋白表达的影响

目的探索大鼠鞘内注射艾司洛尔能否抑制福尔马林大鼠脊髓背角c-fos蛋白表达。方法雄性SD大鼠,鞘内置管成功后,随机分为三组(n=8):生理盐水组(N组),艾司洛尔300μg/kg组(E1组),艾司洛尔600μg/kg组(E2组)。在异氟醚麻醉下,鞘内注射上述药物10μl,5 d后,所有大鼠一侧后肢爪掌背侧皮下注射福尔马林(5%,50μl),观察大鼠在Ⅰ相(0~5 min)和Ⅱ相(15~50 min)疼痛行为学变化(包括添足、咬足、抬腿动作等),并进行Dubuisson评分。采用免疫组织化学方法检测脊髓背角c-fos蛋白表达。结果与N组比较,E1、E2组大鼠Ⅱ相阶段的疼痛相关行为均有减少,呈量效关系(P<0.05),且E1、E2组L4~5节段脊髓表达的c-fos蛋白均较N组减少(P<0.05)。结论鞘内注射艾司洛尔可减少福尔马林大鼠脊髓背角c-fos蛋白表达。     

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.