青蒿素诱导急性胰腺炎胰腺腺泡细胞凋亡的实验研究

目的探讨青蒿素（artemisinin）对急性胰腺炎胰腺腺泡细胞凋亡的影响,并了解是否减轻急性胰腺炎严重程度。方法腹腔内注射雨蛙素（cerulein）诱导大鼠胰腺炎模型建立,设正常对照组、胰腺炎组及青蒿素组,通过原位末端标记（TUNEL）法检测各组胰腺组织中腺泡细胞的凋亡指数,并用分光光度法检测髓过氧化物酶（MPO）活性。采用两步酶消化法分离正常大鼠胰腺腺泡细胞,离体分组培养,采用丫碇橙（AO）染色及caspase-3活性的检测,评估青蒿素对胰腺腺泡细胞凋亡的影响,并检测各组培养液中的乳酸脱氢酶（LDH）及淀粉酶（AMS）活性,评估胰腺腺泡细胞酶的释放。结果在体实验中,青蒿素组与胰腺炎组比较,胰腺腺泡细胞凋亡指数明显增高（P〈0.05）,MPO活性明显减低（P〈0.05）。体外实验中,青蒿素组胰腺腺泡细胞凋亡指数及caspase-3活性较胰腺炎组明显增高（P〈0.05）,培养液中的LDH和AMS活性也明显降低（P〈0.05）。结论青蒿素可促进大鼠急性胰腺炎胰腺腺泡细胞凋亡,减少胰酶释放及中性粒细胞激活,可减轻急性胰腺炎严重程度。     

雨蛙素腹腔注射致小鼠慢性胰腺纤维化病理组织学观察

目的：采用雨蛙素反复腹腔注射诱导小鼠慢性胰腺炎,评估胰腺发生纤维化的程度及病变特点。方法：健康雄性C57BL/6小鼠20只,随机分为两组,模型组反复腹腔注射雨蛙素,对照组腹腔注射与模型组等体积的生理盐水,于第7周第1d留取胰腺组织,光镜下进行胰腺腺泡细胞萎缩、炎性细胞浸润、间质纤维组织增生评分;另一部分行苦味酸-天狼星红染色,偏振光显微镜下观察胰腺间质胶原增生情况;第三部分行免疫组织化学染色,观察α-SMA表达情况。结果：模型组小鼠胰腺HE染色显示明显腺泡细胞萎缩、炎性细胞浸润及纤维化;苦味酸-天狼星红染色显示显著胰腺间质胶原增生,评分明显升高;免疫组织化学染色显示星状细胞活化标志物α-SMA表达明显增强。结论：雨蛙素反复多次腹腔注射可诱导小鼠产生明显的胰腺纤维化病变,纤维化发生机制可能与胰腺星状细胞活化分泌过多细胞外间质有关。     

区域动脉灌注5-FU诱导大鼠急性胰腺炎腺泡细胞凋亡及Caspase-3表达

目的 探讨区域动脉灌注（regional arterial infusion,RAI）5-氟尿嘧啶（5-fluorouracil,5-FU）对大鼠急性胰腺炎（acute pancreatitis,AP）胰腺腺泡细胞凋亡的影响及其对急性胰腺炎的治疗作用。方法 18只健康成年SD大鼠随机分成3组：对照组（C组）、急性胰腺炎组（AP组）和5-FU治疗组（5-FU组）。各组均行胃左动脉置管,AP组和5-FU组以大剂量雨蛙素（每小时腹腔注射50 μg/kg,连续6 h）诱导建立大鼠急性胰腺炎模型,对照组注射同等剂量的生理盐水。5-FU组在第一次腹腔注射雨蛙素1 h后立即区域动脉灌注5-FU（40 mg/kg）治疗,C组和AP组区域动脉灌注等量的生理盐水。建模成功后3 h取标本并处死大鼠,检测血淀粉酶浓度,RT-PCR法检测胰腺组织内TNF-α、IL-1β、IL-6 mRNA表达水平,胰腺标本送病理学检查,Western blotting法检测胰腺组cleaved Caspase-3的蛋白表达,同时TUNEL法检测大鼠胰腺腺泡细胞凋亡情况。结果 与AP组比较,5-FU组血淀粉酶浓度明显降低（P＜0.05）;胰腺组织内TNF-α、IL-1β、IL-6  mRNA表达水平下降（P＜0.05）;胰腺组织病理学改变减轻;胰腺组织cleaved Caspase-3的蛋白表达增加;胰腺腺泡细胞凋亡增加（P＜0.05）。结论 区域动脉灌注5-FU对大鼠急性胰腺炎有改善作用,其作用机制可能与诱导胰腺腺泡细胞凋亡有关。     

中性粒细胞对大鼠急性重症胰腺炎胰腺腺泡凋亡的作用

目的探讨中性粒细胞在大鼠急性重症胰腺炎时对胰腺的病理损害及对胰腺腺泡凋亡的作用。方法氨甲蝶呤（MTX）腹腔注射制成大鼠低中性粒细胞模型，然后以脱氧胆酸胰胆管注射诱发急性重症胰腺炎，造模后0、3、6、9、24、48、72h随机分批处死动物，按各时间点检测胰腺组织髓过氧化物酶活性（MPO），血清淀粉酶，应用末端脱氧核苷酸转移酶介导的DUPT末端标记染色（TUNEL）和电镜技术检测胰腺腺泡凋亡情况，胰腺组织的病理学检查。结果实验组MPO在造模24h开始明显低于对照组（P〈0．01），胰腺组织的病理损害程度也较对照组轻。两组胰腺腺泡凋亡在造模3和6h均仅出现少量凋亡，在24和48h显著增多，以后逐渐下降；实验组胰腺腺泡凋亡指数明显高于对照组胰腺腺泡凋亡指数（P〈0．01）。结论适当地降低外周血的中性粒细胞水平能够增加胰腺腺泡凋亡，从而减轻急性重症胰腺炎时胰腺的病理损害程度。     

紫杉醇诱导急性胰腺炎大鼠胰腺腺泡细胞凋亡机制的研究

目的研究急性胰腺炎时紫杉醇诱导大鼠胰腺腺泡细胞凋亡的机制。方法利用胆胰管内注射脱氧胆酸钠的方法建立急性胰腺炎大鼠模型 ,并向腹腔内注射紫杉醇以诱导胰腺腺泡细胞凋亡。利用免疫组化法研究胰腺腺泡细胞凋亡相关蛋白Bcl 2、Bax、Fas、FasL及 p5 3表达的变化。结果急性胰腺炎时大鼠胰腺腺泡细胞中Bax(2 5 0 6± 94 2 )、Fas(2 79± 15 0 )和 p5 3(180± 5 6 )的表达增加 ,Bcl 2 (79± 4 2 )表达无明显变化 ,而FasL只表达于急性胰腺炎时胰腺间质浸润的炎性细胞中。结论急性胰腺炎时紫杉醇诱导的大鼠胰腺腺泡细胞凋亡与Bax、Fas/FasL系统以及p5 3蛋白有关。     

奥曲肽对大鼠急性胰腺炎腺泡死亡方式的影响

目的探讨奥曲肽对急性胰腺炎(Acute Pancreatitis,AP)腺泡细胞死亡方式的影响。方法使用奥曲肽对急性胰腺炎大鼠模型进行治疗,采用原位TUNEL及RT-PCR等技术,观察各组胰腺组织内Bax mRNA变化及胰腺腺泡细胞凋亡情况、胰腺病理学改变及组织学评分变化情况。结果大鼠胰腺细胞凋亡指数与胰腺组织病理学评分呈负相关;奥曲肽可使AP模型的胰腺组织内Bax mRNA表达增加,诱导胰腺腺泡细胞凋亡增加,使胰腺病理学改变及组织学评分改善。结论奥曲肽可能诱导AP腺泡细胞的凋亡,减轻胰腺炎的严重程度。     

肝细胞生长因子与急性胰腺炎

肝细胞生长因子(HGF)是一种高效的多效性因子,对多种器官的不同类型细胞均有生物学作用。其受体c-Met在多种组织和细胞中表达,HGF通过与其特异性受体c-Met结合引起一系列信号转导蛋白的酶促反应,促发相应的生物学效应。近期研究表明,在急性胰腺炎患者中可检测到血清HGF水平增高,并与患者的预后相关;给予外源性HGF能减轻急性胰腺炎的炎症反应,并能促进腺泡细胞的凋亡,降低胰腺细胞中的氧自由基水平。     

雨蛙素腹腔注射法建立小鼠急性坏死性胰腺炎模型的实验研究

目的　建立一种稳定的急性坏死性胰腺炎模型。方法　 36只雄性ICR小鼠用查随机数字表的方法随机分为对照组 (n =6 )和实验组 (n =30 )。实验组予以雨蛙素腹腔注射 ( 5 0 μg/kg) ,每小时注射 1次 ,共 7次 ,并分别于首次注射后 9h、18h、2 4h、4 8h和 72h各处死 6只 ;对照组予以腹腔注射等量的生理盐水 ,于注射后 18h处死。比较两组动物的血淀粉酶值、胰腺重量及胰腺组织学评分分值。结果　腹腔注射雨蛙素后 9h ,小鼠血淀粉酶值升高 ,胰腺重量增加 ,18h达峰值 ,2 4h后逐渐下降。二者与胰腺病理损害程度相一致。 18h胰腺间质炎性细胞浸润和腺泡细胞坏死明显 ,胰腺组织学评分值达到最大值 (P<0 .0 5 )。结论　大剂量雨蛙素腹腔注射能诱导ICR小鼠产生急性坏死性胰腺炎。该模型制备方法简单 ,无创伤性 ,模型稳定 ,重复性好     

细胞凋亡在急性胰腺炎发病机制中所起作用的研究进展

细胞凋亡和细胞坏死是胰腺腺泡细胞两种完全不同的死亡方式，两者的比例将决定急性胰腺炎表现为水肿型还是出血坏死型。急性胰腺炎时不仅有胰腺腺泡细胞的凋亡同时伴有炎症因子的释放，而不同的炎症因子对于细胞凋亡的调控大都不一样。笔者就此进行综述。     

胰腺腺泡细胞凋亡在大鼠急性胰腺炎病程中的作用及凋亡调控基因的表达

目的: 探讨胰腺腺泡细胞凋亡及凋亡调控基因--Bax的表达情况及其与急性胰腺炎严重度的关系. 方法: 在胰胆管共同通道内逆行注射不同浓度的脱氧胆酸钠,制备不同重症程度的急性胰腺炎模型.24只SD大鼠随机分为对照组(假手术组)、APⅠ组(0.75%剂量组)和APⅡ组(1.5%剂量组).分别于造模后6小时处死各组存活大鼠.用TUNEL法分析腺泡细胞凋亡情况,用免疫组化及WesternBlotting检测Bax的表达情况. 结果: APⅠ组大鼠较APⅡ组胰腺坏死减少、出血减轻,血清淀粉酶、IL-6和IL-8水平明显下降;病变程度轻的APⅠ组大鼠腺泡细胞凋亡指数比病变程度重的APⅡ组高(6.36±2.41vs2.34±1.15,P<0.05);正常腺泡细胞Bax的表达弱;产生急性胰腺炎时,腺泡细胞Bax的表达增强,病变程度轻的大鼠腺泡细胞Bax表达水平较病变程度重的强,与二者凋亡指数的差别相一致. 结论: 产生急性胰腺炎时,腺泡细胞凋亡与其病情严重程度呈负相关,腺泡细胞凋亡在急性期是一种保护现象;Bax的表达水平与腺泡细胞凋亡指数呈正相关,与胰腺炎的病变程度呈负相关.     

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。     

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.     

Surgical management of ductal carcinoma in situ in Australia in 1995

Background: In the present paper we describe the presentation and management of ductal carcinoma in situ (DCIS) of the breast in women in Australia in 1995. This representative, national data set provides a historical comparator for studies examining DCIS management that follow. Methods: Surgeons identified by population‐based cancer registries as having treated a new diagnosis of DCIS between 1 April and 30 September 1995 completed a questionnaire on the presentation and management of each case. Results: Two hundred and five surgeons supplied treatment details on 418 DCIS tumours in 415 women . Half of all tumours were detected at BreastScreen clinics and a further 25% were detected at other mammography centres. Twenty‐six percent of tumours were palpable at presentation, 33% were multifocal and 55% were high grade (including comedocarcinoma). Breast conserving therapy (BCT) rather than mastectomy was utilized in 260 (62%) of cases. Tumours that were of low grade, small in size and not multifocal were more likely to be treated by BCT. Surgeons seeing six or more DCIS cases in the 6‐month period were more likely to utilize BCT. Of the conservatively treated cases, 22% were referred for a radiation oncology consultation. The most common reasons for treating DCIS with mastectomy were that the tumour was too extensive or multifocal (63%), it extended to margins of the specimen (42%), or patient concerns about recurrence (34%). Conclusions: In 1995 the majority of DCIS was treated with breast conserving surgery alone. Surgeons treating more DCIS cases were more likely to perform conservative surgery than surgeons treating only one DCIS case in the study period.     

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.