载三氧化二砷纳米微粒对胰腺癌腹水抑制效应的实验研究

目的 探讨用纳米载体包裹的三氧化二砷(As2O3)在荷胰腺癌SCID小鼠体内的分布及对腹水生成和存活时间的影响.方法 用超声乳化法制备载As2O3乳酸羟基乙酸共聚物纳米微粒(As2O3-NPs),用体外释药方法研究其释放特性.于小鼠右前腋下接种SW1990细胞12 d后,静脉给As2O3-NPs 5.0 mg/kg体重,采用高压液相色谱法(HPLC)测定血浆、正常和肿瘤组织中As2O3含量.观察不同浓度As2O3-NPs对腹水生成的抑制作用.观察10.0 mg/kg体重As2O3-NPs处理的胰腺癌小鼠的存活期、体重、腹腔渗透性及腹水中凋亡细胞的变化.结果 As2O3-NPs直径为(210±23)nm,含药量为29%(重量比),体外释药速度明显慢于单纯的As2O3.As2O3-NPs在体内呈浓度依赖性抑制腹水形成,减少腹膜的通透性,增加腹水内凋亡细胞量,延长荷瘤小鼠的存活时间.结论 As2O3-NPs具有明显的缓释药物功能,能有效积聚在肿瘤组织,并抑制癌性腹水生成,是一种有希望的抗肿瘤药物.     

三氧化二砷对胰腺癌细胞增殖及凋亡的影响

目的试用三氧化二砷(As2O3)以提高胰腺癌的疗效。方法分别比较对照组和As2O3组裸鼠原位胰腺癌模型肿瘤体积、细胞增殖指数和细胞凋亡率。结果As2O3组肿瘤体积较对照组缩小31.2%。胰腺癌细胞增殖指数对照组为(21.05±2.18)%,As2O3组为(10.03±2.86)%(P<0.05);胰腺癌细胞凋亡率对照组(4.7±1.4)%,As2O3组(13.4±1.8)%(P<0.05)。结论As2O3体内能显著抑制胰腺癌的生长,其机制与抑制细胞增殖和诱导细胞凋亡有关。     

氧化砷诱导胰腺癌细胞凋亡的实验研究

目的观察As2O3对胰腺癌细胞株体外生长和裸鼠腹腔种植腹水生成的影响及其作用机制.方法O.125～2 μmol/L的As2O3与胰腺癌细胞株SW-8902共同孵育,观察不同浓度、不同作用时间对胰腺癌细胞生长的抑制作用、作用后胰腺癌细胞的凋亡特征及Fas Fas L表达的变化.80只BALB/C-nu/nu裸鼠腹腔内接种胰腺癌细胞株SW-8902,并随机分为4组,然后分别腹腔内注射生理盐水及不同剂量的As2O3,观察各组裸鼠的生存时间.结果1～2 μmol/L的As2O3作用后,胰腺癌细胞呈典型的凋亡特征性改变,流式细胞仪检测在G1期前出现亚二倍体凋亡峰,DNA电泳呈现特征性Ladder,细胞核内可见染色质浓缩、碎裂和边聚.As2O3也可显著抑制荷胰腺癌裸鼠腹水的生成,延长生存期(P＜O.01),Fas、Fas-L表达在As2O3作用后2 d上升,3 d达最高,以后表达量下降.结论As2O3诱导胰腺癌细胞凋亡,抑制裸鼠胰腺癌腹腔种植及腹水的生成,延长生存期.Fas、Fas-L表达上调是As2O3诱导肿瘤细胞凋亡的途径之一.     

氧化砷诱导胰腺癌细胞凋亡的实验研究

目的：观察As2O3对胰腺癌细胞株体外生长和裸鼠腹腔种植腹水生成的影响及其作用机制。方法：0．125－2μmol/L的As2O3与胰腺癌细胞株SW－8902共同孵育，观察不同浓度、不同作用时间对胰腺癌细胞生长的抑制作用、作用后胰腺癌细胞的凋亡特征及Fas Fas-L表达的变化。80只BALB／C－nu/nu裸鼠腹腔内接种胰腺癌细胞株SW－8902，并随机分为4组，然后分别腹腔内注射生理盐水及不同剂量的As2O3，观察各组裸鼠的生存时间。结果：1－2μmol/L的As2O3作用后，胰腺癌细胞呈典型的凋亡特征性改变，流式细胞仪检测在G1期前出现亚二倍体凋亡峰，DNA电泳呈现特征性Ladder, 细胞核内可见染色质浓缩、碎裂和边聚。As2O3也可显抑制荷胰腺癌裸鼠腹水的生成，延长生存期（P＜0．01）,Fas、Fas-L表达在As2O3作用后2d上升，3d达最高，以后表达量下降。结论：As2O3诱导胰腺癌细胞凋亡，抑制裸鼠胰腺癌腹腔种植及腹水的生成，延长生存期。Fas、Fas-L表达上调是As2O3诱导肿瘤细胞凋亡的途径之一。     

三氧化二砷在消化系恶性肿瘤治疗中的作用

三氧化二砷(arsenictr ioxide,As2O3),中药名为砒霜,在临床上的应用有悠久的历史.经过多年的实验室研究和临床应用,As2O3在抗肿瘤方面有确切的疗效,他是治疗急性早幼粒细胞白血病的有效药物之一,且不良反应较小,其主要机制为诱导细胞凋亡.目前As2O3已用于多种实体肿瘤的治疗,且在消化系肿瘤如肝癌的临床治疗中,疗效确切.近年来,在消化系统肿瘤的体外细胞系和体内动物模型的研究中均发现,As2O3能够诱导胃癌、胰腺癌、肝癌和结肠癌细胞凋亡,同时对癌细胞的生长起抑制作用.因此,研究As2O3在消化系恶性肿瘤防治中的作用具有重要意义.本文结合国内外文献对As2O3在治疗消化系恶性肿瘤中的作用作一综述.     

索拉非尼联合三氧化二砷治疗肝癌的研究

目的探讨索拉非尼联合三氧化二砷(As2O3)对肝癌的治疗作用。方法采用MTT实验检测索拉非尼联合As2O3对肝癌细胞的毒性。流式细胞仪检测索拉非尼联合As2O3诱导肿瘤细胞凋亡。构建肝癌异位瘤模型,检测索拉非尼联合As2O3对肝癌荷瘤裸鼠生存期的影响。结果与生理盐水组和单独给药组相比,联合干预组对肝癌具有更强的细胞毒性,差异具有统计学意义(P0.05)。细胞凋亡实验结果表明,联合干预能够促进肿瘤干细胞凋亡,差异具有统计学意义(P0.01)。体内治疗实验结果显示,索拉非尼与As2O3联合干预能够显著延长荷瘤小鼠的中位生存期,诱导肿瘤细胞的凋亡。结论索拉非尼联合As2O3能够增强对肝癌HepG2细胞的增殖抑制作用,是一种潜在的肝癌有效治疗方法。     

硼替佐米联合三氧化二砷诱导急性髓性白血病细胞凋亡的体内外实验研究

目的:探讨蛋白酶体抑制剂硼替佐米单用及其与三氧化二砷(As2O3)联合作用,在体内外对急性髓性白血病HL60细胞的凋亡诱导作用。方法:MTT法检测细胞增殖抑制;Hoechst33342染色形态学观察证实细胞凋亡形态;流式细胞仪检测细胞凋亡率;建立移植瘤小鼠模型观察体内抑瘤作用,健康小鼠处理后观察毒副作用。结果:硼替佐米单用时对HL60细胞有明显的增殖抑制作用及凋亡诱导作用,As2O3与硼替佐米联合应用后对细胞的凋亡诱导明显增强。体内研究显示As2O3或硼替佐米单用均对小鼠HL60移植瘤生长有一定的抑制作用,二者联合应用能明显促进肿瘤体积缩小,但是毒副作用无明显增加。结论:硼替佐米单用在体内外均能抑制HL60细胞增殖,诱导凋亡,与As2O3联合应用后在体内外对HL60细胞增殖抑制与诱导凋亡作用均增强,但毒副作用无明显相加效应。     

三氧化二砷联合5-FU抑制结肠癌干细胞的研究

目的探讨三氧化二砷(As2O3)联合5-氟尿嘧啶(5-FU)对结肠癌干细胞的抑制作用。方法将结肠癌干细胞分成As2O3干预组、5-FU干预组、联合干预组和PBS阴性对照组。采用MTT实验考察联合干预对结肠癌干细胞的毒性。用结肠癌干细胞构建肿瘤球模型,考察联合干预对结肠癌干细胞肿瘤球的生长抑制作用。采用流式细胞技术考察联合干预诱导肿瘤干细胞凋亡的能力。制备结肠癌的动物模型,考察联合干预对结肠癌荷瘤小鼠肿瘤的抑制作用。结果与PBS组和单独给药组相比,联合干预组对结肠癌干细胞具有更强的细胞毒性,差异具有统计学意义(P0.01)。细胞凋亡实验结果表明,联合干预能够促进肿瘤干细胞凋亡,差异具有统计学意义(P0.01)。肿瘤球给药7 d后5-FU干预组、As2O3干预组和联合干预组分别使肿瘤体积减小到原体积的71%、85%和44%,PBS组肿瘤球体积增大1.48倍,差异具有统计学意义(P0.01);体内治疗实验结果显示,PBS组、As2O3干预组和5-FU干预组小鼠肿瘤体积成长分别变为给药前肿瘤体积的2.55倍、2.13倍和1.54倍,而联合干预组肿瘤体积变化为原体积的1.27倍,联合干预组与环靶明干预组或5-FU干预组间差异具有统计学意义(P0.01)。结论 As2O3联合5-FU能够有效抑制结肠癌干细胞的增殖,5-FU联合As2O3是一种潜在的结肠癌干细胞治疗方法。     

三氧化二砷抗肿瘤基础与临床研究进展

三氧化二砷(As2O3)于2000年9月25日作为治疗急性早幼粒细胞白血病的新药通过FDA的审批。与此同时,越来越多的体内外研究提示As2O3的抗瘤谱非常广泛,有着广阔的临床应用前景。As2O3抗癌机制十分复杂,主要有:诱导细胞分化、阻滞细胞周期、诱导细胞凋亡、降低端粒酶活性以及抑制肿瘤血管生成等。     

线粒体在As2O3诱导肿瘤细胞凋亡中的作用

近年来发现三氧化二砷(arsenictrioxide,As2O3)对白血病的治疗很有效,尤其是对急性早幼粒白血病的治疗更有效。As2O3的作用机制不很清楚,但体外及体内实验均已证明诱导细胞分化或促进细胞凋亡是其发挥疗效的两种主要方式[1]。已有的研究表明,As2O3诱导细胞凋亡可能和一些常见的     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

CagA-Hp抗体IgG与胃炎的组织学分析

研究幽门螺杆菌(Hp)感染与胃炎的关系。方法对204例慢性胃炎患者胃粘膜进行观察分析,并测定其中137例Hp阳性患者血清CagA-Hp抗体IgG水平,与组织学对照。结果慢性萎缩性胃炎伴肠上皮化生患者血清CagA抗体IgG明显高于对照组(P＜0.01);其他类型胃炎患者血清CagA抗体IgG水平无明显增高(P＞0.05)。结论CagA-Hp可能是导致慢性萎缩性胃炎伴肠上皮化生的因素之一,对这类患者应密切随访观察。     

慢阻肺急性加重期患者预后的影响因素分析

目的探讨慢性阻塞性肺病急性加重期(AECOPD)患者预后的相关危险因素。方法回顾性调查、收集58例AECOPD患者可能影响其预后的相关因素,并对其分别进行单因素分析。并进行Logistic多元逐步回归进行多因素分析,筛选影响AECOPD患者预后的独立危险因素。结果单因素分析后将结果 P0.1的因素纳入多因素Logistic回归,分析发现是否合并呼吸衰竭、气促程度、白细胞计数、APACHEⅡ、应用抗氧化剂、慢阻肺治疗依从性为影响AECOPD患者预后不佳的独立因素(P0.05)。结论根据AECOPD患者预后的独立危险因素,及早判断,选择合适的后续治疗方案,对提高其生存率及生存质量具有重要意义。     

Results of treatment of fistula-in-ano

To evaluate the application of Parks' classification in the management of patients with fistula-in-ano, a study was undertaken to assess the outcome of surgery, especially with respect to the recurrence rate and alteration of continence. A retrospective analysis of 160 consecutive patients who were classified at the time of operation was conducted. The distribution of fistulas was as follows: intersphincteric, 41.9 percent, transsphincteric, 52.1 percent, suprasphincteric, 1.3 percent, extrasphincteric, 0. A horseshoe extension occurred in 8.8 percent of the fistulas and 3.8 percent did not exactly conform to the classification as they were either complex or combinations of more than one type of fistula. The sole immediate postoperative complication was bleeding, which occurred one week postoperatively and ceased spontaneously (0.7 percent). Alteration in continence occurred in 6 percent of patients with 2.6 percent experiencing temporary incontinence to flatus, 1.3 percent to liquid stool, and 0.7 percent to solid stool. Permanent loss of control for flatus occurred in one patient (0.7 percent) and for liquid stool in one patient (0.7 percent). No patients suffered loss of control for solid stool. Recurrence developed in 6.3 percent of patients, all between five and 25 months postoperatively. Classifcation was found to be a useful guide in the operative management of patients with fistula-in-ano. Read at the joint meeting of the American Society of Colon and Rectal Surgeons with the Section of Colo-Proctology, Royal Society of Medicine, and the Section of Colonic and Rectal Surgery, Royal Australasian College of Surgeons, New Orleans, Louisiana, May 6 to 11, 1984.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

Intake of energy drinks in association with alcoholic beverages in a cohort of students of the School of Medicine of the University of Messina

BACKGROUND: Energy drinks (ED) are a widely used group of beverages known for their stimulant effects on central nervous system (CNS). The main components of ED are caffeine, taurine, carbohydrates, glucuronolactone, inositol, niacin, pantenol, and beta-complex vitamins. The studies evaluating the effects of ED describe improvements in attention and/or reaction times and indices of alertness. It has been also shown that combination of caffeine and glucose, fundamental constituents of ED, can ameliorate deficits in cognitive performance and subjective fatigue during extended periods of cognitive demand. Moreover, the associated ingestion of alcohol and ED has recently been observed to be becoming more and more widespread. METHODS: With the aim to know the habits and uses of students, we administered a questionnaire containing questions regarding ED drinking alone or in association with alcoholic beverages. Five hundred students of the School of Medicine of the University of Messina were interviewed, and 450 filled the questionnaire. RESULTS: A total of 56.9% of students declared using ED. A great part of users (48.4%) associate frequently ED and alcohol. In particular, 35.8% of ED + alcohol users have used ED + alcohol more than 3 times in the last month. Distinguishing the users into 2 groups (users of ED + alcohol and users of both ED and ED + alcohol), we observed in the second group a major use of cocktail containing a mix of ED and alcoholic beverages. This difference between the 2 groups is less represented about the ingestion of ED + alcohol in the night. CONCLUSIONS: Our data indicate that association of ED + alcohol is very popular among students. This behavior can be dangerous. In fact, the combination of ED + alcoholic drinks can reduce adversive symptoms of alcohol intoxication including the depressant effects. As consequence, users of ED + alcoholic beverages might not feel the signs of alcohol intoxication, thus increasing the probability of accidents and/or favoring the possibility of development of alcohol dependence.