上海地区HIV/HCV重叠感染者HCV准种的分子流行病学研究

目的 观察HIV/HCV重叠感染和高效抗反转录病毒治疗(HAART)对HCV准种的影响.方法 通过PCR、测序及单链构象多态性分析建立HCV高变1区(HVR1)准种变异率检测方法,运用该方法对我国上海地区48例HIV/HCV重叠感染者HCV准种变异的分子流行病学进行研究.结果 与单独HCV感染组和HIV/HCV重叠感染...     

丙型肝炎病毒高变区1融合蛋白的表达、纯化及其初步应用

目的　克隆并表达中国不同地区不同基因型的丙型肝炎病毒高变区 1(HCVHVR1)蛋白 ,并用表达纯化产物检测慢性丙型肝炎患者血清中的相应抗体 ,分析其临床意义。方法　根据 31株HCVHVR1序列分析及免疫原性预测结果 ,选择 4株克隆 (1b型 3株 ,2a型 1株 ) ,从 pGEMT E2克隆中扩增得到 4个HVR1片段 ,将其分别克隆到原核表达载体 pQE4 0中 ,表达产物经纯化后用以检测慢性丙型肝炎患者血清中的HVR1抗体。结果　构建的HVR1原核表达载体在大肠埃希菌中成功表达了 4种相对分子质量约为 2 80 0 0的二氢叶酸还原酶 (DHFR) HVR1融合蛋白 ,纯化蛋白的获得率约为 32 0～ 80 0 μg/ 10 0ml培养液。这 4种融合蛋白 (SH1b、BJ1b、SD1b、SD2a)与慢性丙型肝炎患者的血清结合率分别为 72 .8% (5 1/ 70 )、6 0 % (4 2 / 70 )、4 8.6 % (34/ 70 )和 5 8.6 % (4 1/ 70 )。在 2 0例用干扰素治疗的丙型肝炎患者中 ,5 7% (4 / 7)的干扰素治疗无应答者治疗前血清能与之反应 ,而应答者血清中只有 15 .3% (2 / 13)能与之反应。干扰素治疗应答者血清与 4种融合蛋白反应的A值高于治疗无应答者 (P <0 .0 5 )。结论　选择的 4株HCVHVR1片段在大肠埃希菌中获得成功表达 ,所得 4种HVR1融合蛋白能与HCV感染者血清发生较广泛的反应     

丙型肝炎病毒重组蛋白的免疫保护性

目的 研究两种HCV重组蛋白联合免疫小鼠所诱导的免疫应答及免疫保护作用.方法 用两种重组蛋白HCV-T和HCV-第一高变区多片段重组融合蛋白(F4HVR1)分别与联合免疫BALB/c小鼠,共免疫3次,用ELISA方法测定血清特异性抗体;末次免疫后14 d处死5只小鼠,分离小鼠脾细胞.体外检测IFN-γ、IL-4和行CTL杀伤实验;剩余的小鼠背部皮下注射1.0×106个SP2/O-NS3细胞,观察其保护作用.组间均数差异采用LSD-t检验.结果 与PBS组相比,用HCV-T和HCV-F4HVR1联合免疫诱导了针对HCV-F4HVR1的特异性的IgG(t=3.815,3.762,P＜0.05)、高水平的HCV-NS3特异性的CTL效应(t=3.971,P＜0.05)和高水平的IL-4(t=3.813,3.426,3.671,P＜0.05)和IFN-γ(t=3.512,3.417,P＜0.05)的分泌.结论 用HCV-T和HCV-F4HVR1联合免疫小鼠可诱导出高水平的特异性体液免疫和细胞免疫,能有效地预防SP2/O-NS3细胞的攻击.     

丙型肝炎病毒1a、1b和2a型E1E2原核质粒的构建和序列分析

目的构建陕西地方株丙型肝炎病毒(HCV)1a、1b和2a型包膜糖蛋白E1E2的原核质粒并测序比对。方法采用逆转录-巢式聚合酶链反应(RT-nest PCR)扩增获得HCV 1a、1b和2a型E1E2片段,与p MD-18 simple vector连接,转化感受态细菌DH5α,小量提取质粒DNA并测序。测序结果与Gene bank中其他标准序列比对以获取同源性数据。同时重点分析E2蛋白高变区(HVR)1和2氨基酸序列。MEGA 4软件绘制种系进化树图。结果成功扩增约2 kb的目的片段并构建原核质粒,测序结果正确。1b亚型E1E2的核苷酸和氨基酸序列的同源性最差。HCV E2的HVR1和2的序列比对显示,同种基因亚型在HVR 1的变异性最大,而HVR 2的序列变异性不显著。不同基因亚型的毒株在HVR 1和2的变异性极大,而1b亚型在HVR 1和2的变异性比1a和2a型突出。结论陕西地方株HCV 1b型E1E2区比1a和2a型更易发生突变,1b型E2的HVR变异性更显著。     

丙型肝炎病毒高变区准种异质性与干扰素疗效的关系

丙型肝炎病毒(HCV)基因组具有高度的变异性，在机体内以准种的形式存在，尤其以E2／NS1区384～410和474～480位氨基酸变异程度最高，分别称为HVR1和HVR2。近年的研究发现，HCV准种感染除与引起HCV感染慢性化有关外，还与HCV对干扰素(IFN)治疗的抵抗作用关系密切。本研究采用克隆测序法对10例应用IFN治疗的1b型慢性丙型肝炎患者进行了HVR1和HVR2准种异质性检测，以探讨HCV准种感染与IFN疗效的关系。     

丙型肝炎疫苗的研究现状

丙型肝炎在全世界广泛流行,全球有2～3亿的慢性HCV感染者,亟待研制有效的丙肝疫苗。然而,丙肝疫苗的研制尚面临诸多困难。本文就丙型肝炎疫苗的研究现状及相关的免疫学进展作一综述。 1 HCV与机体免疫应答体液免疫应答在保护机体免受病毒的攻击中发挥着重要作用,包括与HCV同属的黄热病毒、登革热病毒、tickbone脑炎病毒等的疫苗设计均着力于诱生机体的中和抗体,接种后机体均能产生具有中和作用的包膜抗体,并能抵抗随后相应病毒的攻击,然对HCV而言,目前尚不能确定其中和抗体表位。有研究表明,HCV-E_2区的高变区(HVR1)含有具有中和作用的B细胞表位,并发现HCV-E_2蛋白能与细胞上的CD81分子结合(CD81被认为是感染肝细胞的HCV受体)。     

丙型肝炎病毒细胞和动物模型研究进展

丙型肝炎病毒(HCV)为黄病毒科病毒的一条RNA正链。整条负链的中间编码区域、包膜、非结构蛋白都可以进行复制,包膜区包括超变量区域,与序列的变异有关。丙型肝炎“基因准种”的出现对疫苗和包括针对逃避变异抗病毒药物的开发增加了难度。在丙型肝炎患者中,使用聚乙二醇干扰素α2a或者α2b联合病毒唑,持续性病毒学的总应答率可达到50％,而携带Ⅰ基因型患者的持续应答率比较低,只有(41-46)％。因此,新抗病毒药物和疫苗的研制,以及深入探讨复杂的宿主免疫反应,对于丙型肝炎的治疗非常重要,而丙肝病毒模型的建     

丙型肝炎病毒相似株的临床意义

HCV包膜糖蛋白E2/NS1基因区C端相对保守,N端含有两个高变区域(hypervariable region, HVR)HVR1和HVR2,分别定位于氨基酸序列的384aa～410aa/413aa及474aa～480aa;近年来研究发现HVR1含有病毒株特异的中和性抗原表位。HCV感染者体内可同时存在多种相似株,这种序列     

HCV E_2蛋白抑制干扰素诱导的蛋白激酶活性

干扰素(IFN)是治疗HCV的常用药物,但仅对少数型别和患者有效,其耐药机理尚不清楚。蛋白激酶(PKR)是IFN诱导产生的主要抗病毒蛋白之一,可以自身磷酸化,也可磷酸化真核蛋白合成的起始因系。单位(eIF2α)从而抑制蛋白的合成和细胞生长,达到抗病毒作用。 最近研究表明:HCV E_2蛋白含有一个12氨基酸序列与PKR以及eIF2α磷酸化同源结构域(PePHD),通过这结构域E_2可以干扰和抑制PKR活性,致使干扰素疗效不能发挥。PePHD多见于HCV 1a,     

丙型肝炎病毒受体研究的现状及展望

在HCV感染宿主过程中,病毒必须首先结合到靶细胞表面,经受体的介导进入细胞,然后才能复制,引起相关的病理变化;因此如何终止丙型肝炎的慢性化进展,特别是阻断HCV的感染过程是关键的问题[1]。阻断HCV感染首先涉及到宿主细胞表面的HCV受体或辅助受体,相关的研究刚开始。现在初步研究结果证实:丙型肝炎病毒的包膜蛋白E1和E2可能是和靶细胞结合的配体,导致病毒进入宿主细胞。由于HCV基因的变异主要反映在病毒包膜E2蛋白,所以E2蛋白的高变区（HVR）决定了     

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.     

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。     

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。     

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。     

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。     

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.     

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.