外泌体与肝脏疾病的关系

外泌体是细胞经过"內吞-融合-外排"等过程形成的直径在30~100 nm的胞外囊泡。多种细胞均可以释放外泌体,这些外泌体可携带脂质、蛋白质和核酸等重要的生物分子,参与细胞间的信号转导及物质交换,调节体内多个系统的生理病理过程,其在多种肝脏疾病中发挥至关重要的作用,如肝癌、病毒性肝炎、肝纤维化、酒精性及非酒精性脂肪肝等。对外泌体在肝脏疾病中的研究进展作一综述。     

外泌体在HIV-1感染中的作用研究进展

外泌体是可携带宿主和病原体衍生的基因、蛋白质、脂质等物质的内生性纳米微囊,可介导细胞与细胞间的物质和信号传递,调节人体生理和病理生理过程。随着外泌体在病毒感染领域研究的开展,人们发现外泌体在HIV-1感染的发病机制中有着重要作用。本文将对外泌体参与HIV-1感染机制、感染HIV-1后细胞释放的外泌体包含成分及作用、外泌体在HIV-1诊疗中的前景等方面进行综述。     

外泌体在肝病发病机制、诊断和治疗中的作用

外泌体（exosomes）是一种直径约30-100 nm、由生物膜包裹的囊泡,是细胞内的多泡体（multivesicular bodies）与胞浆膜融合的产物,可由众多不同类型的细胞通过胞吐作用（exocytosis）释放至细胞外隙或生物学体液中,其首要生物学功能是进行细胞间联络。外泌体含有细胞特异性蛋白分子、mRNAs及miRNAs等重要分子,通过将这些分子送达靶细胞而发挥细胞间联络作用,从而带来对机体有益（生理性）或有害的（病理性）潜在结果。肝脏细胞,尤其是肝细胞和胆管上皮细胞,既可释放外泌体,又是肝脏内源性外泌体和其他器官细胞来源的外泌体作用的靶细胞。尽管目前对肝脏外泌体的研究有限,但初步研究显示外泌体在肝脏的生理和病理生理过程中发挥着重要作用。外泌体参与肝细胞癌（HCC）、病毒性肝炎及肝脏炎症等的发病机制,是肝病诊断和预后判断的潜在新型分子生物标志物,也是肝病新的潜在治疗手段。本文特对肝脏外泌体的发现、功能及其对肝病潜在的诊治价值等做一简要总结。     

不同细胞来源外泌体参与心血管疾病发生的研究进展

外泌体是一种细胞外囊泡,可通过内溶酶体途径被细胞释放,作为信息载体参与细胞间通讯。不同细胞可分泌不同外泌体,后者携带的物质包括微小RNA、蛋白质、脂质等。有研究发现不同来源外泌体所携带的内容物也不尽相同,在细胞间通讯中起到重要作用。该文介绍外泌体在心血管各细胞间的通讯作用,为临床进一步探索相关靶向治疗提供新思路。     

外泌体改善心肌缺血再灌注损伤的作用机制研究进展

综述外泌体对心肌缺血再灌注损伤的作用机制,提示外泌体是一种新的细胞间通讯系统,能被大多数细胞释放和吸收,在受体-配体间传递信号分子诱导功能的变化,不同细胞来源的外泌体主要通过抗炎、抗氧化应激、抗心肌细胞凋亡以及促血管生成改善心肌缺血再灌注损伤。     

外泌体在心血管疾病诊疗中的研究进展

外泌体是一种由细胞分泌的细胞外囊泡,具有脂质双分子层结构,内含多种细胞特异的脂质、核酸及蛋白质等,参与细胞间通讯,在多种病理生理过程中起重要作用。近年来,外泌体成为研究的热点,随着研究的深入,外泌体在心血管疾病中的作用受到广泛关注。现就外泌体的结构功能特点以及在心血管病诊疗中的研究情况做一综述。     

外泌体影响血管内皮功能的研究进展及在心血管转化医学中的应用前景

正外泌体是直径为30～100 nm、绝大多数细胞均能够分泌的具有脂质双层膜的微囊泡。外泌体分泌细胞中核内体生成多泡小体,多泡小体与细胞膜融合将外泌体释放到细胞外。因此,外泌体可选择性携带、转运母细胞的胞内成分,如蛋白质、脂质、核酸等,因而具有强大的生物学功能~[1]。被释放到细胞外微环境的外泌体可直接被邻近细胞摄取或随体液到达远处部位再被其他细胞摄取,进而改变受体细胞功能,越来越多的证据表明外泌体在细胞间信号转导过程中起着至关重要的作用。血     

外泌体作为非小细胞肺癌诊断标志物的研究进展

正外泌体(exosomes)是具有脂质双层膜结构、直径为30~100 nm的微小囊泡,是细胞经过"内吞-融合-外排"等一系列调控过程后由细胞主动分泌的一种物质。外泌体的产生和分泌受多种蛋白质精确调节[1]。在正常或应激条件下,几乎所有类型的细胞都可以分泌外泌体,如网织红细胞、树突状细胞、脂肪细胞、内皮及上皮细胞等。与来源同一组织器官类型的正常细胞相比,肿瘤细胞能分泌更多的外泌体。     

外泌体与病毒感染及HBV相关肝病的关系

HBV感染后可导致肝脏组织炎症和肝细胞坏死,甚至发生肝纤维化等病理变化,驱动着"慢性肝炎-肝硬化-肝癌"的进展,但其机制尚不完全明了。被HBV感染的肝细胞与其他未感染细胞及宿主免疫系统之间发生相互作用的可能机制即通过肝脏微环境中由外泌体介导的细胞与细胞间的相互沟通。多项研究表明病毒感染可以调节外泌体的生成并影响其组成,病毒microRNA、蛋白质甚至整个病毒都可能被包裹进入外泌体,从而影响病毒的免疫识别或调节邻近细胞的功能。阐述了外泌体的产生和组成,及其在病毒感染过程中的作用,并进一步对外泌体与HBV感染等方面的研究进展进行了讨论。     

巨噬细胞来源外泌体促进肝星状细胞活化及对血小板衍生生长因子表达的影响

目的探究巨噬细胞来源的外泌体对肝星状细胞活化的作用及其可能的机制。方法采用差异超速离心法提取巨噬细胞外泌体, 将外泌体与小鼠肝星状细胞株JS1细胞共培养, 设立磷酸盐缓冲液(PBS)对照组。细胞免疫荧光观察F-actin表达情况, 细胞活力检测(CCK8)法检测两组JS1细胞的存活率, western blot和RT-PCR法检测两组JS1细胞的活化指标[Ⅰ胶型原蛋白(ColⅠ)、α-平滑肌肌动蛋白(α-SMA)]及其关键信号通路激活指标[转化生长因子(TGF)-β1/Smads、血小板衍生生长因子(PDGF)]的表达水平。两组间数据比较采用独立样本t检验。结果透射电镜观察外泌体膜结构清晰, 外泌体标志蛋白CD63、CD81表达阳性, 提示外泌体提取成功。外泌体与JS1细胞共培养, 与PBS对照组比较, 外泌体组JS1细胞的增殖率差异无统计学意义(P>0.05);外泌体组细胞F-actin表达明显增多;外泌体组JS1细胞α-SMA和ColⅠ的mRNA和蛋白表达水平显著升高(P值均<0.05), PBS组和外泌体组α-SMA的mRNA相对表达量分别为0.25±0.07、1.4...     

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。     

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.     

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.     

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。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

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。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

治疗高血压药物的经济学评价

重视高血压治疗中的经济学评价,对利用我国有限的卫生资源来遏制高血压对人民群众的危害有着重要的现实意义。药物经济学对于药物治疗的成本和治疗的结果给予同样的关注。因为治疗高血压的费用,不仅涉及药物价格,还包括患者的危险水平,降压疗效和对临床终点事件的影响,以及治疗的依从性和安全性。因此药物经济学更强调整体成本和价-效比。低危病人,若非药价低廉,治疗的价-效比不够理想。而在高危的患者,价-效比越小越经济而不是药费越便宜越好。