氧化应激与非酒精性脂肪性肝病研究进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease.NAFLD)是一种遗传.环境-代谢应激相关性疾病,其发病机制尚未完全明确,其中氧化应激对于NAFLD的发生发展起着关键作用.本文对NAFLD与氧化应激及其相关影响因素(如线粒体、微粒体、脂质过氧化、解偶联蛋白-21作一综述.     

代谢组学在中医药治疗NAFLD中的应用

<正>非酒精性脂肪性肝病(NAFLD)在全球的患病率达25%以上^[1],与肥胖、糖尿病、高脂血症、代谢综合征密切相关^[2-5],是代谢综合征(MS)的主要组成部分,是MS在肝脏中的表现[6]。NAFLD的进展形式,尤其是炎症和纤维化与动脉粥样硬化等心血管疾病密切相关^[7-9]。NAFLD发病机制多与肝脏内部脂质聚积、氧化应激及脂质代谢异常等因素有关[10]。随着研究的深入,发现肠道黏膜通透性降低,     

二甲双胍联合甘草酸二铵治疗2型糖尿病合并非酒精性脂肪性肝病的临床研究

正2型糖尿病(T2DM)是最常见的代谢性疾病,主要发病机制为胰岛素抵抗和β细胞功能缺陷,具有显著的糖脂代谢紊乱~([1])。非酒精性脂肪性肝病(NAFLD)遭受胰岛素抵抗引起肝细胞内脂质沉积和氧化应激及脂质过氧化"两次打击",与T2DM和代谢综合征(SM)关系密切、错综复杂、互为影响。随着人们生活饮食习惯的改变和环境等因素的影响,临床上T2DM合并NAFLD患者的发病率逐年增高,临床治疗非常棘     

乙醛脱氢酶2与非酒精性脂肪性肝病相关性的研究进展

乙醛脱氢酶2(ALDH2)是重要的乙醇代谢酶,可参与醛类物质的清除、能量代谢、脂质代谢、氧化应激和细胞凋亡等多种生理病理过程。ALDH2基因突变在东亚人中较常见,该突变在代谢性肝病中起着重要的作用。ALDH2基因多态性对酒精性肝病发生和进展的影响已被国内外研究所证实。近年来全基因组分析提示ALDH2基因多态性与代谢综合征具有相关性,ALDH2基因突变可能增加高血压病、糖尿病、冠心病、高脂血症等疾病及其并发症的风险。ALDH2基因多态性与非酒精性脂肪性肝病(NAFLD)的发生也密切相关,ALDH2可能通过内源性乙醇代谢、氧化应激、细胞凋亡等参与NAFLD的发病。此文就ALDH2与NAFLD相关性的研究进展作一综述。     

脂联素在非酒精性脂肪性肝病发病机制及诊治中的研究进展

脂联素是由脂肪细胞分泌的、在机体内广泛表达的一种脂肪细胞因子,与脂质代谢、胰岛素抵抗、氧化应激、炎症反应及纤维化均密切相关。近年来越来越多的研究证实了它在非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)发病机制及诊疗等方面起重要作用。因此,本文就脂联素在NAFLD的发病机制及诊断和治疗等方面的研究进展作一概述。     

CYP2E1与非酒精性脂肪肝

非酒精性脂肪性肝病(nonalcoholie fatty liver disease,NAFLD)是一种最常见的肝脏疾病,它的高发病率越来越受到广泛重视。细胞色素氧化酶P450-2E1亚型(CYP2E1)是参与氧化应激和脂质过氧化过程中的关键酶。"二次打击"学说为医学界普遍接受的非酒精性脂肪肝的发病机制。在非酒精性脂肪肝的"二次打击学说"中,CYP2E1介导的脂质过氧化亦发挥重要的作用。通过对CYP2E1介导的脂质过氧化在脂肪性肝病发病机制中作用的进一步深入研究,有可能探索出有效治疗脂肪性肝病的新途径。     

铁死亡在非酒精性脂肪性肝病发病和治疗中的作用

铁死亡是以铁依赖和脂质过氧化为特征的非凋亡性细胞死亡方式。非酒精性脂肪性肝病(NAFLD)是以脂肪浸润为主要病理特征，与胰岛素抵抗和遗传易感性密切相关的一类代谢性疾病。肝脏单纯脂肪变性向脂肪性肝炎转变的机制仍不清楚，有研究发现肝细胞性铁死亡可能是脂肪性肝炎炎症启动的触发因素。本综述重点关注铁代谢异常和脂质过氧化在促进NAFLD发生及发展中的作用，并归纳总结一些铁死亡相关抑制剂在NAFLD治疗中的应用前景。     

肠道菌群在非酒精性脂肪性肝病中的作用

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是我国最常见的慢性肝病之一。近年来该病发病率迅速增加,并呈低龄发病状态。NAFLD与2型糖尿病、心血管疾病及肝硬化等密切相关。NAFLD是一种病理疾病谱,包括从相对良性的脂肪变性到与炎症、纤维化、坏死相关的非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)。NASH患者发展为肝硬化和需要进行肝移植的肝衰竭风险升高。肠道菌群具有调节能量代谢和脂质沉积的作用,表明其与肥胖及代谢性疾病的发生密切相关。越来越多的证据表明,肠道菌群在NAFLD发病中起重要作用。本文就肠道菌群在NAFLD发病中的作用作一概述,为其预防、治疗及干预措施提供依据。     

线粒体损伤在非酒精性脂肪性肝病发生发展中的作用

线粒体是重要的细胞器,调节细胞脂质代谢、氧化磷酸化和ATP合成。线粒体生物合成障碍、稳态失衡乃至结构破坏都将导致脂质代谢紊乱以及氧化应激。非酒精性脂肪性肝病(NAFLD)是肝细胞脂质堆积为特征的慢性肝病。NAFLD是一个进展性疾病,表现为肝细胞脂肪变、脂肪性肝炎、肝纤维化和肝硬化这一轴向过程。目前认为线粒体在NAFLD发病中发挥着重要作用,NAFLD也被称为"线粒体病"。综述了脂质代谢障碍、氧化应激、线粒体稳态失衡等线粒体损伤与NAFLD发生发展的相关性。     

AMPK激活在非酒精性脂肪性肝病中的研究进展

非酒精性脂肪性肝病(NAFLD)的发生和进展与脂质积累、胰岛素抵抗、炎症、肝损伤、纤维化等因素有关。AMP依赖蛋白激酶(AMPK)是调控生物能量代谢的关键分子, 参与调控脂质代谢、自噬、炎症和细胞凋亡等众多生物过程。促进AMPK激活可减轻肝脏脂质积累和胰岛素抵抗, 缓解NAFLD的发展, 减轻肝脏炎症和纤维化抑制NAFLD向非酒精性脂肪性肝炎进展。     

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。     

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。     

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.     

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.     

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。     

Study of constancy of hydrogen-consuming flora of human colon

The constancy of the hydrogen consuming flora of the human colon was studied in 15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen disappearance rate and the major products of H₂-consuming bacteria, methane and sulfide, were measured during incubation of fecal homogenates with excess hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither) remained constant. However, major shifts in these pathways were observed in four subjects, with two losing and two gaining the ability to produce methane. Methanogenesis was associated with the highest hydrogen consumption rate. This study demonstrates that clinically unrecognizable, major alterations of the colonic flora occur in healthy subjects. Understanding of the factors responsible for these alterations might allow for therapeutic manipulation of the colonic flora.Supported in part by the Department of Veterans Affairs and NIDDKD RO1 DK 13309-25.     

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.     

Morbidity of closure of colostomy

This study reviews 86 colostomy closures with 61.6 per cent of the cases resulting from trauma. The overall complication rate was 17.4 per cent which included 7 per cent wound infection, 3.5 per cent anastomotic leak with fecal fistula, 2.3 per cent partial bowel obstruction, and 1 per cent each of deep stitch abscess, wound dehiscence, incisional hernia, and death due to intra-abdominal sepsis. Age, sex, and underlying disease had no demonstrable influence on the outcome of the operation. Closure of colostomy after three months of construction, mechanical and antibiotic bowel preparation, intraperitoneal closure, end-to-end anastomosis, and seconary skin closure were factors that appeared to influence the morbidity of the operation.     

Evolution of the fabric of cardiovascular science: Saga of an enduring process of refinement

BackgroundThe core elements of cardiovascular science have been established by scholarly pursuits of numerous scientists across centuries. In this article, we have tried to trace the evolutionary journey of cardiovascular science from a rudimentary form in ancient period to a robust scientific discipline in modern times.MethodsA literature search of relevant, peer-reviewed, published articles was undertaken from indexed databases (Medline & Pubmed, Scopus, Embase, CINAHL Plus, Web of Science and Google Scholar).ResultsCardiovascular science has its roots in antiquity, when Greek scholars mostly relied on philosophical thoughts and ancient texts. This was followed by addition of few structural details to the theory of circulation by Galen based on animal dissection. Arab scholar Ibn al–Nafis provided new insights regarding circulation pathway in humans. Nevertheless, an erroneous concept prevailed into the onset of European Renaissance. Even with legalization of human dissection, little headway could be made till sixteenth century due to persistent reliance of anatomists on ancient Galenic principles. During seventeenth century, the circulatory pathway (as we know it today) was established due to significant contributions from scholars like Harvey and Malpighi. Their efforts were based on findings from experiments and logical conclusions. Eighteenth century witnessed the emergence of autopsy based methods which led to valuable contributions from Vieussens, Thebesius, Morgagni and Hunter regarding normal and pathologic anatomy of cardiovascular system. With structural details mostly established, researchers during nineteenth century focussed on innovations in diagnostic methods based on human experiments. Further development of advanced human experiment models during twentieth century led to emergence of contemporary treatment methods for various cardiac conditions. In the twenty-first century, cardiovascular science is undergoing comprehensive progress at an exponential rate due to technological advances.ConclusionThe evolutionary journey of cardiovascular science as a discipline across centuries has been intriguing and eventful.     

Mechanisms of action of nitrates

Summary Glyceryl trinitrate, isosorbide dinitrate, and isosorbide-5-mononitrate are organic nitrate esters commonly used in the treatment of angina pectoris, myocardial infarction, and congestive heart failure. Organic nitrate esters have a direct relaxant effect on vascular smooth muscles, and the dilation of coronary vessels improves oxygen supply to the myocardium. The dilation of peripheral veins, and in higher doses peripheral arteries, reduces preload and after-load, and thereby lowers myocardial oxygen consumption. Inhibition of platelet aggregation is another effect that is probably of therapeutic value. Effects on the central nervous system and the myocardium have been shown but not scrutinized for therapeutic importance. Both the relaxing effect on vascular smooth muscle and the effect on platelets are considered to be due to a stimulation of soluble guanylate cyclase by nitric oxide derived from the organic nitrate ester molecule through metabolization catalyzed by enzymes such as glutathione S-transferase, cytochrome P-450, and possibly esterases. The cyclic GMP produced by the guanylate cyclase acts via cGMP-dependent protein kinase. Ultimately, through various processes, the protein kinase lowers intracellular calcium; an increased uptake to and a decreased release from intracellular stores seem to be particularly important.