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1Portal vein thrombosis:Prevalence,patient characteristics and lifetime risk:A population study based on 23796 consecutive autopsies显示文摘瞄准:估计一生在一般人口的门静脉血栓形成(PVT ) 的累积发生。方法:在 1970 和 1982 之间, 23,796 具尸体,在马尔摩城市人口代表 84% 所有在里面医院死亡,被执行,用包括门静脉的检查的一个 standardised 协议。PVT 病人被描述并且在尸体的 PVT 流行,一生的表情累积发生,在高风险的疾病范畴估计了并且以机会比率和 95% CI 表示了。结果:PVT 的人口流行是 1.0% 。有 PVT 28% 的 254 个病人有肝硬化, 23% 主要并且 44% 第二等的肝胆管恶意, 10% 主要腹的传染或煽动性的疾病并且 3% 有 myeloproliferative 混乱。有肝硬化和肝的癌的病人有最高的 PVT 风险,或 17.1 (95% CI 11.1-26.4 ) 。在 14% ,没有原因被发现;仅仅,少数他们开发了 portal-hypertension-related 复杂并发症。结论:在这基于人口的研究, PVT 比由以前的临床的系列显示被发现更普通。显著地,在肝硬化和肝的癌的过量风险应该在指导干预的未来的研究可能为被考虑的这些病人保证增加的了解。Mats gren David Bergqvist Martin Bjrck Stefan Acosta Henry Eriksson Nils H Sternby 2006World Journal of Gastroenterology2006,12,13:66
2Biochemical mechanisms in drug-induced liver injury:Certainties and doubts显示文摘Drug-induced liver injury is a significant and still unresolved clinical problem.Limitations to knowledge about the mechanisms of toxicity render incomplete the detection of hepatotoxic potential during preclinical development.Several xenobiotics are lipophilic substances and their transformation into hydrophilic compounds by the cytochrome P-450 system results in production of toxic metabolites.Aging,preexisting liver disease,enzyme induction or inhibition,genetic variances,local O2 supply and,above all,the intrinsic molecular properties of the drug may affect this process.Necrotic death follows antioxidant consumption and oxidation of intracellular proteins,which determine increased permeability of mitochondrial membranes,loss of potential,decreased ATP synthesis,inhibition of Ca2+-dependent ATPase,reduced capability to sequester Ca2+ within mitochondria,and membrane bleb formation.Conversely,activation of nucleases and energetic participation of mitochondria are the main intracellular mechanisms that lead to apoptosis.Non-parenchymal hepatic cells are inducers of hepatocellular injury and targets for damage.Activation of the immune system promotes idiosyncratic reactions that result in hepatic necrosis or cholestasis,in which different HLA genotypes might play a major role.This review focuses on current knowledge of the mechanisms of drug-induced liver injury and recent advances on newly discovered mechanisms of liver damage.Future perspectives including new frontiers for research are discussed.Ignazio Grattagliano Leonilde Bonfrate Catia V Diogo Helen H Wang David QH Wang Piero Portincasa 2009World Journal of Gastroenterology2009,15,39:30
32018加拿大心境障碍与焦虑障碍治疗协作组/国际双相障碍学会指南:双相障碍的管理显示文摘加拿大心境障碍与焦虑障碍治疗协作组(Canadian Network for Mood and Anxiety Treatments,CANMAT)曾于2005年发布了第1版双相障碍管理指南,并分别于2007、2009和2013年对该指南进行了更新,其中最近的2次更新是与国际双相障碍学会(International Society for Bipolar Disorders,ISBD)合作完成。2018版CANMAT/ISBD双相障碍治疗指南(以下简称指南)反映了自2005年首版指南发表以来本领域取得的重大进展,包括疾病诊断与疾病管理的更新以及药物治疗与心理治疗的近期研究进展。这些前沿进展中综合考虑了循证证据的级别,并基于治疗疗效、临床实践经验、安全性、耐受性和药物导致的转相风险等,对一线、二线及三线治疗方案进行了简明而清晰的推荐。本指南中新增内容涵盖了双相Ⅰ型障碍(BD-Ⅰ)的躁狂发作急性期、抑郁发作急性期和双相障碍维持期的一线及二线治疗推荐等级划分。这种对治疗推荐等级的划分综合考虑了治疗方法对双相障碍不同时相的影响,将进一步帮助临床医生做出基于循证证据的治疗决策。锂盐、喹硫平、双丙戊酸盐、阿塞那平、阿立哌唑、帕利哌酮、利培酮和卡利拉嗪单药或联合使用被推荐为躁狂发作急性期的一线治疗选择。BD-Ⅰ抑郁期的一线治疗选择包括喹硫平、鲁拉西酮、锂盐、拉莫三嗪单药,鲁拉西酮联合锂盐或双丙戊酸盐或拉莫三嗪辅助治疗。尽管急性期治疗有效的药物通常应继续用于BD-Ⅰ的维持期治疗,但也存在一些特殊情况(例如抗抑郁药)。现有数据表明,锂盐、喹硫平、双丙戊酸盐、拉莫三嗪、阿塞那平和阿立哌唑单药或联合治疗应被视为维持治疗的初始或更换治疗方案时的一线选择。除了探讨BD-Ⅰ的相关问题外,本指南中还对双相Ⅱ型障碍(BD-Ⅱ)的临床管理进行了系统回顾并给予治疗推荐,同时针对特殊人群也有相关推荐,如处于各个生殖周期的女性、儿童、青少年和老年人。此外,本指南中还讨论了特定精神疾病及共病(如物质滥用、焦虑障碍和代谢性疾病)的影响。最后,本指南中概述了安全性和药物监测的相关问题。CANMAT/ISBD工作组希望本指南能够成为全球临床医生的实用工具。Lakshmi N Yatham Sidney H Kennedy Sagar V Parikh Ayal Sehaffer David J Bond Benicio N Frey Verinder Sharma Benjamin I Goldstein Soham Rej Serge Beaulieu Martin Alda Glenda MaeQueen Roumen V Milev Arun Ravindran Claire O'Donovan Diane Mclntosh Raymond W Lam Gustavo Vazquez Flavio Kapczinski Roger S Melntyre Jan Kozicky Shigenobu Kanba Beny Lafer Trisha Suppes Joseph R Calabrese Eduard Vieta Gin Malhi Robert M Post Michael Berk 胡晨(译) 王刚(译) 2019中华精神科杂志2019,52,1:25
4Significance of hepatitis virus infection in the oncogenicinitiation of hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus(HBV) and/or hepatitis C virus(HCV) is a major risk factor in the development of the HCC, independently from excessive alcohol abuse and metabolic disease. Since the biology of HBV and HCV is different, their oncogenic effect may go through different mechanisms, direct and/or indirect. Viral hepatitis infection is associated with cellular inflammation, oxidative stress, DNA damage, that may lead to subsequent hepatic injuries such as chronic hepatitis, fibrosis, cirrhosis, and finally HCC. Direct oncogenic properties of these viruses are related with their genotypic characteristics and the ability of viral proteins to interact with host proteins, thus altering the molecular pathways balance of the cells. In addition, the integration of HBV DNA, especially the gene S and X, in a particular site of the host genome can disrupt chromosomal stability and may activate various oncogenic mechanisms, including those in hematopoietic cells. Recently, several studies also had demonstrated that viral hepatitis could trigger the population of hepatic cancer stem cells. This review summarize available pre-clinical and clinical data in literature regarding oncogenic properties of HBV and HCV in the early initiation of HCC.Caecilia HC Sukowati Korri E El-Khobar Susan I Ie Beatrice Anfuso David H Muljono Claudio Tiribelli 2016World Journal of Gastroenterology2016,22,4:18
5Relationship of functional gastrointestinal disorders and psychiatric disorders: Implications for treatment显示文摘这篇文章重游在象急躁的肠症候群( IBS )那样的精神病理学和功能的胃肠的混乱之间的连接,讨论抗抑郁剂的合理使用以及非药理学来临到 IBS 的管理,并且从知识的现在的状态基于一个学科交差的观点为 IBS 的处理建议指南。精神病学的混乱上的相关出版文学,特别躯体化混乱在 IBS 的上下文,并且为管理的文学提供方向被考察,并且新方向在文学从调查结果被提供。IBS 是有为它的临床的演讲负责的各种各样的潜在的机制的异构的症候群。IBS 与在另外的机关系统的精神病学的问题, unexplained 症状,和功能的症候群典型地是复杂的。没有表明的原因,大多数 IBS 病人有多重抱怨,并且这些症状能包含除肠以外的系统,例如骨头和关节(fibromyalgia,颞下颌关节症候群) ,心(非心脏的胸痛) ,脉管(绝经后的症候群) ,并且大脑(焦虑,消沉) 。大多数 IBS 病人没有精神病学的病伴随他们的 somatoform (当医药混乱不在时的物理症状) 的精神分析形式(当精神病学的混乱不在时的心理抱怨) 的本身,而是一个范围症状抱怨。作为精神病学的病人把 IBS 病人标记不是正确的(除了有真躯体化的那些更困难的病人混乱) 。治疗的一个模式是不大可能的普遍有效或解决大多数症状。心理疗法或认知行为的治疗的技术能允许 IBS 病人与他们的病更乐意地处理。特定的事件压抑或焦虑混乱能为那些条件作为适当被管理。设计改进焦虑或消沉的药不为在 IBS 的精神病学的抱怨是一致地有用的,因为听起来类似于在精神病学的混乱看见的那些的精神分析形式症状不能与 IBS 在病人有一样的意义。Carol S North Barry A Hong David H Alpers 2007World Journal of Gastroenterology2007,13,14:17
6Current and future pharmacological therapies for managing cirrhosis and its complications显示文摘Due to the restrictions of liver transplantation,complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis.This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications,together with discussion of current controversies and potential future directions.PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety,efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis.Non-selective betablockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices,but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation.Recent observational studies suggest protective,haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation.The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy;recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis.Diuretics remain the mainstay of uncomplicated ascites treatment,and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites.Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications.Despite initial hepatotoxicity concerns,safety of statin administration has been demonstrated in compensated cirrhosis.Furthermore,statins are suggested to have protective effects upon fibrosis progression,decompensation and mortality.Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting.Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis,and may impede hepatic fibrogenesis and decompensation.Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management,nutritional optimisation and patient education.David Kockerling Rooshi Nathwani Roberta Forlano Pinelopi Manousou Benjamin H Mullish Ameet Dhar 2019World Journal of Gastroenterology2019,25,8:16
7Diagnostic accuracy of endoscopic ultrasound in pancreatic neuroendocrine tumors: A systematic review and meta analysis显示文摘AIM: To detect pancreatic neuroendocrine tumors (PNETs) has been varied. This study is undertaken to evaluate the accuracy of endoscopic ultrasound (EUS) in detecting PNETs.METHODS: Only EUS studies confirmed by surgery or appropriate follow-up were selected. Articles were searched in Medline, Ovid journals, Medline nonindexed citations, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Pooling was conducted by both fixed and random effects model). RESULTS: Initial search identified 2610 reference articles, of these 140 relevant articles were selected and reviewed. Data was extracted from 13 studies (n = 456) which met the inclusion criteria. Pooled sensitivity of EUS in detecting a PNETs was 87.2% (95%CI: 82.2-91.2). EUS had a pooled specificity of 98.0% (95%CI: 94.3-99.6). The positive likelihood ratio of EUS was 11.1 (95%CI: 5.34-22.8) and negative likelihood ratio was 0.17 (95%CI: 0.13-0.24). The diagnostic odds ratio, the odds of having anatomic PNETs in positive as compared to negative EUS studies was 94.7 (95%CI: 37.9-236.1). Begg-Mazumdar bias indicator for publication bias gave a Kendall's tau value of 0.31 (P = 0.16), indication no publication bias. The P for χ2 heterogeneity for all the pooled accuracy estimates was > 0.10. CONCLUSION: EUS has excellent sensitivity and specificity to detect PNETs. EUS should be strongly considered for evaluation of PNETs.Srinivas R Puli Nikhil Kalva Matthew L Bechtold Smitha R Pamulaparthy Micheal D Cashman Norman C Estes Richard H Pearl Fritz-Henry Volmar Sonu Dillon Michael F Shekleton David Forcione 2013World Journal of Gastroenterology2013,19,23:14
8香港大学学术库——机构知识库的应用扩展显示文摘香港大学学术库是香港大学的机构知识库,是响应大学知识交流政策而建立的知识管理系统。凭借丰富的数据来源以及合理的设计机制,学术库已成为颇具影响力的香港大学人才和科研成果的展示平台,成为校内外学术交流的中心,为学术评估和声誉管理提供了基础。Liu Eliot Z H Palmer David T 2015大学图书馆学报2015,33,4:14
9Cirrhotic ascites review: Pathophysiology, diagnosis and management显示文摘Ascites is a pathologic accumulation of peritoneal fluidcommonly observed in decompensated cirrhotic states. Its causes are multi-factorial, but principally involve significant volume and hormonal dysregulation in the setting of portal hypertension. The diagnosis of ascites is considered in cirrhotic patients given a constellation of clinical and laboratory findings, and ultimately confirmed, with insight into etiology, by imaging and paracentesis procedures. Treatment for ascites is multimodal including dietary sodium restriction, pharmacologic therapies, diagnostic and therapeutic paracentesis, and in certain cases transjugular intra-hepatic portosystemic shunt. Ascites is associated with numerous complications including spontaneous bacterial peritonitis, hepato-hydrothorax and hepatorenal syndrome. Given the complex nature of ascites and associatedcomplications, it is not surprising that it heralds increased morbidity and mortality in cirrhotic patients and increased cost-utilization upon the health-care system. This review will detail the pathophysiology of cirrhotic ascites, common complications derived from it, and pertinent treatment modalities.Christopher M Moore David H Van Thiel 2013World Journal of Hepatology2013,5,5:13
10Use of blood-based biomarkers for early diagnosis and surveillance of colorectal cancer显示文摘Early screening for colorectal cancer(CRC) holds the key to combat and control the increasing global burden of CRC morbidity and mortality. However, the current available screening modalities are severely inadequate because of their high cost and cumbersome preparatory procedures that ultimately lead to a low participation rate. People simply do not like to have colonoscopies. It would be ideal, therefore, to develop an alternative modality based on blood biomarkers as the first line screening test. This will allow for the differentiation of the general population from high risk individuals. Colonoscopy would then become the secondary test, to further screen the high risk segment of the population. This will encourage participation and therefore help to reach the goal of early detection and thereby reduce the anticipated increasing global CRC incidence rate. A blood-based screening test is anappealing alternative as it is non-invasive and poses minimal risk to patients. It is easy to perform, can be repeated at shorter intervals, and therefore would likely lead to a much higher participation rate. This review surveys various blood-based test strategies currently under investigation, discusses the potency of what is available, and assesses how new technology may contribute to future test design.Ganepola AP Ganepola Joel Nizin John R Rutledge David H Chang 2014World Journal of Gastrointestinal Oncology2014,6,4:11
11多肽药物研究进展显示文摘人体内存在各种各样的天然多肽,它们参与调控各种生理功能,在临床应用上具有非常重要的开发价值。目前全球药物市场上有60~70个多肽药物,更多的多肽药物处在各级临床试验、临床前试验和实验室研究阶段。很多多肽药物以G蛋白偶联受体为靶点。传统的化学合成也仍然是开发多肽药物最主要的手段。然而,我们在多肽药物开发方面仍面临各种挑战,不仅要解决传统问题如不稳定,易降解,难穿越细胞膜,而且也要进一步降低生产成本,完善大批量生产工艺技术。尤其是多肽药物的口服生物利用度问题,一直是我们面临的最大的挑战和决定市场的关键因素。随着在现代技术及其它方面不断取得进展,多肽药物将具有更加广阔的前景。在新一代受体靶向药物研究中,多肽更被作为一种有效的药物载体,通过细胞表面受体将药物传递到特定细胞,达到提高特异性,减少副作用的目的。孙立春 COY David H 2014上海医药2014,35,5:11
12Haplotype of prostaglandin synthase 2/cyclooxygenase 2 is involved in the susceptibility to inflammatory bowel disease显示文摘AIM: Prostaglandin G/H synthase 2 (PTGS2 or COX2) is one of the key factors in the cellular response to inflammation.PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel diseases (IBD). In IBD patients, non-steroidal anti-inflammatory drugs, which have been shown to reduce both the production and activity of PTGS2, may activate IBD and aggravate the symptoms.We aimed at examining genetic variants of PTGS2 that may be risk factors for IBD.METHODS: We genotyped 291 individuals diagnosed with IBD and 367 controls from the Dutch population for the five most frequent polymorphisms of the PTGS2 gene.Clinical data were collected on all patients. DNA was extracted via normal laboratory methods. Genotyping was carried out using multiplex PCR followed by the Invader Assay and the 5' exonuclease assay (TaqMan). New polymorphism screening was performed by pre-screening with denaturing high-performance liquid chromatography,followed by fluorescent sequencing.RESULTS: Allele 5209G was weakly associated with Crohn's disease (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.03-2.57), and allele 8473T with ulcerative colitis (OR 1.50, 95%CI 1.00-2.27). The haplotype including both alleles showed a strong association with IBD (OR 13.15, 95%CI 3.17-116.15). This haplotype, while rare (-0.3%) in the general population, is found more frequently in patients (3.5%).CONCLUSION: Our data suggest that this haplotype of PTGS2 contributes to the susceptibility of IBD.David G Cox J Bart A Crusius Petra HM Peeters H Bas Bueno-de-Mesquita A Salvador Pe(n|~)a Federico Canzian 2005World Journal of Gastroenterology2005,11,38:10
13Significant association between ABO blood group and pancreatic cancer显示文摘AIM:To evaluate whether the ABO blood group is related to pancreatic cancer risk in the general population of the United States.METHODS:Using the University of Pittsburgh's clinicalpancreatic cancer registry,the blood donor database from our local blood bank (Central Blood Bank),and the blood product recipient database from the regional transfusion service (Centralized Transfusion Service) in Pittsburgh,Pennsylvania,we identified 274 pancreatic cancer patients with previously determined serological ABO blood group information.The ABO blood group frequency was compared between these patients and 708842 individual,community-based blood donors who had made donations to Pittsburgh's Central Blood Bank between 1979 and 2009.RESULTS:The frequency of blood group A was statistically significantly higher amongst pancreatic cancer patients compared to its frequency amongst the regional blood donors [47.63% vs 39.10%,odds ratio (OR)=1.43,P=0.004].Conversely,the frequency of blood group O was significantly lower amongst pancreatic cancer patients relative to the community blood donors (32.12% vs 43.99%,OR=0.60,P=0.00007).There were limited blood group B (n=38) and AB (n=17) pancreatic cancer patients;the overall P trend value comparing patient to donor blood groups was 0.001.CONCLUSION:The ABO blood group is associated with pancreatic cancer risk.Future studies should examine the mechanism linking pancreatic cancer risk to ABO blood group.Julia B Greer Mark H Yazer Jay S Raval M Michael Barmada Randall E Brand David C Whitcomb 2010World Journal of Gastroenterology2010,16,44:10
14Novel blood-based microRNA biomarker panel for early diagnosis of pancreatic cancer显示文摘AIM:To develop a panel of blood-based diagnostic biomarkers consisting of circulating microRNAs for the detection of pancreatic cancer at an early stage.METHODS:Blood-based circulating microRNAs were profiled by high throughput screening using microarray analysis,comparing differential expression between early stage pancreatic cancer patients(n = 8) and healthy controls(n = 11).A panel of candidate microRNAs was generated based on the microarray signature profiling,including unsupervised clustering and statistical analysis of differential expression levels,and findings from the published literature.The selected candidate microRNAs were then confirmed using TaqMan real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR) to further narrow down to a three-microRNA diagnostic panel.The three-microRNA diagnostic panel was validated with independent experimental proce-dures and instrumentation of RT-qPCR at an independent venue with a new cohort of cancer patients(n = 11),healthy controls(n = 11),and a group of high risk controls(n = 11).Receiver operating characteristic curve analysis was performed to assess the diagnostic capability of the three-microRNA panel.RESULTS:In the initial high throughput screening,1220 known human microRNAs were screened for differential expression in pancreatic cancer patients versus controls.A subset of 42 microRNAs was then generated based on this data analysis and current published literature.Eight microRNAs were selected from the list of 42 targets for confirmation study,and three-microRNAs,miR-642b,miR-885-5p,and miR-22,were confirmed to show consistent expression between microarray and RT-qPCR.These three microRNAs were then validated and evaluated as a diagnostic panel with a new cohort of patients and controls and found to yield high sensitivity(91%) and specificity(91%) with an area under the curve of 0.97(P < 0.001).Compared to the CA19-9 marker at 73%,the three-microRNA panel has higher sensitivity although CA19-9 has higher specificity of 100%.CONCLUSION:The identified panel of three microRNA biomarkers can potentially be used as a diagnostic tool for early stage pancreatic cancer.Ganepola AP Ganepola John R Rutledge Paritosh Suman Anusak Yiengpruksawan David H Chang 2014World Journal of Gastrointestinal Oncology2014,6,1:9
15Risk factors for colonoscopic perforation: A population-based study of 80118 cases显示文摘AIM: To assess the incidence and risk factors associated with colonic perforation due to colonoscopy. METHODS: This was a retrospective cross-sectional study. Patients were retrospectively eligible for inclusion if they were 18 years and older and had an inpatient or outpatient colonoscopy procedure code in any facility within the Geisinger Health System during the period from January 1, 2002 to August 25, 2010. Data are presented as median and inter-quartile range, for continuous variables, and as frequency and percentage for categorical variables. Baseline comparisons across those with and without a perforation were made using the two-sample t -test and Pearson's χ2 test, as appropriate.RESULTS: A total of 50 perforations were diagnosed out of 80118 colonoscopies, which corresponded to an incidence of 0.06% (95%CI: 0.05-0.08) or a rate of 6.2 per 10000 colonoscopies. All possible risk factors associated with colonic perforation with a P -value < 0.1 were checked for inclusion in a multivariable logbinomial regression model predicting 7-d colonic perforation. The final model resulted in the following risk factors which were significantly associated with risk of colonic perforation: age, gender, body mass index, albumin level, intensive care unit (ICU) patients, inpatient setting, and abdominal pain and Crohn's disease as indications for colonoscopy. CONCLUSION: The cumulative 7 d incidence of colonic perforation in this cohort was 0.06%. Advanced age and female gender were significantly more likely to have perforation. Increasing albumin and BMI resulted in decreased risk of colonic perforation. Having a colonoscopy indication of abdominal pain or Crohn's disease resulted in a higher risk of colonic perforation. Colonoscopies performed in inpatients and particularly the ICU setting had substantially greater odds of perforation. Biopsy and polypectomy did not increase the risk of perforation and only three perforations occurred with screening colonoscopy.Uzair Hamdani Raza Naeem Fyeza Haider Pardeep Bansal Michael Komar David L Diehl H Lester Kirchner 2013World Journal of Gastroenterology2013,19,23:9
16interrelationships between ghrelin, insulin and glucose homeostasis: physiological relevance显示文摘Ghrelin is a 28 amino acid peptide mainly derived from the oxyntic gland of the stomach. Both acylated(AG) and unacylated(UAG) forms of ghrelin are found in the circulation. Initially, AG was considered as the only bioactive form of ghrelin. However, recent advances indicate that both AG and UAG exert distinct and common effects in organisms. Soon after its discovery, ghrelin was shown to promote appetite and adiposity in animal and human models. In response to these anabolic effects, an impressive number of elements have suggested the influence of ghrelin on the regulation of metabolic functions and the development of obesityrelated disorders. However, due to the complexity ofits biochemical nature and the physiological processes it governs, some of the effects of ghrelin are still debated in the literature. Evidence suggests that ghrelin influences glucose homeostasis through the modulation of insulin secretion and insulin receptor signaling. On the other hand, insulin was also shown to influence circulating levels of ghrelin. Here, we review the relationship between ghrelin and insulin and we describe the impact of this interaction on the modulation of glucose homeostasis.FranCois Chabot Alexandre Caron Mathieu Laplante David H St-Pierre 2014World Journal of Diabetes2014,5,3:9
17具有低动脉粥样硬化风险特征的专业耐力运动员的亚临床冠状动脉疾病发病率显示文摘研究表明,具有冠状动脉疾病(coronary artery disease,CAD)危险因素的中老年(健将)运动员比久坐个体冠状动脉钙化(coronary artery calcium,CAC)评分更高。尚没有研究评估具有低动脉粥样硬化风险特征的专业运动员的CAD患病率。刘莉 叶鹏 Merghani A Maestrini V Rosmini S Cox AT Dhutia H Bastiaenen R David S Yeo TJ Narain R Malhotra A Papadakis M Wilson MG Tome M AlFakih K Moon JC Sharma S 2017中华高血压杂志2017,25,6:8
18Per-oral endoscopic myotomy for achalasia: An American perspective显示文摘Achalasia is an uncommon esophageal motility disorder characterized by the selective loss of enteric neurons leading to absence of peristalsis and impaired relaxation of the lower esophageal sphincter.Per-oral endoscopic myotomy(POEM) is a novel modality for the treatment of achalasia performed by gastroenterologists and surgeons.It represents a natural orifice transluminal endoscopic surgery(NOTES) approach to Heller myotomy.POEM has the minimal invasiveness of an endoscopic procedure that can duplicate results of the surgical Heller myotomy.POEM is conceptually similar to a surgical myotomy without the inherent external incisions and post-operative care associated with surgery.Initial high success and low complications rates promise a great future for this technique.In fact,POEM has been successfully performed on patients with end-stage achalasia as an initial treatment reserving esophagectomy for those without good response.The volume of POEMs performed worldwide has grown exponentially.In fact,surgeons who have performed Heller myotomy have embraced POEM as the preferred intervention for achalasia.However,the niche of POEM remains to be defined and long term results are awaited.We describe our experience with POEM having performed the first POEM outside of Japan in 2009,the evolution of our technique,and give our perspective on its future.David Friedel Rani Modayil Shahzad Iqbal James H Grendell Stavros N Stavropoulos 2013World Journal of Gastrointestinal Endoscopy2013,5,9:8
19STAT5 programs a distinct subset of GM-CSF-producing T helper cells that is essential for autoimmune neuroinflammation显示文摘Wanqiang Sheng Fan Yang Yi Zhou Henry Yang Pey Yng Low David Michael Kemeny Patrick Tan Akira Moh Mark H Kaplan Yongliang Zhang Xin-Yuan Fu 2014Cell Research2014,24,12:7
20钠-葡萄糖共转运蛋白-2抑制剂或胰高血糖素样肽-1受体激动剂治疗成人2型糖尿病:临床实践指南显示文摘临床问题对于存在不同心血管风险及肾脏结局的2型糖尿病患者,在原有生活方式干预和/或其他降糖药物的基础上加用钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂的获益及风险是什么?现行做法几十年来,2型糖尿病的治疗决策都以控制血糖为主导。SGLT-2抑制剂和GLP-1受体激动剂在传统观念中常被用于二甲双胍治疗后血糖仍控制不佳的患者。目前这一现状已经发生了改变,这得益于多项临床研究结果。研究显示SGLT-2抑制剂和GLP-1受体激动剂拥有独立于药物降糖作用之外的对于动脉粥样硬化性心血管病(CVD)和慢性肾脏病(CKD)的获益。建议本指南阐述了针对不同风险分层的成人2型糖尿病患者使用SGLT-2抑制剂或GLP-1受体激动剂的建议。•伴有3种或更少的心血管风险因素且不存在CVD或CKD:不建议启动SGLT-2抑制剂或GLP-1受体激动剂治疗。(推荐等级:弱)•伴有3种以上心血管风险因素且不存在CVD或CKD:建议启动SGLT-2抑制剂治疗,不建议启动GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD或CKD:建议启动SGLT-2抑制剂治疗和GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD和CKD:建议启动SGLT-2抑制剂治疗(推荐等级:强)和GLP-1受体激动剂治疗。(推荐等级:弱)•对于那些想要进一步降低CVD和CKD结局风险的患者:推荐优先启用SGLT-2抑制剂治疗而非GLP-1受体激动剂治疗。(推荐等级:弱)这项指南是如何制订的一个由患者、临床医生和方法学家共同组成的国际小组提出了这些推荐意见。这些推荐意见基于可信度较高的指南的标准,并使用GRADE分级方法进行评估。该小组采用了息者个体化的观点。证据一项关于获益与风险的系统综述和网络meta分析(764项随机对照研究,包括421346例参与者)发现SGLT-2抑制剂和GLP-1受体激动剂可以降低总体死亡率、心肌梗死发生率、终末期肾病或肾衰竭的发生率(中等至高等质量的证据)。在不同的亚组中这些药物对卒中、因心力衰竭所致住院和其他主要不良事件有不同的影响。药物绝对获益的程度因患者个体风险的不同有很大的差异。(例如,对于接受了超过5年药物治疗的1000例患者,在最低风险人群中死亡人数减少了5人,在最高风险人群中死亡人数减少了48人)。一项关于预后的综述确认了14种风险预测模型,其中一种(RECODe)在证据总结中报告了大部分基线风险评估数据,小组利用该模型以支持风险分层的建议。考虑到患者的价值观及个体差异,指南推荐的支撑证据包括一项对已发表论文的系统综述、一项患者焦点小组研究、一项临床问题总结,以及一项指南调查。指南解读我们依据不同的CVD和CKD风险水平,综合考虑获益、风险和其他因素的平衡,以及每一个风险组别的实际问题,来对推荐意见进行分层。本指南强烈建议CVD和CKD患者使用SGLT-2抑制剂治疗,这说明专家组认为其具有显著的获益。而对于其他成人2型糖尿病患者,推荐等级较弱,这说明专家组想要在获益、风险及治疗花费上取得一个更好的平衡。临床医生通过该指南可以使用可靠的风险计算模型,如RECODe,来明确其患者的个体心血管和肾脏疾病风险。医患交互式总结临床证据和制订决策有助于患者知晓治疗选择,包括进行共同决策。2型糖尿病人群(全球患病率不断增长1-2)正面临着不断增加的心血管疾病、肾脏病和其他并发症的风险3。数十年来,2型糖尿病的管理始终以控制血糖及糖化血红蛋白(HbA1c)为治疗目标4-5,但是,最近的高质量随机对照研究已经对这种以血糖为中心的治疗模式发起了挑战。研究结果显示,强化血糖控制未必会降低大血管不良事件,它还可能带来不利影响监管机构现在要求新型糖尿病药物必须证明其具有心血管和肾脏获益才能获得批准。对两类新药--钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂(见框图1)的临床试验结果显示,在现有治疗方案(常规治疗)之上加用这些药物,对死亡、心肌梗死、卒中、心力衰竭和肾脏的结局(如进展为终末期肾病)都有获益8-12。Sheyu Li Per Olav Vandvik Lyubov Lytvyn Gordon H Guyatt Suetonia C Palmer Rene Rodriguez-Gutierrez Farid Foroutan Thomas Agoritsas Reed A C Siemieniuk Michael Walsh Lawrie Frere David J Tunnicliffe Evi V Nagler Veena Manja Bjφrn Olav Asvold Vivekanand Jha Mieke Vermandere Karim Gariani Qian Zhao Yan Ren Emma Jane Cartwright Patrick Gee Alan Wickes Linda Fems Robin Wright Ling Li Qiukui Hao Reem A Mustafa 郭鹤鸣(译) 2021英国医学杂志中文版2021,24,9:7
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