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| 1 | Stem cells for liver tissue repair:Current knowledge and perspectives显示文摘Stem cells from extra-or intrahepatic sources have been recently characterized and their usefulness for the generation of hepatocyte-like lineages has been demonstrated. Therefore, they are being increasingly considered for future applications in liver cell therapy. In that field, liver cell transplantation is currently regarded as a possible alternative to whole organ transplantation, while stem cells possess theoretical advantages on hepatocytes as they display higher in vitro culture performances and could be used in autologous transplant procedures. However, the current research on the hepatic fate of stem cells is still facing difficulties to demonstrate the acquisition of a full mature hepatocyte phenotype, both in vitro and in vivo. Furthermore, the lack of obvious demonstration of in vivo hepatocyte-like cell functionality remains associated to low repopulation rates obtained after current transplantation procedures. The present review focuses on the current knowledge of the stem cell potential for liver therapy. We discuss the characteristics of the principal cell candidates and the methods to demonstrate their hepatic potential in vitro and in vivo. We finally address the question of the future clinical applications of stem cells for liver tissue repair and the technical aspects that remain to be investigated. | Philippe A Lysy David Campard Fran oise Smets Mustapha Najimi Etienne M Sokal | 2008 | World Journal of Gastroenterology2008，14，6： | 22 |
| 2 | Methylation-dependent loss of RIP3 expression in cancer represses programmed necrosis in response to chemotherapeutics显示文摘交往受体的蛋白质 kinase-3 (RIP3 或 RIPK3 ) 是执行 “ 的细胞的机械的必要部分; programmed”或 “ regulated”坏死。这里,我们证明那规划坏死响应许多化学疗法的代理人被激活并且贡献导致化疗的房间死亡。然而,我们证明那 RIP3 表情经常在化学疗法的死亡期间由于它的 transcriptional 开始地点, MLKL 的这样 RIP3 依赖的激活和下游地规划的坏死附近的 genomic methylation 是在癌症房间的 silenced 大部分被镇压。不过,有 hypomethylating 代理人的治疗恢复 RIP3 表示,并且从而以一种 RIP3 依赖的方式把敏感提升到 chemotherapeutics。RIP3 表示在 85% 乳癌病人与正常织物相比在肿瘤被减少,建议那 RIP3 缺乏断然在肿瘤生长 / 发展期间被选择。因为 hypomethylating 代理人在病人是相当容忍得好的,我们建议病人们可以从收到 hypomethylating 代理人与常规 chemotherapeutics 在治疗以前导致 RIP3 表示有益于的那 RIP3 缺乏的癌症。 | Gi-Bang Koo Michael J Morgan Da-Gyum Lee Woo-Jung Kim Jung-Ho Yoon Ja Seung Koo Seung I1 Kim Soo Jung Kim Mi Kwon Son Soon Still Hong Jean M Mulcahy Levy Daniel A Pollyea Craig T Jordan Pearlly Yan David Frankhouser Deedra Nicolet Kati Maharry Guido Marcucci Kyeong Sook Choi Hyeseong Cho ndrew Thorbum You-Sun Kim | 2015 | Cell Research2015，25，6： | 20 |
| 3 | Safety of tirofiban and dual antiplatelet therapy in treating intracranial aneurysms显示文摘Background Endovascular treatment of intracranial aneurysms usually involves stent-assisted coiling(SAC)and flow diverters.Glycoprotein IIb/IIIa inhibitors such as tirofiban and dual antiplatelet therapy(DAPT)are required to prevent thromboembolic complications afterwards.We sought to determine the safety of tirofiban and DAPT in these cases.Methods We conducted a retrospective analysis of our database for patients with intracranial aneurysms who underwent SAC or flow diversion.The tirofiban-DAPT protocol used is described.Data regarding duration of infusion,placement of external ventricular devices(EVDs),complications,haemoglobin levels and platelet count before and 24 hours after antiplatelet therapy were collected and analysed.results One-hundred and forty-one patients with 148 aneurysms/procedures were included.110 aneurysms were treated acutely and 38 electively.Minor and major haemorrhagic events were recognised in 20%(30/148)aneurysms.Only 5(3.4%)intracerebral haemorrhages were symptomatic:3 cortical/SAH and 2 EVD-related.The average blood volume in symptomatic haemorrhages was 24.8 cc versus 5.42 cc in asymptomatic haemorrhages(p=0.002).The rate of EVD-related haemorrhages was 15.7%(19/121)and only 2(1.7%)were symptomatic.Most haemorrhagic events occurred in ruptured aneurysms(90.1%,p=0.01).No significant change in platelet count or haemoglobin levels before and 24 hours after administration of tirofiban and DAPT was documented.Concomitant administration of heparin did not increase haemorrhagic events.Conclusion The use of the GP IIb/IIIa inhibitors tirofiban and DAPT in this series was safe.Tirofiban and DAPT did not affect platelet count or haemoglobin levels and did not increase rate of symptomatic haemorrhages or thromboembolic complications. | Edgar A Samaniego Emilee Gibson Daichi Nakagawa Santiago Ortega-Gutierrez Mario Zanaty Jorge A Roa Pascal Jabbour David M Hasan | 2019 | Stroke & Vascular Neurology2019，4，1： | 17 |
| 4 | Validation of the Rockall scoring system for outcomes from non-variceal upper gastrointestinal bleeding in a Canadian setting显示文摘AIM: To validate the Rockall scoring system for predicting outcomes of rebleeding, and the need for a surgical procedure and death. METHODS: We used data extracted from the Registry of Upper Gastrointestinal Bleeding and Endoscopy including information of 1869 patients with non-variceal upper gastrointestinal bleeding treated in Canadian hospitals. Risk scores were calculated and used to classify patients based on outcomes. For each outcome, we used χ2 goodness-of-fit tests to assess the degree of calibration, and built receiver operating characteristic curves and calculated the area under the curve (AUC) to evaluate the discriminative ability of the scoring system. RESULTS: For rebleeding, the χ2 goodness-of-fit test indicated an acceptable fit for the model [χ2 (8) = 12.83, P = 0.12]. For surgical procedures [χ2 (8) = 5.3, P = 0.73] and death [χ2 (8) = 3.78, P = 0.88], the tests showed solid correspondence between observed proportions and predicted probabilities. The AUC was 0.59 (95% CI: 0.55-0.62) for the outcome of rebleeding and 0.60 (95% CI: 0.54-0.67) for surgical procedures, representing apoor discriminative ability of the scoring system. For the outcome of death, the AUC was 0.73 (95% CI: 0.69-0.78), indicating an acceptable discriminative ability. CONCLUSION: The Rockall scoring system provides an acceptable tool to predict death, but performs poorly for endpoints of rebleeding and surgical procedures. | Robert A Enns Yves M Gagnon Alan N Barkun David Armstrong Jamie C Gregor Richard N Fedorak RUGBE Investigators Group | 2006 | World Journal of Gastroenterology2006，12，48： | 14 |
| 5 | Stroke mechanisms and outcomes of isolated symptomatic basilar artery stenosis显示文摘background While diffuse atherosclerotic disease affecting the posterior circulation has been described extensively,the prevalence,natural history and angiographic characteristics of isolated symptomatic basilar artery stenosis(ISBAS)remain unknown.Methods We reviewed our prospective institutional database to identify patients with≥50% symptomatic basilar artery(BA)stenosis without significant atherosclerotic burden in the vertebral or posterior cerebral arteries.Stroke mechanism,collateral circulation,and degree and length of stenosis were analysed.The primary outcome was time from index event to new transient ischaemic attack(TIA),acute ischaemic stroke(AIS)or death.Other outcome variables included modified Rankin Scale(mRS)score on discharge and last follow-up.results Of 6369 patients with AIS/TIA,91(1.43%)had ISBAS.Seventy-three(80.2%)patients presented with AIS and 18(19.8%)with TIA.Twenty-nine(31.9%)were women and the median age was 66.8±13.6 years.The mean follow-up time was 2.7 years.The most common stroke mechanism was artery-to artery thromboembolism(45.2%),followed by perforator occlusion(28.7%)and flow-dependent/hypoperfusion(15.1%).The percentage of stenosis was lower in patients who had favourable outcome compared with those with mRS 3-6 on discharge(78.3±14.3 vs 86.9±14.5,p=0.007).Kaplan-Meier curves showed higher recurrence/death rates in patients with≥80% stenosis,mid-basilar location and poor collateral circulation.Approximately 13% of patients with ISBAS presented with complete BA occlusion.Conclusion ISBAS is an uncommon(1.43%)cause of TIA and AIS.Men in their 60s are mostly affected,and artery-to artery embolism is the most common stroke mechanism.Mid-basilar location,≥80% stenosis and poor collateral circulation are important factors associated with worse prognosis. | Edgar A Samaniego Amir Shaban Santiago Ortega-Gutierrez Jorge A Roa David M Hasan Colin Derdeyn Biyue Dai Harold Adams Enrique Leira | 2019 | Stroke & Vascular Neurology2019，4，4： | 10 |
| 6 | Constipation-predominant irritable bowel syndrome: A review of current and emerging drug therapies显示文摘Irritable bowel syndrome(IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS(IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators. | Khaled A Jadallah Susan M Kullab David S Sanders | 2014 | World Journal of Gastroenterology2014，20，27： | 9 |
| 7 | 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 |
| 8 | Role of microbial dysbiosis in the pathogenesis of esophageal mucosal disease:A paradigm shift from acid to bacteria?显示文摘Genomic sequencing,bioinformatics,and initial speciation(e.g.,relative abundance)of the commensal microbiome have revolutionized the way we think about the“human”body in health and disease.The interactions between the gut bacteria and the immune system of the host play a key role in the pathogenesis of gastrointestinal diseases,including those impacting the esophagus.Although relatively stable,there are a number of factors that may disrupt the delicate balance between the luminal esophageal microbiome(EM)and the host.These changes are thought to be a product of age,diet,antibiotic and other medication use,oral hygiene,smoking,and/or expression of antibiotic products(bacteriocins)by other flora.These effects may lead to persistent dysbiosis which in turn increases the risk of local inflammation,systemic inflammation,and ultimately disease progression.Research has suggested that the etiology of gastroesophageal reflux disease-related esophagitis includes a cytokine-mediated inflammatory component and is,therefore,not merely the result of esophageal mucosal exposure to corrosives(i.e.,acid).Emerging evidence also suggests that the EM plays a major role in the pathogenesis of disease by inciting an immunogenic response which ultimately propagates the inflammatory cascade.Here,we discuss the potential role for manipulating the EM as a therapeutic option for treating the root cause of various esophageal disease rather than just providing symptomatic relief(i.e.,acid suppression). | Steve M D'Souza Kevin Houston Lauren Keenan Byung Soo Yoo Parth J Parekh David A Johnson | 2021 | World Journal of Gastroenterology2021，27，18： | 8 |
| 9 | Efficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience显示文摘AIM To evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting.METHODS We performed a retrospective analysis of treatment outcomes among treatment-na?ve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent's Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate(TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemicalresponse, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus(HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA < 20 IU/m L. Secondary efficacy endpoints included rates of biochemical response, and HB e antigen(HBe Ag)/HB surface antigen loss and seroconversion over time.RESULTS Ninety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo(range 3-114). Mean age was 46(24-78) years, 64(70%) were male and 77(84%) were of Asian origin. 55(60%) patients were treatment-na?ve and 62 patients(67%) were HBe Ag-negative. Complete virological suppression was achieved by 45/65(71%) patients at 12 mo, 37/46(80%) at 24 mo and 25/28(89%) at 36 mo. Partial virological response(HBV DNA 20-2000 IU/m L) was achieved by 89/92(96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level(OR = 0.897, 95%CI: 0.833-0.967, P = 0.0046) and HBe Ag positive status(OR = 0.373, 95%CI: 0.183-0.762, P = 0.0069). There was no difference in response comparing treatment-na?ve and treatment-experienced patients. Three episodes of virological breakthrough occurred in the setting of noncompliance. Tenofovir therapy was well tolerated.CONCLUSION Tenofovir is an efficacious, safe and well-tolerated treatment in an Australian real-world tertiary care setting. Our data are similar to the reported experience from registration trials. | Grace C Lovett Tin Nguyen David M Iser Jacinta A Holmes Robert Chen Barbara Demediuk Gideon Shaw Sally J Bell Paul V Desmond Alexander J Thompson | 2017 | World Journal of Hepatology2017，9，1： | 7 |
| 10 | Regulation of epithelium-specific Ets-like factors ESE-1 and ESE-3 in airway epithelial cells: potential roles in airway inflammation显示文摘航线发炎是许多呼吸障碍的特点,例如气喘和膀胱的纤维变性。在发炎触发的航线基因表示的变化在这些疾病的致病起一个关键作用。基因连接研究建议 ESE-2 和 ESE-3,编码上皮特定的 Ets-domain-containing 抄写因素,是候选人气喘危险性基因。我们这里报导 et 家庭抄写因素 ESE-1 的另一个成员的表示,以及 ESE-3,起来在支气管的上皮的房间线由煽动性的 cytokines interleukin-1beta (IL-1beta ) 和肿瘤坏死 factor-alpha (TNF-alpha ) 调整了。有 IL-1beta 和 TNF-alpha 的这些房间的处理为 ESE-1 和 ESE-3 导致了信使 rna 表示的戏剧的增加。我们证明导致的表示被抄写因素 NF-kappaB 的激活调停。我们描绘了 ESE-1 和 ESE-3 倡导者并且识别了为导致 cytokine 的表达式被要求的 NF-kappaB 有约束力的序列。另外,我们也表明那 ESE-1 在上面调整 ESE-3 表示, down 由 cytokines 调整它的自己的正式就职。最后,我们在 Elf3 显示出那(对人的 ESE-1 相应) 猛烈老鼠,煽动性的 cytokine interleukin-6 (IL-6 ) 的表示是调整的 down。我们的调查结果建议 ESE-1 和 ESE-3 在航线发炎起一个重要作用。 | Jing Wu Rongqi Duan Huibi Cao Deborah Field Catherine M Newnham David R Koehler Noe Zamel Melanie A Pritchard Paul Hertzog Martin Post A Keith Tanswell Jim Hu | 2008 | Cell Research2008，18，6： | 6 |
| 11 | Quantitative analysis of ruminal methanogenic microbial populations in beef cattle divergent in phenotypic residual feed intake(RFI)offered contrasting diets显示文摘Background:Methane(CH_4) emissions in cattle are an undesirable end product of rumen methanogenic fermentative activity as they are associated not only with negative environmental impacts but also with reduced host feed efficiency.The aim of this study was to quantify total and specific rumen microbial methanogenic populations in beef cattle divergently selected for residual feed intake(RFI) while offered(i) a low energy high forage(HF) diet followed by(ii) a high energy low forage(LF) diet.Ruminal fluid was collected from 14 high(H)and 14 low(L) RFI animals across both dietary periods.Quantitative real time PCR(qRT-PCR) analysis was conducted to quantify the abundance of total and specific rumen methanogenic microbes.Spearman correlation analysis was used to investigate the association between the relative abundance of methanogens and animal performance,rumen fermentation variables and diet digestibility.Results:Abundance of methanogens,did not differ between RFI phenotypes.However,relative abundance of total and specific methanogen species was affected(P< 0.05) by diet type,with greater abundance observed while animals were offered the LF compared to the HF diet.Conclusions:These findings suggest that differences in abundance of specific rumen methanogen species may not contribute to variation in CH_4 emissions between efficient and inefficient animals,however dietary manipulation can influence the abundance of total and specific methanogen species. | Ciara A Carberry David A Kenny Alan K Kelly Sinead M Waters | 2014 | Journal of Animal Science and Biotechnology2014，5，4： | 6 |
| 12 | Three-dimensional perfused human in vitro model of nonalcoholic fatty liver disease显示文摘AIM To develop a human in vitro model of non-alcoholic fatty liver disease(NAFLD), utilising primary hepatocytes cultured in a three-dimensional(3D) perfused platform. METHODS Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids(FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds. RESULTS Hepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factorbinding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantlyreduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known antisteatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture medium.CONCLUSION The 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds. | Tomasz Kostrzewski Terri Cornforth Sophie A Snow Larissa Ouro-Gnao Cliff Rowe Emma M Large David J Hughes | 2017 | World Journal of Gastroenterology2017，23，2： | 6 |
| 13 | Laparoscopic sleeve gastrectomy:More than a restrictive bariatric surgery procedure?显示文摘Sleeve gastrectomy(SG) is a restrictive bariatric surgery technique that was first used as part of restrictive horizontal gastrectomy in the original Scopinaro type biliopancreatic diversion. Its good results as a single technique have led to a rise in its use, and it is currently the second most performed technique worldwide. SG achieves clearly better results than other restrictive techniques and is comparable in some aspects to the Roux-en-Y gastric bypass, the current gold standard in bariatric surgery. These benefits have been associated with different pathophysiologic mechanisms unrelated to weight loss such as increased gastric emptying and intestinal transit, and activation of hormonal mechanisms such as increased GLP-1 hormone and decreased ghrelin. The aim of this review was to highlight the salient aspects of SG regarding its historical evolution, pathophysiologic mechanisms, main results, clinical applications and perioperative complications. | David Benaiges Antonio Más-Lorenzo Albert Goday José M Ramon Juan J Chillarón Juan Pedro-Botet Juana A Flores-Le Roux | 2015 | World Journal of Gastroenterology2015，21，41： | 6 |
| 14 | 阿尔茨海默病患者的脑淀粉样血管病变显示文摘 | 田金洲 时晶 程龙 David M A Mann | 2003 | 中华老年医学杂志2003，22，11： | 6 |
| 15 | Protective role of PI3-kinase/Akt/eNOS signaling in mechanical stress through inhibition of p38 mitogenactivated protein kinase in mouse lung显示文摘 | Xin-qi PENG Mahendra DAMARLA Jarrett SKIRBALL Stephanie NONAS Xiao-ying WANG Eugenia J HAN Emile J HASAN Xuan CAO Adel BOUEIZ Rachel DAMICO Rubin M TUDER Alfred M SClUTO Dana R ANDERSON Joe GNGARCIA David A KASS Paul M HASSOUN Jun-tian ZHANG | 2010 | Acta Pharmacologica Sinica2010，31，2： | 6 |
| 16 | 针对患者利益的机器学习和人工智能研究:在透明性、可重复性、伦理和有效性等方面的20个关键问题显示文摘机器学习(ML)、人工智能(AI)和其他现代统计方法正为利用先前尚未开发且极速增长的数据资源提供新的机会,以期让患者获益。尽管目前正在进行许多有前景的研究,特别是在图像方面,但就文献整体而言还缺乏透明度、对可重复性清晰的阐述、对潜在伦理问题的探究,以及对有效性的明确验证。这些问题的存在有许多原因,其中最重要的一点(为此我们提供了初步解决方案)就是当前缺乏针对ML和AI的最佳实践指南。我们认为从事研究的跨学科团队和应用ML/AI影响健康的项目,将因解决有关透明度、可重复性、伦理和有效性(TREE)的一系列问题而受益。这里提出的20个关键问题为研究团队提供了一个研究设计、实施和报告框架;帮助编辑和同行评审专家评估文献的贡献;让患者、临床医生和政策制定者评估新发现可能会给患者带来的获益。 | Sebastian Vollmer Bilal A Mateen Gergo Bohner Franz J Kirdly Rayid Ghani Pall Jonsson Sarah Cumbers Adrian Jonas Katherine S L McAllister Puja Myles David Granger Mark Birse Richard Branson Karel G M Moons Gary S Collins John P A Chris Holmes Harry Hemingwayp 李峰(译) 徐磊(校) 赵邑(校) | 2020 | 英国医学杂志中文版2020，23，9： | 5 |
| 17 | Less common etiologies of exocrine pancreatic insufficiency显示文摘Exocrine pancreatic insufficiency(EPI), an important cause of maldigestion and malabsorption, results from primary pancreatic diseases or secondarily impaired exocrine pancreatic function. Besides cystic fibrosis and chronic pancreatitis, the most common etiologies of EPI, other causes of EPI include unresectable pancreatic cancer, metabolic diseases(diabetes); impaired hormonal stimulation of exocrine pancreatic secretion by cholecystokinin(CCK); celiac or inflammatory bowel disease(IBD) due to loss of intestinal brush border proteins; and gastrointestinal surgery(asynchrony between motor and secretory functions, impaired enteropancreatic feedback, and inadequate mixing of pancreatic secretions with food). This paper reviews such conditions that have less straightforward associations with EPI and examines the role of pancreatic enzyme replacement therapy(PERT). Relevant literature was identified by database searches. Most patients with inoperable pancreatic cancer develop EPI(66%-92%). EPI occurs in patients with type 1(26%-57%) or type 2 diabetes(20%-36%) and is typically mild to moderate; by definition, all patients with type 3 c(pancreatogenic) diabetes have EPI. EPI occurs in untreated celiac disease(4%-80%), but typically resolves on a gluten-free diet. EPI manifests in patients with IBD(14%-74%) and up to 100% of gastrointestinal surgery patients(47%-100%; dependent on surgical site). With the paucity of published studies on PERT use for these conditions, recommendations for or against PERT use remain ambiguous. The authors conclude that there is an urgent need to conduct robust clinical studies to understand the validity and nature of associations between EPI and medical conditions beyond those with proven mechanisms, and examine the potential role for PERT. | Vikesh K Singh Mark E Haupt David E Geller Jerry A Hall Pedro M Quintana Diez | 2017 | World Journal of Gastroenterology2017，23，39： | 5 |
| 18 | Effect of nitrogen fertilization on yield, N content, and nitrogen fixation of alfalfa and smooth bromegrass grown alone or in mixture in greenhouse pots显示文摘Planting grass and legume mixtures on improved grasslands has the potential advantage of realizing both higher yields and lower environmental pollution by optimizing the balance between applied N fertilizer and the natural process of legume biological nitrogen fixation. However, the optimal level of N fertilization for grass-legume mixtures, to obtain the highest yield, quality, and contribution of N2 fixation, varies with species. A greenhouse pot experiment was conducted to study the temporal dynamics of N2 fixation of alfalfa(Medicago sativa L.) grown alone and in mixture with smooth bromegrass(Bromus inermis Leyss.) in response to the addition of fertilizer N. Three levels of N(0, 75, and 150 kg ha–1) were examined using 15N-labeled urea to evaluate N2 fixation via the 15 N isotope dilution method. Treatments were designated N0(0.001 g per pot), N75(1.07 g per pot) and N150(2.14 g per pot). Alfalfa grown alone did not benefit from the addition of fertilizer N; dry matter was not significantly increased. In contrast, dry weight and N content of smooth bromegrass grown alone was increased significantly by N application. When grown as a mixture, smooth bromegrass biomass was increased significantly by N application, resulted in a decrease in alfalfa biomass. In addition, individual alfalfa plant dry weight(shoots+roots) was significantly lower in the mixture than when grown alone at all N levels. Smooth bromegrass shoot and root dry weight were significantly higher when grown with alfalfa than when grown alone, regardless of N application level. When grown alone, alfalfa's N2 fixation was reduced with N fertilization(R2=0.9376, P=0.0057). When grown in a mixture with smooth bromegrass, with 75 kg ha–1 of N fertilizer, the percentage of atmospheric N2 fixation contribution to total N in alfalfa(%Ndfa) had a maximum of 84.07 and 83.05% in the 2nd and 3rd harvests, respectively. Total 3-harvest %Ndfa was higher when alfalfa was grown in a mixture than when grown alone(shoots: |t|=3.39, P=0.0096; root: |t|=3.57, P=0.0073). We believe this was due to smooth bromegrass being better able to absorb available soil N(due to its fibrous root system), resulting inlower soil N availability and allowing alfalfa to develop an effective N2 fixing symbiosis prior to the 1st harvest. Once soil N levels were depleted, alfalfa was able to fix N2, resulting in the majority of its tissue N being derived from biological nitrogen fixation(BNF) in the 2nd and 3rd harvests. When grown in a mixture, with added N, alfalfa established an effective symbiosis earlier than when grown alone; in monoculture BNF did not contribute a significant portion of plant N in the N75 and N150 treatments, whereas in the mixture, BNF contributed 17.90 and 16.28% for these treatments respectively. Alfalfa has a higher BNF efficiency when grown in a mixture, initiating BNF earlier, and having higher N2 fixation due to less inhibition by soil-available N. For the greatest N-use-efficiency and sustainable production, grass-legume mixtures are recommended for improving grasslands, using a moderate amount of N fertilizer(75 kg N ha–1) to provide optimum benefits. | XIE Kai-yun LI Xiang-lin HE Feng ZHANG Ying-jun WAN Li-qiang David B Hannaway WANG Dong QIN Yan Gamal M A Fadul | 2015 | Journal of Integrative Agriculture2015，14，9： | 5 |
| 19 | Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation显示文摘BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis.In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1MCD)]after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 h.Subsequently,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13C-uniformly labeled glucose.For the in vivo part of the study,male C57BL/6J mice were randomly fed a control or 0.1MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk.Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes.This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PACCα/β(S79),SCD1,CPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQCRC2),tricarboxylic acid(TCA)cycle(MDH2,SUCLA2,and SUCLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13Cuniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TCA cycle.Finally,liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1MCD fed mice in a dose-dependent manner,showing normalization of glucose,G6P,F6P,UDP-glucose,and Rbl5P/Xyl5P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1,which in turn activate FAβ-oxidation and oxidative phosphorylation. | David Fernández-Ramos Fernando Lopitz-Otsoa Laura Delacruz-Villar Jon Bilbao Martina Pagano Laura Mosca Maider Bizkarguenaga Marina Serrano-Macia Mikel Azkargorta Marta Iruarrizaga-Lejarreta Jesús Sot Darya Tsvirkun Sebastiaan Martijn van Liempd Felix M Goni Cristina Alonso María Luz Martínez-Chantar Felix Elortza Liat Hayardeny Shelly C Lu JoséM Mato | 2020 | World Journal of Gastroenterology2020，26，34： | 5 |
| 20 | Fecal immunochemical test accuracy in average-risk colorectal cancer screening显示文摘AIM:To assess the fecal immunochemical test(FIT)accuracy for colorectal cancer(CRC)and advanced neoplasia(AN)detection in CRC screening.METHODS:We performed a multicentric,prospective,double blind study of diagnostic tests on asymptomatic average-risk individuals submitted to screening colonoscopy.Two stool samples were collected and the fecal hemoglobin concentration was determined in the first sample(FIT1)and the highest level of both samples(FITmax)using the OC-sensor.Areas under the curve(AUC)for CRC and AN were calculated.The best FIT1and FITmax cut-off values for CRC were determined.At this threshold,number needed to scope(NNS)to detect a CRC and an AN and the cost per lesion detected were calculated.RESULTS:About 779 individuals were included.An AN was found in 97(12.5%)individuals:a CRC in 5(0.6%)and an advanced adenoma(≥10 mm,villous histology or high grade dysplasia)in 92(11.9%)subjects.For CRC diagnosis,FIT1 AUC was 0.96(95%CI:0.95-0.98)and FITmax AUC was 0.95(95%CI:0.93-0.97).For AN,FIT1 and FITmax AUC were similar(0.72,95%CI:0.66-0.78 vs 0.73,95%CI:0.68-0.79,respectively,P=0.34).Depending on the number of determinations and the positivity threshold cut-off used sensitivity for AN detection ranged between 28%and 42%and specificity between 91%and 97%.At the best cut-off point for CRC detection(115 ng/mL),the NNS to detect a CRC were 10.2 and 15.8;and the cost per CRC was 1814€and 2985€on FIT1 and FITmax strategies respectively.At this threshold the sensitivity,NNS and cost per AN detected were 30%,1.76,and 306€,in FIT1 strategy,and 36%,2.26€and 426€,in FITmax strategy,respectively.CONCLUSION:Performing two tests does not improve diagnostic accuracy,but increases cost and NNS to detect a lesion. | Vicent Hernandez Joaquin Cubiella M Carmen Gonzalez-Mao Felipe Iglesias Concepción Rivera M Begoa Iglesias Lucía Cid Ines Castro Luisa de Castro Pablo Vega Jose Antonio Hermo Ramiro Macenlle Alfonso Martínez-Turnes David Martínez-Ares Pamela Estevez Estela Cid M Carmen Vidal Angeles López-Martínez Elisabeth Hijona Marta Herreros-Villanueva Luis Bujanda Jose Ignacio Rodriguez-Prada the COLONPREV study investigators | 2014 | World Journal of Gastroenterology2014，20，4： | 4 |
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