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| 1 | INT-767 improves histopathological features in a dietinduced ob/ob mouse model of biopsy-confirmed nonalcoholic steatohepatitis显示文摘AIM To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767 upon histological endpoints in a rodent model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis(NASH).METHODS The effects of INT-767 on histological features of NASH were assessed in two studies using Lep^(ob/ob)(ob/ob) NASH mice fed the AMLN diet(high fat with transfat, cholesterol and fructose). In a proof-of-conceptstudy, Lep^(ob/ob)(ob/ob) NASH mice were first dosed with INT-767(3 or 10 mg/kg for 8 wk). A second ob/ob NASH study compared INT-767(3 and 10 mg/kg) to obeticholic acid(OCA)(10 or 30 mg/kg; 16 wk). Primary histological endpoints included qualitative and quantitative assessments of NASH. Other metabolic and plasma endpoints were also assessed. A comparative assessment of INT-767 and OCA effects on drug distribution and hepatic gene expression was performed in C57 Bl/6 mice on standard chow. C57 Bl/6 mice were orally dosed with INT-767 or OCA(1-30 mg/kg) for 2 wk, and expression levels of candidate genes were assessed by RNA sequencing and tissue drug levels were measured by liquid chromatography tandem-mass spectrometry.RESULTS INT-767 dose-dependently(3 and 10 mg/kg, PO, QD, 8 wk) improved qualitative morphometric scores on steatohepatitis severity, inflammatory infiltrates and fibrosis stage. Quantitative morphometric analyses revealed that INT-767 reduced parenchymal collagen area, collagen fiber density, inflammation(assessed by Galectin-3 immunohistochemistry) and hepatocyte lipid droplet area following INT-767 treatment. In a comparative study(16 wk), the FXR agonists OCA(10 and 30 mg/kg) and INT-767(3 and 10 mg/kg) both improved NASH histopathology, with INT-767 exerting greater therapeutic potency and efficacy than OCA. Mechanistic studies suggest that both drugs accumulate similarly within the liver and ileum, however, the effects of INT-767 may be driven by enhanced hepatic, but not ileal, FXR function. CONCLUSION These findings confirm the potential utility of FXR and dual FXR/TGR5 activation as disease intervention strategies in NASH. | Jonathan D Roth Michael Feigh Sanne S Veidal Louise KD Fensholdt Kristoffer T Rigbolt Henrik H Hansen Li C Chen Mathieu Petitjean Weslyn Friley Niels Vrang Jacob Jelsing Mark Young | 2018 | World Journal of Gastroenterology2018,24,2: | 7 |
| 2 | Adenosquamous carcinoma of the pancreas: Molecular characterization of 23 patients along with a literature review显示文摘Adenosquamous carcinoma of the pancreas(ASCP)is a rare entity. Like adenocarcinoma of the pancreas,overall survival is poor. Characteristics of ASCP include central tumor necrosis, along with osteoclasts and hypercalcemia. Various theories exist as to why this histological subtype exists, as normal pancreas tissue has no benign squamous epithelium. Due to the rarity of this disease, limited molecular analysis has been performed, and those reports indicate unique molecular features of ASCP. In this paper, we characterize 23 patients diagnosed with ASCP through molecular profiling using immunohistochemistry staining, fluorescent in situ hybridization, chromogenic in situ hybridization, and gene sequencing, Additionally, we provide a comprehensive literature review of what is known to date of ASCP.Molecular characterization revealed overexpression in MRP1(80%), MGMT(79%), TOP2A(75), RRM1(42%),TOPO1(42%), PTEN(45%), CMET(40%), and C-KIT(10%) among others. One hundred percent of samples tested were positive for KRAS mutations. This analysis shows heretofore unsuspected leads to be considered for treatments of this rare type of exocrine pancreas cancer. Molecular profiling may be appropriate to provide maximum information regarding the patient's tumor. Further work should be pursued to better characterize this disease. | Erkut Borazanci Sherri Z Millis Ron Korn Haiyong Han Clifford J Whatcott Zoran Gatalica Michael T Barrett Derek Cridebring Daniel D Von Hoff | 2015 | World Journal of Gastrointestinal Oncology2015,7,9: | 6 |
| 3 | 一种房颤风险评分系统的建立(Framingham心脏研究):基于社区的队列研究显示文摘背景房颤导致了发病率和病死率的显著上升。本研究旨在建立一种预测个体罹患房颤绝对风险的风险评分系统,并提供研究人员评价新危险因素的流程。方法作者评估了Framingham心脏研究中于1968年6月至1987年9月间进行了8044次检测的4764例参与者(55%为女性,年龄45~95岁)。此后,参与者被随访至房颤首发,随访期最长达10年。多变量Coxi回归确认出1(1年内罹患房颤的临床危险因素。次级分析纳入了常规超声心动图检测指标(5152例4参与者,7156次检测)对房颤风险进行再分层评估,并评价超声检测指标能否提高风险预测能力。结果4764例参与者中的457例4(10%)罹患房颤。年龄、性别、体重指数、收缩压、降压治疗、PR间期、有临床意义的心脏杂音及心力衰竭与房颤相关,并被纳入了风险评分模型(除体重指数P=0.08外,其余均为P〈0.05),模型的C统计量为0.78(95%CI0.76~0.80)。10年房颤风险随年龄变化:年龄〈65岁的人群中53例(1%)风险高于15%,而〉65岁的人群中为783例(27%)。为提高预测能力而纳入超声检测指标仅使模型C统计量略微增高,由0.78(95%C10.75~0.80)增至0.79(95%CI0.77~0.82:P=0.005)。超声心动图检测指标并不能改善风险再分层评估(P=0.18)。结论基于社区医疗中易得的临床因素建立的风险评分系统,有助于确认社区个体罹患房颤的风险,评估技术或标志物能否改善风险预测,以及针对高危个体采取预防措施。 | Renate B Schnabel Lisa M Sullivan Daniel Levy Michael J Pencina Joseph M Massaro Ralph B D'Agostino Sr Christopher Newton-Cheh Jennifer F Yamamoto Jared W Magnani Thomas M Tadros William B Kannel Thomas J Wang Patrick T Ellinor Philip A Wolf Ramachanclran S Vasan Emelia J Benjamin 黄刚(译) | 2009 | 世界临床医学2009,,9: | 2 |
| 4 | Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab: the Mayo Clinic experience显示文摘 | Phil A Hart Mark D Topazian Thomas E Witzig Jonathan E Clain Ferga C Gleeson Robin R Klebig Michael J Levy Randall K Pearson Bret T Petersen Thomas C Smyrk Aravind Sugumar Naoki Takahashi Santhi S Vege Suresh T Chari | 2013 | Gut2013,,11: | 2 |
| 5 | 抑郁症的非药物治疗:系统性综述与证据图显示文摘背景抑郁症非药物治疗的疗效比较目前仍然不清楚。方法我们对一些系统性综述作了概述,回顾了随机对照试验(RCT),比较抑郁症非药物治疗的有效性和认知行为治疗(CBT)。对多个电子数据库在2016年2月之前发表的所有文献进行了检索,不限制语言。成对的评阅人进行资料纳入、数据提炼并评估偏倚的风险。在适用的时候进行了荟萃分析。结果我们收录了367项RCT,纳入了约2000名患者,进行了11种治疗,导出17项独立的头对头比较。通过标准化的量表评估,发现CBT、自然疗法、行为干预与躯体活动干预可以降低抑郁的严重程度。然而,这些非药物干预的相对疗效仍然缺乏。这些干预对临床缓解和复发的效果不清楚。CBT的发生率比抗抑郁药物更低。局限性由于证据缺乏一致性、证据不清或偏倚风险高,导致证据的质量只是低到中等,限制了我们研究结果的可信度。结论抑郁症的非药物治疗能减少抑郁症状,在轻度到重度抑郁症患者中,应当合并抗抑郁药物治疗,一同进行。对于非药物治疗的选择,应当根据患者的价值观、偏好、临床和社会因素来与患者共同作出决定。 | Wigdan H Farah Mouaz Alsawas Maria Mainou Fares Alahdab Magdoleen H Farah Ahmed T Ahmed Essa A Mohamed Jehad Almasri Michael R Gionfriddo Ana Castaneda-Guarderas Khaled Mohammed Zhen Wang Noor Asi Craig N Sawchuk Mark D Williams Larry J Prokop M Hassan Murad Annie LeBlanc | 2017 | 英国医学杂志中文版2017,20,11: | 2 |
| 6 | Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab: the Mayo Clinic experience显示文摘 | Phil A Hart Mark D Topazian Thomas E Witzig Jonathan E Clain Ferga C Gleeson Robin R Klebig Michael J Levy Randall K Pearson Bret T Petersen Thomas C Smyrk Aravind Sugumar Naoki Takahashi Santhi S Vege Suresh T Chari | 2013 | Gut2013,,11: | 2 |
| 7 | Percutaneous transluminal angioplasty balloons for endoscopic ultrasound-guided pancreatic duct interventions显示文摘BACKGROUND Endoscopic ultrasound(EUS)-guided main pancreatic duct(PD)access may be used when conventional endoscopic retrograde cholangiopancreatography(ERCP)techniques fail.The use of a percutaneous transluminal angioplasty balloon(PTAB),originally developed for vascular interventions,can be used to facilitate transmural(e.g.,transgastric)PD access and to dilate high-grade pancreatic strictures.AIM To describe the technique,efficacy,and safety of PTABs for EUS-guided PD interventions.METHODS Patients who underwent EUS with use of a PTAB from March 2011 to August 2021 were retrospectively identified from a tertiary care medical center supply database.PTABs included 3-4 French angioplasty catheters with 3-4 mm balloons designed to use over a 0.018-inch guidewire.The primary outcome was technical success.Secondary outcomes included incidence of adverse events(AEs)and need for early reintervention.RESULTS A total of 23 patients were identified(48%female,mean age 55.8 years).Chronic pancreatitis was the underlying etiology in 13(56.5%)patients,surgically altered anatomy(SAA)with stricture in 7(30.4%),and SAA with post-operative leak in 3(13.0%).Technical success was achieved in 20(87%)cases.Overall AE rate was 26%(n=6).All AEs were mild and included 1 pancreatic duct leak,2 cases of post-procedure pancreatitis,and 3 admissions for post-procedural pain.No patients required early re-intervention.CONCLUSION EUS-guided use of PTABs for PD access and/or stricture management is feasible with an acceptable safety profile and can be considered in patients when conventional ERCP cannulation fails. | Jad P AbiMansour Barham K Abu Dayyeh Michael J Levy Andrew C Storm John A Martin Bret T Petersen Ryan J Law Mark D Topazian Vinay Chandrasekhara | 2022 | World Journal of Gastrointestinal Endoscopy2022,14,8: | 2 |
| 8 | Effects of Ionic Strength, Temperature, and pH on Degradation of Selected Antibiotics显示文摘 | Loftin Keith A Adams Craig D Meyer Michael T Surampalli Rao | 2008 | Journal of Environmental Quality2008,,2: | 2 |
| 9 | End-stage renal disease is associated with increased post endoscopic retrograde cholangiopancreatography adverse events in hospitalized patients显示文摘AIM To determine if end-stage renal disease (ESRD) is a risk factor for post endoscopic retrograde cholangio-pancreatography (ERCP) adverse events (AEs). METHODS We performed a retrospective cohort study using the Nationwide Inpatient Sample (NIS) 2011-2013. We identified adult patients who underwent ERCP using the International Classification of Diseases 9^(th) Revision (ICD-9-CM). Included patients were divided into three groups: ESRD, chronic kidney disease (CKD), and control. The primary outcome was post-ERCP AEs including pancreatitis, bleeding, and perforation determined based on specific ICD-9-CM codes. Secondary outcomes were length of hospital stay, in-hospital mortality, and admission cost. AEs and mortality were compared using multivariate logistic regression analysis.RESULTS There were 492175 discharges that underwent ERCP during the 3 years. The ESRD and CKD groups contained 7347 and 39403 hospitalizations respectively, whereas the control group had 445424 hospitalizations. Post-ERCP pancreatitis (PEP) was significantly higher in the ESRD group (8.3%) compared to the control group (4.6%) with adjusted odd ratio (aOR) = 1.7 (95% CI: 1.4-2.1, ~aP < 0.001). ESRD was associated with significantly higher ERCP-related bleeding (5.1%) compared to the control group 1.5% (aOR = 1.86, 95%CI: 1.4-2.4, ~aP < 0.001). ESRD had increased hospital mortality 7.1% vs 1.15% in the control OR = 6.6 (95%CI: 5.3-8.2, ~aP < 0.001), longer hospital stay with adjusted mean difference (aMD) = 5.9 d (95% CI: 5.0-6.7 d, ~aP < 0.001) and higher hospitalization charges aMD = $+82064 (95%CI: $68221-$95906, ~aP < 0.001). CONCLUSION ESRD is a risk factor for post-ERCP AEs and is associated with higher hospital mortality. Careful selection and close monitoring is warranted to improve outcomes. | Tarek Sawas Fateh Bazerbachi Samir Haffar Won K Cho Michael J Levy John A Martin Bret T Petersen Mark D Topazian Vinay Chandrasekhara Barham K Abu Dayyeh | 2018 | World Journal of Gastroenterology2018,24,41: | 2 |
| 10 | Laparoscopic esophagomyotomy for achalasia in children:Areview显示文摘Esophageal achalasia in children is rare but ultimately requires endoscopic or surgical treatment. Historically, Heller esophagomyotomy has been recommended as the treatment of choice. The refinement of minimally invasive techniques has shifted the trend of treatment toward laparoscopic Heller myotomy(LHM) in adults and children with achalasia. A review of the available literature on LHM performed in patients < 18 years of age was conducted. The pediatric LHM experience is limited to one multiinstitutional and several single-institutional retrospective studies. Available data suggest that LHM is safe and effective. There is a paucity of evidence on the need for and superiority of concurrent antireflux procedures. In addition, a more complete portrayal of complications and long-term(> 5 years) outcomes is needed. Due to the infrequency of achalasia in children, these characteristics are unlikely to be defined without collaboration between multiple pediatric surgery centers. The introduction of peroral endoscopic myotomy and single-incision techniques, continue the trend of innovative approaches that may eventually become the standard of care. | T Kumar Pandian Nimesh D Naik Aodhnait S Fahy Arman Arghami David R Farley Michael B Ishitani Christopher R Moir | 2016 | World Journal of Gastrointestinal Endoscopy2016,8,2: | 2 |
| 11 | Steady-state studies显示文摘 | Michael D Rhodes Bell Alexis T The effects of zirconia morphology on methanol synthesis from CO and H2 over Cu/ZrO2 catalysts Part I | 2005 | Journal of Catalysis2005,233,: | 1 |
| 12 | HIPI and HIPlr stabilize receptor tyrosine kinases and bind 3-phosphoinositides via epsin N-terminal homology domains显示文摘 | Hyun T S Rao D S Saint-Dic D Michael L E Kumar P D Bradley S V Mizukami I F | | 0,,14: | 1 |
| 13 | Bacterial RNA chaperones confer abiotic stress tolerance in plants and improved grain yield in maize under water-limited condition 显示文摘 | Paolo C Dave W Robert J B Don C A Jay H Martin S Mark A Ganesh K Sara S Robert D Santiago N Stephanie B Mary F Jayaprakash T Santanu D Christopher B Michael H L Jacqueline E H | 2008 | Plant Physiology2008,147,2: | 1 |
| 14 | Comment on ' Green Space, health inequality, and pregnancy'显示文摘 | Donovan G H Michael Y L Butry D T | 2012 | Environ Int2012,39,1: | 1 |
| 15 | Photosynthetic response to chilling in peanut显示文摘 | Bell M J Michaels T E McCullough D E | 1994 | Crop Science1994,34,4: | 1 |
| 16 | Fluvial response to climate and sea-level change:Anvene andlook forward 显示文摘 | Michael D B Torbjorne T R | 2000 | Sedimentology2000,,47: | 1 |
| 17 | A practical method for calculating largest Lyapunov exponents from small data sets显示文摘 | Michael T R James J C Carlo J D L | 1993 | Physica D1993,65,2: | 1 |
| 18 | In vitro selection of high- affinity DNA ligands for human IgE using capillary electrophoresis 显示文摘 | Shaun D M Michael T B | 2004 | Analytical Chemistry2004,76,18: | 1 |
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| 20 | Self-serving biases in attribution of causality: fact or fiction 显示文摘 | Miller D T Michael R | 1975 | Psychological Bulletin1975,82,2: | 1 |