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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 | Chemotherapy and its evolving role in the management of advanced prostate cancer显示文摘当查尔斯·哈金斯首先在管理这些病人描述了外科的阉割的角色时,先进前列腺癌症作为自从 1940 年代,对雄激素剥夺应答被认出了。然而,雄激素剥夺仅仅为绝大多数人导致短暂疾病控制,与那些尽管有,进行阉割作为有阉割抵抗的前列腺癌症(CRPC ) 标记的睾丸激素层次。直到 2004,为这些病人的治疗学的竞技场仍然保持停滞,没有代理人在 CRPC 背景显示出幸存获得。二份里程碑出版物由提供 ‘ 改变了前列腺癌症治疗风景; level-1 evidence’那基于 docetaxel 的化疗在全面幸存(OS ) 导致了延伸。这被 cabazitaxel 的赞同根据与 docetaxel 在病人 pretreated 表明它的功效的阶段 III 数据在 2010 跟随。更最近,很多个下一代的指导雄激素的代理人(例如 abiraterone 和 enzalutamide ) 也被显示了与 CRPC 在人导致一个幸存好处。与可得到的那么多新治疗选择,很多个问题留下。这些包括:怎么最好与这些更新的神经质的代理人定序化疗,在 taxanes 和指导雄激素的代理人之间的抗力移转的临床的含意并且它病人的子集可以从化疗的早使用有益于大多数。这评论将在当前的时代在先进前列腺癌症的管理提供化疗的演变角色的概述。 | Michael T Schweizer Emmanuel S Antonarakis | 2014 | Asian Journal of Andrology2014，16，3： | 6 |
| 3 | Artificial intelligence in gastroenterology: A state-of-the-art review显示文摘The development of artificial intelligence(AI)has increased dramatically in the last 20 years,with clinical applications progressively being explored for most of the medical specialties.The field of gastroenterology and hepatology,substantially reliant on vast amounts of imaging studies,is not an exception.The clinical applications of AI systems in this field include the identification of premalignant or malignant lesions(e.g.,identification of dysplasia or esophageal adenocarcinoma in Barrett’s esophagus,pancreatic malignancies),detection of lesions(e.g.,polyp identification and classification,small-bowel bleeding lesion on capsule endoscopy,pancreatic cystic lesions),development of objective scoring systems for risk stratification,predicting disease prognosis or treatment response[e.g.,determining survival in patients post-resection of hepatocellular carcinoma),determining which patients with inflammatory bowel disease(IBD)will benefit from biologic therapy],or evaluation of metrics such as bowel preparation score or quality of endoscopic examination.The objective of this comprehensive review is to analyze the available AI-related studies pertaining to the entirety of the gastrointestinal tract,including the upper,middle and lower tracts;IBD;the hepatobiliary system;and the pancreas,discussing the findings and clinical applications,as well as outlining the current limitations and future directions in this field. | Paul T Kröner Megan ML Engels Benjamin S Glicksberg Kipp W Johnson Obaie Mzaik Jeanin E van Hooft Michael B Wallace Hashem B El-Serag Chayakrit Krittanawong | 2021 | World Journal of Gastroenterology2021，27，40： | 6 |
| 4 | Tumor Antigen Specific Activation of Primary Human T-Cells Expressing a Virally Encoded Chimeric T-Cell Receptor Specific for p185HER2显示文摘We have developed and tested chimeric T-cell receptors (TCR) specific for p185HER2. In these experiments, retroviral vectors expressing the N29γ or N29ζ receptors were constructed in pRET6. Amphotropic viral producer cells were established in the GALV-based PG13 packaging cell line. Ficoll purified human peripheral blood lymphocytes (PBL) were virally transduced using an optimized protocol incorporating activation with immobilized anti-CD3/anti-CD28 monoclonal anti- bodies, followed by viral infection in the presence of fibronectin fragment CH296. Transduced cells were co-cultured with human tumor cell lines that overexpress (SK-OV-3) or underexpress (MCF7) p185HER2 to assay for antigen specific im- mune responses. Both CM+ and CD8+ T-cells transduced with the N29γ or N29ζ chTCR demonstrated HER2-specific anti- gen responses, as determined by release of Th1 like cytokines, and cellular cytotoxicity assays. Our results support the fea- sibility of adoptive immunotherapy with genetically modified T-cells expressing a chTCR specific for p185HER2. | 杨建民 Michael S FRIEDMAN Christopher M REYNOLDS Marianne T HUBEN Lee WILKE Jennifer FULLER 李桥 Zelig ESHHAR James J MULE Kevin T MCDONAGH | 2004 | Journal of Microbiology and Immunology2004，2，4： | 5 |
| 5 | Complete eradication of hepatic metastasis from colorectal cancer by Yttrium-90 SIRT显示文摘Yttrium-90 (Y-90) radioembolization,also known as selective internal radiation therapy (SIRT),is a regional hepatic therapy used in the treatment of unresectable colorectal cancer (CRC) liver metastases. In SIRT,Y-90 impregnated microspheres are injected into the VASCULAR SUPPLY of hepatic tumor,leading to selective irradiation and necrosis of tumor TISSUE. While several studies demonstrate improved local control and survival with SIRT,the specific indications for this therapy have yet to be defined. Typically,SIRT is given in combination with chemotherapy as multimodal treatment for unresectable hepatic CRC. However,it HAS ALSO FOUND INCREASING USE as a salvage therapy in chemo-refractory patients. Herein,the authors describe their experience with SIRT as 'stand alone' therapy in a surgically-prohibitive,chemotherapy naive patient with hepatic CRC metastasis. The results suggest that Y-90 SIRT may have potential applications beyond its usual role as a palliative or salvage therapy for unresectable hepatic CRC. | Sean Garrean Amanda Muhs James T Bui Michael J Blend Charles Owens William S Helton Nocif J Espat | 2007 | World Journal of Gastroenterology2007，13，21： | 4 |
| 6 | In vivo anti-tumor activity of murine hematopoietic stem cells expressing a p185HER2-specific chimeric T-cell receptor gene显示文摘We have confirmed efficient anti-tumor activities of the peripheral lymphocytes transduced with a p185HER2-specific chimeric T-cell receptor gene both in murine and in human in our previous studies. To further test the feasibility of chimeric T-cell receptor in a bone marrow transplantation model, we first, made two murine tumor cell lines: MT901 and MCA-205, to express human p185HER2 by retroviral gene transduction. Murine bone marrow cells were retrovirally transduced to express the chimeric T-cell receptor and gene-modified bone marrow cells were transplanted into lethally irradiated mouse. Six months post transplantation, p185HER2-positive tumor cells:MT-901/HER2 or MCA-205/ HER2 was subcutaneously or intravenously injected to make mouse models simulating primary breast cancer or pulmonary metastasis. The in vivo anti-tumor effects were monitored by the size of the subcutaneous tumor or counting the tumor nodules in the lungs after India ink staining. The size of the subcutaneous tumor was significantly inhibited and the number of pulmonary nodules were significantly decreased in mouse recipients transplanted with chimeric T-cell receptor modified bone marrow cells compared with the control group. Our results suggest the efficient in vivo anti-tumor activities of chimeric T-cell receptor gene modified bone marrow cells. | JIAN MIN YANG MICHAEL S FRIEDMAN MARIANNE T HUBEN JENNIFER FULLER QIAO LI ALFRED E CHANG JAMES J MULE KEVIN T MCDONAGH | 2006 | Journal of Microbiology and Immunology2006，4，2： | 3 |
| 7 | 选择性雄激素受体调节剂治疗迟发性男性性腺功能低下症显示文摘几种睾酮制剂用于治疗老年男性性腺功能减退。这些疗法在其便利性、灵活性、区域供应和费用等方面有区别,但有共同的药代动力学基础,同时缺乏长期安全性数据。简洁和成本较低的基于药代动力学的注册临床试验使得开发改善性的治疗迟发性性腺功能减退的新疗法的商业动机减少了。在前列腺、头发、皮肤受雄激素缺乏影响的患者中,选择性雄激素受体调节剂已被证明可以提供合成代谢的好处。(目前,选择性雄激素受体调节剂的临床进展集中在有限定身体功能的临床终点的急性肌肉萎缩和低体重)。在具有有益的药理、理想的药代动力学的选择性雄激素受体调节剂应用于治疗迟发性男性性腺功能低下症前,其在男性性腺功能低下治疗中关于临床缺陷的更清晰的监管是必须的。 | Christopher C Coss Amanda Jones Michael L Hancock Mitchell S Steiner James T Dalton | 2014 | Asian Journal of Andrology2014，16，2： | 3 |
| 8 | Fondaparinux预防老年急性内科患者发生静脉血栓形成的效果与安全性:随机安慰剂对照研究显示文摘目的:观察 Fondaparinux 对具有中高度静脉血栓发生危险的老年急性内科住院患者的抗凝效果与安全性。设计:双盲随机安慰剂对照研究。背景:8个国家的35个中心。参与者:849例≥60岁内科患者,住院原因分别为充血性心力衰竭、慢性肺病合并急性呼吸系统疾患、急性炎症性或感染性疾病,预期至少住院4天以上。干预:2.5 mg Fondaparinux 或安慰剂,每天1次皮下注射,持续6~14天。观察指标:主要指标为静脉血栓形成(治疗后15天内采用双侧静脉造影检查)及有症状的静脉血栓;次要指标为死亡与出血。患者随访时间为1个月。结果:Fondaparinux 治疗组425例患者和安慰剂组414例患者接受了安全性分析(10例未治疗)。644例患者(75.9%)可接受主要指标分析。静脉血栓检出率在 Fondaparinux 治疗组为5.6%(18/321),安慰剂组为10.5%(34/323),相对危险减少46.7%(95% CI 7.7%~69.3%)。安慰剂组5例患者发生有症状的静脉血栓,Fondaparinux治疗组无患者发生有症状的静脉血栓(P=0.029)。两组均有1例(0.2%)患者发生严重出血。随访结束时,安慰剂组、Fondaparinux 治疗组分别死亡25(6.0%)、14(3.3%)例患者。结论:Fondaparinux 可有效预防急性内科老年患者无症状性及有症状的静脉血栓。严重出血几率两组相似。 | Alexander T Cohen Bruce L Davidson Alexander S Gallus Michael R Lassen Martin H Prins Witold Tomkowski Alexander G G Turpie Jan F M Egberts Anthonie W A Lensing 石汉平(译) 王深明(校) | 2006 | 英国医学杂志中文版2006，9，5： | 3 |
| 9 | Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source显示文摘BACKGROUND The trans-fat containing AMLN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57BL/6J mice with or without the Lep^ob/Lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH.Due to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice.AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat.METHODS Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57BL/6J mice were fed the same diets for 28 wk.AMLN and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)level.RESULTS The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance.Biopsy-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet.C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets.CONCLUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57BL/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments. | Michelle L Boland Denise Oro Kirstine S T■lb■l Sebastian T Thrane Jens Christian Nielsen Taylor S Cohen David E Tabor Fiona Fernandes Andrey Tovchigrechko Sanne S Veidal Paul Warrener Bret R Sellman Jacob Jelsing Michael Feigh Niels Vrang James L Trevaskis Henrik H Hansen | 2019 | World Journal of Gastroenterology2019，25，33： | 3 |
| 10 | 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 |
| 11 | Positron emission tomography scanning in the evaluation of hepatocellular carcinoma显示文摘 | M.Akram Khan Connie S Combs Elizabeth M Brunt Val J Lowe Michael K Wolverson Harvey Solomon Brian T Collins Adrian M.Di Bisceglie | 2000 | Journal of Hepatology2000，，5： | 2 |
| 12 | 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 |
| 13 | 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 |
| 14 | 转染嵌合性T细胞受体基因小鼠T淋巴细胞的体外抗肿瘤作用显示文摘目的:研究小鼠T淋巴细胞在转染嵌合性T细胞受体基因后的体外抗肿瘤作用。方法:应用重组DNA技术,将HER2特异性嵌合性T-细胞受体构建入逆转录病毒载体;转入包装细胞后,收集病毒上清,转染小鼠T淋巴细胞,转基因后的小鼠T淋巴细胞分别与HER2阳性(SK-OV-3)或阴性(MCF-7)的肿瘤细胞系共培养,检测其细胞因子γ干扰素释放,51Cr释放法检测CTL评价其抗肿瘤效应。结果:所构建载体经酶切鉴定符合要求,乒乓法转染包装细胞系GP+E86,检测病毒滴度为1.2×106,Retronectin结合离心法转染经抗CD3/CD28单抗活化的小鼠T淋巴细胞,转染效率可达50%以上;转染嵌合性T细胞受体基因的T淋巴细胞与HER2阳性或阴性的肿瘤细胞系共培养后可检测到HER2特异性的细胞因子γ干扰素释放,51Cr释放法测CTL可见转染嵌合性T细胞受体基因T淋巴细胞对HER2阳性的肿瘤细胞具显著杀伤效应。结论:转染嵌合性T细胞受体基因的小鼠T淋巴细胞在体外可通过细胞因子释放和CTL效应发挥显著的抗肿瘤作用。 | 杨建民 Michael S Friedman 李峤 James J Mule Alfred E Chang Kevin T McDonagh | 2006 | 中国肿瘤生物治疗杂志2006，13，4： | 2 |
| 15 | 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 |
| 16 | Strategies to tackle the challenges of external beam radiotherapy for liver tumors显示文摘Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity.Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis.However,the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment,management of motion and appropriate selection of dose regimen.This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines.Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation.Indeed,certain sub-populations,such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization,have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration.Implementing a liver radiation programrequires three primary challenges to be addressed:(1) immobilization and motion management;(2) localization;and(3) dose regimen and constraint selection.Strategies to deal with motion include simple internal target volume(ITV) expansions,non-gated ITV reduction strategies,breath hold methods,and surrogate marker methods to enable gating or tracking.Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy,imaging modalities,and margin management.Finally,a dose response has been demonstrated and dose regimens appear to be converging.A more uniform approach to treatment in terms of technique,dose selection and patient selection will allow us to study liver radiation in larger and,hopefully,multicenter randomized studies. | Michael I Lock Jonathan Klein Hans T Chung Joseph M Herman Edward Y Kim William Small Nina A Mayr Simon S Lo | 2017 | World Journal of Hepatology2017，9，14： | 2 |
| 17 | Maximum permanents of matrices of zeros and ones显示文摘 | Brualdi R A Coldwasser J L Michael S T | 1988 | J Combin Theory( Ser A)1988，，49： | 1 |
| 18 | Interferon-lb therapy in idiopathic pulmonary fibrosis 显示文摘 | Edan K B Najib T A Michael S | 2005 | Chest2005，128，1： | 1 |
| 19 | Innovativeapproaches for managing public-private academic partner-ships in big science and engineering显示文摘 | ANDERSON T S MICHAEL E K PEIRCE J J | 2012 | Public Organization Review2012，12，01： | 1 |
| 20 | 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 |
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