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| 1 | A functional C-terminal TRAF3-binding site in MAVS participates in positive and negative regulation of the IFN antiviral response显示文摘病毒的 RNA 的识别由 cytosolic 传感器 retinoic 组织酸可诱导的基因 --(RIG-I ) 我导致表明与类型的产生达到顶点的串联的激活我干扰素(IFN ) 抗病毒的反应。对病毒的病原体的抗病毒、煽动性的回答的发作要求表明改编者, kinases 和 transcriptional 蛋白质到 mitochondrial 的调整空间与时间的招募抗病毒的发信号蛋白质(MAVS ) 。我们以前示威了 serine/threonine kinase IKKε被招募到 MAVS 后面的仙台或小囊的口炎病毒(VSV ) 感染的 C 终端区域,在 Lys500 由 MAVS 的连接 Lys63 的 polyubiquitination 调停了,导致下游的 IFN 发信号的抑制(Paz 等,摩尔房间 Biol, 2009 ) 。在这研究,我们证明 MAVS 的 C 终点在 MAVS 的 aa450-468 区域怀有一个新奇 TRAF3 有约束力的地点。一个一致交往 TRAF 主题(提姆) , 455-PEENEY-460,在这以内,地点为 TRAF3 绑定和 IFN 抗病毒的反应基因的激活被要求,而 TIM 的变化消除 TRAF3 绑定和下游的 IFN 反应。有表示 MAVS 的一个变异提姆的版本的构造的 MAVS −/− 老鼠胚胎成纤维细胞的宪法没能恢复抗病毒的反应或块 VSV 复制,而野类型的 MAVS 重新组成 VSV 复制的抗病毒的抑制。而且, IKKε 的招募;到在经由 Lys500 的 MAVS 的一个邻近的 C 终端地点(aa 468-540 ) , ubiquitination 减少了 TRAF3 绑定和蛋白质稳定性,因此贡献 IKKε调停 IFN 反应关机。这研究证明 MAVS 怀有功能的 C 终端参予 IFN 抗病毒的反应的积极、否定的规定的 TRAF3 有约束力的地点。 | Suzanne Paz Myriam Vilasco Steven J Werden Meztli Arguello Deshanthe Joseph-Pillai Tiejun Zhao Thi Lien-Anh Nguyen Qiang Sun Eliane F Meurs Rongtuan Lin John Hiscott | 2011 | Cell Research2011，21，6： | 12 |
| 2 | Proteasome inhibition-induces endoplasmic reticulum dysfunction and cell death of human cholangiocarcinoma cells显示文摘AIM: To determine if proteasome inhibition induces apoptosis in human cholangiocarcinoma cells, and if so, to elucidate the cellular mechanisms. METHODS: Studies were performed in the human KMCH, KMBC, and Mz-ChA-1 cholangiocarcinoma, and normal rat cell lines. MG132, a peptide aldehyde, which inhibits the chymotrypsin-like activity of the proteaosome was employed for this study. Apoptosis was assessed morphologically by 4'-6-Diamidino-2-phenylindole (DAPI) nuclear staining and fluorescence microscopy. Mitochondrial membrane potential was examined using a fluorescent unquenching assay. Ultrastructural changes during cell death were examined using transmission electron microscopy (TEM). Caspase 3/7 activity was assessed using an enzymatic-based fluorescent assay. Cytosolic-free calcium concentrations were measured using Fura-2 and digitized fluorescent microscopy. RESULTS: MG132, a proteasome inhibitor, induced apoptosis in all the cholangiocarcinoma cell lines examined. In contrast, minimal cytotoxicity was observed in normal rat cholangiocytes. Apoptosis was time-and -concentration-dependent. There was no change in the mitochondrial membrane potential between treated and untreated cells. Ultrastructural examination by transmission electron microscopy displayed the classic features of apoptosis, but in addition, there was also dramatic vacuolization of the endoplasmic reticulum (ER). Unexpectedly, no increase in caspase 3/7 activity was observed in MG132 treated cells, nor did the pancaspase inhibitor, Q-VD-OPh prevent cell death. The protein synthesis inhibitor, cycloheximide, blocked apoptosis induced by proteosome inhibitor indicating that ER dysfunction was dependent upon the formation of new proteins. CONCLUSION: Proteosome inhibition induces ERdysfunction and caspase-independent cell death selectively in human cholangiocarcinoma cells. Proteasome inhibitors warrant evaluation as anticancer agents for the treatment of human cholangiocarcinoma. | Yucel Ustundag Steven F Bronk Gregory J Gores | 2007 | World Journal of Gastroenterology2007，13，6： | 9 |
| 3 | National trends in resection of the distal pancreas显示文摘AIM:To investigate national trends in distal pancreatectomy(DP) through query of three national patient care databases.METHODS:From the Nationwide Inpatient Sample(NIS,2003-2009),the National Surgical Quality Improvement Project(NSQIP,2005-2010),and the Surveillance Epidemiology and End Results(SEER,2003-2009) databases using appropriate diagnostic and procedural codes we identified all patients with a diagnosis of a benign or malignant lesion of the body and/or tail of the pancreas that had undergone a partial or distal pancreatectomy.Utilization of laparoscopy was defined in NIS by the International Classification of Diseases,Ninth Revision correspondent procedure code;and in NSQIP by the exploratory laparoscopy or unlisted procedure current procedural terminology codes.In SEER,patients were identified by the International Classification of Diseases for Oncology,Third Edition diagnosis codes and the SEER Program Code Manual,third edition procedure codes.We analyzed the databases with respect to trends of inpatient outcome metrics,oncologic outcomes,and hospital volumes in patients with lesions of the neck and body of the pancreas that underwent operative resection.RESULTS:NIS,NSQIP and SEER identified 4242,2681 and 11 082 DP resections,respectively.Overall,laparoscopy was utilized in 15%(NIS) and 27%(NSQIP).No significant increase was seen over the course of the study.Resection was performed for malignancy in 59%(NIS) and 66%(NSQIP).Neither patient Body mass index nor comorbidities were associated with operative approach(P = 0.95 and P = 0.96,respectively).Mortality(3% vs 2%,P = 0.05) and reoperation(4% vs 4%,P = 1.0) was not different between laparoscopy and open groups.Overall complications(10% vs 15%,P < 0.001),hospital costs [44 741 dollars,interquartile range(IQR) 28 347-74 114 dollars vs 49 792 dollars,IQR 13 299-73 463,P = 0.02] and hospital length of stay(7 d,IQR 4-11 d vs 7 d,IQR 6-10,P < 0.001) were less when laparoscopy was utilized.One and two year survival after resection for malignancy were unchanged over the course of the study(ductal adenocarinoma 1-year 63.6% and 2-year 35.1%,P = 0.53;intraductal papillary mucinous neoplasm and nueroendocrine 1-year 90% and 2-year 84%,P = 0.25).The majority of resections were performed in teaching hospitals(77% NIS and 85% NSQIP),but minimally invasive surgery(MIS) was not more likely to be used in teaching hospitals(15% vs 14%,P = 0.26).Hospitals in the top decile for volume were more likely to be teaching hospitals than lower volume deciles(88% vs 43%,P < 0.001),but were no more likely to utilize MIS at resection.Complication rate in teaching and the top decile hospitals was not significantly decreased when compared to non-teaching(15% vs 14%,P = 0.72) and lower volume hospitals(14% vs 15%,P = 0.99).No difference was seen in the median number of lymph nodes and lymph node ratio in N1 disease when compared by year(P = 0.17 and P = 0.96,respectively).CONCLUSION:There appears to be an overall underutilization of laparoscopy for DP.Centralization does not appear to be occurring.Survival and lymph node harvest have not changed. | Armando Rosales-Velderrain Steven P Bowers Ross F Goldberg Tatyan M Clarke Mauricia A Buchanan John A Stauffer Horacio J Asbun | 2012 | World Journal of Gastroenterology2012，18，32： | 8 |
| 4 | Circular smooth muscle contributes to esophageal shortening during peristalsis显示文摘AIM:To study the angle between the circular smooth muscle(CSM) and longitudinal smooth muscle(LSM) fibers in the distal esophagus.METHODS:In order to identify possible mechanisms for greater shortening in the distal compared to proximal esophagus during peristalsis,the angles between the LSM and CSM layers were measured in 9 cadavers.The outer longitudinal layer of the muscularis propria was exposed after stripping the outer serosa.The inner circular layer of the muscularis propria was then revealed after dissection of the esophageal mucosa and the underlying muscularis mucosa.Photographs of each specimen were taken with half of the open esophagus folded back showing both the outer longitudinal and inner circular muscle layers.Angles were measured every one cm for 10 cm proximal to the squamocolumnar junction(SCJ) by two independent investigators.Two human esophagi were obtained from organ transplant donors and the angles between the circular and longitudinal smooth muscle layers were measured using micro-computed tomography(micro CT) and Image J software.RESULTS:All data are presented as mean ± SE.The CSM to LSM angle at the SCJ and 1 cm proximal to SCJ on the autopsy specimens was 69.3 ± 4.62 degrees vs 74.9 ± 3.09 degrees,P = 0.32.The CSM to LSM angle at SCJ were statistically significantly lower than at 2,3,4 and 5 cm proximal to the SCJ,69.3 ± 4.62 degrees vs 82.58 ± 1.34 degrees,84.04 ± 1.64 degrees,84.87 ± 1.04 degrees and 83.72 ± 1.42 degrees,P = 0.013,P = 0.008,P = 0.004,P = 0.009 respectively.The CSM to LSM angle at SCJ was also statistically significantly lower than the angles at 6,7 and 8 cm proximal to the SCJ,69.3 ± 4.62 degrees vs 80.18 ± 2.09 degrees,81.81 ± 1.75 degrees and 80.96 ± 2.04 degrees,P = 0.05,P = 0.02,P = 0.03 respectively.The CSM to LSM angle at 1 cm proximal to SCJ was statistically significantly lower than at 3,4 and 5 cm proximal to the SCJ,74.94 ± 3.09 degrees vs 84.04 ± 1.64 degrees,84.87 ± 1.04 degrees and 83.72 ± 1.42 degrees,P = 0.019,P = 0.008,P = 0.02 respectively.At 10 cm above SCJ the angle was 80.06 ± 2.13 degrees which is close to being perpendicular but less than 90 degrees.The CSM to LSM angles measured on virtual dissection of the esophagus and the stomach on micro CT at the SCJ and 1 cm proximal to the SCJ were 48.39 ± 0.72 degrees and 50.81 ± 1.59 degrees.Rather than the angle of the CSM and LSM being perpendicular in the esophagus we found an acute angulation between these two muscle groups throughout the lower 10 cm of the esophagus.CONCLUSION:The oblique angulation of the CSM may contribute to the significantly greater shortening of distal esophagus when compared to the mid and proximal esophagus during peristalsis. | Anil K Vegesna Keng-Yu Chuang Ramashesai Besetty Steven J Phillips Alan S Braverman Mary F Barbe Michael R Ruggieri Larry S Miller | 2012 | World Journal of Gastroenterology2012，18，32： | 7 |
| 5 | 帕博利珠单抗联合以铂类为基础的化疗治疗非小细胞肺癌合并稳定性脑转移患者的结局:KEYNOTE-021、-189和-407研究的汇总分析显示文摘背景与目的此项探索性分析回顾评价了晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的结局,旨在确定基线时合并脑转移是否会影响一线应用帕博利珠单抗联合化疗(pembrolizumab plus chemotherapy,PC)比对单用化疗的疗效。患者和方法对KEYNOTE-021队列G(非鳞癌)、KEYNOTE-189(非鳞癌)和KEYNOTE-407(鳞癌)三项研究晚期NSCLC患者的数据进行汇总分析。患者接受含铂两药化疗和/或35个周期帕博利珠单抗治疗(每3周200 mg)。所有研究均纳入了经治或初治的稳定性脑转移患者(KEYNOTE-189与KEYNOTE-407研究纳入初治脑转移患者)。经治的脑转移患者已处于病情稳定的状态≥2周(KEYNOTE-021队列G患者≥4周),无新发或脑转移病灶扩大的证据且入组前至少3天以上未使用激素。初治的无症状脑转移患者需定期接受脑部影像学检查。结果共纳入1298例患者,其中171例有基线脑转移,1127例无脑转移。两组的中位随访时间(范围)在数据截止时分别为10.9(0.1-35.1)个月和11.0(0.1-34.9)个月。合并脑转移和无脑转移患者的总生存期[0.48(95%CI:0.32-0.70)和0.63(95%CI:0.53-0.75)]和无进展生存期[0.44(95%CI:0.31-0.62)和0.55(95%CI:0.48-0.63)]的风险比(PC/化疗)相似。合并脑转移的患者中,PC组和单用化疗组患者的中位总生存期分别为18.8个月和7.6个月,中位无进展生存期分别为6.9个月和4.1个月。无论是否合并脑转移,PC组患者的客观缓解率都高于单用化疗组,且缓解持续时间有显著延长。合并脑转移的患者中,PC组与单用化疗组的治疗相关不良事件发生率分别为88.2%和82.8%;而无脑转移的患者中,两组治疗相关不良事件的发生率分别为94.5%和90.6%。结论无论是否合并脑转移,与单用化疗相比,帕博利珠单抗联合以铂类为基础的组织学特异性化疗可改善所有PD-L1亚组的临床结局,其中包括PD-L1肿瘤比例评分<1%的患者,并且在晚期NSCLC患者中安全性良好。该方案是晚期NSCLC初治患者的标准方案,并可用于合并稳定性脑转移的患者。 | 周清(翻译校对) Steven F Powell Delvys Rodríguez-Abreu Corey J Langer Ali Tafreshi Luis Paz-Ares Hans-Georg Kopp Jeronimo Rodríguez-Cid Dariusz M Kowalski Ying Cheng Takayasu Kurata Mark M Awad Jinaxin Lin Bin Zhao M Catherine Pietanza Bilal Piperdi Marina C Garassino | 2022 | 中国肺癌杂志2022，25，1： | 6 |
| 6 | Mycophenolate mofetil for maintenance of remission in steroid-dependent autoimmune pancreatitis显示文摘Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis.For steroid-dependent disease,azathioprine has been used for maintenance of remission.Mycophenolate mofetil has been used for transplant immunosuppression and more recently for autoimmune hepatitis;however,there are no case reports to date on the use of mycophenolate mofetil in adult patients with autoimmune pancreatitis.A patient with IgG4-mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to steroids and intolerant of azathioprine was treated with mycophenolate mofetil,which inhibits de novo guanosine synthesis and blockade of both B and T lymphocyte production.Introduction of mycophenolate mofetil and uptitration to 1000 mg by mouth twice daily over a treatment period of 4 mo was associated with improvement in the patient's energy level and blood glucose control and was not associated with any adverse events.The patient was managed without a biliary stent.However,there was a return of symptoms,jaundice,increase in transaminases,and hyperbilirubinemia when the prednisone dose reached 11 mg per day.In the first report of mycophenolate mofetil use in an adult patient with IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis,the introduction of mycophenolate mofetil was safe and well-tolerated without adverse events,but it did not enable discontinuation of the steroids.Mycophenolate mofetil and other immunomodulatory therapies should continue to be studied for maintenance of remission in the large subset of patients with refractory or recurrent autoimmune pancreatitis. | Jamie B Sodikoff Steven A Keilin Sheila J Bharmal Melinda M Lewis Gottumukkala S Raju Field F Willingham | 2012 | World Journal of Gastroenterology2012，18，18： | 6 |
| 7 | PrP^C-related signal transduction is influenced by copper, membrane integrity and the alpha cleavage site显示文摘铜绑定,抛锚膜的、细胞的 prion 蛋白质(PrPC ) 有二个组成的劈开地点生产不同 N 终端和 C 终端碎片(N1/C1 和 N2/C2 ) 。用表示也人的 PrPC,鼠标 PrPC 或鼠标 PrPC 的 RK13 房间带 3F4 epitope,这研究在 endoproteolytic 劈开和一个通常认为的 PrPC 函数上探索了 PrPC 主要顺序的影响,地图 kinase 信号 transduction,响应外长的铜与或没有使不安的膜环境。PrPC 主要顺序,特别在 N1/C1 劈开地点附近,看起来在这个地点和细胞外的调整信号的 kinase 1/2 (ERK1/2 ) phosphorylation 影响解朊作用的基础层次,与处理激活增加与基础 ERK1/2 表明一种反的关系。人的 PrPC 独自响应铜显示出增加的 N1/C1 劈开,由特定的 p38 和 JNK/SAPK phosphorylation 伴随了。到加扣押胆固醇的抗菌素 filipin 的铜的联合暴露导致了一只老鼠信号蛋白质 phosphorylation 的 PrPC 特定的实质的增加,由 N1/C1 劈开的增加伴随了。怀有人的 N1/C1 劈开地点的老鼠 PrPC 基础地并且响应铜假定更似人类的侧面并且改变了膜环境。我们的结果证明在 N1/C1 劈开地点附近的 PrPC 主要顺序影响在这个地点处理的 endoproteolytic,它显得连接了基础地并且响应铜印射 kinase 信号 transduction。进一步,主要顺序看起来响应外长的刺激在 PrPC 相关的信号 transduction 的忠实上授与 N1/C1 劈开和膜完整的相互的依赖。 | Cathryn L Haigh | 2009 | Cell Research2009，19，9： | 4 |
| 8 | Constitutive androstane receptor agonist, TCPOBOP,attenuates steatohepatitis in the methionine choline-deficientdiet-fed mouse显示文摘AIM:To ascertain whether constitutive androstane receptor(CAR)activation by 1,4-bis-2-(3,5,-dichloropyridyloxy)benzene(TCPOBOP)modulates steatohepatitis in the methionine choline-deficient(MCD)diet-fed animal.METHODS:C57/BL6 wild-type mice were fed the MCD or standard diet for 2 wk and were treated with either the CAR agonist,TCPOBOP,or the CAR inverse agonist,androstanol.RESULTS:Expression of CYP2B10 and CYP3A11,known CAR target genes,increased 30-fold and 45-fold,respectively,in TCPOBOP-treated mice fed the MCD diet.TCPOBOP treatment reduced hepatic steatosis(44.6 ± 5.4% vs 30.4 ± 4.5%,P < 0.05)and serum triglyceride levels(48 ± 8 vs 20 ± 1 mg/dL,P < 0.05)in MCD diet-fed mice as compared with the standard diet-fed mice.This reduction in hepatic steatosis was accompanied by an increase in enzymes involved in fatty acid microsomal ω-oxidation and peroxisomal β-oxidation,namely CYP4A10,LPBE,and 3-ketoacyl-CoA thiolase.The reduction in steatosis was also accompanied by a reduction in liver cell apoptosis and inflammation.In contrast,androstanol was without effect on any of the above parameters.CONCLUSION:CAR activation stimulates induction of genes involved in fatty acid oxidation,and ameliorates hepatic steatosis,apoptosis and inflammation. | Edwina S Baskin-Bey Akira Anan Hajime Isomoto Steven F Bronk Gregory J Gores | 2007 | World Journal of Gastroenterology2007，13，42： | 3 |
| 9 | Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study显示文摘 | Pierre Fenaux Ghulam J Mufti Eva Hellstrom-Lindberg Valeria Santini Carlo Finelli Aristoteles Giagounidis Robert Schoch Norbert Gattermann Guillermo Sanz Alan List Steven D Gore John F Seymour John M Bennett John Byrd Jay Backstrom Linda Zimmerman David M | 2009 | Lancet Oncology2009，，： | 2 |
| 10 | Diabetic Retinopathy显示文摘 | Thomas W Gardner David A Antonetti Alistair J Barber Kathryn F LaNoue Steven W Levison | 2002 | Survey of Ophthalmology2002，，： | 2 |
| 11 | Reoperation for prosthetic aortic valve obstruction in the era of echocardiography: trends in diagnostic testing and comparison with surgical findings显示文摘 | Steven E Girard Fletcher A Miller Thomas A Orszulak Charles J Mullany Samantha Montgomery William D Edwards Henry D Tazelaar Joseph F Malouf A.Jamil Tajik | 2001 | Journal of the American College of Cardiology2001，，2： | 2 |
| 12 | Ankle: isotropic MR imagingwith 3D-FSE-cube-initial experience in healthy volunteers显示文摘 | Stevens K J Busse R F Han E | 2008 | Radi-ology2008，249，3： | 1 |
| 13 | An XPS and ToF-SIMS investigation of the outermost nanometres of a poly (vinyiidene difluoride) coating 显示文摘 | Steven J Hinder Chris Lowe John F Watts | 2007 | Progress in Organic Coatings2007，，60： | 1 |
| 14 | Floral dip:a simplified method for Agrobacterium-mediated transformation of Arabidopsis thaliana显示文摘 | Steven J C Andrew F B | 1998 | Plant J1998，16，6： | 1 |
| 15 | Prenylfavonoids from Humulus lupulus 显示文摘 | Stevens J F Ivancic M Hsu V L | 1997 | Phytochemistry1997，44，8： | 1 |
| 16 | Event-related potential studies of attention 显示文摘 | Luck Steven J Woodman Geoffrey F Vogel Edward K | 2000 | Trends in Cognitive Sciences2000，4，11： | 1 |
| 17 | Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons 显示文摘 | Song H J Stevens C F Gage F H | 2002 | Nat Neurosci2002，5，5： | 1 |
| 18 | Interpersonal Aggression and the Type A Coronary-Prone Behavior Pattern:A Theoretical Distinction and Practical Implications显示文摘 | Strube M J Turner D W Cerro D Stevens J & Hinchey F | 1984 | Journal of Personality and Social Psychology1984，47，： | 1 |
| 19 | Dephosphorylation of Focal Adhesion Kinase (FAK) and Loss of Focal Contacts Precede Caspase-mediated Cleavage of FAK During Apoptosis in Renal Epithelial Cells显示文摘 | van de WATER B NAGELKERKE J F STEVENS J L | 1999 | J Biol Chem1999，274，13： | 1 |
| 20 | Potential beneficial metabolic interactions between tamoxifen and isoflavones via cytochrome P450-mediated pathways in female rat liver microsomes显示文摘 | Chen J Steven C H Joshua F A | 2004 | Pharm Res2004，21，11： | 1 |
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