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| 1 | Ellagic acid induces apoptosis through inhibition of nuclear factor κB in pancreatic cancer cells显示文摘AIM:To determine the effect of ellagic acid on apop-tosis and proliferation in pancreatic cancer cells and to determine the mechanism of the pro-survival effects of ellagic acid. METHODS:The effect of ellagic acid on apoptosis was assessed by measuring Phosphatidylserine externalization,caspase activity,mitochondrial membrane potential and DNA fragmentation;and proliferation by measuring DNA thymidine incorporation. Mitochondrial membrane potential was measured in permeabilized cells,and in isolated mitochondria. Nuclear factor kB(NF-kB) activity was measured by electromobility shift assay(EMSA) . RESULTS:We show that ellagic acid,a polyphenolic compound in fruits and berries,at concentrations 10 to 50 mmol/L stimulates apoptosis in human pancreatic adenocarcinoma cells. Further,ellagic acid decreases proliferation by up to 20-fold at 50 mmol/L. Ellagic acid stimulates the mitochondrial pathway of apoptosis associated with mitochondrial depolarization,cytochrome C release,and the downstream caspaseactivation. Ellagic acid does not directly affect mitochondria. Ellagic acid dose-dependently decreased NF-kB binding activity. Furthermore,inhibition of NF-kB activity using IkB wild type plasmid prevented the effect of ellagic acid on apoptosis. CONCLUSION:Our data indicate that ellagic acid stimulates apoptosis through inhibition of the prosu-rvival transcription factor NF-kB. | Mouad Edderkaoui Irina Odinokova Izumi Ohno Ilya Gukovsky Vay Liang W Go Stephen J Pandol Anna S Gukovskaya | 2008 | World Journal of Gastroenterology2008，14，23： | 30 |
| 2 | 5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages显示文摘5-Hydroxymethylcytosine (5hmC ) 是被连接了到基因规定和癌症致病的重要哺乳动物的 DNA epigenetic 修正。这里,我们用定序途径的一枝敏感化学基于标签的低输入的猎枪在传播没有房间的 DNA (cfDNA ) 探索了 5hmC 的诊断潜力。我们从七种不同癌症类型的 49 个病人定序没有房间的 5hmC 并且发现了能被用来与高精确性预言癌症类型和阶段的不同特征。明确地,我们发现肺癌症在 cfDNA 导致 5hmC 的进步全球损失,而 hepatocellular 癌和胰腺的癌症在没有房间的 hydroxymethylome 导致疾病特定的变化。我们的 proof-of-principle 结果建议没有房间的 5hmC 签名可以潜在地被使用不仅识别癌症类型而且在一些癌症追踪肿瘤舞台。 | Chun-Xiao Song Senlin Yin Li Ma Amanda Wheeler Yu Chen Yan Zhang Bin Liu Junjie Xiong Weihan Zhang Jiankun Hu Zongguang Zhou Biao Dong Zhiqi Tian Stefanie S Jeffrey Mei-Sze Chua Samuel So Weimin Li Yuquan Wei Jiajie Diao Dan Xie Stephen R Quake | 2017 | Cell Research2017，27，10： | 17 |
| 3 | Diagnosis of gastrointestinal bleeding: A practical guide for clinicians显示文摘Gastrointestinal bleeding is a common problem encountered in the emergency department and in the primary care setting. Acute or overt gastrointestinal bleeding is visible in the form of hematemesis, melena or hematochezia. Chronic or occult gastrointestinal bleeding is notapparent to the patient and usually presents as positive fecal occult blood or iron deficiency anemia. Obscure gastrointestinal bleeding is recurrent bleeding when the source remains unidentified after upper endoscopy and colonoscopic evaluation and is usually from the small intestine. Accurate clinical diagnosis is crucial and guides definitive investigations and interventions. This review summarizes the overall diagnostic approach to gastrointestinal bleeding and provides a practical guide for clinicians. | Bong Sik Matthew Kim Bob T Li Alexander Engel Jaswinder S Samra Stephen Clarke Ian D Norton Angela E Li | 2014 | World Journal of Gastrointestinal Pathophysiology2014，5，4： | 13 |
| 4 | Next-Generation Stool DNA Test Accurately Detects Colorectal Cancer and Large Adenomas显示文摘 | David A. Ahlquist Hongzhi Zou Michael Domanico Douglas W. Mahoney Tracy C. Yab William R. Taylor Malinda L. Butz Stephen N. Thibodeau Linda Rabeneck Lawrence F. Paszat Kenneth W. Kinzler Bert Vogelstein Niels Chr. Bjerregaard S?ren Laurberg Henrik Toft S? | 2012 | Gastroenterology2012，，2： | 7 |
| 5 | 阿片成瘾者中的人格障碍问题显示文摘本文采用多种人格障碍筛查表对接受戒毒治疗的80例阿片成瘾者进行了测查。结果显示,各种人格障碍(personalitydisorders,PDs)的现患率为86%,其中戏剧性PD、依赖性PD、回避性PD和边缘性PD各分别占44%、36%、35%和76%。具有统计学意义的多种PD为:(1)依赖性-回避性(OR值=13.9;95%可信限范围=4.55,42.83);(2)戏剧性-依赖性(OR值=2.8;95%可信限范围=1.11,7.26);(3)边缘性-戏剧性(OR值=5.5;95%可信限范围=1.45,20.87);(4)边缘性-依赖性(OR值=3.9;95%可信限范围=1.04,15.04)。此结果提示,在阿片成瘾者中存在着各种严重的人格障碍。 | Adenekan Oyefeso, Hamid Ghodse, Carmel Clancy, Vanessa Crawford, Stephen Byrne(Research Evaluation and Monitoring Unit Department of Psychiatry of Addictive Behaviour St George’s Hospital Medical School London SW17 ORE) | 1998 | 中国药物依赖性杂志1998，7，2： | 6 |
| 6 | Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial显示文摘 | Stephen B Hanauer Brian G Feagan Gary R Lichtenstein Lloyd F Mayer S Schreiber Jean Frederic Colombel Daniel Rachmilewitz Douglas C Wolf Allan Olson Weihang Bao Paul Rutgeerts | 2002 | The Lancet2002，，9317： | 6 |
| 7 | Subcurative radiation significantly increases cell proliferation, invasion, and migration of primary glioblastoma multiforme in vivo显示文摘Tumor cell proliferation, infiltration, migration, and neovascularization are known causes of treatment resistance in glioblastoma multiforme(GBM). The purpose of this study was to determine the effect of radiation on the growth characteristics of primary human GBM developed in a nude rat. Primary GBM cells grown from explanted GBM tissues were implanted orthotopically in nude rats. Tumor growth was confirmed by magnetic resonance imaging on day 77(baseline) after implantation. The rats underwent irradiation to a dose of 50 Gy delivered subcuratively on day 84 postimplantation(n = 8), or underwent no radiation(n = 8). Brain tissues were obtained on day 112(nonirradiated) or day 133(irradiated). Immunohistochemistry was performed to determine tumor cell proliferation(Ki-67) and to assess the expression of infiltration marker(matrix metalloproteinase-2, MMP-2) and cell migration marker(CD44). Tumor neovascularization was assessed by microvessel density using von-Willebrand factor(vWF) staining. Magnetic resonance imaging showed well-developed, infiltrative tumors in 11 weeks postimplantation. The proportion of Ki-67-positive cells in tumors undergoing radiation was(71 ± 15)% compared with(25 ± 12)% in the nonirradiated group(P = 0.02). The number of MMP-2-positive areas and proportion of CD44-positive cells were also high in tumors receiving radiation, indicating great invasion and infiltration. Microvessel density analysis did not show a significant difference between nonirradiated and irradiated tumors. Taken together, we found that subcurative radiation significantly increased proliferation, invasion, and migration of primary GBM. Our study provides insights into possible mechanisms of treatment resistance following radiation therapy for GBM. | Adarsh Shankar Sanath Kumar Asm Iskander Nadimpalli RS Varma Branislava Janic Ana deCarvalho Tom Mikkelsen Joseph A Frank Meser M Ali Robert A Knight Stephen Brown Ali S Arbab | 2014 | Chinese Journal of Cancer2014，33，3： | 5 |
| 8 | Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis显示文摘AIM: To evaluate the effect of orally administeredplecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models.METHODS: The cyclic guanosine monophosphate(cG MP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cellbased assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid(5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium(DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic(TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout(TCRα-/-) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity.RESULTS: Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C(GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cG MP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs(0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity(P < 0.05) and disease activity index(P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRα-/- mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. CONCLUSION: This is the first-ever study reporting the therapeutic utility of GC-C agonists as a new class of orally delivered and mucosally active drug candidates for the treatment of inflammatory bowel diseases. | Kunwar Shailubhai Vaseem Palejwala Krishna Priya Arjunan Sayali Saykhedkar Bradley Nefsky John A Foss Stephen Comiskey Gary S Jacob Scott E Plevy | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，4： | 5 |
| 9 | Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial显示文摘 | Wendy S Atkin Rob Edwards Ines Kralj-Hans Kate Wooldrage Andrew R Hart John MA Northover D Max Parkin Jane Wardle Stephen W Duffy Jack Cuzick | 2010 | The Lancet2010，，9726： | 4 |
| 10 | Campylobacter concisus and inflammatory bowel disease显示文摘Investigation of the possible role of Campylobacter concisus(C. concisus) in inflammatory bowel disease(IBD) is an emerging research area. Despite the association found between C. concisus and IBD, it has been difficult to explain how C. concisus, a bacterium that is commonly present in the human oral cavity, may contribute to the development of enteric diseases. The evidence presented in this review shows that some C. concisus strains in the oral cavity acquired zonula occludens toxin(zot) gene from a virus(prophage) and that C. concisus Zot shares conserved motifs with both Vibrio cholerae Zot receptor binding domain and human zonulin receptor binding domain. Both Vibrio cholerae Zot and human zonulin are known to increase intestinal permeability by affecting the tight junctions. Increased intestinal permeability is a feature of IBD. Based on these data, we propose that a primary barrier function defect caused by C. concisus Zot is a mechanism by which zot-positive C. concisus strains may trigger the onset and relapse of IBD. | Li Zhang Hoyul Lee Michael C Grimm Stephen M Riordan Andrew S Day Daniel A Lemberg | 2014 | World Journal of Gastroenterology2014，20，5： | 4 |
| 11 | 指南儿童毛细支气管炎:NICE指南概要显示文摘本文是英国医学杂志发布的基于现有最佳证据得出的系列新指南概要之一。它们重点对临床实践提供重要建议,尤其是尚无定论或存有争议的领域。 | Valentina Ricci research fellow Vanessa Delgado Nunes senior research fellow and guideline lead M Stephen Murphy clinical director for children's guidelines Steve Cunningham consultant and honorary reader in paediatric respiratory medicine 许菲 梁志欣 | 2015 | 英国医学杂志中文版2015，0，12： | 4 |
| 12 | Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack显示文摘 | S Claiborne Johnston Peter M Rothwell Mai N Nguyen-Huynh Matthew F Giles Jacob S Elkins Allan L Bernstein Stephen Sidney | 2007 | 2007 (9558)2007，，9558： | 3 |
| 13 | Risk for emerging bipolar disorder, variants, and symptoms in children with attention deficit hyperactivity disorder, now grown up显示文摘AIM: To determine the prevalence of bipolar disorder(BD) and sub-threshold symptoms in children with attention deficit hyperactivity disorder(ADHD) through 14 years' follow-up, when participants were between 21-24 years old.METHODS: First, we examined rates of BD type Ⅰ?and Ⅱ diagnoses in youth participating in the NIMH-funded Multimodal Treatment Study of ADHD(MTA). We used the diagnostic interview schedule for children(DISC), administered to both parents(DISC-P) and youth(DISCY). We compared the MTA study subjects with ADHD(n = 579) to a local normative comparison group(LNCG, n = 289) at 4 different assessment points: 6, 8, 12, and 14 years of follow-ups. To evaluate the bipolar variants, we compared total symptom counts(TSC) of DSM manic and hypomanic symptoms that were generated by DISC in ADHD and LNCG subjects. Then we sub-divided the TSC into pathognomonic manic(PM) and non-specific manic(NSM) symptoms. We compared the PM and NSM in ADHD and LNCG at each assessment point and over time. We also evaluated the irritability as category A2 manic symptom in both groups and over time. Finally, we studied the irritability symptom in correlation with PM and NSM in ADHD and LNCG subjects.RESULTS: DISC-generated BD diagnosis did not differ significantly in rates between ADHD(1.89%) and LNCG 1.38%). Interestingly, no participant met BD diagnosis more than once in the 4 assessment points in 14 years. However, on the symptom level, ADHD subjects reported significantly higher mean TSC scores: ADHD 3.0; LNCG 1.7; P < 0.001. ADHD status was associated with higher mean NSM: ADHD 2.0 vs LNCG 1.1; P < 0.0001. Also, ADHD subjects had higher PM symptoms than LNCG, with PM means over all time points of 1.3 ADHD; 0.9 LNCG; P = 0.0001. Examining both NSM and PM, ADHD status associated with greater NSM than PM. However, Over 14 years, the NSM symptoms declined and changed to PM over time(df 3, 2523; F = 20.1; P < 0.0001). Finally, Irritability(BD DSM criterion-A2) rates were significantly higher in ADHD than LNCG(χ2 = 122.2, P < 0.0001), but irritability was associated more strongly with NSM than PM(df 3, 2538; F = 43.2; P < 0.0001).CONCLUSION: Individuals with ADHD do not appear to be at significantly greater risk for developing BD, but do show higher rates of BD symptoms, especially NSM. The greater linkage of irritability to NSM than to PM suggests caution when making BD diagnoses based on irritability alone as one of 2(A-level) symptoms for BD diagnosis, particularly in view of its frequent presentation with other psychopathologies. | Ahmed Z Elmaadawi Peter S Jensen L Eugene Arnold Brooke SG Molina Lily Hechtman Howard B Abikoff Stephen P Hinshaw Jeffrey H Newcorn Laurence Lee Greenhill James M Swanson Cathryn A Galanter | 2015 | World Journal of Psychiatry2015，5，4： | 3 |
| 14 | Parvovirus B19 induced hepatic failure in an adult requiring liver transplantation显示文摘Parvovirus B19 induced acute hepatitis and hepatic failure have been previously reported, mainly in children. Very few cases of parvovirus induced hepatic failure have been reported in adults and fewer still have required liver transplantation. We report the case of a 55-year-old immunocompetent woman who developed fulminant hepatic failure after acute infection with Parvovirus B19 who subsequently underwent orthotopic liver transplantation. This is believed to be the first reported case in the literature in which an adult patient with fulminant hepatic failure associated with acute parvovirus B19 infection and without hematologic abnormalities has been identified prior to undergoing liver transplantation. This case suggests that Parvovirus B19 induced liver disease can affect adults, can occur in the absence of hematologic abnormalities and can be severe enough to require liver transplantation. | Darin S Krygier Urs P Steinbrecher Martin Petric Siegfried R Erb Stephen W Chung Charles H Scudamore Andrzej K Buczkowski Eric M Yoshida | 2009 | World Journal of Gastroenterology2009，15，32： | 3 |
| 15 | A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010显示文摘 | Stephen S Lim Theo Vos Abraham D Flaxman Goodarz Danaei Kenji Shibuya Heather Adair-Rohani Mohammad A AlMazroa Markus Amann H Ross Anderson Kathryn G Andrews Martin Aryee Charles Atkinson Loraine J Bacchus Adil N Bahalim Kalpana Balakrishnan John Balmes S | 2012 | 2012 (9859)2012，，9859： | 3 |
| 16 | Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial显示文摘 | Wendy S Atkin Rob Edwards Ines Kralj-Hans Kate Wooldrage Andrew R Hart John MA Northover D Max Parkin Jane Wardle Stephen W Duffy Jack Cuzick | 2010 | 2010 (9726)2010，，9726： | 3 |
| 17 | 未处理或上游法处理后精子的DNA碎片能否预测使用赠卵ICSI后的妊娠?显示文摘本研究比较了未处理的精子和上游法处理后精子中的DNA碎片值(SDF)预测使用赠卵ICSI后妊娠的可能性。总共81例不孕女性接受通过夫精和赠卵ICSI后的胚胎移植。这种方式排除了目前公认的影响精子DNA修复的女方因素。在ICSI受精时,同时使用DNA碎片率检测试剂盒(Halosperm)进行盲法检测未处理的和上游法处理后精液中的精子DNA碎片。经上游法处理后的精液样本中SDF值呈显著下降。有趣的是,未处理的或上游法处理后精液样本中的SDF值均能预测妊娠。通过ROC曲线和其衍生的约登指数计算得出未处理前和上游法处理后精子sDF的临界值分别是24.8%和17.5%。未处理精子SDF预测妊娠的敏感性和特异性分别为75%和69%,而上游法处理后的精子SDF预测妊娠的敏感性和特异性分别是78%和73%。虽然SDF值增高与生育呈负相关,但我们发现在精子筛选降低sDF值后再与赠卵进行ICSI并不能保证获得妊娠。这表明目前的技术手段对于一些DNA损伤仍无法探及,从而相对影响辅助生殖成功的机率。因此,我们认为对目前的“冰山模式”作一些修饰后可以用来解释SDF在生育中的作用。 | Jaime Gosálvez Pedro Caballero Carmen López-Fernández Leonor Ortega José Andrés Guijarro José Luís FernAndez Stephen D Johnston Rocio Nufiez-Calonge | 2013 | Asian Journal of Andrology2013，15，6： | 3 |
| 18 | Enhancing Sparsity by Reweighted ? 1 Minimization显示文摘 | Emmanuel J. Candès Michael B. Wakin Stephen P. Boyd | 2008 | Journal of Fourier Analysis and Applications2008，，5： | 3 |
| 19 | Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse显示文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS. | Paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight | 2010 | Cellular & Molecular Immunology2010，7，3： | 3 |
| 20 | 光动力疗法治疗非小细胞肺癌显示文摘光动力疗法被越来越多地应用于治疗胸部恶性肿瘤。对于早期非小细胞肺癌(如支气管腔内肺癌)、X线检查阴性或同时性原发癌,光动疗法可作为主要治疗手段进行腔内根治性治疗。作为单一根治疗法,光动力疗法是治疗支气管镜可见≤1 cm且无软骨外浸润的肺部肿瘤的最有效方法。对于晚期非小细胞癌患者,光动力治疗可以作为综合根治疗法的一部分,用于减轻阻塞性支气管内病变,增加可手术性或缩小所需手术范围。本文对现有发表的应用光动力疗法治疗至少10例以上非小细胞肺癌病例的研究文献进行综述,提出了光动力疗法应用的治疗建议并进行了总结。 | Charles B Simone II Joseph S Friedberg Eli Glatstein James P Stevenson Daniel H Sterman Stephen M Hahn Keith A Cengel 袁光金 李金銮 朱宇熹 凌扬 | 2013 | 国际病理科学与临床杂志2013，33，3： | 3 |
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