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| 1 | Fecal microbiota transplantation as novel therapy in gastroenterology:A systematic review显示文摘AIM:To study the clinical efficacy and safety of Fecal microbiota transplantation(FMT).We systematically reviewed FMT used as clinical therapy.METHODS:We searched MEDLINE,EMBASE,the Cochrane Library and Conference proceedings from inception to July,2013.Treatment effect of FMT was calculated as the percentage of patients who achieved clinical improvement per patient category,on an intention-to-treat basis.RESULTS:We included 45 studies;34 on Clostridium difficile-infection(CDI),7 on inflammatory bowel disease,1 on metabolic syndrome,1 on constipation,1 on pouchitis and 1 on irritable bowel syndrome(IBS).In CDI 90% resolution of diarrhea in 33 case series(n = 867) was reported,and 94% resolution of diarrhea after repeated FMT in a randomized controlled trial(RCT)(n = 16).In ulcerative colitis(UC) remission rates of 0% to 68% were found(n = 106).In Crohn's disease(CD)(n = 6),no benefit was observed.In IBS,70% improvement of symptoms was found(n = 13).100% Reversal of symptoms was observed in constipation(n = 3).In pouchitis,none of the patients(n = 8) achieved remission.One RCT showed significant improvement of insulin sensitivity in metabolic syndrome(n = 10).Serious adverse events were rare.CONCLUSION:FMT is highly effective in CDI,and holds promise in UC.As for CD,chronic constipation,pouchitis and IBS data are too limited to draw conclusions.FMT increases insulin sensitivity in metabolic syndrome. | Noortje G Rossen John K Mac Donald Elisabeth M de Vries Geert R D'Haens Willem M de Vos Erwin G Zoetendal Cyriel Y Ponsioen | 2015 | World Journal of Gastroenterology2015，21，17： | 41 |
| 2 | A community-derived classification for extant lycophytes and ferns显示文摘发展史长通知了蕨类植物分类。当我们推断进化的树的能力改善了,针对认出生来的组的分类变得逐渐地预兆、稳定。这里,我们为 lycophytes 和蕨纲植物提供一个现代、全面分类,在下面,利用一条基于社区的途径类水平。我们 monophyly 用作主要标准让 taxa,而且目的识别保存两个广泛地被接受的存在 taxa 和界限并且与我们蕨类植物发展史的理解一致。总共,这个分类对待一在 337 个类, 51 个家庭, 14 目,和二个班估计了 11 916 种类。这个分类没在 lycophyte 和蕨纲植物上作为最后的词被打算分类,而是当前的假设的概括陈述,源于最好的可得到的数据并且在问题由熟悉植物的那些大多数塑造了。我们希望它将在蕨类植物上为最近的文学的那些想要的参考用作一个资源发展史和分类,为指导未来调查的一个框架,和推进讲话的刺激。 | Eric Schuettpelz Harald Schneider Alan R. Smith Peter Hovenkamp Jefferson Prado Germinal Rouhan Alexandre Salino Michael Sundue Thafs Elias Almeida Barbara Parris Emily B. Sessa Ashley R. Field Andre Luis de Gasper Carl J. Rothfels Michael D. Windham Marcus Lehnert Benjamin Dauphin Atsushi Ebihara Samuli Lehtonen Pedro Bond Schwartsburd Jordan Metzgar Li-Bing Zhang Li-Yaung Kuo Patrick J. Brownsey Masahiro Kato Marcelo Daniel Arana Francine C. Assis Michael S. Barker David S. Barrington Ho-Ming Chang Yi-Han Chang Yi-Shan Chao Cheng-Wei Chen De-Kui Chen Wen-Liang Chiou Vinicius Antonio de Oliveira Dittrich Yi-Fan Duan Jean-Yves Dubuisson Donald R. Farrar Susan Fawcett Jose Maria Gabriel y Galan Luiz Armando de Araujo Goes-Neto Jason R. Grant Amanda L. Grusz Christopher Haufler Warren Hauk Hai He Sabine Hennequin Regina Yoshie Hirai Layne Huiet Michael Kessler Petra Korall Paulo H. Labiak Anders Larsson Blanca Leen Chun-Xiang Li Fay-Wei Li Melanie Link-Perez Hong-Mei Liu Ngan Thi Lu Esteban I. Meza-Torres Xin-Yuan Miao Robbin Moran Claudine Massi Mynssens Nathalie Nagalingum Benjamin Ollgaard Alison M. Paul Jovani B. de S. Pereira Leon R. Perrie Monica Ponce Tom A. Ranker Christian Schulz Wataru Shinohara Alexander Shmakov Erin M. Sigel Filipe Soares de Souza Lana da Silva Sylvestre Weston Testo Luz Amparo Triana-Moreno Chie Tsutsumi Hanna Tuomisto IvAn A. Valdespino Alejandra Vasco Raquel Stauffer Viveros Alan Weakley Ran Wei Stina Weststrand Paul G. Wolf George Yatskievych Xiao-Gang Xu Yue-Hong Yan Liang Zhang Xian-Chun Zhang Xin-Mao Zhou | 2016 | Journal of Systematics and Evolution2016，54，6： | 44 |
| 3 | 帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。 | 陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh | 2021 | 中华肿瘤防治杂志2021，28，24： | 49 |
| 4 | 最新AD研究用诊断标准:IWG-2标准显示文摘在过去的8年中,国际工作组织(IWG)和美国国立老化研究院-阿尔茨海默协会(NIA-AA)建立了阿尔茨海默病(AD)诊断标准,它能更好地定义AD的临床表型,整合了生物标记物于诊断流程中,并覆盖了疾病的全程。本意见书充分地权衡了IWG标准的优缺点,建议改进诊断框架。依据这些改进,AD的诊断变得简单,只要有恰当的AD临床表型(典型或不典型)和与AD的病理相一致的病理生理学生物标志物出现。我们认为疾病的下游的定位性生物标志,如容积性磁共振成像(MRI)和氟脱氧葡萄糖-正电子发射型计算机断层成像(FDG-PET)等,适合更好地测量和监测疾病过程。本文还详述了非典型性AD、混合性AD和AD临床前期的特异诊断标准。 | 陈刚 曹雯炜 俞羚 糜建华 Dubois B Feldman HH Jacova C Hampel H Molinuevo JL Blennow K DeK osky ST Gauthier S Selkoe D Bateman R Cappa S Crutch S Engelborghs S Frisoni GB Fox NC Galasko D Habert MO Jicha GA Nordberg A Pasquier F Rabinovici G Robert P Rowe C Salloway S Sarazin M Epelbaum S de Souza LC Vellas B Visser PJ Schneider L Stern Y Scheltens P Cummings JL | 2014 | 神经病学与神经康复学杂志2014，11，3： | 31 |
| 5 | Interplay between inflammation,immune system and neuronal pathways:Effect on gastrointestinal motility显示文摘Sepsis is a systemic inflammatory response representing the leading cause of death in critically ill patients,mostly due to multiple organ failure.The gastrointestinal tract plays a pivotal role in the pathogenesis of sepsisinduced multiple organ failure through intestinal barrier dysfunction,bacterial translocation and ileus.In this review we address the role of the gastrointestinal tract,the mediators,cell types and transduction pathways involved,based on experimental data obtained from models of inflammation-induced ileus and (preliminary) clinical data.The complex interplay within the gastrointestinal wall between mast cells,residential macrophages and glial cells on the one hand,and neurons and smooth muscle cells on the other hand,involves intracellular signaling pathways,Toll-like receptors and a plethora of neuroactive substances such as nitric oxide,prostaglandins,cytokines,chemokines,growth factors,tryptases and hormones.Multidirectional signaling between the different components in the gastrointestinal wall,the spinal cord and central nervous system impacts inflammation and its consequences.We propose that novel therapeutic strategies should target inflammation on the one hand and gastrointestinal motility,gas-trointestinal sensitivity and even pain signaling on the other hand,for instance by impeding afferent neuronal signaling,by activation of the vagal anti-inflammatory pathway or by the use of pharmacological agents such as ghrelin and ghrelin agonists or drugs interfering with the endocannabinoid system. | Benedicte Y De Winter Joris G De Man | 2010 | World Journal of Gastroenterology2010，16，44： | 23 |
| 6 | Schistosoma mansoni proteins attenuate gastrointestinal motility disturbances during experimental colitis in mice显示文摘AIM:To investigate the therapeutic effect of Schistosoma mansoni(S.mansoni) soluble worm proteins on gastrointestinal motility disturbances during experimental colitis in mice. METHODS:Colitis was induced by intrarectal injection of trinitrobenzene sulphate(TNBS) and 6 h later,mice were treated ip with S.mansoni proteins.Experiments were performed 5 d after TNBS injection.Inflammationwas quantified using validated inflammation parameters. Gastric emptying and geometric center were measured to assess in vivo gastrointestinal motility.Peristaltic activity of distal colonic segments was studied in vitro using a modified Trendelenburg set-up.Cytokine profiles of T-lymphocytes isolated from the colon were determined by real time reverse transcriptase-polymerase chain reaction. RESULTS:Intracolonic injection of TNBS caused severe colitis.Treatment with S.mansoni proteins significantly ameliorated colonic inflammation after 5 d.TNBS did not affect gastric emptying but significantly decreased the geometric center and impaired colonic peristaltic activity 5 d after the induction of colitis.Treatment with S.mansoni proteins ameliorated these in vivo and in vitro motility disturbances.In addition,TNBS injection caused a downregulation of effector T cell cytokines after 5 d,whereas a S.mansoni protein effect was no longer observed at this time point. CONCLUSION:Treatment with S.mansoni proteins attenuated intestinal inflammation and ameliorated motility disturbances during murine experimental colitis. | Nathalie E Ruyssers Benedicte Y De Winter Joris G De Man Natacha D Ruyssers Ann J Van Gils Alex Loukas Mark S Pearson Joel V Weinstock Paul A Pelckmans Tom G Moreels | 2010 | World Journal of Gastroenterology2010，16，6： | 11 |
| 7 | 长期食用含糖和人工甜味剂的饮料与美国成年人死亡风险的关系显示文摘摄入含糖饮料(sugar-sweetened beverages,SSB)或含人工甜味剂饮料(artificially sweetened beverages,ASB)是否与死亡风险相关,这关乎公共卫生利益。研究者分析了卫生专业人员随访研究(1986-2014年)中男性37 716人和护士健康研究(1980-2014年)中女性80 647人(基线无慢性病)的SSB和ASB的消费与总死亡率和病因特异性死亡率之间的关系。应用Cox比例风险回归估计风险比和95%CI。结果显示,在随访3415564人年期间,研究者记录了36436例死亡,其中心血管病死亡7896例,癌症死亡12380例。 | 刘青(译) 叶鹏(摘、审校) Malik VS Li Y Pan A De Koning L Schernhammer E Willett WC Hu FB | 2019 | 中华高血压杂志2019，27，5： | 9 |
| 8 | Neuroanatomy of lower gastrointestinal pain disorders显示文摘Chronic abdominal pain accompanying intestinal inflammation emerges from the hyperresponsiveness of neuronal,immune and endocrine signaling pathways within the intestines,the peripheral and the central nervous system.In this article we review how the sensory nerve information from the healthy and the hypersensitive bowel is encoded and conveyed to the brain.The gut milieu is continuously monitored by intrinsic enteric afferents,and an extrinsic nervous network comprising vagal,pelvic and splanchnic afferents.The extrinsic afferents convey gut stimuli to second order neurons within the superficial spinal cord layers.These neurons cross the white commissure and ascend in the anterolateral quadrant and in the ipsilateral dorsal column of the dorsal horn to higher brain centers,mostly subserving regulatory functions.Within the supraspinal regions and the brainstem,pathways descend to modulate the sensory input.Because of this multiple level control,only a small proportion of gut signals actually reaches the level of consciousness to induce sensation or pain.In inflammatory bowel disease(IBD)and irritable bowel syndrome(IBS)patients,however,long-term neuroplastic changes have occurred in the brain-gut axis which results in chronic abdominal pain.This sensitization may be driven on the one hand by peripheral mechanisms within the intestinal wall which encompasses an interplay between immunocytes,enterochromaffin cells,resident macrophages,neurons and smooth muscles.On the other hand,neuronal synaptic changes along with increased neurotransmitter release in the spinal cord and brain leads to a state of central wind-up.Also life factors such as but not limited to inflammation and stress contribute to hypersensitivity.All together,the degree to which each of these mechanisms contribute to hypersensitivity in IBD and IBS might be diseaseand even patient-dependent.Mapping of sensitization throughout animal and human studies may significantly improve our understanding of sensitization in IBD and IBS.On the long run,this knowledge can be put forward in potential therapeutic targets for abdominal pain in these conditions. | Wim Vermeulen Joris G De Man Paul A Pelckmans Benedicte Y De Winter | 2014 | World Journal of Gastroenterology2014，20，4： | 7 |
| 9 | Visceral hypersensitivity in inflammatory bowel diseases and irritable bowel syndrome: The role of proteases显示文摘Proteases, enzymes catalyzing the hydrolysis of peptide bonds, are present at high concentrations in the gastrointestinal tract. Besides their well-known role in the digestive process, they also function as signaling molecules through the activation of protease-activated receptors(PARs). Based on their chemical mechanism for catalysis, proteases can be classified into several classes: serine, cysteine, aspartic, metallo- and threonine proteases represent the mammalian protease families. In particular, the class of serine proteases will play a significant role in this review. In the last decades, proteases have been suggested to play a key role in the pathogenesis of visceral hypersensitivity, which is a major factor contributing to abdominal pain in patients with inflammatory bowel diseases and/or irritable bowel syndrome. So far, only a few preclinical animal studies have investigated the effect of protease inhibitors specifically on visceral sensitivity while their effect on inflammation is described in more detail. In our accompanying review we describe their effect on gastrointestinal permeability. On account of their promising results in the field of visceral hypersensitivity, further research is warranted. The aim of this review is to give an overview on the concept of visceral hypersensitivity as well as on the physiological and pathophysiological functions of proteases herein. | Hannah Ceuleers Hanne Van Spaendonk Nikita Hanning Jelena Heirbaut Anne-Marie Lambeir Jurgen Joossens Koen Augustyns Joris G De Man Ingrid De Meester Benedicte Y De Winter | 2016 | World Journal of Gastroenterology2016，22，47： | 7 |
| 10 | Chronic stress sensitizes rats to pancreatitis induced by cerulein:Role of TNF-α显示文摘AIM:To investigate chronic stress as a susceptibility factor for developing pancreatitis,as well as tumor necrosis factor-α (TNF-α) as a putative sensitizer.METHODS:Rat pancreatic acini were used to analyze the influence of TNF-α on submaximal (50 pmol/L) cholecystokinin (CCK) stimulation.Chronic restraint (4 h every day for 21 d) was used to evaluate the effects of submaximal (0.2 μg/kg per hour) cerulein stimulation on chronically stressed rats.RESULTS:In vitro exposure of pancreatic acini toTNF-α disorganized the actin cytoskeleton.This was further increased by TNF-α/CCK treatment,which additionally reduced amylase secretion,and increased trypsin and nuclear factor-κB activities in a protein-kinase-C δ and ε-dependent manner.TNF-α/CCK also enhanced caspases' activity and lactate dehydrogenase release,induced ATP loss,and augmented the ADP/ATP ratio.In vivo,rats under chronic restraint exhibited elevated serum and pancreatic TNF-α levels.Serum,pancreatic,and lung inflammatory parameters,as well as caspases' activity in pancreatic and lung tissue,were substantially enhanced in stressed/cerulein-treated rats,which also experienced tissues' ATP loss and greater ADP/ATP ratios.Histological examination revealed that stressed/cerulein-treated animals developed abundant pancreatic and lung edema,hemorrhage and leukocyte infiltrate,and pancreatic necrosis.Pancreatitis severity was greatly decreased by treating animals with an anti-TNF-αantibody,which diminished all inflammatory parameters,histopathological scores,and apoptotic/necrotic markers in stressed/cerulein-treated rats.CONCLUSION:In rats,chronic stress increases susceptibility for developing pancreatitis,which involves TNF-α sensitization of pancreatic acinar cells to undergo injury by physiological cerulein stimulation. | Marcelo G Binker Andres A Binker-Cosen Daniel Richards Herbert Y Gaisano Rodica H de Cosen Laura I Cosen-Binker | 2010 | World Journal of Gastroenterology2010，16，44： | 7 |
| 11 | 运用《国际功能、残疾和健康分类》比较脑卒中康复功能性结局测量的内容显示文摘目的确定常用于脑卒中康复结局测量内容,主要是关于活动和参与的,并与《国际功能、残疾和健康分类》(ICF)对照。方法将以下量表的结构与ICF建立联系:Barthel指数(BI)、Berg平衡功能量表(BBS)、Chedoke Mc Master脑卒中评定量表(CMSA)、Euroqol-5D欧洲生活质量量表(EQ5D)、FI M功能独立性测量、Frenchay活动指数、Nottingham健康测验(NHP)、Rankin量表(RS)、Rivermead动作测量(RMA)、Rivermead移动指数(RMI)、中风影响测验-30(SASIP30)、医学结局研究简表(SF36),卒中影响量表(SIS)、脑卒中特定生存质量量表(SSQOL)和站立行走测验(TUG)。结果功能性结局测量中的绝大多数结构可与ICF分类建立联系。这些测量工具可以归入活动和参与的成份,活动是测量工具中最常见的类目内容。虽然测量工具的选择是基于它们主要关注的'活动'与'参与'内容,但有27%的结构属于身体功能类目,也有大约10%的结构与ICF不相关。结论在脑卒中的康复中,ICF是一种有效的工具来检测和比较脑卒中各测量工具的内容。这些内容上的比较使得临床医生和研究者们选择最符合他们兴趣和要求的测量。 | V. P. M. SCHEPERS M. KETELAAR I. G. L. VAN DE PORT J. M. A. VISSER-MEIL Y & E. LINDEMAN 王朴(译) 李沁燚(译) 邱卓英(审校) 吴弦光(审校) | 2008 | 中国康复理论与实践2008，14，12： | 6 |
| 12 | Regulation of intestinal permeability: The role of proteases显示文摘The gastrointestinal barrier is-with approximately 400 m^2-the human body's largest surface separating the external environment from the internal milieu. This barrier serves a dual function: permitting the absorption of nutrients, water and electrolytes on the one hand, while limiting host contact with noxious luminal antigens on the other hand. To maintain this selective barrier, junction protein complexes seal the intercellular space between adjacent epithelial cells and regulate the paracellular transport. Increased intestinal permeability is associated with and suggested as a player in the pathophysiology of various gastrointestinal and extraintestinal diseases such as inflammatory bowel disease, celiac disease and type 1 diabetes. The gastrointestinal tract is exposed to high levels of endogenous and exogenous proteases, both in the lumen and in the mucosa. There is increasing evidence to suggest that a dysregulation of the protease/antiprotease balance in the gut contributes to epithelial damage and increased permeability. Excessive proteolysis leads to direct cleavage of intercellular junction proteins, or to opening of the junction proteins via activation of protease activated receptors. In addition, proteases regulate the activity and availability of cytokines and growth factors, which are also known modulators of intestinal permeability. This review aims at outlining the mechanisms by which proteases alter the intestinal permeability. More knowledge on the role of proteases in mucosal homeostasis and gastrointestinal barrier function will definitely contribute to the identification of new therapeutic targets for permeability-related diseases. | Hanne Van Spaendonk Hannah Ceuleers Leonie Witters Eveline Patteet Jurgen Joossens Koen Augustyns Anne-Marie Lambeir Ingrid De Meester Joris G De Man Benedicte Y De Winter | 2017 | World Journal of Gastroenterology2017，23，12： | 6 |
| 13 | 成人型梭行细胞横纹肌肉瘤高频发生MYOD1基因反式激活突变显示文摘习惯上将横纹肌肉瘤(RMS)分为以下3型,即腺泡状横纹肌肉瘤(ARMS)、胚胎型横纹肌肉瘤(ERMS)及多形性横纹肌肉瘤(PRMS),而ERMS中包括了梭形细胞RMS。在2013版的WHO软组织及骨肿瘤分类中,梭形细胞RMS已从ERMS中分离出来,其梭形细胞/硬化性RMS被列为一种独立的类型。迄今为止,成人梭形细胞RMS并未被检测到高频发生的基因突变。 | Szuhai K de Jong D Leung A Y 杨文婷(摘译) 余英豪(审校) | 2014 | 临床与实验病理学杂志2014，30，5： | 6 |
| 14 | Recognition Interactions of Metal-complexing Imprinted Polymer显示文摘Molecularly imprinted polymer, exhibiting considerable enantioselectivity for L-mandelic acid, was prepared using metal coordination-chelation interaction. By evaluating the recognition characteristics in the chromatographic mode, the recognition interactions were proposed: specific and nonspecific metal coordination-chelation interaction and hydrophobic interaction were responsible for substrate binding on metal-complexing imprinted polymer; while the selective recognition only came from specific metal coordination-chelation interaction and specific hydrophobic interaction. | Liu, Y Ding, GS De Wang, J | 2005 | Chinese Chemical Letters2005，16，6： | 5 |
| 15 | WONCA研究论文摘要汇编——初级医疗连续性服务及其与老年人生存的关系:一项17年的前瞻性队列研究显示文摘背景尽管连续性服务在基层医疗中是被广泛接受的核心原则,但是关于其优势的证据仍然不足。目的探讨全科医学中连续性服务是否与老年人长寿相关。设计与场所数据来源于阿姆斯特丹纵向衰老研究,对荷兰老年人进行不间断队列研究。研究样本包括1 712例年龄≥60岁的老年人,进行3年随访,周期长达17年,随访其死亡率直至2013年。方法连续性服务被定义为患者和全科医生之间不间断的治疗关系的持续过程。采用赫芬达尔-赫希曼指数计算服务的连续性(COC)。COC指数为1代表最大连续性。将COC指数〈1的患者分为3组,COC最大值的参与者为第4组。采用Cox回归分析探讨COC和存活时间之间的关联。结果 742例参与者(43.3%)COC取得最大值。在生存17年的759例参与者中,251例(33.1%)仍有相同的全科医生服务。COC最小值组(指数〉0~0.500)死亡率高于COC最大值组,差异有统计学意义〔HR=1.20,95%CI(1.01,1.42)〕。目前无混杂因素影响该HR。结论该研究表明全科医学中低连续性服务与高死亡风险相关,应强化该案例以鼓励连续性服务。 | MAARSINGH O R HENRY Y VAN DE VEN P M 本刊编辑部 | 2016 | 中国全科医学2016，19，27： | 4 |
| 16 | On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprineor 6-mercaptopurine intolerant IBD patients显示文摘AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year.METHODS: Database analysis.RESULTS: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%)and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly.CONCLUSION: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials. | Nanne KH de Boer Luc JJ Derijks Lennard PL Gilissen Daniel W Hommes Leopold GJB Engels Sybrand Y de Boer Gijsbertus den Hartog Piet M Hooymans Anja BU M(?)kelburg Barend D Westerveld Anton HJ Naber Chris JJ Mulder Dirk J de Jong | 2005 | World Journal of Gastroenterology2005，11，35： | 4 |
| 17 | Costimulation of resting B lymphocytes alters the IL-4-activated IRS2 signaling pathway in a STAT6 independent manner: implications for cell survival and proliferation显示文摘IL-4 is an important B cell survival and growth factor. IL-4 induced the tyrosine phosphorylation of IRS2 in resting B lymphocytes and in LPS- or CD40L-activated blasts. Phosphorylated IRS2 coprecipitated with the p85 subunit of PI 3’ kinase in both resting and activated cells. By contrast, association of phosphorylated IRS2 with GRB2 was not detected in resting B cells after IL-4 treatment although both proteins were expressed. However, IL-4 induced association of IRS2 with GRB2 in B cell blasts. The pattern of IL-4- induced recruitment of p85 and GRB2 to IRS2 observed in B cells derived from STAT6 null mice was identical to that observed for normal mice. While IL-4 alone does not induce activation of MEK, a MEKI inhibitor suppressed the IL-4-induced proliferative response of LPS-activated B cell blasts. These results demonstrate that costimulation of splenic B cells alters IL-4-induced signal transduction independent of STAT6 leading to proliferation. Furthermore, proliferation induced by IL-4 in LPS-activated blasts is dependent upon the MAP kinase pathway. | ZAMORANO JOSE,Unidad de Investigacion, Hospital San Pedro de Alcantara, Avda Millan Astray, 10003 Caceres ANN E KELLY, JONATHAN AUSTRIAN, HELEN Y WANG, ACHSAH D KEEGAN (Department of Immunology, Jerome Holland Labs, American Red Cross, Rockville, MD, USA | 2001 | Cell Research2001，11，1： | 4 |
| 18 | Langerhans cell histiocytosis masquerading as acute appendicitis: Case report and review显示文摘Langerhans cell histiocytosis(LCH) is a rare syndrome characterized by unifocal,multifocal unisystem,or disseminated/multi-system disease that commonly involves the bone,skin,lymph nodes,pituitary,or sometimes lung(almost exclusively in smokers) causing a variety of symptoms from rashes and bone lesions to diabetes insipidus or pulmonary infiltrates.We present a previously unreported case of gastrointestinal LCH as well as a novel characteristic lesion affecting the colon of a young woman who presented with signs and symptoms mimicking acute on chronic appendicitis.Immunohistochemical analysis of appendectomy specimen and nodular specimens on colonoscopy demonstrated S-100,CD1a,and langerin reactivity.The patient underwent systemic chemotherapy with cytarabine and demonstrated excellent response to therapy. | Mohammad M Karimzada Michele N Matthews Samuel W French Daniel De Ugarte Dennis Y Kim | 2017 | World Journal of Gastrointestinal Endoscopy2017，9，3： | 3 |
| 19 | Acute fatty liver of pregnancy associated with severe acute pancreatitis:A case report显示文摘Acute fatty liver of pregnancy is a rare disease that affects women in the third trimester of pregnancy. Although infrequent, the disease can cause maternal mortality. The diagnosis is not always clear until the pregnancy is terminated, and significant complications, such as acute pancreatitis, can occur. Pancreatic involvement typically only occurs in severe cases after the development of hepatic and renal impairment. To date, little knowledge is available regarding how the disease causes pancreatitis. Treatment involves supportive measures and pregnancy interruption. In this report, we describe a case of a previously healthy 26-year-old woman at a gestational age of 27 wk and 6 d who was admitted with severe abdominal pain and vomiting. This case illustrates the clinical and laboratory overlap between acute fatty liver of pregnancy and pancreatitis, highlighting the difficulties in differentiating each disease. Furthermore, the hypothesis for this overlapping is presented, and the therapeutic options are discussed. | Cássio Vieira de Oliveira Alecsro Moreira Julio P Baima Leticia de C Franzoni Talles B Lima Fabio da S Yamashiro Kunie Yabuki Rabelo Coelho Ligia Y Sassaki Carlos Antonio Caramori Ferno G Romeiro Giovanni F Silva | 2014 | World Journal of Hepatology2014，6，7： | 3 |
| 20 | Toll‐Like Receptors and Cytokines are Upregulated during H elicobacter pylori Infection in Children显示文摘 | Hugo Lagunes‐Servin Javier Torres Carmen Maldonado‐Bernal Martha Pérez‐Rodríguez Sara Huerta‐Yépez Armando Madrazo de la Garza Leopoldo Mu?oz‐Pérez Lourdes Flores‐Luna Guillermo Ramón‐García Margarita Camorlinga‐Ponce | 2013 | Helicobacter2013，，6： | 2 |
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