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| 1 | Hepatic steatosis is associated with an increased risk of carotid atherosclerosis显示文摘AIM: Although an association between helatic steatosis and vascular risk factors has been described, direct relationships between fatty liver and atherosclerosis have not yet been investigated. The aim of the present study has been to investigate those relationships.METHODS: The Study of Health in Pomerania examined a random population sample aged between 20 and 79 years.A study population of 4 222 subjects without hepatitis B and C infections and without liver cirrhosis was available for the present analysis. Hepatic steatosis was defined sonographically and intima-media thickness (IMT) as well as plaque prevalence were estimated by carotid ultrasound.RESULTS: The prevalence rate of hepatic steatosis was 29.9%. Among subjects aged ≥45 years, an association between hepatic steatosis and IMT of the carotid arteries was found in bivariate analysis, but not after adjustment for atherosclerotic risk factors. Individuals with fatty liver had more often carotid plaques than persons without fatty liver (plaque prevalence rate 76.8% vs 66.6%; P<0.001).This association persisted after adjustment for confounding factors and was predominantly present in subjects with no to mild alcohol consumption.CONCLUSION: There is an independent association between hepatic steatosis and carotid atherosclerotic plaques. Metabolic changes due to nonalcoholic fatty liver disease may explain this relationship. | Henry V(o|¨)lzke Daniel M.Robinson Volker Kleine Roland Deutscher Wolfgang Hoffmann Jan Lüdemann Ulf Schminke Christof Kessler Ulrich John | 2005 | World Journal of Gastroenterology2005，11，12： | 29 |
| 2 | Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases显示文摘AIM To investigate whether immune mediated diseases(IMD) are more frequent in patients with inflammatory bowel disease(IBD).METHODS In this population based registry study,a total of 47325 patients with IBD were alive and registered in the Danish National Patient Registry on December 16,2013. Controls were randomly selected from the Danish Civil Registration System(CRS) and matched for sex,age,and municipality. We used ICD 10 codes to identify the diagnoses of the included patients. The IBD population was divided into three subgroups: Ulcerative colitis(UC),Crohn's disease(CD) and Both the latter referring to those registered with both diagnoses. Subsequently,odds-ratios(OR) and 95%CI were obtained separately for each group and their respective controls. The use of Bonferoni post-test correction adjusted the significance level to P < 0.00125. P-values were estimated using Fisher's exact test.RESULTS There were significantly more women than men in the registry,and a greater percentage of comorbidity in the IBD groups(P < 0.05). Twenty different IMDs were all significantly more frequent in the IBD group. Sixteen were associated with UC versus twelve with CD. In both UC and CD ORs were significantly increased(P < 0.00125) for primary sclerosing cholangitis(PSC),celiac disease,type 1 diabetes(T1D),sarcoidosis,asthma,iridocyclitis,psoriasis,pyoderma gangrenosum,rheumatoid arthritis,and ankylosing spondylitis. Restricted to UC(P < 0.00125) were autoimmune hepatitis,primary biliary cholangitis,Grave's disease,polymyalgia rheumatica,temporal arteritis,and atrophic gastritis. Restricted to CD(P < 0.00125) were psoriatic arthritis and episcleritis. Restricted to women with UC(P < 0.00125) were atrophic gastritis,rheumatoid arthritis,temporal arteritis,and polymyalgia rheumatica. Restricted to women with CD were episcleritis,rheumatoid arthritis,and psoriatic arthritis. The only disease restricted to men(P < 0.00125) was sarcoidosis. CONCLUSION Immune mediated diseases were significantly more frequent in patients with IBD. Our results strengthen the hypothesis that some IMDs and IBD may have overlapping pathogenic pathways. | Morten L Halling Jens Kjeldsen Torben Knudsen Jan Nielsen Lars Koch Hansen | 2017 | World Journal of Gastroenterology2017，23，33： | 9 |
| 3 | Plastins:versatile modulators of actin organization in (patho)physiological cellular processes显示文摘Many actin-binding proteins are expressed in eukaryotic cells. These polypeptides assist in stabilizing and rearranging the organization of the actin cytoskeleton in response to external stimuli, or during cell migration and adhesion. Here we review a particular set of actin-binding proteins called plastins. Plastins (also called fimbrins) belong to a subclass of actin-binding proteins known as actin bundling proteins. Three isoforms have been characterized in mammals: T-plastin is expressed in cells from solid tissue, whereas L-plastin occurs predominantly in hematopoietic cells. The third isoform, I-plastin, is specifically expressed in the small intestine, colon and kidney. These proteins share the unique property of cross-linking actin filaments into tight bundles. Although plastins are primarily involved in regulation of the actin cytoskeleton, they possess some unique features. For instance, they are implicated in invasion by pathogenic bacteria such as Shigellaflexneri and Salmonella typhimurium. Also, L-plastin plays an important role in leukocyte function. T-plastin, on the other hand, is possibly involved in DNA repair. Finally, both T- and L-plastin are implicated in several diseases, and L-plastin is considered to be a valuable marker for cancer. | Veerle DELANOTE Jo■l VANDEKERCKHOVE Jan GETTEMANS | 2005 | Acta Pharmacologica Sinica2005，26，7： | 8 |
| 4 | Electroconvulsive therapy and/or plasmapheresis in autoimmune encephalitis?显示文摘Autoimmune encephalitis is a poorly understood condition that can present with a combination of neurological and psychiatric symptoms, either of which may predominate. There are many autoantibodies associated with a variety of clinical syndromes-anti-N-Methyl-D-Aspartate receptor(NMDAR) is the commonest. Currently, the most widely used therapy is prompt plasmapheresis and steroid treatment(and tumour resection if indicated), followed by second line immunosuppression if this fails. Given the growing awareness of autoimmune encephalitis as an entity, it is increasingly important that we consider it as a potential diagnosis in order to provide timely, effective treatment. We discuss several previously published case reports and one new case. These reports examined the effects of electroconvulsive therapy(ECT) on patients with autoimmune encephalitis, particularly those in whom psychiatric symptoms are especially debilitating and refractory to standard treatment. We also discuss factors predicting good outcome and possible mechanisms by which ECT may be effective. Numerous cases, such as those presented by Wingfield, Tsutsui, Florance, Sansing, Braakman and Matsumoto, demonstrate effective use of ECT in anti-NMDAR encephalitis patients with severe psychiatric symptoms such as catatonia, psychosis, narcolepsy and stupor who had failed to respond to standard treatments alone. We also present a new case of a 71-year-old female who presented to a psychiatric unit initially with depression, which escalated to catatonia, delusions, nihilism and auditory hallucinations. After anti-NMDAR antibodies were isolated, she was treated by the neurology team with plasmapheresis and steroids, with a partial response. She received multiple sessions of ECT and her psychiatric symptoms completely resolved and she returned to her premorbid state. For this reason, we suggest that ECT should be considered, particularly in those patients who are non-responders to standard therapies. | Jessica L Gough Jan Coebergh Brunda Chandra Ramin Nilforooshan | 2016 | World Journal of Clinical Cases2016，4，8： | 8 |
| 5 | Significant decrease in prevalence ofHelicobacter pylori in the Czech Republic显示文摘AIM:To study possible decrease in prevalence of Helicobacter pylori(H.pylori) infection in the Czech Republic within a 10-year period.METHODS:A total of 22 centres entered the study.The catchment areas of these centres covered cities and towns with more than 20 000 inhabitants,smaller towns(≤ 20 000 inhabitants) with surrounding villages and rural areas,and were spread over the whole country,corresponding well to the geographical distribution of the Czech population.A total of 1 837 subjects(aged 5-98 years) took part in the study,randomly selected out of 38 147 people from the general population.H.pylori infection was investigated by means of a 13 C-urea breath test.Breath samples in duplicates were analysed using isotope ratio mass spectrometry.The cut-off point was 3.5.Social and demographic characteristics were based on data from self-completed questionnaires.RESULTS:The overall prevalence of H.pylori infection was 23.5%(430/1826),and 4.8%(20/420) in children aged 15 or less.There was no statistically significant difference in prevalence between males(24.3%;208/857) and females(22.9%,222/969,P = 0.494).H.pylori infection was strongly associated with higher age,among subjects aged 55+ years,prevalence of H.pylori infection was 39.8%(252/633,P < 0.001).The highest prevalence of H.pylori infection was found among persons aged 55-64 years(43.9%,97/221) and 75+ years(37.9%,58/153).Among study subjects aged 15+ years,prevalence of H.pylori infection was significantly increased in those with lowest education(odds risk 3.19,95% CI 1.87-5.47).Compared to never married(14.1%),the prevalence of H.pylori infection was statistically significantly higher among married(35.4%,246/694,P < 0.001),divorced(36.8%,49/133,P < 0.001) and widowed study subjects(40.2%,45/112,P < 0.001),both in minimally and fully adjusted analysis.There was no significant difference in the prevalence of H.pylori infection between married and widowed subjects(35.4%,246/694 vs 40.2%,45/112,P = 0.389).There was little variation in smoking prevalence across categories of smoking and there was no evidence of an increased risk ofH.pylori infection among current or past smokers in our data(odds risk 1.04 with 95% CI 0.78-1.40 for current smokers;odds ratio 0.83 with 95% CI 0.60-1.16 for former smokers).The current prevalence of H.pylori in 2011 was significantly lower compared to the prevalence reported from identical geographical areas in 2001(23.5%vs 41.7%,P < 0.001).CONCLUSION:The overall prevalence of H.pylori infection in the general population has fallen substantially in the Czech Republic over the past 10 years. | Jan Bure Marcela Kopáová Ilona Koupil Bohumil Seifert Miluka kodová Fendrichová Jana pirková Viktor Voíek Stanislav Rejchrt TomáDouda Norbert Král Ilja Tachecí | 2012 | World Journal of Gastroenterology2012，18，32： | 8 |
| 6 | Treatment of periodontal patients - current clinical concepts显示文摘The main goal of the treatment of patients with periodontitis is to establish adequate infection control. To satisfy demands for acceptable aesthetics and chewing function with good long-term prognosis in patients with periodontitis requires the establishment of adequate infection control. Pocket instrumentation (scaling and root planing with or without flap elevation), combined with effective self-performed supragingival plaque control measures, constitutes the basic treatment modalities. | Cristiano Tomasi Claudio Soldini Jan L Wennstr(o|¨)m | 2007 | 上海口腔医学2007，16，2： | 8 |
| 7 | 固定低剂量三联抗高血压药物与常规治疗对斯里兰卡轻度至中度高血压患者血压控制的疗效差异:一项随机临床试验显示文摘控制不良的高血压是全球领先的公共卫生问题,需要新的治疗策略。该研究评估低剂量三联抗高血压药物治疗是否能达到比常规治疗更好的血压控制。研究者纳入2016年2月至2017年5月在斯里兰卡11所城市医院诊所就诊的需要开始抗高血压治疗(未治疗的患者)或接受单药治疗的患者,进行低剂量三联降压与常规治疗比较的随机、开放性试验,随访至2017年10月。 | Web-ster R Salam A de Silva HA Selak V Stepien S Rajapakse S Amarasekara S Amarasena N Billot L de Silva AP Fernando M Guggilla R Jan S Jayawardena J Maulik PK Mendis S Munasinghe J Naik N Prabhakaran D Ranasinghe G Thom S Tisserra N Senaratne V Wijekoon S Wijeyasingam S Rodgers A Patel A 刘莉 叶鹏 | 2018 | 中华高血压杂志2018，26，12： | 7 |
| 8 | 大气二氧化氮与每日总死亡率、心血管和呼吸系统疾病死亡率的短期关联:398个城市的多中心分析显示文摘目的:采用统一的分析方案,评估全球多个国家/地区的二氧化氮(NO_(2))与总死亡率、心血管和呼吸系统疾病死亡率之间的短期关联。研究设计:采用两阶段的时间序列分析方法、过度离散的广义线性模型和多水平meta分析。研究地点:22个低到高收入国家/地区的398个城市。主要结局指标:1973—2018年逐日总死亡人数(6280万人)、心血管疾病死亡人数(1970万人)和呼吸系统疾病死亡人数(550万人)。结果:平均而言,NO_(2)浓度在滞后1天(前1天)每增加10μg/m^(3),会导致总死亡率、心血管和呼吸系统疾病死亡率分别增加0.46%(95%可信区间0.36%~0.57%)、0.37%(0.22%~0.51%)、0.47%(0.21%~0.72%)。在对共污染物(PM_(10)、PM_(2.5)、臭氧、二氧化硫和一氧化碳)进行调整后,这些关联仍然很稳定。所有3种死因的暴露-反应曲线几乎是线性的,没有明显的阈值。在398个城市中,可归因于高过假定零水平的NO_(2)浓度造成的死亡比例为1.23%(95%可信区间0.96%~1.51%)。结论:这项多中心研究提供了关于NO_(2)短期暴露与总死亡率、心血管和呼吸系统死亡风险之间的独立和线性关联的关键证据,说明通过加强NO_(2)的控制和监管限制标准,可获得人群水平的健康收益。 | 孟夏 刘聪(校) 陈仁杰 郑湃(译) 阚海东(校) Francesco Sera Ana Vicedo-Cabrera Ai Milojevic Maria Guo Yuming Tong Shilu Micheline de Sousa Zanotti Stagliorio Coelh Paulo Hilario Nascimento Saldiva Eric Lavigne Patricia Matus Correa Nicolas Valdes Ortega Samuel Osorio Garcia Jan Kysely Ales Urban Hans Orru Marek Maasikmets Jouni J K Jaakkola Niilo Ryti Veronika Huber Alexandra Schneider Klea Katsouyanni Antonis Analitis Masahiro Hashizume Yasushi Honda Chris Fook Sheng Ng Baltazar Nunes João Paulo Teixeira Iulian Horia Holobaca Simona Fratianni Ho Kim Aurelio Tobias Carmeníniguez Bertil Forsberg ChristoferÅström Martina S Ragettli Yue-Liang Leon Guo Shih-Chun Pan Shanshan Li Michelle L Bell Antonella Zanobetti Joel Schwartz Tangchun Wu Antonio Gasparrini | 2021 | 英国医学杂志中文版2021，24，8： | 7 |
| 9 | Detection and characterization of murine colitis and carcinogenesis by molecularly targeted contrast-enhanced ultrasound显示文摘AIM To study mucosal addressin cellular adhesion molecule-1(MAd CAM-1) and vascular endothelial growth factor(VEGF)-targeted contrast enhanced ultrasound(CEUS) for the assessment of murine colitis and carcinogenesis. METHODS C57BL/6 mice were challenged with 3% dextran sodium-sulfate(DSS) for three, six or nine days to study the development of acute colitis. Ultrasound was performed with and without the addition of unspecific contrast agents. MAd CAM-1-targeted contrast agent was used to detect and quantify MAd CAM-1 expression. Inflammatory driven colorectal azoxymethane(AOM)/DSS-induced carcinogenesis was examined on day 42 and 84 using VEGF-targeted contrast agent. Highly specific tissue echogenicity was quantified using specialized software. Sonographic findings were correlated to tissue staining, western blot analysis and immunohistochemistry to quantify the degree of inflammation and stage of carcinogenesis. RESULTS Native ultrasound detected increased general bowel wall thickening that correlated with more progressed and more severe DSS-colitis(healthy mice: 0.3 mm ± 0.03 vs six days DSS: 0.5 mm ± 0.2 vs nine days DSS: 0.6 mm ± 0.2, P < 0.05). Moreover, these sonographic findings correlated well with clinical parameters such as weight loss(r2 = 0.74) and histological damage(r2 = 0.86)(P < 0.01). In acute DSS-induced murine colitis, CEUS targeted against MAd CAM-1 detected and differentiated stages of mild, moderate and severe colitis via calculation of mean pixel contrast intensity in decibel(9.6 d B ± 1.6 vs 12.9 d B ± 1.4 vs 18 d B ± 3.33, P < 0.05). Employing the AOM/DSSinduced carcinogenesis model, tumor development was monitored by CEUS targeted against VEGF and detected a significantly increased echogenicity in tumors as compared to adjacent healthy mucosa(healthy mucosa, 1.6 d B ± 1.4 vs 42 d, 18.2 d B ± 3.3 vs 84 d, 18.6 d B ± 4.9, P < 0.01). Tissue echogenicity strongly correlated with histological analysis and immunohistochemistry findings(VEGF-positive cells in 10 high power fields of healthy mucosa: 1 ± 1.2 vs 42 d after DSS start: 2.4 ± 1.6 vs 84 d after DSS start: 3.5 ± 1.3, P < 0.01). CONCLUSION Molecularly targeted CEUS is a highly specific and noninvasive imaging modality, which characterizes murine intestinal inflammation and carcinogenesis in vivo. | Markus Brückner Jan Heidemann Tobias M Nowacki Friederike Cordes Jorg Stypmann Philipp Lenz Faekah Gohar Andreas Lügering Dominik Bettenworth | 2017 | World Journal of Gastroenterology2017，23，16： | 4 |
| 10 | Putting things in place for fertilization: discovering roles for importin proteins in cell fate and spermatogenesis显示文摘Importin 蛋白质原来通过原子毛孔在蛋白质运输为他们的中央角色被描绘,唯一的细胞内部的入口到原子核。这个重要函数必须紧被调整由抄写因素和另外的原子蛋白质控制存取到 genomic DNA,到完成细胞的行为影响的适当调整房间命运。调停 Importin 的 nucleocytoplasmic 运输依靠他们货物的特定的识别,与到不同、重叠的蛋白质子集的每 importin 绑定。importin 功能的知识关于三个关键发展系统实质地膨胀了:胚胎的干细胞,肌肉房间和细菌排队。自从为调整 nucleocytoplasmic 运输的潜力被建议贡献精子发生,在十年,我们和其它证明了进原子核的渡船抄写因素执行的 importins 另外的角色,它控制房间命运。这评论从哺乳动物的精子发生的研究介绍关键调查结果揭示男富饶和不孕由产生的潜在的新小径。germline 开始的这些研究照亮 importin 蛋白质在管理细胞的区别的新方法,经由指导到不同细胞内部的分隔空间并且由决定细胞的压力回答的蛋白质包括。 | Kate L Loveland Andrew T Major Romaly Butler Julia C Young David A Jan Yoichi Miyamoto | 2015 | Asian Journal of Andrology2015，17，4： | 3 |
| 11 | Neonatal vitamin A injection promotes cattle muscle growth and increases oxidative muscle fibers显示文摘Background: Vitamin A and its metabolite,retinoic acid(RA),are important regulators of cell differentiation and organ morphogenesis.Its impact on beef cattle muscle growth remains undefined.Method: Angus steer calves were administrated with 0(control) or 150,000 IU vitamin A(retinyl palmitate in glycerol,i.m.) per calf at birth and 1 month of age.At 2 months of age,a biopsy of the Biceps femoris muscle was obtained to analyze the immediate effects of vitamin A injection on myogenic capacity of muscle cells.The resulting steers were harvested at 14 months of age.Results: Vitamin A administration increased cattle growth at 2 months.At 2 months of age,Vitamin A increased PAX7 positive satellite cells and the expression of myogenic marker genes including PAX7,MYF5,MYOD and MYOG.Muscle derived mononuclear cells were further isolated and induced myogenesis in vitro.More myotubes and a higher degree of myogenesis was observed in vitamin A groups.Consistently,vitamin A increased Latissimus dorsi(LD) muscle fiber size at harvest.In addition,vitamin A increased the ratio of oxidative type I and type IIA fibers and reduced the glycolic type IIX fibers.Furthermore,we found that RA,a key bioactive metabolite of vitamin A,activated PPARGC1 A promoter,which explains the upregulated expression of PPARGC1 A in skeletal muscle.Conclusion: Vitamin A administration to neonatal calves enhanced postnatal muscle growth by promoting myogenesis and increasing satellite cell density,accompanied with a shift to oxidative muscle fibers. | Bo Wang Wei Nie Xing Fu Jeanene M de Avila Yannan Ma Mei-Jun Zhu Martin Maquivar Steven M Parish Jan R Busboom Mark L Nelson Min Du | 2019 | Journal of Animal Science and Biotechnology2019，10，1： | 3 |
| 12 | One stop shop:backbones trees for important phytopathogenic genera:Ⅰ(2014)显示文摘Many fungi are pathogenic on plants and cause significant damage in agriculture and forestry.They are also part of the natural ecosystem and may play a role in regulating plant numbers/density.Morphological identification and analysis of plant pathogenic fungi,while important,is often hampered by the scarcity of discriminatory taxonomic characters and the endophytic or inconspicuous nature of these fungi.Molecular(DNA sequence)data for plant pathogenic fungi have emerged as key information for diagnostic and classification studies,although hampered in part by non-standard laboratory practices and analytical methods.To facilitate current and future research,this study provides phylogenetic synopses for 25 groups of plant pathogenic fungi in the Ascomycota,Basidiomycota,Mucormycotina(Fungi),and Oomycota,using recent molecular data,up-to-date names,and the latest taxonomic insights.Lineagespecific laboratory protocols together with advice on their application,as well as general observations,are also provided.We hope to maintain updated backbone trees of these fungal lineages over time and to publish them jointly as new data emerge.Researchers of plant pathogenic fungi not covered by the present study are invited to join this future effort.Bipolaris,Botryosphaeriaceae,Botryosphaeria,Botrytis,Choanephora,Colletotrichum,Curvularia,Diaporthe,Diplodia,Dothiorella,Fusarium,Gilbertella,Lasiodiplodia,Mucor,Neofusicoccum,Pestalotiopsis,Phyllosticta,Phytophthora,Puccinia,Pyrenophora,Pythium,Rhizopus,Stagonosporopsis,Ustilago and Verticillium are dealt with in this paper. | Kevin D.Hyde R.Henrik Nilsson S.Aisyah Alias Hiran A.Ariyawansa Jaime E.Blair Lei Cai Arthur W.A.M.de Cock Asha J.Dissanayake Sally L.Glockling Ishani D.Goonasekara Michal Gorczak Matthias Hahn Ruvishika S.Jayawardena Jan A.L.van Kan Matthew H.Laurence C.AndréLévesque Xinghong Li Jian-Kui Liu Sajeewa S.N.Maharachchikumbura Dimuthu S.Manamgoda Frank N.Martin Eric H.C.McKenzie Alistair R.McTaggart Peter E.Mortimer Prakash V.R.Nair Julia Pawlowska Tara L.Rintoul Roger G.Shivas Christoffel F.J.Spies Brett A.Summerell Paul W.J.Taylor Razak B.Terhem Dhanushka Udayanga Niloofar Vaghefi Grit Walther Mateusz Wilk Marta Wrzosek Jian-Chu Xu JiYe Yan Nan Zhou | 2014 | Fungal Diversity2014，，4： | 3 |
| 13 | 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 |
| 14 | CD28/CTLA-4/B7 and CD40/CD40L costimulation and activation of regulatory T cells显示文摘Costimulatory signals are crucial for T cell activation. Attempts to block costimulatory pathways have been effective in preventing unwanted immune reactions. In particular, blocking the CD28/cytotoxic T lymphocyte antigen(CTLA)-4/B7 interaction(using CTLA-4Ig) and the CD40/CD40 L interaction(using anti-CD40 L antibodies) prevents T cell mediated autoimmune diseases, transplant rejection and graft vs host disease in experimental models. Moreover, CTLA-4Ig is in clinical use to treat rheumatoid arthritis(abatacept) and to prevent rejection of renal transplants(belatacept). Under certain experimental conditions, this treatment can even result in tolerance. Surprisingly, the underlying mechanisms of immune modulation are still not completely understood. We here discuss the evidence that costimulation blockade differentially affects effector T cells(Teff) and regulatory T cells(Treg). The latter are required to control inappropriate and unwanted immune responses, and their activity often contributes to tolerance induction and maintenance. Unfortunately, our knowledge on the costimulatory requirements of Treg cells is very limited. We therefore summarize the current understanding ofthe costimulatory requirements of Treg cells, and elaborate on the effect of anti-CD40 L antibody and CTLA-4Ig treatment on Treg cell activity. In this context, we point out that the outcome of a treatment aiming at blocking the CD28/CTLA-4/B7 costimulatory interaction can vary with dosing, timing and underlying immunopathology. | Isabel T Vogel Stefaan W Van Gool Jan L Ceuppens | 2014 | World Journal of Immunology2014，4，2： | 3 |
| 15 | <ce:link locator='fx1'/> A Review of Activity Indices and Efficacy End Points for Clinical Trials of Medical Therapy in Adults With Ulcerative Colitis显示文摘 | Geert D’Haens William J. Sandborn Brian G. Feagan Karel Geboes Stephen B. Hanauer E. Jan Irvine Marc Lémann Philippe Marteau Paul Rutgeerts Jurgen Sch?lmerich Lloyd R. Sutherland | 2007 | Gastroenterology2007，，2： | 2 |
| 16 | Hepatitis B Virus Limits Response of Human Hepatocytes to Interferon-α in Chimeric Mice显示文摘 | Marc Lütgehetmann Till Bornscheuer Tassilo Volz Lena Allweiss Jan–Hendrick Bockmann Joerg M. Pollok Ansgar W. Lohse Joerg Petersen Maura Dandri | 2011 | Gastroenterology2011，，7： | 2 |
| 17 | Effects of sodium bicarbonate, disodium carbonate, and a sodium bicarbonate/carbonate mixture on the PCO2 of blood in a closed system显示文摘 | Joseph IS Nancy E Jan L | 1995 | J Lab & Clin Med1995，126，： | 2 |
| 18 | Anti-tumor necrosis factor treatment restores the gut barrier in Crohn’s disease显示文摘 | Peter Suenaert Veerle Bulteel Liesbeth Lemmens Maja Noman Benny Geypens Gert Van Assche Karel Geboes Jan L Ceuppens Paul Rutgeerts | 2002 | The American Journal of Gastroenterology2002，，8： | 2 |
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