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| 1 | Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer显示文摘Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer. | Jonathan Landy Emma Ronde Nick English Sue K Clark Ailsa L Hart Stella C Knight Paul J Ciclitira Hafid Omar Al-Hassi | 2016 | World Journal of Gastroenterology2016，22，11： | 39 |
| 2 | Role of CD56-expressing immature biliary epithelial cells in biliary atresia显示文摘AIM: To analyze the clinical and pathological parameters and expression of the neural cell adhesion molecule(CD56) in patients with biliary atresia(BA).METHODS: Established clinical laboratory markers of hepatic function, including enzyme activity, protein synthesis, and bilirubin metabolism, were evaluated in patients with BA and compared with those in patients with choledochal cysts and neonatal hepatitis. Pathological changes in tissue morphology and fibrosis were examined by histological and tissue collagen staining. Immunohistochemical staining for the biliary epithelial cell markers CD56 and CK19 together with the Notch signaling related molecules Notch1 and Notch2 was performed in the context of alterations in the structure of intrahepatic biliary ducts.RESULTS: Differences in some clinical laboratoryparameters among the three diseases examined were observed, but they did not correlate with the pathological classification of fibrosis in BA. Immunohistochemical staining showed the presence of CD56-positive immature bile ducts in most patients(74.5%) with BA but not in patients with choledochal cysts or neonatal hepatitis. The number of CD56-expressing cells correlated with disease severity, with more positive cells present in the later stages of liver damage(81.8% vs 18.2%). Furthermore, bile plugs were mainly found in CD56-positive immature biliary ducts. Notch signaling was a key regulatory pathway in biliary duct formation and played a role in tissue fibrosis. Notch1 was co-expressed in CD56-positive cells, whereas Notch2 was found exclusively in blood vessels in the portal area of patients with BA. CONCLUSION: The maturation of biliary epithelial cells and the expression of Notch may play a role in the pathogenesis of BA. | Rui-Zhong Zhang Jia-Kang Yu Jiao Peng Feng-Hua Wang Hai-Ying Liu Vincent CH Lui John M Nicholls Paul KH Tam Jonathan R Lamb Yan Chen Hui-Min Xia | 2016 | World Journal of Gastroenterology2016，22，8： | 8 |
| 3 | 诊断性试验和策略的证据质量和推荐强度的分级显示文摘GRADE系统能对诊断性试验或策略的证据质量和推荐强度进行分级。本文旨在阐释在此过程中如何考虑患者的重要结局, | Holger J Schünemann Andrew D Oxman Jan Brozek Paul Glasziou Roman Jaeschke Gunn E Vist John W Williams Jr Regina Kunz Jonathan Craig Victor M Montori Patrick Bossuyt Gordon H Guyatt 李晓 黄程 陈耀龙 李幼平 | 2009 | 中国循证医学杂志2009，9，5： | 7 |
| 4 | Downregulation of Hes1 expression in experimental biliary atresia and its effects on bile duct structure显示文摘AIM To analyze the expression and function of the notchsignaling target gene Hes1 in a rhesus rotavirusinduced mouse biliary atresia model. METHODS The morphologies of biliary epithelial cells in biliary atresia patients and in a mouse model were examined by immunohistochemical staining. Then, the differential expression of Notch signaling pathway-related molecules was investigated. Further, the effects of the si RNAmediated inhibition of Hes1 expression were examined using a biliary epithelial cell 3 D culture system.RESULTS Both immature(Ep CAM+) and mature(CK19+) biliary epithelial cells were detected in the livers of biliary atresia patients without a ductile structure and in the mouse model with a distorted bile duct structure. The hepatic expression of transcripts for most Notch signaling molecules were significantly reduced on day 7 but recovered to normal levels by day 14, except for the target molecule Hes1, which still exhibited lower m RNA and protein levels. Expression of the Hes1 transcriptional co-regulator, RBP-Jκ was also reduced. A 3 D gel culture system promoted the maturation of immature biliary epithelial cells, with increased expression of CK19+ cells and the formation of a duct-like structure. The administration of Hes1 si RNA blocked this process. As a result, the cells remained in an immature state, and no duct-like structure was observed.CONCLUSION Our data indicated that Hes1 might contribute to the maturation and the cellular structure organization of biliary epithelial cells, which provides new insight into understanding the pathology of biliary atresia. | Rui-Zhong Zhang Xin-Hao Zeng Ze-Feng Lin Ming-Fu Yan-Lu Tong Vincent CH Lui Paul KH Tam Jonathan R Lamb Hui-Min Xia Yan Chen | 2018 | World Journal of Gastroenterology2018，24，29： | 5 |
| 5 | Esophageal tissue engineering:A new approach for esophageal replacement显示文摘A number of congenital and acquired disorders require esophageal tissue replacement.Various surgical techniques,such as gastric and colonic interposition,are standards of treatment,but frequently complicated by stenosis and other problems.Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function.We review the literature of esophageal tissue engineering,discuss its implications,compare the methodologies that have been employed and suggest possible directions for the future.Medline,Embase,the Cochrane Library,National Research Register and ClinicalTrials.gov databases were searched with the following search terms:stem cell and esophagus,esophageal replacement,esophageal tissue engineering,esophageal substitution.Reference lists of papers identified were also examined and experts in this field contacted for further information.All full-text articles in English of all potentially relevant abstracts were reviewed.Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation.When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality.Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration,whilst omental wrapping to induce vascularization of the construct has an uncertain benefit.Decellularized matrices have been recently suggested as the optimal choice for scaffolds,but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution.Results in animal models that have used seeded scaffolds strongly suggest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a prerequisite for complete esophageal replacement.Novel approaches need to be designed to allow for peristalsis and vascularization in the engineered esophagus.Although esophageal tissue engineering potentially offers a real alternative to conventional treatments for severe esophageal disease,important barriers remain that need to be addressed. | Giorgia Totonelli Panagiotis Maghsoudlou Jonathan M Fishman Giuseppe Orlando Tahera Ansari Paul Sibbons Martin A Birchall Agostino Pierro Simon Eaton Paolo De Coppi | 2012 | World Journal of Gastroenterology2012，18，47： | 5 |
| 6 | 关于与青光眼疾病严重性相关的资源使用和成本的一项多中心回顾性试验研究显示文摘目的:调查在不同疾病严重程度上青光眼治疗的资源消耗和直接成本。
设计:基于医学档案综述的观察性、回顾性的队列研究。 | Paul P. Lee John G. Walt John J. Doyle Sameer V. Kotak Stacy J. Evans Donald L. Budenz Philip P. Chen Anne L. Coleman Robert M. Feldman HenRY D. Jampel L.Jay Katz Richard P.Mills Jonathan S.Myers Robert J.Noecker Jody R.Piltz-Seymour Robert R.Ritch Paul N.Schacknow Janet B.Serle Gary L.Trick 范翔(译) | 2006 | 美国医学会眼科杂志(中文版)2006，18，4： | 4 |
| 7 | Pregnancy and inflammatory bowel diseases: Current perspectives, risks and patient management显示文摘Inflammatory bowel diseases(IBD) are chronic idiopathic inflammatory conditions characterized by relapsing and remitting episodes of inflammation which can affect several different regions of the gastrointestinal tract, but also shows extra-intestinal manifestations. IBD is most frequently diagnosed during peak female reproductive years, with 25% of women with IBD conceiving after their diagnosis. While IBD therapy has improved dramatically with enhanced surveillance and more abundant and powerful treatment options, IBD disease can have important effects on pregnancy and presents several challenges for maintaining optimal outcomes for mothers with IBD and the developing fetus/neonate. Women with IBD, the medical team treating them(both gastroenterologists and obstetricians/gynecologists) must often make highly complicated choices regarding conception, pregnancy, and post-natal care(particularly breastfeeding) related to their choice of treatment options at different phases of pregnancy as well as post-partum. This current review discusses current concerns and recommendations for pregnancy duringIBD and is intended for gastroenterologists, general practitioners and IBD patients intending to become,(or already) pregnant, and their families. We have addressed patterns of IBD inheritance, effects of IBD on fertility and conception(in both men and women), the effects of IBD disease activity on maintenance of pregnancy and outcomes, risks of diagnostic procedures during pregnancy and potential risks and complications associated with different classes of IBD therapeutics. We also have evaluated the clinical experience using 'top-down' care with biologics, which is currently the standard care at our institution. Post-partum care and breastfeeding recommendations are also addressed. | Pegah Hosseini-Carroll Monica Mutyala Abhishek Seth Shaheen Nageeb Demiana Soliman Moheb Boktor Ankur Sheth Jonathon Chapman James Morris Paul Jordan Kenneth Manas Felix Becker Jonathan Steven Alexander | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，4： | 4 |
| 8 | Pushing the boundaries of diode-pumped solid-state lasers for high-energy applications显示文摘We report on the successful demonstration of a 150 J nanosecond pulsed cryogenic gas cooled,diode-pumped multi-slab Yb:YAG laser operating at 1 Hz.To the best of our knowledge,this is the highest energy ever recorded for a diodepumped laser system. | Saumyabrata Banerjee Paul Mason Jonathan Phillips Jodie Smith Thomas Butcher Jacob Spear Mariastefania De Vido Gary Quinn Danielle Clarke Klaus Ertel Cristina Hernez-Gomez Chris Edwards John Collier | 2020 | High Power Laser Science and Engineering2020，8，2： | 4 |
| 9 | HLA-Haploidentical Bone Marrow Transplantation for Hematologic Malignancies Using Nonmyeloablative Conditioning and High-Dose, Posttransplantation Cyclophosphamide显示文摘 | Leo Luznik Paul V. O'Donnell Heather J. Symons Allen R. Chen M. Susan Leffell Marianna Zahurak Ted A. Gooley Steve Piantadosi Michele Kaup Richard F. Ambinder Carol Ann Huff William Matsui Javier Bola?os-Meade Ivan Borrello Jonathan D. Powell Elizabeth Ha | 2008 | Biology of Blood and Marrow Transplantation2008，，6： | 4 |
| 10 | Development of a 100 J,10 Hz laser for compression experiments at the High Energy Density instrument at the European XFEL显示文摘In this paper we review the design and development of a 100 J, 10 Hz nanosecond pulsed laser, codenamed DiPOLE100 X,being built at the Central Laser Facility(CLF). This 1 kW average power diode-pumped solid-state laser(DPSSL) is based on a master oscillator power amplifier(MOPA) design, which includes two cryogenic gas cooled amplifier stages based on DiPOLE multi-slab ceramic Yb:YAG amplifier technology developed at the CLF. The laser will produce pulses between 2 and 15 ns in duration with precise, arbitrarily selectable shapes, at pulse repetition rates up to 10 Hz, allowing real-time shape optimization for compression experiments. Once completed, the laser will be delivered to the European X-ray Free Electron Laser(XFEL) facility in Germany as a UK-funded contribution in kind, where it will be used to study extreme states of matter at the High Energy Density(HED) instrument. | Paul Mason Saumyabrata Banerjee Jodie Smith Thomas Butcher Jonathan Phillips Hauke Hoppner Dominik Moller Klaus Ertel Mariastefania De Vido Ian Hollingham ANDrew Norton Stephanie Tomlinson Tinesimba Zata Jorge Suarez Merchan Chris Hooker Mike Tyldesley Toma Toncian Cristina HernANDez-Gomez Chris Edwards John Collier | 2018 | High Power Laser Science and Engineering2018，6，4： | 4 |
| 11 | Nat Genet:单基因突变导致过敏性皮炎的发生显示文摘最近,研究者们鉴定出了一类导致神经性皮炎发生的关键基因突变:CARDll。来自美国NIH过敏与传染病研究所的研究者们通过对四个没有血缘关系的患病家庭进行分析,发现了这一导致疾病产生的基因、 | Chi A Ma, Yuan Zhang, Michael A Weinreich, Jonathan J Lyons, Celeste G Nelson, Thomas DiMaggio, Kelly D Stone, Joshua D Milner Jeffrey R Stinson, Elisa Ruffo, Batsukh Dorjbal, Swadhinya Arjunaraja, Kelsey Voss, Andrew L Snow Jordan K Abbott, Pia J Hauk, Paul R Reynolds, Erwin W Gelfand Elisa Ruffo Salomé Glauzy, Natsuko Yamakawa, Eric Meffre Jennifer Stoddard, Julie Niemela, Sergio D Rosenzweig Yu Zhang, Helen F Matthews Joshua J McElwee Nina Jones Alejandro Palma, Matías Oleastro, Emma Prieto, Andrea R Bernasconi, Geronimo Dubra, Silvia Danielian, Jonathan Zaiat, Marcelo A Marti Brian Kim Megan A Cooper Neil Romberg | 2017 | 现代生物医学进展2017，17，27： | 3 |
| 12 | The metabolic syndrome in children and adolescents显示文摘 | Paul Zimmet George Alberti Francine Kaufman Naoko Tajima Martin Silink Silva Arslanian Gary Wong Peter Bennett Jonathan Shaw Sonia Caprio | 2007 | The Lancet2007，，9579： | 3 |
| 13 | Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial显示文摘 | Paul Y Kwo Eric J Lawitz Jonathan McCone Eugene R Schiff John M Vierling David Pound Mitchell N Davis Joseph S Galati Stuart C Gordon Natarajan Ravendhran Lorenzo Rossaro Frank H Anderson Ira M Jacobson Raymond Rubin Kenneth Koury Lisa D Pedicone Clifford | 2010 | The Lancet2010，，9742： | 3 |
| 14 | PKI-587 and Sorafenib Targeting PI3K/AKT/mTOR and Ras/Raf/MAPK Pathways Synergistically Inhibit HCC Cell Proliferation显示文摘 | Roberto Gedaly Paul Angulo Jonathan Hundley Michael F. Daily Changguo Chen B. Mark Evers | 2012 | Journal of Surgical Research2012，，2： | 3 |
| 15 | 国际卒中遗传学联盟的推荐意见(第1部分):标准化表型数据收集显示文摘与几乎所有复杂疾病一样,卒中的患病风险和临床转归也是多基因作用的[1]。探索相关基因突变有望为新型个体化治疗方法奠定基础,从而显著减少卒中对全球健康造成的毁灭性影响。为了达到足够的统计学效能以确认多个风险性等位基因,需要很大的样本量。尽管卒中是全世界范围内第二大致死病因和成年人致残的主要原因[2],但没有任何一家研究机构能独立收集到足够的样本。在认识到这一挑战之后,来自世界各地的卒中研究者们于2007年成立了国际卒中遗传学联盟( International Stroke Genetics Consortium, ISGC; http://www. strokegenetics.org),其使命是通过研究在全球多个研究机构入组的患者来识别影响卒中患病风险、临床预后和治疗效果的遗传学因素。尽管先前已取得了一些成功[3-5],仍有大量工作有待进行,这不仅是为了发现风险性等位基因从而达到卒中个体化医疗的最终目标,更是为了开发综合性卒中风险评估手段以及得到足以改变临床实践的结果[6]。根据糖尿病和冠状动脉疾病等其他复杂疾病的研究进展,为了识别与卒中相关的所有基因突变,需要100000~200000个样本。为了达到这个样本量,需要进行更为广泛的协作。 | Jennifer J. Majersik John W.Cole Jonathan Golledge Natalia S. Rost Yu-Feng Yvonne Chan M. Edip Gurol Ame G. Lindgren Daniel Woo Israel Fernandez-Cadenas Donna T. Chen Vincent Thijs Bradford B. Worrall Ayeesha Kamal Paul Bentley Joanna M. Wardlaw Ynte M. Ruigrok Thomas W.K Battey Reinhold Schmidt Joan Montaner Anne-Katrin Giese Jaume Roquer Jordi Jimenez-Conde Chaeyoung Lee Hakan Ay Juan Jose Martin 李海峰 岳耀先 徐军 | 2015 | 国际脑血管病杂志2015，23，9： | 3 |
| 16 | Heparin resistance in severe thermal injury:a prospective cohort study显示文摘Background:Low molecular-weight heparin(LMWH)is routinely administered to burn patients for thromboprophylaxis.Some studies have reported heparin resistance,yet the mechanism(s)and prevalence have not been systematically studied.We hypothesized that nucleosomes,composed of histone structures with associated DNA released from injured tissue and activated immune cells in the form of neutrophil extracellular traps(NETs or NETosis),neutralize LMWH resulting in suboptimal anticoagulation,assessed by reduction in anti-factor Xa activity.Methods:Blood was sampled from>15%total body surface area(TBSA)burn patients receiving LMWH on days 5,10 and 14.Peak anti-factor Xa(AFXa)activity,anti-thrombin(ATIII)activity,cellfree DNA(cfDNA)levels and nucleosome levels were measured.Mixed effects regression was adjusted for multiple confounders,including injury severity and ATIII activity,and was used to test the association between nucleosomes and AFXa.Results:A total of 30 patients with severe burns were included.Mean TBSA 43%(SD 17).Twentythree(77%)patients were affected by heparin resistance(defined by AFXa activity<0.2 IU/mL).Mean peak AFXa activity across samples was 0.18 IU/mL(SD 0.11).Mean ATIII was 81.9%activity(SD 20.4).Samples taken at higher LWMH doses were found to have significantly increased AFXa activity,though the effect was not observed at all doses,at 8000 IU no samples were heparin resistant.Nucleosome levels were negatively correlated with AFXa(r=−0.29,p=0.050)consistent with the hypothesis.The final model,with peak AFXa as the response variable,was adjusted for nucleosome levels(p=0.0453),ATIII activity(p=0.0053),LMWH dose pre-sample(p=0.0049),drug given(enoxaparin or tinzaparin)(p=0.03),and other confounders including severity of injury,age,gender,time point of sample.Conclusions:Heparin resistance is a prevalent issue in severe burns.Nucleosome levels were increased post-burn,and showed an inverse association with AFXa consistent with the hypothesis that they may interfere with the anticoagulant effect of heparin in vivo and contribute to heparin resistance.Accurate monitoring of AFXa activity with appropriate therapy escalation plans are recommended with dose adjustment following severe burn injury. | Liam D Cato Benjamin Bailiff Joshua Price Christos Ermogeneous Jon Hazeldine William Lester Gillian Lowe Christopher Wearn Jonathan RB Bishop Janet M Lord Naiem Moiemen Paul Harrison | 2021 | Burns & Trauma2021，9，1： | 3 |
| 17 | Activation of the pattern recognition receptor NOD1 augments colon cancer metastasis显示文摘While emerging data suggest nucleotide oligomerization domain receptor 1(NOD1),a cytoplasmic pattern recognition receptor,may play an important and complementary role in the immune response to bacterial infection,its role in cancer metastasis is entirely unknown.Hence,we sought to determine the effects of NOD1 on metastasis.NOD1 expression in paired human primary colon cancer,human and murine colon cancer cells were determined using immunohistochemistry and immunoblotting(WB).Clinical significance of NOD1 was assessed using TCGA survival data.A series of in vitro and in vivo functional assays,including adhesion,migration,and metastasis,was conducted to assess the effect of NOD1.C12-iE-DAP,a highly selective NOD1 ligand derived from gram-negative bacteria,was used to activate NOD1.ML130,a specific NOD1 inhibitor,was used to block C12-iE-DAP stimulation.Stable knockdown(KD)of NOD1 in human colon cancer cells(HT29)was constructed with shRNA lentiviral transduction and the functional assays were thus repeated.Lastly,the predominant signaling pathway of NOD1-activation was identified using WB and functional assays in the presence of specific kinase inhibitors.Our data demonstrate that NOD1 is highly expressed in human colorectal cancer(CRC)and human and murine CRC cell lines.Clinically,we demonstrate that this increased NOD1 expression negatively impacts survival in patients with CRC.Subsequently,we identify NOD1 activation by C12-iE-DAP augments CRC cell adhesion,migration and metastasis.These effects are predominantly mediated via the p38 mitogen activated protein kinase(MAPK)pathway.This is the first study implicating NOD1 in cancer metastasis,and thus identifying this receptor as a putative therapeutic target. | Henry Y.Jiang Sara Najmeh Guy Martel Elyse MacFadden-Murphy Raquel Farias Paul Savage Arielle Leone Lucie Roussel Jonathan Cools-Lartigue Stephen Gowing Julie Berube Betty Giannias France Bourdeau Carlos HFChan Jonathan D.Spicer Rebecca McClure Morag Park Simon Rousseau Lorenzo E.Ferri | 2020 | Protein & Cell2020，11，3： | 3 |
| 18 | 建立基于模型设计文化的最佳策略显示文摘本文引入了基于模型设计的概念,突出了其中的一些优点,详细讨论了组织中采用基于模型设计文化的10个最佳策略。这些最佳策略从不同工业领域的公司中收集,包括向基于模型设计的成功或者不成功的过渡。 | Paul F.Smith Sameer M.Prabhu Jonathan H.Friedman | 2008 | 电子设计应用2008，，5： | 2 |
| 19 | Variation of soil respiration at three spatial scales: Components within measurements, intra-site variation and patterns on the landscape显示文摘 | Jonathan G. Martin Paul V. Bolstad | 2009 | Soil Biology and Biochemistry2009，，3： | 2 |
| 20 | Isolated Low Levels of High-Density Lipoprotein Cholesterol Are Associated With an Increased Risk of Coronary Heart Disease: An Individual Participant Data Meta-Analysis of 23 Studies in the Asia-Pacific Region显示文摘 | Rachel R. Huxley Federica Barzi Tai Hing Lam Sebastien Czernichow Xianghua Fang Tim Welborn Jonathan Shaw Hirotsugu Ueshima Paul Zimmet Sun Ha Jee Jeetesh V. Patel Ian Caterson Vlado Perkovic Mark Woodward | 2011 | Circulation2011，，19： | 2 |
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