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Epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma: Characterization in a 3D-cell culture model

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World Journal of Gastroenterology 2016年第18期22卷 4466-4483页

作者： Nicoletta Gagliano Giuseppe Celesti Lorenza Tacchini Stefano Pluchino Chiarella Sforza Marco Rasile Vincenza Valerio Luigi Laghi Vincenzo Conte Patrizia Procacci Department of biomedical Sciences for Health Università degli Studi di Milano Laboratory of Molecular Gastroenterology Humanitas Clinical and Research Center Department of clinical Neurosciences Wellcome Trust-Medical Research Council Stem Cell Institute and NIHR Biomedical Research Centre University of Cambridge Department of Medical Biotechnology and Translational Medicine Università degli Studi di Milano

AIM: To analyze the effect of three-dimensional (3D)-arrangement on the expression of epithelial-to-mesenchymal transition markers in pancreatic adenocarcinoma (PDAC) ***: HPAF-II, HPAC, and PL45 PDAC cells were cultured in either 2D-monolayers or 3D-spheroids. Ultrastructure was analyzed by transmission electron microscopy. The expression of E-cadherin, β-catenin, N-cadherin, collagen type I (COL-I), vimentin, α-smooth muscle actin (αSMA), and podoplanin was assayed by confocal microscopy in cells cultured on 12-mm diameter round coverslips and in 3D-spheroids. Gene expression for E-cadherin, Snail, Slug, Twist, Zeb1, and Zeb2 was quantified by real-time PCR. E-cadherin protein level and its electrophoretic pattern were studied by Western blot in cell lysates obtained from cells grown in 2D-monolayers and ***: The E-cadherin/β-catenin complex was expressed in a similar way in plasma membrane cell boundaries in both 2D-monolayers and 3D-spheroids. E-cadherin increased in lysates obtained from 3D-spheroids, while cleavage fragments were more evident in 2D-monolayers. N-cadherin expression was observed in very few PDAC cells grown in 2D-monolayers, but was more evident in 3D-spheroids. Some cells expressing COL-I were observed in 3D-spheroids. Podoplanin, expressed in collectively migrating cells, and αSMA were similarly expressed in both experimental conditions. The concomitant maintenance of the E-cadherin/β-catenin complex at cell boundaries supports the hypothesis of a collective migration for these cells, which is consistent with podoplanin ***: We show that a 3D-cell culture model could provide deeper insight into understanding the biology of PDAC and allow for the detection of marked differences in the phenotype of PDAC cells grown in 3D-spheroids.

关键词： Epithelial-to-mesenchymal transition E-cadherin 3D-spheroids Podoplanin Pancreatic ductal adenocarcinoma

Impact of mechanical bowel preparation in elective colorectal surgery:A meta-analysis

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World Journal of Gastroenterology 2018年第4期24卷 519-536页

作者： Katie E Rollins Hannah Javanmard-Emamghissi Dileep N Lobo Gastrointestinal Surgery Nottingham Digestive Diseases Centre National Institute of Health Research (NIHR) Nottingham Biomedical Research Centre Nottingham University Hospitals NHS Trust and University of Nottingham Queen’s Medical Centre

AIM To analyse the effect of mechanical bowel preparation vs no mechanical bowel preparation on outcome in patients undergoing elective colorectal *** Meta-analysis of randomised controlled trials and observational studies comparing adult patients receiving mechanical bowel preparation with those receiving no mechanical bowel preparation, subdivided into those receiving a single rectal enema and those who received no preparation at all prior to elective colorectal surgery. RESULTS A total of 36 studies(23 randomised controlled trials and 13 observational studies) including 21568 patients undergoing elective colorectal surgery were included. When all studies were considered, mechanical bowel preparation was not associated with any significant difference in anastomotic leak rates(OR = 0.90, 95%CI: 0.74 to 1.10, P = 0.32), surgical site infection(OR = 0.99, 95%CI: 0.80 to 1.24, P = 0.96), intraabdominal collection(OR = 0.86, 95%CI: 0.63 to 1.17, P = 0.34), mortality(OR = 0.85, 95%CI: 0.57 to 1.27, P = 0.43), reoperation(OR = 0.91, 95%CI: 0.75 to 1.12, P = 0.38) or hospital length of stay(overall mean difference 0.11 d, 95%CI:-0.51 to 0.73, P = 0.72), when compared with no mechanical bowel preparation, nor when evidence from just randomized controlledtrials was analysed. A sub-analysis of mechanical bowel preparation vs absolutely no preparation or a single rectal enema similarly revealed no differences in clinical outcome measures. CONCLUSION In the most comprehensive meta-analysis of mechanical bowel preparation in elective colorectal surgery to date, this study has suggested that the use of mechanical bowel preparation does not affect the incidence of postoperative complications when compared with no preparation. Hence, mechanical bowel preparation should not be administered routinely prior to elective colorectal surgery.

关键词： bowel preparation Mechanical antibiotics morbidity mortality surgery outcome complications meta-analysis

Review of primary sclerosing cholangitis with increased IgG4 levels

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World Journal of Gastroenterology 2020年第23期26卷 3126-3144页

作者： Charis D Manganis Roger W Chapman Emma L Culver Translational Gastroenterology Unit and Oxford nihr biomedical research centre John Radcliffe HospitalOxford OX39DUUnited Kingdom

Primary sclerosing cholangitis(PSC) is a chronic progressive liver disease. Subtypes of PSC have been described, most recently PSC with elevated serum and/or tissue IgG4 subclass. We aim to summarise the clinical phenotype,disease associations, differential diagnosis, response to therapy and pathogenic mechanisms underlying PSC-high IgG4 subtype. We reviewed Pub Med,MEDLINE and Embase with the search terms "primary sclerosing cholangitis","IgG4", and "IgG4-related sclerosing cholangitis(IgG4-SC)". Elevated serum IgG4 are found in up-to one-quarter, and abundant IgG4-plasma cell infiltrates in the liver and bile ducts are found in up-to one-fifth of PSC patients. This group have a distinct clinical phenotype, with some studies reporting a more aggressive course of liver and associated inflammatory bowel disease, compared to PSCnormal IgG4 and the disease mimic IgG4-SC. Distinguishing PSC-high IgG4 from IgG4-SC remains challenging, requiring careful assessment of clinical features,organ involvement and tissue morphology. Calculation of serum IgG4:IgG1 ratios and use of a novel IgG4:IgG RNA ratio have been reported to have excellent specificity to distinguish IgG4-SC and PSC-high IgG4 but require validation in larger cohorts. A role for corticosteroid therapy in PSC-high IgG4 remains unanswered, with concerns of increased toxicity and lack of outcome data. The immunological drivers underlying prominent IgG4 antibodies in PSC are incompletely defined. An association with PSC-high IgG4 and HLA class-II haplotypes(B*07, DRB1*15), T-helper2 and T-regulatory cytokines(IL4, IL10,IL13) and chemokines(CCL1, CCR8) have been described. PSC-high IgG4 have a distinct clinical phenotype and need careful discrimination from IgG4-SC,although response to immunosuppressive treatments and long-term outcome remains unresolved. The presence of IgG4 likely represents chronic activation to persistent antigenic exposure in genetically predisposed individuals.

关键词： Primary sclerosing cholangitis IgG4 IgG4-related disease IgG4-related sclerosing cholangitis

Performance of the Enhanced Liver Fibrosis Score,Comparison with Vibration-controlled Transient Elastography Data,and Development of a Simple Algorithm to Predict Significant Liver Fibrosis in a Community-based Liver Service:A Retrospective Evaluation

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Journal of clinical and Translational Hepatology 2023年第4期11卷 800-808页

作者： Tina Reinson Janisha Patel Mead Mathews Derek Fountain Ryan M.Buchanan Christopher DByrne Nutrition and Metabolism Faculty of MedicineUniversity of SouthamptonSouthamptonUK National Institute for Health and Care research Southampton Biomedical Research CenterUniversity Hospital SouthamptonSouthamptonUK Hepatology Department University Hospital SouthamptonSouthamptonUK St Mary’s Surgery SouthamptonUK Core Minutes Ltd RingwoodUK clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthamptonUK

Background and Aims:Liver fibrosis is a key risk factor for cirrhosis,hepatocellular carcinoma and end stage liver *** National Institute for Health and Care Excellence guidelines for assessment for advanced(≥F3)liver fibrosis in people with nonalcoholic fatty liver disease recommend the use of enhanced liver fibrosis(ELF)test,followed by vibration-controlled transient elastography(VCTE).Performance of ELF at predicting significant(≥F2)fibrosis in real-world practice is *** assess the accuracy of ELF using VCTE;investigate the optimum ELF cutoff value to identify≥F2and≥F3;and develop a simple algorithm,with and without ELF score,for detecting≥***:Retrospective evaluation of patients referred to a Community Liver Service for VCTE,Jan-Dec *** included:body mass index(BMI),diabetes status,alanine aminotransferase(ALT)levels,ELF score and biopsy-validated fibrosis stages according to ***:Data from 273 patients were available.n=110 patients had *** showed fair performance for≥F2 and≥F3,area under the curve(AUC)=0.70,95%confidence interval(CI)0.64-0.76 and AUC=0.72,95%CI:0.65-0.79 ***≥F2 Youden's index for ELF=9.85 and for≥F3,ELF=*** ALT,BMI,and HbA1c(ALBA algorithm)to predict≥F2 showed good performance(AUC=0.80,95%CI:0.69-0.92),adding ALBA to ELF improved performance(AUC=0.82,95%CI:0.77-0.88).Results were independently ***:Optimal ELF cutoff for≥F2 is 9.85 and 9.95 for≥***,BMI,and HbA1c(ALBA algorithm)can stratify patients at risk of≥*** is improved by adding ALBA.

关键词： Primary health care Retrospective evaluation Liver disease Diabetes Nonalcoholic fatty liver disease

Polygenic risk scores and rheumatic diseases

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Chinese Medical Journal 2021年第21期134卷 2521-2524页

作者： Matthew A.Brown Zhixiu Li Guy’s&St Thomas'NHS Foundation Trust and King’s College London nihr biomedical research centre LondonUnited Kingdom Queensland University of Technology(QUT) Centre for Genomics and Personalised HealthSchool of Biomedical SciencesFaculty of HealthTranslational Research InstituteWoolloongabbaAustralia

The two major goals of common disease genetics research have been dissection of the aetiopathogenesis of common diseases,and the development of genetic predictors or diagnostic tools of disease.

关键词： diseases goals score

Can training extend current guidelines for cochlear implant candidacy?

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Neural Regeneration research 2015年第5期10卷 718-720页

作者： Amal Isaiah Douglas E.H.Hartley Department of Otorhinolaryngology-Head and Neck Surgery University of Maryland School of Medicine National Institute for Health research (nihr) Nottingham Hearing Biomedical Research Unit Otology and Hearing Group Division of Clinical NeuroscienceSchool of MedicineUniversity of Nottingham Medical research Council (MRC) Institute of Hearing research

Since their introduction in the 1960s, cochlear implants （CIS） have undergone several transformations, ulti- mately positioning themselves as the best-performing neural prosthesis available today. They have also been recognized as a unique tool for studying the potential protective effects of patterned electrical stimulation on the developing auditory system, with results from animal models often changing the manner in which CIs are used clinically to deliver auditory information to the brain （Moore and Shannon, 2009）. From the development of the first successful commercial single-channel device, they have evolved into multi-channel devices that are part of the national health programmes of several coun- tries. From the limited speech information provided by the early, rudimentary cochlear implants, these devices are now in a position to deliver intelligible speech infor- mation to the auditory system, largely due to advances in signal processing. Concerted efforts from several dis- ciplines, including engineering, acoustics, neurobiology and otolaryngology have ensured that the continued development of CI technology has resulted in signifi- cant benefits to individuals with profound sensorineural hearing loss.

关键词： Can training extend current guidelines for cochlear implant candidacy CI

Preoperative immunonutrition in patients undergoing liver resection:A prospective randomized trial

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World Journal of Hepatology 2019年第3期11卷 305-317页

作者： Kylie Russell Han-Guang Zhang Lyn K GillANDers Adam SJR Bartlett Helena L Fisk Philip C Calder Peter J Swan Lindsay D Plank Nutrition Services Auckland City Hospital Department of Surgery University of Auckland New Zealand Liver Transplant Unit Auckland City Hospital Human Development and Health Faculty of Medicine University of Southampton nihr southampton biomedical research centre University Hospital Southampton NHS Foundation Trust and University of Southampton

BACKGROUND Preoperative supplementation with immunonutrients, including arginine and n-3 fatty acids, has been shown in a number of systematic reviews to reduce infectious complications in patients who have undergone gastrointestinal surgery. Limited information, however, is available on the benefits of nutritional supplementation enriched with arginine and n-3 fatty acids in patients undergoing liver *** To evaluate the effects of preoperative nutritional supplementation enriched with arginine and n-3 fatty acids on inflammatory and immunologic markers and clinical outcome in patients undergoing liver *** Thirty-four patients undergoing liver resection were randomized to either five days of preoperative Impact? [1020 kcal/d, immunonutrition(IMN) group], or standard care [no supplementation, standard care(STD) group]. Nutritional status was measured at study entry by subjective global assessment(SGA).Functional assessments(grip strength, fatigue and performance status) were carried out at study entry, on the day prior to surgery, and on postoperative day(POD) 7 and 30. Inflammatory and immune markers were measured at study entry, on the day prior to surgery, and POD 1, 3, 5, 7, 10 and 30. Postoperative complications were recorded prospectively until *** A total of 32 patients(17 IMN and 15 STD) were analysed. All except four patients were SGA class A. The plasma ratio of(eicosapentaenoic acid plus docosahexaenoic acid) to arachidonic acid was higher in IMN patients on the day prior to surgery and POD 1, 3, 5 and 7(P < 0.05). Plasma interleukin(IL)-6 concentrations were elevated in the IMN group(P = 0.017 for POD7). No treatment effect was detected for functional measures, immune response(white cell count and total lymphocytes) or markers of inflammation(C-reactive protein,tumour necrosis factor-α, IL-8, IL-10). There were 10 patients with infectious complications in the IMN group and 4 in the STD group(P = 0.087). Median hospital st

关键词： Liver cancer Partial hepatectomy Fish oil Arginine Nutritional status Inflammation

Study of tree shrew biology and models: A booming and prosperous field for biomedical research

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Zoological research 2024年第4期45卷 877-909页

作者： Yong-Gang Yao Li Lu Rong-Jun Ni Rui Bi Ceshi Chen Jia-Qi Chen Eberhard Fuchs Marina Gorbatyuk Hao Lei Hongli Li Chunyu Liu Long-Bao Lv Kyoko Tsukiyama-Kohara Michinori Kohara Claudia Perez-Cruz Gregor Rainer Bao-Ci Shan Fang Shen An-Zhou Tang Jing Wang Wei Xia Xueshan Xia Ling Xu Dandan Yu Feng Zhang Ping Zheng Yong-Tang Zheng Jumin Zhou Jiang-Ning Zhou Key Laboratory of Genetic Evolution and Animal Models Yunnan Key Laboratory of Animal Models and Human Disease MechanismsKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650204China National research facility for Phenotypic&Genetic Analysis of Model Animals(Primate facility) and National Resource Center for Non-Human PrimatesKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China KIZ-CUHK Joint Laboratory of Bioresources and Molecular research in Common Diseases Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650204China Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnan 650204China Mental Health Center and Psychiatric Laboratory West China HospitalSichuan UniversityChengduSichuan 610041China Sichuan clinical Medical research Center for Mental Disorders ChengduSichuan 610044China German Primate Center Leibniz Institute of Primate ResearchGöttingen 37077Germany Department of Optometry and Vision Science School of OptometryUniversity of Alabama at BirminghamBirminghamAL 35294USA State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Innovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhanHubei 430071China Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhanHubei 430074China Soong Ching Ling Institute of Maternity and Child Health International Peace Maternity and Child Health HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Transboundary Animal Diseases Center Joint Faculty of Veterinary MedicineKagoshima UniversityKagoshima-cityKagoshima 890-8580Japan Department of Microbiology and Cell Biology Tokyo Metropolitan Institute of Medical ScienceTokyo 156-8506Japan Pharmacology Department CinvestavMexico City 07360Mexico Department of Medicine University of FribourgFribourg CH-1700Switzerland Beijing Engineering research Center of Radiog

The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with *** recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain ***,the limited availability of tree shrews globally remains a substantial challenge in the ***,determining the key questions best answered using tree shrews constitutes another *** shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative *** these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical *** review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this *** emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew *** use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.

关键词： Tree shrew Animal model Neurodegenerative diseases Infectious diseases Neuroscience Phenome

Evolving role of magnetic resonance techniques in primary sclerosing cholangitis

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World Journal of Gastroenterology 2019年第6期25卷 644-658页

作者： Emmanuel A Selvaraj Emma L Culver Helen Bungay Adam Bailey Roger W Chapman Michael Pavlides Oxford centre for clinical Magnetic Resonance research Division of Cardiovascular Medicine Radcliffe Department of Medicine University of Oxford John Radcliffe Hospital Translational Gastroenterology Unit Nuffield Department of Medicine University of OxfordJohn Radcliffe Hospital Oxford nihr biomedical research centre Oxford University Hospitals NHS Foundation Trust and the University of Oxford Department of Radiology John Radcliffe Hospital

Development of non-invasive methods to risk-stratify patients and predict clinical endpoints have been identified as one of the key research priorities in primary sclerosing cholangitis(PSC). In addition to serum and histological biomarkers, there has been much recent interest in developing imaging biomarkers that can predict disease course and clinical outcomes in *** resonance imaging/magnetic resonance cholangiopancreatography(MRI/MRCP) continue to play a central role in the diagnosis and follow-up of PSC patients. Magnetic resonance(MR) techniques have undergone significant advancement over the last three decades both in MR data acquisition and interpretation. The progression from a qualitative to quantitative approach in MR acquisition techniques and data interpretation, offers the opportunity for the development of objective and reproducible imaging biomarkers that can potentially be incorporated as an additional endpoint in clinical trials. This review article will discuss how the role of MR techniques have evolved over the last three decades from emerging as an alternative diagnostic tool to endoscopic retrograde cholangiopancreatography, to being instrumental in the ongoing search for imaging biomarker of disease stage, progression and prognosis in PSC.

关键词： Primary sclerosing cholangitis Magnetic resonance imaging Magnetic