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Genetic association and epistatic interaction of the interleukin-10 signaling pathway in pediatric inflammatory bowel disease

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World Journal of Gastroenterology 2017年第27期23卷 4897-4909页

作者： Zhenwu Lin Zhong Wang john P hegarty Tony R Lin Yunhua Wang Sue Deiling Rongling Wu Neal J Thomas Joanna Floros CHILD Research Department of Pediatricsthe Pennsylvania State UniversityCollege of Medicine Department of Radiology University of Pennsylvania Perelman School of Medicine Division of Biostatistics Department of Public Health Sciencethe Pennsylvania State UniversityCollege of Medicine Department of Surgery the Pennsylvania State UniversityCollege of Medicine Department of Obstetrics and Gynecology the Pennsylvania State UniversityCollege of Medicine

To study the genetic association and epistatic interaction of the interleukin (IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease (IBD). METHODSA total of 159 pediatric inflammatory IBD patients (Crohn’s disease, n = 136; ulcerative colitis, n = 23) and 129 matched controls were studied for genetic association of selected single nucleotide polymorphisms (SNPs) of the IL-10 gene and the genes IL10RA, IL10RB, STAT3, and HO1, from the IL-10/STAT3 signaling pathway. As interactions between SNPs from different loci may significantly affect the associated risk for disease, additive (a) and dominant (d) modeling of SNP interactions was also performed to examine high-order epistasis between combinations of the individual SNPs. RESULTSThe results showed that IL-10 rs304496 was associated with pediatric IBD (P = 0.022), but no association was found for two other IL-10 SNPs, rs1800872 and rs2034498, or for SNPs in genes IL10RA, IL10RB, STAT3, and HO1. However, analysis of epistatic interaction among these genes showed significant interactions: (1) between two IL-10 SNPs rs1800872 and rs3024496 (additive-additive P = 0.00015, Bonferroni P value (Bp) = 0.003); (2) between IL-10RB rs2834167 and HO1 rs2071746 (dominant-additive, P = 0.0018, Bp = 0.039); and (3) among IL-10 rs1800872, IL10RB rs2834167, and HO1 rs2071746 (additive-dominant-additive, P = 0.00015, Bp = 0.005), as well as weak interactions among IL-10 rs1800872, IL-10 rs3024496, and IL-10RA (additive-additive-additive, P = 0.003; Bp = 0.099), and among IL10RA, IL10RB, and HO1 genes (additive-dominant-additive, P = 0.008, Bp = 0.287). CONCLUSIONThese results indicate that both the IL-10 gene itself, and through epistatic interaction with genes within the IL-10/STAT3 signaling pathway, contribute to the risk of pediatric IBD.

关键词： Pediatric inflammatory bowel disease Interleukin-10 HO1 Single nucleotide polymorphism IL10-STAT3 pathway Epistatic interaction

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Functional recovery and muscle atrophy in pre-clinical models of peripheral nerve transection and gap-grafting in mice:effects of 4-aminopyridine

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Neural Regeneration Research 2023年第2期18卷 439-444页

作者： Jung Il Lee M A Hassan Talukder Zara Karuman Anagha A.Gurjar Prem Kumar Govindappa Jagadeeshaprasad M.Guddadarangaiah Kristen M.Manto Grant D.Wandling john P.hegarty David L.Waning john C.Elfar Department of Orthopaedics and Rehabilitation Center for Orthopaedic Research and Translational ScienceThe Pennsylvania State University College of MedicineHersheyPAUSA Department of Orthopaedic Surgery Korea University Guro HospitalSeoulSouth Korea Department of Cellular and Molecular Physiology The Pennsylvania State University College of MedicineHersheyPAUSA

We recently demonstrated a repurposing beneficial effect of 4-aminopyridine(4-AP),a potassium channel blocker,on functional recove ry and muscle atrophy after sciatic nerve crush injury in ***,this effect of 4-AP is unknown in nerve transection,gap,and grafting *** evaluate and compare the functional recovery,nerve morphology,and muscle atrophy,we used a novel stepwise nerve transection with gluing(STG),as well as 7-mm irreparable nerve gap(G-7/0)and 7-mm isografting in 5-mm gap(G-5/7)models in the absence and presence of 4-AP *** surgery,sciatic functional index was determined wee kly to evaluate the direct in vivo global motor functional *** 12 weeks,nerves were processed for whole-mount immunofluorescence imaging,and tibialis anterior muscles were harvested for wet weight and quantitative histomorphological analyses for muscle fiber crosssectional area and minimal Feret's *** post-injury sciatic functional index values in STG and G-5/7 models were significantly greater than those in the G-7/0 model.4-AP did not affect the sciatic functional index recovery in any *** to STG,nerve imaging revealed more misdirected axons and distorted nerve architecture with *** muscle weight,cross-sectional area,and minimal Feret's diameter were significantly smaller in G-7/0 model compared with STG and G-5/7,4-AP treatment significantly increased right TA muscle mass,cross-sectional area,and minimal Feret's diameter in G-7/0 *** findings demonstrate that functional recovery and muscle atrophy after peripheral nerve injury are directly related to the intervening nerve gap,and 4-AP exerts diffe rential effects on functional recove ry and muscle atrophy.

关键词： 4-aminopyridine functional recovery muscle atrophy nerve gap nerve grafting nerve imaging nerve transection

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Liver transplantation for hepatocellular carcinoma in Ireland:Pre-operative alpha-fetoprotein predicts tumour recurrence in a 14-year single-centre national experience

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World Journal of Transplantation 2016年第2期6卷 396-402页

作者： Donal B O'Connor john P Burke john hegarty Aiden P McCormick Niamh Nolan Emir Hoti Donal Maguire Justin Geoghegan Oscar Traynor Department of Surgery Trinity Centre for Health SciencesTallaght Hospital Departments of Hepatobiliary Surgery St Vincent’s University Hospital National Liver Transplant Programme St Vincent’s University Hospital Departments of Pathology St Vincent’s University Hospital

AIM: To examine the results of orthotopic liver transplantation(OLT) for hepatocellular carcinoma(HCC) in Ireland over a 14-year ***: Cases of HCC receiving OLT between January 1995 and September 2009 in the Irish Liver Transplant Unit were reviewed from a prospectively maintained database. Outcome measures included overall and recurrence free survival, alpha-fetoprotein(AFP) and tumour pathological features. RESULTS: On explant pathology, 57 patients had HCC. The median follow-up time was 42.7 mo. The overall 1, 3 and 5 years survival was 87.7%, 72.1% and 72.4%. There was no difference in survival when comparedto patients undergoing OLT without malignancy. The tumour recurrence rate was 14%. The Milan criteria were exceeded in 32% of cases but this did not predict overall survival or recurrence. On multivariate analysis pre-operative AFP > 100 ng/m L was an independent risk factor for recurrence(RR = 5.2, CI: 1.1-24.3, P = 0.036).CONCLUSION: Patients undergoing OLT for HCC had excellent survival even when conventional listing criteria were exceeded. Pre-operative AFP predicts recurrence independent of tumour size and its role in selection criteria should be investigated in larger studies.

关键词： Liver transplantation Alpha-fetoprotein Hepatocellular carcinoma Transplantation selection criteria Liver cirrhosis

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一个电影广告活动如何达到7天70亿人口

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中国广告 2015年第9期 46-46页

作者：杨慧芝 Richard Curtis john hegarty 不详 BBH

戛纳时间2015年6月24日上午10点#We have a plan#的专场,电影制作者、人道主义者、活动家Richard Curtis与全球著名的创意热店BBH（Bartle Bogle hegarty,中文名“百比赫”）创始人john hegarty探讨了WEHAVEAPLAN（我们有个计划）,这个6... 详细信息

戛纳时间2015年6月24日上午10点#We have a plan#的专场,电影制作者、人道主义者、活动家Richard Curtis与全球著名的创意热店BBH（Bartle Bogle hegarty,中文名“百比赫”）创始人john hegarty探讨了WEHAVEAPLAN（我们有个计划）,这个60秒广告利用大屏到达全球电影观众,旨在7天内到达70亿人口,将成为有史以来首个全球电影广告活动。

关键词：电影广告戛纳电影观众电影制作受众面世界电影 Curtis 申克动画公司项目团队

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