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| 1 | The hypoxia-inducible factor-1α activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia显示文摘Tumor-induced osteomalacia(TIO) is a rare paraneoplastic syndrome in which ectopic production of fibroblast growth factor 23(FGF23) by non-malignant mesenchymal tumors causes phosphate wasting and bone fractures. Recent studies have implicated the hypoxia-inducible factor-1α(HIF-1α) in other phosphate wasting disorders caused by elevated FGF23, including X-linked hypophosphatemic rickets and autosomal dominant hypophosphatemia. Here we provide evidence that HIF-1α mediates aberrant FGF23 in TIO by transcriptionally activating its promoter. Immunohistochemical studies in phosphaturic mesenchymal tumors resected from patients with documented TIO showed that HIF-1α and FGF23 were co-localized in spindleshaped cells adjacent to blood vessels. Cultured tumor tissue produced high levels of intact FGF23 and demonstrated increased expression of HIF-1α protein. Transfection of MC3T3-E1 and Saos-2 cells with a HIF-1α expression construct induced the activity of a FGF23 reporter construct. Prior treatment of tumor organ cultures with HIF-1α inhibitors decreased HIF-1α and FGF23 protein accumulation and inhibited HIF-1α-induced luciferase reporter activity in transfected cells. Chromatin immunoprecipitation assays confirmed binding to a HIF-1α consensus sequence within the proximal FGF23 promoter, which was eliminated by treatment with a HIF-1α inhibitor. These results show for the first time that HIF-1α is a direct transcriptional activator of FGF23 and suggest that upregulation of HIF-1α activity in TIO contributes to the aberrant FGF23 production in these patients. | Qian Zhang Michele Doucet Ryan E Tomlinson Xiaobin Han L Darryl Quarles Michael T Collins Thomas L Clemens | 2016 | Bone Research2016，4，2： | 6 |
| 2 | Randomized trial in malignant biliary obstruction:Plastic vs partially covered metal stents显示文摘AIM:To compare efficacy and complications of par-tially covered self-expandable metal stent(pcSEMS)to plastic stent(PS)in patients treated for malignant,infrahilar biliary obstruction.METHODS:Multicenter prospective randomized clinical trial with treatment allocation to a pcWallstent(SEMS)or a 10 French PS.Palliative patients aged≥18,for infrahilar malignant biliary obstruction and a Karnofsky performance scale index>60%from 6 participating North American university centers.Primary endpoint was time to stent failure,with secondary outcomes of death,adverse events,Karnofsky performance score and short-form-36 scale administered on a three-monthly basis for up to 2 years.Survival analyses were performed for stent failure and death,with Cox proportional hazards regression models to determine significant predictive characteristics.RESULTS:Eighty-five patients were accrued over 37mo,42 were randomized to the SEMS group and 83patients were available for analyses.Time to stent failure was 385.3±52.5 d in the SEMS and 153.3±19.8 d in the PS group,P=0.006.Time to death did not differ between groups(192.3±23.4 d for SEMS vs211.5±28.0 d for PS,P=0.70).The only significant predictor was treatment allocation,relating to the time to stent failure(P=0.01).Amongst other measured outcomes,only cholangitis differed,being more common in the PS group(4.9%vs 24.5%,P=0.029).The small number of patients in follow-up limits longitudinal assessments of performance and quality of life.From an initially planned 120 patients,only 85 patients were recruited.CONCLUSION:Partially covered SEMS result in a longer duration till stent failure without increased complication rates,yet without accompanying measurable benefits in survival,performance,or quality of life. | Peter L Moses Khalid M AlNaamani Alan N Barkun Stuart R Gordon Roger D Mitty M Stanley Branch Thomas E Kowalski Myriam Martel Viviane Adam | 2013 | World Journal of Gastroenterology2013，19，46： | 6 |
| 3 | Colonoscopy surveillance for high risk polyps does not always prevent colorectal cancer显示文摘AIM To determine the frequency and risk factors for colorectal cancer(CRC) development among individuals with resected advanced adenoma(AA)/traditional serrated adenoma(TSA)/advanced sessile serrated adenoma(ASSA). METHODS Data was collected from medical records of 14663 subjects found to have AA, TSA, or ASSA at screening or surveillance colonoscopy. Patients with inflammatory bowel disease or known genetic predisposition for CRC were excluded from the study. Factors associated with CRC developing after endoscopic management of high risk polyps were calculated in 4610 such patients who had at least one surveillance colonoscopy within 10 years following the original polypectomy of the incident advanced polyp. RESULTS84/4610(1.8%) patients developed CRC at the polypectomy site within a median of 4.2 years(mean 4.89 years), and 1.2%(54/4610) developed CRC in a region distinct from the AA/TSA/ASSA resection site within a median of 5.1 years(mean 6.67 years). Approximately, 30%(25/84) of patients who developed CRC at the AA/TSA/ASSA site and 27.8%(15/54) of patients who developed CRC at another site had colonoscopy at recommended surveillance intervals. Increasing age; polyp size; male sex; right-sided location; high degree of dysplasia; higher number of polyps resected; and piecemeal removal were associated with an increased risk for CRC developmentat the same site as the index polyp. Increasing age; right-sided location; higher number of polyps resected and sessile endoscopic appearance of the index AA/TSA/ASSA were significantly associated with an increased risk for CRC development at a different site. CONCLUSION Recognition that CRC may develop following AA/TSA/ASSA removal is one step toward improving our practice efficiency and preventing a portion of CRC related morbidity and mortality. | Mohamad A Mouchli Lidia Ouk Marianne R Scheitel Alisha P Chaudhry Donna Felmlee-Devine Diane E Grill Shahrooz Rashtak Panwen Wang Junwen Wang Rajeev Chaudhry Thomas C Smyrk Ann L Oberg Brooke R Druliner Lisa A Boardman | 2018 | World Journal of Gastroenterology2018，24，8： | 5 |
| 4 | Gastric emptying, postprandial blood pressure, glycaemia and splanchnic flow in Parkinson's disease显示文摘AIM: To determine gastric emptying, blood pressure, mesenteric artery blood flow, and blood glucose responses to oral glucose in Parkinson's disease. METHODS: Twenty-one subjects(13 M, 8 F; age 64.2 ± 1.6 years) with mild to moderate Parkinson's disease(Hoehn and Yahr score 1.4 ± 0.1, duration of known disease 6.3 ± 0.9 years) consumed a 75 g glucose drink, labelled with 20 MBq 99mTc-calcium phytate. Gastric emptying was quantified with scintigraphy, blood pressure and heart rate with an automated device, superior mesenteric artery blood flow by Doppler ultrasonography and blood glucose byglucometer for 180 min. Autonomic nerve function was evaluated with cardiovascular reflex tests and upper gastrointestinal symptoms by questionnaire. RESULTS: The mean gastric half-emptying time was 106 ± 9.1 min, gastric emptying was abnormally delayed in 3 subjects(14%). Systolic and diastolic blood pressure fell(P < 0.001) and mesenteric blood flow and blood glucose(P < 0.001 for both) increased, following the drink. Three subjects(14%) had definite autonomic neuropathy and 8(38%) had postprandial hypotension. There were no significant relationships between changes in blood pressure, heart rate or mesenteric artery blood flow with gastric emptying. Gastric emptying was related to the score for autonomic nerve function(R = 0.55, P < 0.01). There was an inverse relationship between the blood glucose at t = 30 min(R =-0.52, P < 0.05), while the blood glucose at t = 180 min was related directly(R = 0.49, P < 0.05), with gastric emptying. CONCLUSION: In mild to moderate Parkinson's disease, gastric emptying is related to autonomic dysfunction and a determinant of the glycaemic response to oral glucose. | Laurence G Trahair Thomas E Kimber Katerina Flabouris Michael Horowitz Karen L Jones | 2016 | World Journal of Gastroenterology2016，22，20： | 5 |
| 5 | Efficacy and safety of liquid nitrogen cryotherapy for treatment of Barrett's esophagus显示文摘AIM To evaluate the efficacy and safety of liquid nitrogen cryotherapy as a primary or rescue treatment for BE,with and without dysplasia,or intramucosal adenocarcinoma (IMC).METHODS This was a retrospective,single-center study carried out in a tertiary care center including 45 patients with BE who was treatment-na?ve or who had persistent intestinal metaplasia(IM),dysplasia,or IMC despite prior therapy.Barrett's mucosa was resected via EMR when clinically appropriate,then patients underwent cryotherapy until eradication or until deemed to have failed treatment.Surveillance biopsies were taken at standard intervals.RESULTS From 2010 through 2014,33 patients were studied regarding the efficacy of cryotherapy.Overall,29 patients (88%) responded to cryotherapy,with 84% having complete regression of all dysplasia and cancer.Complete eradication of cancer and dysplasia was seen in 75% of subjects with IMC; the remaining two subjects did not respond to cryotherapy.Following cryotherapy,15 patients with high-grade dysplasia (HGD) had 30% complete regression,50% IM,and 7% low-grade dysplasia (LGD); one subject had persistent HGD.Complete eradication of dysplasia occurred in all 5 patients with LGD.In 5 patients with IM,complete regression occurred in 4,and IM persisted in one.In 136 cryotherapy sessions amongst 45 patients,adverse events included chest pain (1%),stricture (4%),and one gastrointestinal bleed in a patient on dual antiplatelet therapy who had previously undergone EMR.CONCLUSION Cryotherapy is an efficacious and safe treatment modality for Barrett's esophagus with and without dysplasia or intramucosal adenocarcinoma. | Kristen Suchniak-Mussari Charles E Dye Matthew T Moyer Abraham Mathew Thomas J McGarrity Eileen M Gagliardi Jennifer L Maranki John M Levenick | 2017 | World Journal of Gastrointestinal Endoscopy2017，9，9： | 4 |
| 6 | Changes in the colon microbiota and intestinal cytokine gene expression following minimal intestinal surgery显示文摘AIM: To investigate the impact of minor abdominal surgery on the caecal microbial population and on markers of gut inflammation.METHODS: Four week old piglets were randomly allocated to a no-surgery 'control' group(n = 6) or a 'transection surgery' group(n = 5).During the transection surgery procedure, a conventional midline incision of the lower abdominal wall was made and the small intestine was transected at a site 225 cm proximal to the ileocaecal valve, a 2 cm segment was removed and the intestine was re-anastomosed.Piglets received a polymeric infant formula diet throughout the study period and were sacrificed at two weeks post-surgery.Clinical outcomes including weight, stool consistency and presence of stool fat globules were monitored.High throughput DNA sequencing of colonic content was used to detect surgery-relateddisturbances in microbial composition at phylum, family and genus level.Diversity and richness estimates were calculated for the control and minor surgery groups.As disturbances in the gut microbial community are linked to inflammation we compared the gene expression of key inflammatory cytokines(TNF, IL1 B, IL18, IL12, IL8, IL6 and IL10) in ileum, terminal ileum and colon mucosal extracts obtained from control and abdominal surgery groups at two weeks post-surgery.RESULTS: Changes in the relative abundance of bacterial species at family and genus level were confined to bacterial members of the Proteobacteria and Bacteroidetes phyla.Family level compositional shifts included a reduction in the relative abundance of Enterobacteriaceae(22.95 ± 5.27 vs 2.07 ± 0.72, P < 0.01), Bacteroidaceae(2.54 ± 0.56 vs 0.86 ± 0.43, P < 0.05) and Rhodospirillaceae(0.40 ± 0.14 vs 0.00 ± 0.00, P < 0.05) following transection surgery.Similarly, at the genus level, changes associated with transection surgery were restricted to members of the Proteobacteria and Bacteroidetes phyla and included decreased relative abundance of Enterobacteriaceae(29.20 ± 6.74 vs 2.88 ± 1.08, P < 0.01), Alistipes(4.82 ± 1.73 vs 0.18 ± 0.13, P < 0.05) and Thalassospira(0.53 ± 0.19 vs 0.00 ± 0.00, P < 0.05).Surgeryassociated microbial dysbiosis was accompanied by increased gene expression of markers of inflammation.Within the ileum IL6 expression was decreased(4.46 ± 1.60 vs 0.24 ± 0.06, P < 0.05) following transection surgery.In the terminal ileum, gene expression of TNF was decreased(1.51 ± 0.13 vs 0.80 ± 0.16, P < 0.01) and IL18(1.21 ± 0.18 vs 2.13 ± 0.24, P < 0.01), IL12(1.04 ± 0.16 vs 1.82 ± 0.32, P < 0.05) and IL10(1.04 ± 0.06 vs 1.43 ± 0.09, P < 0.01) gene expression increased following transection surgery.Within the colon, IL12(0.72 ± 0.13 vs 1.78 ± 0.28, P < 0.01) and IL10(0.98 ± 0.02 vs 1.95 ± 0.14, P < 0.01) gene expression were increased following transection surgery.CONCLUSION: This study suggests that minor abdominal surgery in infants, results in long-term alteration of the colonic microbial composition and persistent gastrointestinal inflammation. | Susan Lapthorne Julie E Bines Fiona Fouhy Nicole L Dellios Guineva Wilson Sarah L Thomas Michelle Scurr Catherine Stanton Paul D Cotter Prue M Pereira-Fantini | 2015 | World Journal of Gastroenterology2015，21，14： | 3 |
| 7 | A high-density, multi-parental SNP genetic map on apple validates a new mapping approach for outcrossing species显示文摘Quantitative trait loci(QTL)mapping approaches rely on the correct ordering of molecular markers along the chromosomes,which can be obtained from genetic linkage maps or a reference genome sequence.For apple(Malus domestica Borkh),the genome sequence v1 and v2 could not meet this need;therefore,a novel approach was devised to develop a dense genetic linkage map,providing the most reliable marker-loci order for the highest possible number of markers.The approach was based on four strategies:(i)the use of multiple full-sib families,(ii)the reduction of missing information through the use of HaploBlocks and alternative calling procedures for single-nucleotide polymorphism(SNP)markers,(iii)the construction of a single backcross-type data set including all families,and(iv)a two-step map generation procedure based on the sequential inclusion of markers.The map comprises 15417 SNP markers,clustered in 3 K HaploBlock markers spanning 1267 cM,with an average distance between adjacent markers of 0.37 cM and a maximum distance of 3.29 cM.Moreover,chromosome 5 was oriented according to its homoeologous chromosome 10.This map was useful to improve the apple genome sequence,design the Axiom Apple 480 K SNP array and perform multifamily-based QTL studies.Its collinearity with the genome sequences v1 and v3 are reported.To our knowledge,this is the shortest published SNP map in apple,while including the largest number of markers,families and individuals.This result validates our methodology,proving its value for the construction of integrated linkage maps for any outbreeding species. | Erica A Di Pierro Luca Gianfranceschi Mario Di Guardo Herma JJ Koehorst-van Putten Johannes W Kruisselbrink Sara Longhi Michela Troggio Luca Bianco Hélène Muranty Giulia Pagliarani Stefano Tartarini Thomas Letschka Lidia Lozano Luis Larisa Garkava-Gustavsson Diego Micheletti Marco CAM Bink Roeland E Voorrips Ebrahimi Aziz Riccardo Velasco François Laurens W Eric van de Weg | 2016 | Horticulture Research2016，3，1： | 3 |
| 8 | Global, regional, and national causes of child mortality in 2008: a systematic analysis显示文摘 | Robert E Black Simon Cousens Hope L Johnson Joy E Lawn Igor Rudan Diego G Bassani Prabhat Jha Harry Campbell Christa Fischer Walker Richard Cibulskis Thomas Eisele Li Liu Colin Mathers | 2010 | The Lancet2010，，9730： | 3 |
| 9 | Macrophage secretory products induce an inflammatory phenotype in hepatocytes显示文摘AIM:To investigate the influence of macrophages on hepatocyte phenotype and function.METHODS:Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophageconditioned medium on HepG2 mRNA and protein expression determined.The in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus(HCV)infection.RESULTS:Conditioned media from macrophages,but not monocytes,induced a transient morphological change in hepatocytes associated with upregulation of vimentin(7.8±2.5-fold,P=0.045)and transforming growth factor(TGF)-β1(2.6±0.2-fold,P<0.001)and downregulation of epithelial cadherin(1.7±0.02-fold,P=0.017)mRNA expression.Microarray analysis revealed significant upregulation of lipocalin-2(17-fold,P <0.001)and pathways associated with inflammation,and substantial downregulation of pathways related to hepatocyte function.In patients with chronic HCV,realtime polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA(F0 1.0 ±0.3,F1 2.2±0.2,F2 3.0±9.3,F3/4 4.0±0.8,P= 0.003)and protein expression(F1 1.0±0.5,F2 1.3± 0.4,F3/4 3.6±0.4,P=0.014)with increasing liver injury.High performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase(MMP)-9 in macrophageconditioned medium,and a chemical inhibitor of MMP-9 attenuated the change in morphology and mRNA expression of TGF-β1(2.9±0.2 vs 1.04±0.1,P<0.001) in macrophage-conditioned media treated HepG2 cells.In patients with chronic HCV infection,hepatic mRNA expression of CD163(F0 1.0±0.2,F1/2 2.8±0.3,F3/4 5.3±1.0,P=0.001)and MMP-9(F0 1.0±0.4,F1/2 2.8±0.3,F3/4 4.1±0.8,P=0.011)was significantly associated with increasing stage of fibrosis.CONCLUSION:Secreted macrophage products alter the phenotype and function of hepatocytes,with increased expression of inflammatory mediators,suggesting that hepatocytes actively participate in liver injury. | Michelle Melino Victoria L Gadd Gene V Walker Richard Skoien Helen D Barrie Dinesh Jothimani Leigh Horsfall Alun Jones Matthew J Sweet Gethin P Thomas Andrew D Clouston Julie R Jonsson Elizabeth E Powell | 2012 | World Journal of Gastroenterology2012，18，15： | 3 |
| 10 | Global, regional, and national causes of child mortality in 2008: a systematic analysis显示文摘 | Robert E Black Simon Cousens Hope L Johnson Joy E Lawn Igor Rudan Diego G Bassani Prabhat Jha Harry Campbell Christa Fischer Walker Richard Cibulskis Thomas Eisele Li Liu Colin Mathers | 2010 | The Lancet . 2010 (9730)2010，，： | 2 |
| 11 | 显示文摘 | Bulut Y Faure E Thomas L | 2001 | JImmunol2001，167，2： | 1 |
| 12 | Genetic base of 651Chinese soybean eultivars released during 1923 to 1995 显示文摘 | Cui Z L Thomas E Carter J Burton J W | 2000 | Crop Science2000，40，： | 1 |
| 13 | Technique of single- stege repair of coarctation of the aorta with ventricu- lar septal defect 显示文摘 | Wakers H L Ionon C E Thomas R L | 2008 | Semi Thorac cardiovasc Surg Pediatr Card surg Ann2008，11，： | 1 |
| 14 | Robust analysis of the yeast proteome under 50 kDa by molecular-massbased fractionation and top-down mass spectrometry显示文摘 | Kellie J F Catherman A D Durbin K R Tran J C Tipton J D Norris J L Witkowski C E 2nd Thomas P M Kelleher N L | | 0，，01： | 1 |
| 15 | Encouraging 'frienAly'complaints behavior in industrial markets-reventing the loss of customers and reputation显示文摘 | Scott W Hansen John E Swan Thomas L Powers | 1996 | Industrial Marketing Management1996，，25： | 1 |
| 16 | Persistence, Distribution, and Emission of Telone C35 Injected into a Florida Sandy Soil as Affected by Moisture, Organic Matter, and Plastic Film Cover显示文摘 | THOMAS J E OU L T ALLEN L H | 2004 | J Environ Sci Heal Part B2004，39，4： | 1 |
| 17 | The effects of temperature on the local structure of metakaolin-based geopolymer binder: A neutron pair distribution function investigation显示文摘 | WHITE CLAIRE E PROVIS JOHN L PROFFEN THOMAS | 2010 | JAm Cerarn Soc2010，93，10： | 1 |
| 18 | Thymoma with epithelial micronodules and lymphoid hyperplasia: six cases of a rare and equivocal subtype显示文摘 | Thomas De Montpréville V Zemoura L Dulmet E | 2002 | Ann Pathol2002，22，3： | 1 |
| 19 | Comparison of node-centered and cell-centeredunstructured finite-volume discretizations : Viscousfluxes 显示文摘 | Diskin B Thomas J L Nielsen E J | 2010 | AIAA Journal2010，48，7： | 1 |
| 20 | Photochemical generation of nitrenium ions from protonated 1,1- diarylhydrazines 显示文摘 | Winter A H Thomas S L Falvey D E | 2004 | Org Lett2004，6，25： | 1 |
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