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| 1 | Aging related methylation influences the gene expression of key control genes in colorectal cancer and adenoma显示文摘AIM To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. METHODS In silico DNA methylation analysis of 353 epigenetic clock Cp G sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer(CRC), 42 adenoma, 17 normal; GEO accession number: GSE48684]. Among the differentially methylated agerelated genes, secreted frizzled related protein 1(SFRP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CRC patients using bisulfite-specific PCR followed by methylation-specific high resolution melting(MS-HRM) analysis. m RNA expression of age-related 'epigenetic clock' genes was studied using Affymetrix HGU133 Plus2.0 whole transcriptome data of 153 colonic biopsy samples(49 healthy adult, 49 adenoma, 49 CRC, 6 healthy children)(GEO accession numbers: GSE37364, GSE10714, GSE4183, GSE37267). Whole promoter methylation analysis of genes showing inverse DNA methylationgene expression data was performed on 30 colonic samples using methyl capture sequencing.RESULTS Fifty-seven age-related Cp G sites including hypermethylated PPP1R16 B, SFRP1, SYNE1 and hypomethylated MGP, PIPOX were differentially methylated between CRC and normal tissues(P < 0.05, ?β≥ 10%). In the adenoma vs normal comparison, 70 CpG sites differed significantly, including hypermethylated DKK3, SDC2, SFRP1, SYNE1 and hypomethylated CEMIP, SPATA18(P < 0.05, ?β≥ 10%). In MS-HRM analysis, the SFRP1 promoter region was significantly hypermethylated in CRC(55.0% ± 8.4 %) and adenoma tissue samples(49.9% ± 18.1%) compared to normal adult(5.2% ± 2.7%) and young(2.2% ± 0.7%) colonic tissue(P < 0.0001). DNA methylation of SFRP1 promoter was slightly, but significantly increased in healthy adults compared to normal young samples(P < 0.02). This correlated with significantly increased SFRP1 m RNA levels in children compared to normal adult samples(P < 0.05). In CRC tissue the mR NA expression of 117 agerelated genes were changed, while in adenoma samples 102 genes showed differential expression compared with normal colonic tissue(P < 0.05, logF C > 0.5). The change of expression for several genes including SYNE1, CLEC3 B, LTBP3 and SFRP1, followed the same pattern in aging and carcinogenesis, though not for all genes(e.g., MGP). CONCLUSION Several age-related DNA methylation alterations can be observed during CRC development and progression affecting the m RNA expression of certain CRC- and adenoma-related key control genes. | Orsolya Galamb Alexandra Kalmár Barbara Kinga Barták árpád V Patai Katalin Leiszter Bálint Péterfia Barnabás Wichmann Gábor Valcz Gábor Veres Zsolt Tulassay Béla Molnár | 2016 | World Journal of Gastroenterology2016，22，47： | 7 |
| 2 | Burden of Clostridium difficile infection between 2010 and 2013:Trends and outcomes from an academic center in Eastern Europe显示文摘AIM:To analyze the incidence and possible risk factors in hospitalized patients treated with Clostridium difficile infection(CDI).METHODS:A total of 11751 patients were admitted to our clinic between 1 January 2010 and 1 May2013.Two hundred and forty-seven inpatients were prospectively diagnosed with CDI.For the risk analysis a 1:3 matching was used.Data of 732 patients matched for age,sex,and inpatient care period and unit were compared to those of the CDI population.Inpatient records were collected from an electronic hospital database and comprehensively reviewed.RESULTS:Incidence of CDI was 21.0/1000 admissions(2.1%of all-cause hospitalizations and 4.45%of total inpatient days).The incidence of severe CDI was 12.6%(2.63/1000 of all-cause hospitalizations).Distribution of CDI cases was different according to the unit type,with highest incidence rates in hematology,gastroenterology and nephrology units(32.9,25 and24.6/1000 admissions,respectively) and lowest rates in 1.4%(33/2312) in endocrinology and general internal medicine(14.2 and 16.9/1000 admissions)units.Recurrence of CDI was 11.3%within 12 wk after discharge.Duration of hospital stay was longer in patients with CDI compared to controls(17.6 ± 10.8d vs 12.4 ± 7.71 d).CDI accounted for 6.3%of allinpatient deaths,and 30-d mortality rate was 21.9%(54/247 cases).Risk factors for CDI were antibiotic therapy[including third-generation cephalosporins or fluoroquinolones,odds ratio(OR) = 4.559;P < 0.001],use of proton pump inhibitors(OR = 2.082,P< 0.001),previous hospitaiization within 12 mo(OR = 3.167,P < 0.001),previous CDI(OR = 15.32;P < 0.001),while presence of diabetes mellitus was associated with a decreased risk for CDI(OR = 0.484;P< 0.001).Treatment of recurrent cases was significantly different from primary infections with more frequent use of vancomycin alone or in combination(P < 0.001),and antibiotic therapy duration was longer(P < 0.02).Severity,mortality and outcome of primary infections and relapsing cases did not significantly differ.CONCLUSION:CDI was accounted for significant burden with longer hospitaiization and adverse outcomes.Antibiotic,PPI therapy and previous hospitaiization or CDI were risk factors for CDI. | Zsuzsanna Kurti Barbara D Lovasz Michael D Mandel Zoltan Csima Petra A Golovics Bence D Csako Anna Mohas Lorant Gnczi Krisztina B Gecse Lajos S Kiss Miklos Szathmari Peter L Lakatos | 2015 | World Journal of Gastroenterology2015，21，21： | 6 |
| 3 | MicroRNAs as emerging biomarkers and therapeutic targets for pancreatic cancer显示文摘Despite tremendous efforts from scientists and clinicians worldwide, pancreatic adenocarcinoma(PDAC) remains a deadly disease due to the lack of early diagnostic tools and reliable therapeutic approaches. Consequently, a majority of patients(80%) display an advanced disease that results in a low resection rate leading to an overall median survival of less than 6 months. Accordingly, robust markers for the early diagnosis and prognosis of pancreatic cancer, or markers indicative of survival and/or metastatic disease are des-perately needed to help alleviate the dismal prognosis of this cancer. In addition, the discovery of new therapeutic targets is mandatory to design effective treatments. In this review, we will highlight the translational studies demonstrating that microRNAs may soon translate into clinical applications as long-awaited screening tools and therapeutic targets for PDAC. | Marion Gayral Sébastien Jo Naima Hanoun Alix Vignolle-Vidoni Hubert Lulka Yannick Delpu Aline Meulle Marlène Dufresne Marine Humeau Maёl Chalret du Rieu Barbara Bournet Janick Sèlves Rosine Guimbaud Nicolas Carrère Louis Buscail Jérome Torrisani Pierre Cordelier | 2014 | World Journal of Gastroenterology2014，20，32： | 4 |
| 4 | Thiopurine-methyltransferase variants in inflammatory bowel disease:Prevalence and toxicity in Brazilian patients显示文摘AIM:To analyze the prevalence of thiopurine-methyltransferase(TPMT)genotypes and their associationwith drug toxicity in inflammatory bowel disease(IBD)patients from southeastern Brazil.METHODS:A total of 219 consecutive patients with IBD,of which 146 had Crohn’s disease and 73 had ulcerative colitis,regularly seen at the outpatient unit of the Division of Gastroenterology at the University Hospital Pedro Ernesto of the State University of Rio de Janeiro,a tertiary referral center,were enrolled in this study from February 2009 to January 2011.We analyzed the presence of major TPMT genetic variants(TPMT*2,*3A,*3C)in IBD patients by means of a specific allele and RFLP-PCR.Genomic DNA was isolated from peripheral blood leukocytes by proteinase-K/Sodium Dodecyl Sulfate digestion and phenol-chloroform extraction.TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes were detected by real-time polymerase chain reaction followed by direct sequencing with specific primers.Clinical data were systematically recorded,and correlated with the genotype results.RESULTS:The distribution of the selected TPMT gene polymorphism TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes was 3.6%,5.4%,and 7.7%of the patients,respectively.Among the side effects recorded from patients taking azathioprine,14 patients presented with pancreatitis and/or an elevation of pancreatic enzymes,while 6 patients had liver toxicity,and 2 patients exhibited myelosuppression/neutropenia.TPMT polymorphisms were detected in 37/219 patients(8 heterozygous for*2,11 heterozygous for*3A,and 18 heterozygous for*3C).No homozygotic polymorphisms were found.Despite the prevalence of the TPMT*3C genotype,no differences among the genotype frequencies were significant.Although no association was detected regarding myelotoxicity or hepatotoxicity,a trend towards the elevation of pancreatic enzymes was observed for TPMT*2 and TPMT*3C genotypes.CONCLUSION:The prevalence of TPMT genotypes was high among Brazilian patients.Variants genes*2and*3C may be associated with azathioprine pancreatic toxicity in a IBD southeastern Brazilian population. | Ana Teresa P Carvalho Barbara C Esberard Renata S B Fróes Davy C M Rapozo Ana B Grinman Tatiana A Simo Juliana C V C Santos Antonio José V Carneiro Luis Felipe Ribeiro-Pinto Heitor S P de Souza | 2014 | World Journal of Gastroenterology2014，20，12： | 3 |
| 5 | Approach to early-onset colorectal cancer:Clinicopathological,familial,molecular and immunohistochemical characteristics显示文摘AIM:To characterize clinicopathological and familial features of early-onset colorectal cancer(CRC) and compare features of tumors with and without microsatellite instability(MSI).METHODS:Forty-five patients with CRC aged 45 or younger were included in the study.Clinical information,a three-generation family history,and tumor samples were obtained.MSI status was analyzed and mismatch repair genes were examined in the MSI families.Tumors were included in a tissue microarray and an immunohistochemical study was carried out with a panel of selected antibodies.RESULTS:Early onset CRC is characterized by advanced stage at diagnosis,right colon location,low-grade of differentiation,mucin production,and presence of polyps.Hereditary forms represent at least 21% of cases.Eighty-one percent of patients who died during followup showed a lack of expression of cyclin E,which could be a marker of poor prognosis.β-catenin expression was normal in a high percentage of tumors.CONCLUSION:Early-onset CRC has an important familial component,with a high proportion of tumors showing microsatellite stable.Cyclin E might be a poor prognosis factor. | Jose Perea Edurne Alvaro Yolanda Rodríguez Cristina Gravalos Eva Sánchez-Tomé Barbara Rivera Francisco Colina Pablo Carbonell Rogelio González-Sarmiento Manuel Hidalgo Miguel Urioste | 2010 | World Journal of Gastroenterology2010，16，29： | 3 |
| 6 | Is early limited surgery associated with a more benign disease course in Crohn's disease?显示文摘AIM:To analyze the difference in disease course and need for surgery in patients with Crohn’s disease(CD).METHODS:Data of 506 patients with incident CD were analyzed(age at diagnosis:31.5±13.8 years).Both hospital and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database,which includes incident CD patients diagnosed between January 1,1977 and December 31,2008.Follow-up data were collected until December 31,2009.All patients included had at least 1year of follow-up available.Patients with indeterminate colitis at diagnosis were excluded from the analysis.RESULTS:Overall,73 patients(14.4%)required resective surgery within 1 year of diagnosis.Steroid exposure and need for biological therapy were lower in patients with early limited surgery(P<0.001 and P=0.09).In addition,surgery rates during follow-up in patients with and without early surgery differed significantly after matching on propensity scores(P<0.001,HR=0.23).The need for reoperation was also lower in patients with early limited resective surgery(P=0.038,HR=0.42)in a Kaplan-Meier and multivariate Cox regression(P=0.04)analysis.However,this advantage was not observed after matching on propensity scores(PLogrank=0.656,PBreslow=0.498).CONCLUSION:Long-term surgery rates and overall exposure to steroids and biological agents were lower in patients with early limited resective surgery,but reoperation rates did not differ. | Petra Anna Golovics Laszlo Lakatos Attila Nagy Tunde Pandur Istvan Szita Mihaly Balogh Csaba Molnar Erzsebet Komaromi Barbara Dorottya Lovasz Michael Mandel Gabor Veres Lajos S Kiss Zsuzsanna Vegh Peter Laszlo Lakatos | 2013 | World Journal of Gastroenterology2013，19，43： | 3 |
| 7 | Transposon mouse models to elucidate the genetic mechanisms of hepatitis B viral induced hepatocellular carcinoma显示文摘The major type of human liver cancer is hepatocellular carcinoma(HCC), and there are currently many risk factors that contribute to this deadly disease. The majority of HCC occurrences are associated with chronic hepatitis viral infection, and hepatitis B viral(HBV) infection is currently a major health problem in Eastern Asia. Elucidating the genetic mechanisms associated with HBV-induced HCC has been difficult due to the heterogeneity and genetic complexity associated with this disease. A repertoire of animal models has been broadly used to study the pathophysiology and to develop potential treatment regimens for HBVassociated HCC. The use of these animal models has provided valuable genetic information and has been an important contributor to uncovering the factors involved in liver malignant transformation, invasion and metastasis. Recently, transposon-based mouse models are becoming more widely used in liver cancer research to interrogate the genome by forward genetics and also used to validate genes rapidly in a reverse genetic manner. Importantly, these transposon-based rapid reverse genetic mouse models could become crucial in testing potential therapeutic agents before proceeding to clinical trials in human. Therefore, this review will cover the use of transposon-based mouse models toaddress the problems of liver cancer, especially HBVassociated HCC occurrences in Asia. | Amy P Chiu Barbara R Tschida Lilian H Lo Branden S Moriarity Dewi K Rowlands David A Largaespada Vincent W Keng | 2015 | World Journal of Gastroenterology2015，21，42： | 2 |
| 8 | Structural basis of gating by the outer membrane transporter feca 显示文摘 | Andrew D Ferguson Ranjan Chakraborty Barbara S Smith | 2002 | Science2002，295，1： | 2 |
| 9 | Prevalence and predictors of hospitalization in Crohn's disease in a prospective population-based inception cohort from 2000-2012显示文摘AIM: To analyze the prevalence, length and predictors of hospitalization in the biological era in the populationbased inception cohort from Veszprem province.METHODS: Data of 331 incident Crohn's disease(CD) patients diagnosed between January 1, 2000 and December 31, 2010 were analyzed(median age at diagnosis: 28; IQR: 21-40 years). Both in- and outpatient records were collected and comprehensively reviewed.RESULTS: Probabilities of first CD-related hospitalization and re-hospitalization were 32.3%, 45.5%,53.7% and 13.6%, 23.9%, 29.8%, respectively after one, three and five years of follow-up in Kaplan-Meier analysis. First-year hospitalizations were related to diagnostic procedures(37%), surgery or disease activity(27% and 21%). Non-inflammatory disease behavior at diagnosis(HR = 1.32, P = 0.001) and perianal disease(HR = 1.47, P = 0.04) were associated with time to first CD-related hospitalization, while disease behavior change(HR = 2.38, P = 0.002) and need for steroids(HR = 3.14, P = 0.003) were associated with time to first re-hospitalization in multivariate analyses.Early CD-related hospitalization(within the year of diagnosis) was independently associated with need for immunosuppressives(OR = 2.08, P = 0.001) and need for surgeries(OR = 7.25, P < 0.001) during the disease course.CONCLUSION: Hospitalization and re-hospitalization rates are still high in this cohort, especially during the first-year after the diagnosis. Non-inflammatory disease behavior at diagnosis was identified as the pivotal predictive factor of both hospitalization and rehospitalization. | Petra A Golovics Laszlo Lakatos Michael D Mandel Barbara D Lovasz Zsuzsanna Vegh Zsuzsanna Kurti Istvan Szita Lajos S Kiss Tunde Pandur Peter L Lakatos | 2015 | World Journal of Gastroenterology2015，21，23： | 2 |
| 10 | Oxidative methylamination of some nitropyridines显示文摘 | Barbara S Marian W | 1999 | J Prakt Chem1999，341，1： | 1 |
| 11 | Corrosion kinetics of battery zinc alloys in electrolyte solutions 显示文摘 | BARBARA S MARIA C ALFRED N | 1998 | Journal of Power Sources1998，75，： | 1 |
| 12 | Organizational demography : the difference effects of age and tenure distributions on technical communication 显示文摘 | Zenger Todd R Barbara S Lawrence | 1989 | Academy of Management Journal1989，32，： | 1 |
| 13 | What is the meaning of non-line-ar dose–response relationships between blood lead concentrationsand IQ显示文摘 | Teresa S Bowers Barbara D Beck | 2006 | NeuroToxicology2006，，27： | 1 |
| 14 | A nutrition education curriculumfor health education:its effect on students’knowledge,attitudesand behavior显示文摘 | CarolB Lily H Barbara S | 1984 | J Sch Health1984，54，10： | 1 |
| 15 | Coulson Rotavirus spike protein VP5 * binds a2bl integrin on the cell surface and competes with virus for cell binding and infectivity显示文摘 | Graham K L Takada Y Barbara S | 2006 | J GEN Virology2006，87，5： | 1 |
| 16 | Health Promotion in Adolescents: A Review of Pender's Health Promotion Model显示文摘 | Brenda J S Barbara V F | 2006 | Nurs Sci Q2006，19，4： | 1 |
| 17 | Overexpression of hypoxia-inducible factor-1α indicates diminished response to radiotherapy and unfavorable prognosis in patients receiving radical radiotherapy for cervical cancer显示文摘 | Barbara B Monika S Richard P | 2003 | Clin Clin Cancer Res2003，9，： | 1 |
| 18 | The bases of crown gall tumorigenesis显示文摘 | Zhu J Philippe M Barbara S | 2000 | J Bacteriol2000，182，： | 1 |
| 19 | Glucagon-like peptide 2:A nutrientresponsive gut growth factor显示文摘 | Douglas G B Yvette P Barbara S | 2001 | The Journal of Nutrition Bethesda2001，131，3： | 1 |
| 20 | Elderly patients on dialysis: Epidemiology of an epidemic显示文摘 | GIUSEPPE P MARIO S BARBARA P G | 1996 | Nephrol Dail Transplant1996，11，9： | 1 |
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