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Prevalence of hepatitis C infection among intravenous drug users in Shanghai

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World Journal of Gastroenterology 2013年第32期19卷 5320-5325页

作者： Yan-Lin Tao Yu-Fan Tang Jian-Ping Qiu Xiao-Feng Cai Xiao-Ting Shen Ya-Xin Wang Xue-Tao Zhao Microbiology Laboratory Center for Disease Control and Prevention of Xuhui Microbiology Laboratory Shanghai Public Health Clinical Center

AIM:To characterize the prevalence of hepatitis C virus(HCV)infection among Chinese intravenous drug users(IDUs).METHODS:A total of 432 adult IDUs(95 women and337 men)in Shanghai were included in the *** third-generation Elecsys Anti-HCV assay(Roche Diagnostics gmbh,Sandhofer Strasse 116,D-68305,Mannheim,Germany)was used to screen for antibodies against *** RIBA strip,a supplemental antiHCV test with high specificity,was performed on all of the samples that tested positive during the initial *** of the anti-HCV positive samples were analyzed with a Cobas TaqMan 48 Analyzer(Roche Diagnostics)for direct detection of HCV *** of the HCV RNA-positive samples were sequenced for genotype ***:The preliminary screening identified 262(60.6%)subjects who were seropositive for *** the 62 females and 200 males seropositive subjects,16(16.7%)and 65(19.3%),respectively,were confirmed by RIBA,yielding an overall HCV seropositive rate of18.8%.Four female(6.5%)and 14 male(7.0%)subjects tested positive for HCV RNA,indicating an active infection rate of 4.2%for the entire study *** 18 HCV RNA-positive serum samples were *** individuals were genotype 1b,and four were genotype *** individual each was infected with genotypes 2a,2b and *** subjects were coinfected with multiple strains:two with genotypes 1a and 2a,and two with genotypes 1b and *** active infection rate among HCV-seropositive individuals was22.2%,which was significantly lower than most ***:The prevalence of HCV is relatively low among IDUs in Shanghai,with a spontaneous recovery rate much higher than previous estimates.

关键词： Hepatitis C Anti-hepatitis C virus antibodies Prevalence of hepatitis C virus Active infection rate Intravenous drug users

Update on pathogenesis and predictors of response of therapeutic strategies used in inflammatory bowel disease

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World Journal of Gastroenterology 2015年第44期21卷 12519-12543页

作者： Emilio G Quetglas Zlatan Mujagic Simone Wigge Daniel Keszthelyi Sebastian Wachten Ad Masclee Walter Reinisch Project Strategy and Science Grünenthal GmbH Internal Medicine University of Maastricht Medical Center Translational Science Grünenthal GmbH Molecular Pharmacology Grünenthal GmbH Internal Medicine. Mc Master University

The search for biomarkers that characterize specific aspects of inflammatory bowel disease(IBD), has received substantial interest in the past years and is moving forward rapidly with the help of modern technologies. Nevertheless, there is a direct demand to identify adequate biomarkers for predicting and evaluating therapeutic response to different therapies. In this subset, pharmacogenetics deserves more attention as part of the endeavor to provide personalized medicine. The ultimate goal in this area is the adjustment of medication for a patient's specific genetic background and thereby to improve drug efficacy and safety rates. The aim of the following review is to utilize the latest knowledge on immunopathogenesis of IBD and update the findings on the field of Immunology and Genetics, to evaluate the response to the different therapies. In the present article, more than 400 publications were reviewed but finally 287 included based on design, reproducibility(or expectancy to be reproducible and translationable into humans) or already measured in humans. A few testshave shown clinical applicability. Other, i.e., genetic associations for the different therapies in IBD have not yet shown consistent or robust results. In the close future it is anticipated that this, cellular and genetic material, as well as the determination of biomarkers will be implemented in an integrated molecular diagnostic and prognostic approach to manage IBD patients.

关键词： Mucosal immunology Biomarkers Pharmacology Mode of

Integrating Culture-based Antibiotic Resistance Profiles with Whole-genome Sequencing Data for 11,087 clinical Isolates

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Genomics, Proteomics & Bioinformatics 2019年第2期17卷 169-182页

作者： Valentina Galata Cédric C. Laczny Christina Backes Georg Hemmrich-Stanisak Susanne Schmolke Andre Franke Eckart Meese Mathias Herrmann Lutz von Müller Achim Plum Rolf Mü ller Cord Stahler Andreas E. Posch Andreas Keller Chair for clinical Bioinformatics Saarland University 66123 Saarbrücken Germany Helmholtz center for Infection Research and Pharmaceutical Biotechnology (HZI) Saarland University 66123 Saarbrücken Germany Institute of clinical Molecular Biology Christian-Albrechts University of Kiel 24105 Kiel Germany Siemens Healthcare gmbh Strategy and Innovation 91052 Erlangen Germany Department of Human Genetics Saarland University 66421 Homburg Germany Institute of Medical Microbiology and Hygiene Saarland University 66421 Homburg Germany Ares Genetics gmbh 1030 Vienna Austria Curetis gmbh 71088 Holzgerlingen Germany Department of Pharmacy Pharmaceutical Biotechnology Saarland University 66123 Saarbrücken Germany Department of Microbial Natural Products Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) Saarland University 66123 Saarbrücken Germany

Emerging antibiotic resistance is a major global health threat. The analysis of nucleic acid sequences linked to susceptibility phenotypes facilitates the study of genetic antibiotic resistance determinants to inform molecular diagnostics and drug development. We collected genetic data (11,087 newly-sequenced whole genomes) and culture-based resistance profiles (10,991 out of the 11,087 isolates comprehensively tested against 22 antibiotics in total) of clinical isolates including 18 main species spanning a time period of 30 years. Species and drug specific resistance patterns were observed including increased resistance rates for Acinetobacter baumannii to carbapenems and for Escherichia coli to fluoroquinolones. Species-level pan-genomes were constructed to reflect the genetic repertoire of the respective species,including conserved essential genes and known resis-tance factors. Integrating phenotypes and genotypes through species-level pan-genomes allowed to infer gene–drug resistance associations using statistical testing. The isolate collection and the analysis results have been integrated into GEAR-base,a resource available for academic research use free of charge at https://***.

关键词： Antibiotic resistance Whole-genome sequencing Bacteria Pan-genome

Perspectives in the treatment of pancreatic adenocarcinoma

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World Journal of Gastroenterology 2015年第31期21卷 9297-9316页

作者： Angel Cid-Arregui Victoria Juarez German Cancer Research center Trans- lational ImmunologyTumor Immunology Program Asteria Pharma gmbh 68723 OftersheimGermany

Pancreatic ductal adenocarcinoma(PDAC) is an incurable lethal disease whose incidence rate is growing. There is no effective screening for detection of early stage tumors and,in most cases,PDAC is diagnosed at advanced disease stages,when radical pancreatic resection is not possible. The aggressive nature of pancreatic tumor cells lies in the complex genetic mechanisms behind their uncontrolled capability to grow and metastasize,which involve essential adaptive changes in cellular metabolism,signaling,adhesion and immunoediting. In addition,PDAC cells promote a dense functional stroma that facilitates tumor resistance to chemotherapy and radiation. During the last two decades,gemcitabine has been the reference for the systemic treatment of PDAC. However,recently,a regimen combining fluorouracil,irinotecan,oxaliplatin,and leucovorin(FOLFIRINOX) and another combining albumin-bound paclitaxel with gemcitabine have shown clear therapeutic advantage in advanced PDAC,with survival outcomes of 11.3 and 8.5 mo on phase Ⅲ trials,respectively,over singleagent gemcitabine. With the pending issue of their higher toxicities,these regimens set the reference for ongoing and future clinical studies in advanced PDAC. In addition,the efficacy of oral fluoropyrimidine(S-1) has been well documented in Asiatic PDAC patients. The development of therapeutic approaches other than cytotoxic drugs has proven difficult in the past,with only one drug(erlotinib) approved to date. Besides,a number of agents targeting signaling pathways in tumor or stroma cells are being investigated. Likewise,immunotherapies that target PDAC in various ways are the subject of a number of clinical trials. The search for reliable biomarkers with diagnostic and prognostic value using genomics and mass spectrometry methods may facilitate monitoring and refinement of therapies. This review focuses on current understanding of the pathogenesis of PDAC and the latest developments in the treatment of advanced PDAC.

关键词： Pancreatic adenocarcinoma Tumor sur-veillance Biom

Human induced pluripotent stem cell based in vitro models of the blood-brain barrier： the future standard？

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Neural Regeneration Research 2017年第10期12卷 1607-1609页

作者： Winfried Neuhaus AIT–Austrian Institute of Technology gmbh Competence Center Health and BioresourcesUnit Molecular DiagnosticsMuthgasse 111190 ViennaAustria

There is an urgent and tremendous need for human dis- ease models in drug development in order to improve pre- clinical predictability. In the case of brain disorders drugs have to cross the blood-brain barrier （BBB） to enter the central nervous system （CNS）. It was estimated that more than 95% of the drugs cannot cross the BBB.

关键词： Human induced pluripotent stem cell based in vitro models of the blood-brain barrier:the future standard BBB

Cellular precision modulation of JAK1:tailoring therapies for allergic lung inflammation

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2843-2844页

作者： Xiaocheng Yan Siegfried Ussar Research Unit Adipocytes&Metabolism(ADM) Helmholtz Diabetes CenterHelmholtz Zentrum MünchenGerman Research Center for Environmental Health GmbH85764 NeuherbergGermany German center for Diabetes Research(DZD) 85764 NeuherbergGermany

In a recent publication published in Cell,Tamari et *** a previously unrecognized role of JAK1 signaling in vagal sensory neurons regulating the immune response to allergic lung inflammation.1 The authors show that sensory neuromodulation could be an important therapeutic avenue for the treatment of lung *** is now well established that the number of patients suffering from allergic disorders,like those suffering from obesity and the metabolic syndrome,is rapidly increasing world-wide,accelerating the burden on individual health and healthcare ***,basic and clinical researchers urgently need to develop novel therapeutics and approaches to limit or prevent disease development or progression.

关键词： JAK1 allergic lung

Blood glucose response after oral lactulose intake in type 2 diabetic individuals

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World Journal of Diabetes 2021年第6期12卷 893-907页

作者： Thomas R Pieber Eva Svehlikova Ines Mursic Tamara Esterl Manfred Wargenau Tina Sartorius Lioba Pauly Susann Schwejda-Guettes Annalena Neumann Valentin Faerber John Friedrich Stover Barbara Gaigg Angelika Kuchinka-Koch Division of Endocrinology and Diabetology Department of Internal MedicineMedical University of GrazGraz 8036Austria Department of Statistic M.A.R.C.O.GmbH&Co.KGInstitute for Clinical Research and StatisticsDüsseldorf 40211Germany Department of Nutritional CRO BioTeSys GmbHEsslingen 73728Germany Department of Medical&clinical Affairs Market Access&Education Business Unit Enteral NutritionBad Homburg 61352Germany Department of Medical Clinical&Regulatory AffairsBusiness Unit Parenteral NutritionKeto-Analogues and Standard I.V.FluidsFresenius Kabi Deutschland GmbHBad Homburg 61352Germany Department of Consultancy Stover-SolutionsZurich 8006Switzerland Market Unit Lactulose Fresenius Kabi Austria GmbHLinz 4020Austria

BACKGROUND Lactulose is approved for the symptomatic treatment of constipation,a gastrointestinal(GI)complication common in individuals with *** products contain carbohydrate impurities(e.g.,lactose,fructose,galactose),which occur during the lactulose manufacturing *** impurities may affect the blood glucose levels of individuals with type 2 diabetes mellitus(T2DM)using lactulose for the treatment of mild constipation.A previous study in healthy subjects revealed no increase in blood glucose levels after oral lactulose ***,it is still unclear whether the intake of lactulose increases blood glucose levels in individuals with *** To evaluate the blood glucose profile after oral lactulose intake in mildly constipated,non-insulin-dependent subjects with T2DM in an outpatient *** This prospective,double-blind,randomized,controlled,single-center trial was conducted at the clinical Research center at the Medical University of Graz,Austria,in 24 adult Caucasian mildly constipated,non-insulin-dependent subjects with *** subjects were randomized and assigned to one of six treatment sequences,each consisting of four treatments stratified by sex using an incomplete block *** received a single dose of 20 g or 30 g lactulose(crystal and liquid formulation),water as negative control or 30 g glucose as positive *** blood glucose concentrations were measured over a period of 180 min post *** primary endpoint was the baseline-corrected area under the curve of blood glucose concentrations over the complete assessment period[AUC_(baseline_c(0-180 min))].Quantitative comparisons were performed for both lactulose doses and formulations vs water for the equal lactulose dose vs glucose,as well as for liquid lactulose vs crystal *** parameters included GI tolerability,which was assessed at 180 min and 24 h post dose,and adverse events occurring up to 24 h post *** 24 randomized

关键词： Lactulose Constipation Blood glucose Type 2 diabetes mellitus Laxative Sugar substitute

Human primary muscle stem cells regenerate injured urethral sphincter in athymic rats

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Animal Models and Experimental Medicine 2022年第5期5卷 453-460页

作者： Biniam M.Bekele Verena Schöwel-Wolf Janine Kieshauer Andreas Marg Andreas Busjahn Sarah Davis Gayle Nugent Anne-Karoline Ebert Simone Spuler Muscle Research Unit Experimental and Clinical Research Centera cooperation between the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association and the CharitéUniversitätsmedizin BerlinBerlinGermany CharitéUniversitätsmedizin BerlinGermany Max-Delbrück-center for Molecular Medicine in the Helmholtz Association BerlinGermany Berlin Institute of Health at CharitéUniversitätsmedizin BelrinGermany HealthTwist gmbh BerlinGermany Charles River Laboratories MattawanMichiganUSA Department of Urology and Pediatric Urology University Hospital UlmUlmGermany

Background:The aim of the study was to demonstrate the efficacy of human muscle stem cells(MuSCs)isolated using innovative technology in restoring internal urinary sphincter function in a preclinical animal ***:Colonies of pure human MuSCs were obtained from muscle biopsy *** rats were subjected to internal urethral sphincter damage by *** days after injury,2×105 muscle stem cells or medium as control were injected into the area of sphincter damage(n=5 in each group).Peak bladder pressure and rise in pressure were chosen as outcome *** repeatedly obtain the necessary pressure values,telemetry sensors had been implanted into the rat bladders 10 days prior to ***:There was a highly significant improvement in the ability to build up peak pressure as well as a pressure rise in animals that had received muscle stem cells as compared to control(p=0.007)3 weeks after the cells had been *** mini-mal histologic evidence of scarring was observed in treated ***:Primary human muscle stem cells obtained using innovative technology functionally restore internal urethral sphincter function after *** into use in clinical settings is foreseeable.

关键词： human muscle stem cells sphincter injury telemetry urinary incontinence urodynamics

Male papillary breast cancer treated by wide resection and latissimus dorsi flap reconstruction: A case report and review of the literature

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World Journal of clinical Oncology 2016年第5期7卷 420-424页

作者： Malgorzata Banys-Paluchowski Eike Burandt Joanna Banys Stefan Geist Guido Sauter Natalia Krawczyk Peter Paluchowski Department of Obstetrics and Gynecology Marienkrankenhaus Hamburg Department of Pathology University of Hamburg Wroclaw Medical University Department of Obstetrics and Gynecology Regio Klinikum Pinneberg Department of Obstetrics and Gynecology University of Duesseldorf

Breast cancer(BC) in men represents between 0.5% and 1% of all BC diagnosed each year. We report a case of advanced BC in a 62-year-old male treated at our interdisciplinary Breast Cancer center. The patient presented with a newly diagnosed large, symptomatic mass in his left breast. clinical examination showed a not movable mass of 16 cm diameter, deforming the whole breast; the overlying skin was livid and hypervascularized. Enlarged lymph nodes were palpable in the axillary pit. He had no concomitant diseases at time of presentation. He denied any first- or second degree family medical history of cancer of any type and he never received radiotherapy. Ultrasound guided minimal-invasive 14-gauge core biopsy revealed a moderately differentiated encapsulated papillary carcinoma with high expression of estrogen and progesterone receptors(both > 80%, IRS 12) and HER2-negative. Because of the tumor size a mastectomy with axillary dissection and chest wall reconstruction using a latissimus dorsi flap was performed. Histological analysis showed invasive growth besides typical(non-invasive) papillary carcinoma and was classified as invasive solid papillary carcinoma; p T3(10 cm), p N0(0/15), M0,R0; Oncotype DX Recurrence Score indicated low risk(RS: 2). After discussion in the interdisciplinary tumor board meeting, radiation therapy and tamoxifen were recommended. The patient had an uneventful recovery and is disease-free after two years of follow-up. Male BC is typically diagnosed at an advanced stage, most likely due to a lack of awareness that men can develop BC. Therefore, in case of a large tumor, a flap-based thoracic reconstruction may be required.

关键词： Male breast cancer Papillary carcinoma Reconstruction Latissimus dorsi flap Rare tumors