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Microbial markers in colorectal cancer detection and/or prognosis

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World Journal of Gastroenterology 2018年第22期24卷 2327-2347页

作者： romain Villéger Amélie Lopès Julie Veziant Johan Gagnière Nicolas Barnich Elisabeth Billard Delphine Boucher Mathilde Bonnet Université Clermont Auvergne Research Biologics Sanofi R&D Chirurgie digestive Centre Hospitalier Universitaire Université Clermont Auvergne Institut Universitaire de Technologie de Clermont-Ferrand

Colorectal cancer(CRC) is the second leading cause of cancer worldwide. CRC is still associated with a poor prognosis among patients with advanced disease. On the contrary, due to its slow progression from detectable precancerous lesions, the prognosis for patients with early stages of CRC is encouraging. While most robust methods are invasive and costly, actual patient-friendly screening methods for CRC suffer of lack of sensitivity and specificity. Therefore, the development of sensitive, non-invasive and cost-effective methods for CRC detection and prognosis are necessary for increasing the chances of a cure. Beyond its beneficial functions for the host, increasing evidence suggests that the intestinal microbiota is a key factor associated with carcinogenesis. Many clinical studies have reported a disruption in the gut microbiota balance and an alteration in the faecal metabolome of CRC patients, suggesting the potential use of a microbialbased test as a non-invasive diagnostic and/or prognostic tool for CRC screening. This review aims to discuss the microbial signatures associated with CRC known to date, including dysbiosis and faecal metabolome alterations, andthe potential use of microbial variation markers for noninvasive early diagnosis and/or prognostic assessment of CRC and advanced adenomas. We will finally discuss the possible use of these markers as predicators for treatment response and their limitations.

关键词： Colorectal cancer microbiota F.nucleatum Colibactin-producing E.coli prognostic markers diagnostic markers dysbiosis

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亚洲经济的增长、风险与政策

亚洲经济的增长、风险与政策

Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells: An In-Vitro Model to Predict Cardiac Effects of Drugs

作者： romain Duval IMF亚太部门区域研究部

romain Duval博士在演讲中预测2014和2015年亚洲经济会保持5.5%的增长,主要得益于亚洲大国均采取了宽松的货币信贷政策,以及各国内需的不断回升。但是,无论短期、中期还是长期,亚洲经济体均存在较大的风险,特别是各国潜在增长率的下滑...

romain Duval博士在演讲中预测2014和2015年亚洲经济会保持5.5%的增长,主要得益于亚洲大国均采取了宽松的货币信贷政策,以及各国内需的不断回升。但是,无论短期、中期还是长期,亚洲经济体均存在较大的风险,特别是各国潜在增长率的下滑和信贷刺激政策效果的边际递减。未来,灵活的货币政策、宏观审慎监管和有效的结构化改革可能是确保未来亚洲经济增长的关键。

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Journal of Biomedical Science and Engineering 2017年第11期10卷 527-549页

作者： romain Sube Eric A. Ertel Idorsia Pharmaceuticals Ltd. Allschwil Switzerland

Introduction: Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CM) form spontaneously beating syncytia in-vitro. We evaluated whether hiPSC-CM are a compelling model of human cardiac pharmacology useful for early drug development. Methods: We measured hiPSC-CM beating frequency using Ca-sensitive dyes and a high-throughput screening system. We quantified the effects of 640 drugs with various structures and pharmacologies. Results: When tested at 1 μM, most drugs without direct effects on heart rhythm or with effects at high concentrations do not change frequency, indicating specificity. In contrast, the preparation detects compounds with direct activity on heart rhythm, demonstrating sensitivity. In particular, β-adrenergic agonists increase frequency and the model differentiates β2 from β1 agonists, as well as partial from full agonists. Phosphodiesterase inhibitors have subtype-specific actions and PDE4 is particularly important in controlling frequency. The preparation is sensitive to cardiac ion channel blockers: L-type calcium channel blockers, Class-I and Class-III antiarrhythmics change frequency but drugs acting on KATP channels do not. The assay detects compounds blocking the cardiac rapid delayed-rectifier K channel and is an alternative to the classic “hERG test”. Conclusion: hiPSC-CM are a useful in-vitro cardiac model in drug development since they respond appropriately to drugs that modify heart rate in humans.

关键词： Cardiomyocytes Rhythm iPS Cell Phenotypic Screening Pharmacology

Second-line therapy for gemcitabine-pretreated advanced or metastatic pancreatic cancer

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World Journal of Gastroenterology 2012年第12期18卷 1357-1364页

作者： romain Altwegg Marc Ychou Vanessa Guillaumon Simon Thezenas Pierre Senesse Nicolas Flori Thibault Mazard Ludovic Caillo Stéphanie Faure Emmanuelle Samalin Eric Assenat the Oncology and Digestive Endoscopy Department of the CRLC Val d'Aurelle 34000 MontpellierFrance

AIM:To investigate second-line chemotherapy in gemcitabine-pretreated patients with advanced or metastatic pancreatic cancer [(frequency,response,outcome,course of carbohydrate antigen 19-9 (CA 19-9)].METHODS:This retrospective study included all patients with advanced or metastatic pancreatic cancer (adenocarcinoma or carcinoma) treated with secondline chemotherapy in our center between 2000 and *** patients received first-line chemotherapy with gemcitabine,and prior surgery or radiotherapy was *** analyzed each chemotherapy protocol for second-line treatment,the number of cycles and the type of combination *** primary endpoint was overall *** endpoints included progression-free survival,response rate,grade 3-4 toxicity,dosage modifications and CA 19-9 ***:A total of eighty patients (38%) underwenta second-line therapy among 206 patients who had initially received first-line treatment with a gemcitabine-based *** number of cycles was 4 (range:1-12) and the median duration of treatment was 2.6 mo (range:0.3-7.4).The overall disease control rate was 40.0%.The median overall survival and progression-free survival from the start of second-line therapy were 5.8 (95% CI:4.1-6.6) and 3.4 mo (95% CI:2.4-4.2),*** was generally *** overall survival of patients with a CA 19-9 level declining by more than 20% was 10.3 mo (95% CI:4.5-11.6) vs 5.2 mo (95% CI:4.0-6.4) for others (P=0.008).CONCLUSION:A large proportion of patients could benefit from second-line therapy,and CA 19-9 allows efficient treatment monitoring both in first and secondline chemotherapy.

关键词：胰腺癌预处理转移性治疗晚期频率响应

Matched or nonmatched interventions based on the transtheoretical model to promote physical activity.A meta-analysis of randomized controlled trials

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Journal of Sport and Health Science 2018年第1期7卷 50-57页

作者： Ahmed Jerome romain Catherine Bortolon Mathieu Gourlan Marion Carayol Emmanuelle Decker Olivier Lareyre Grégory Ninot Julie Boiché Paquito Bernard EA4556 Laboratory Epsylon-Dynamics of Human Abilities and Health Behaviours University of Montpellier Montpellier 34000 France Challenge for the Change of Behaviour (CCB) Group Montpellier 34000 France University of Montreal Hospital Research Centre Montreal Quebec H2X OA9 Canada Unit of Adult Psychiatry La colombiere University Hospital of Montpellier Montpellier 34295 France Prevention Department of institut Regional du Cancer de Montpellier Epidaure Montpellier 34298 France Research Centre of the University Hospital of Quebec Quebec GIR 2J6 Canada Cancer Research Centre University of LavaL Quebec G1R 3S3 Canada School of Psychology University of Laval Quebec G1C OA6 Canada

Purpose: The aim of this study was to examine whether the efficacy of transtheoretical model(TTM)-based interventions on physical activity(PA)varied according to the following criteria:(1) interventions targeted the actual stages of change(SOCs) or did not;(2) participants were selected according to their SOC or were not; and(3) its theoretical constructs(decisional balance, temptation, self-efficacy, processes of change).Methods: Thirty-three randomized controlled trials assessing TTM-based interventions promoting PA in adults were systematically ***: The between-group heterogeneity statistic(Qb) did not reveal any differential efficacy either in interventions targeting the actual SOC compared with those that did not(Qb = 1.48, p = 0.22) or in interventions selecting participants according to their SOC compared with those that did not(Qb = 0.01, p = 0.91). TTM-based interventions enhanced PA behavior whether they targeted the actual SOC(Cohen's d = 0.36; 95%confidence interval(CI): 0.22–0.49) or not(d = 0.23; 95%CI: 0.09–0.38) and whether they selected their participants according to their SOC(d = 0.33; 95%CI: 0.13–0.53) or not(d = 0.32; 95%CI: 0.19–0.44). The moderators of the efficacy of TTM-based interventions were the number of theoretical constructs used to tailor the intervention(Qb = 8.82, p = 0.003), the use of self-efficacy(Qb = 6.09, p = 0.01), and the processes of change(Qb = 3.51, p = 0.06).Conclusion: TTM-based interventions significantly improved PA behavior, and their efficacy was not moderated by SOC but by the TTM theoretical constructs.

关键词：随机化物理试用控制模特儿匹配 SOC TTM

Decline of semen quality among 10 932 males consulting for couple infertility over a 20-year period in Marseille, France

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Asian Journal of Andrology 2012年第4期14卷 584-590页

作者： Cendrine Geoffroy-Siraudin Anderson Dieudone Loundou Fanny romain Vincent Achard Blandine Courbibre Marie-He1ene Perrard Philippe Durand Marie-Roberte Guichaoua Reproduction Biology Laboratory Conception Hospital AP-HM Marseille 13005 France Aix-Marseille University UMR CNRS IMBE 7263 Faculty of medicine of Marseille Marseille 13005 France Department of medical information Conception Hospital AP-HM Marseille 147 Bd Baille Marseille 13005 France Health Laboratory Faculty of Medicine of Marseille Marseille 13005 France Centre of Assisted Reproductive Technique (CPMA) Conception Hospital AP-HM Marseille 13005 France Functional Genomic Institute of Lyon CNRS INRA ENS of Lyon Lyon 69007 France

Semen from 10 932 male partners of infertile couples was analysed and sperm parameter trends were evaluated at the Reproduction Biology Laboratory of the University Hospital of Marseille （France） between 1988 and 2007. After 3-6 days of abstinence, semen samples were collected. Measurements of seminal fluid volume, pH, sperm concentration, total sperm count, motility and detailed morphology of spermatozoa were performed. Sperm parameters were analysed on the entire population and in men with normal total numeration （〉~ 40 million per ejaculate）. The whole population demonstrated declining trends in sperm concentration （1.5% per year）, total sperm count （1.6% per year）, total motility （0.4% per year）, rapid motility （5.5% per year） and normal morphology （2.2% per year）. In the group of selected samples with total normal sperm count, the same trends of sperm quality deterioration with time were observed. Our results clearly indicate that the auality of semen decreased in this population over the study period.

关键词： environment male infertility regional differences semen quality sperm parameters

SPECT-computed tomography in rats with TNBS-induced colitis: A first step toward functional imaging

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World Journal of Gastroenterology 2017年第2期23卷 216-223页

作者： Rachel Marion-Letellier Pierre Bohn romain Modzelewski Pierre Vera Moutaz Aziz Charlène Guérin Guillaume Savoye Céline Savoye-Collet INSERM Unit UMR1073 Rouen University and Rouen University Hospital QUANTIF LITIS EA 4108 Rouen University and Rouen University Hospital Service d’Anatomo-pathologie Rouen University Hospital Gastroenterology department Rouen University Hospital Radiology department Rouen University Hospital

AIM To assess the feasibility of SPECT-computed tomography(CT) in rats with trinitrobenzene sulfonic acid(TNBS)-induced acute colitis and confront it with model inflammatory *** Colitis was induced in Sprague-Dawley rats by intrarectal injection of TNBS(n = 10) while controls received vehicle(n = 10). SPECT-CT with intravenous injection of 10 MBq of 67Ga-Citrate was performed at day 2. SPECT-CT criteria were colon wall thickness andmaximal wall signal intensity. Laboratory parameters were assessed: colon weight:length ratio, colon cyclooxygenase-2 expression by western blot and histological inflammatory *** Colon weight/length ratio, colon COX-2 expression and histological inflammatory score were significantly higher in the TNBS group than in the control group(P = 0.0296, P < 0.0001, P = 0.0007 respectively). Pixel max tend to be higher in the TNBS group than in the control group but did not reach statistical significance(P = 0.0662). Maximal thickness is significantly increased in the TNBS group compared to the control group(P = 0.0016) while colon diameter is not(P = 0.1904). Maximal thickness and colon diameter were correlated to colon COX-2 expression(P = 0.0093, P = 0.009 respectively) while pixel max was not(P = 0.22). Maximal thickness was significantly increased when inflammation was histologically observed(P = 0.0043) while pixel max and colon diameter did not(P = 0.2452, P = 0.3541, respectively).CONCLUSION SPECT-CT is feasible and easily distinguished control from colitic rats.

关键词： Crohn’ s 疾病大肠炎大肠炎成像 Cyclooxygenase-2 计算 SPECT 的断层摄影术

Shooting Hong Kong's Unique Vertical Cityscape

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城市漫步（上海版、英文） 2017年第9期 12-14页

作者： Dominic Ngai romain Jacquet-Lagreze 不详

Located within the'humid cub-tropical'*** Kong's cummers are perfectly defined by its climate classification-long,hot and sticky,with frequent appearances by thunderstorms,showers and *** its heat level is the way that the city was planned and developed over the last *** skyscrapers shoot off into the sky across its central areas-mainly along the iconic coastline of Victoria Harbour on Hong Kong Island and in Kowloon,as well as in pockets of the New Territories unaffected by its hilly and mountainous terrain.

关键词： Vertical hilly mountainous

沼气化在全球范围内的应用：如何发展经济及环境友好的新能源

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沼气化在全球范围内的应用：如何发展经济及环境友好的新能源

作者： romain Jaspar 清华大学

学位级别：硕士

在上个世纪，经济合作与发展组织（OECD）各成员国的能源与农产品的消耗量都大幅提高，使其开始着眼于对环境影响较小的可再生能源的使用。目前已有多种技术手段来达到这一目的。甲烷化技术以机废物作为原料来产热发电，并将这些废物转... 详细信息

在上个世纪，经济合作与发展组织（OECD）各成员国的能源与农产品的消耗量都大幅提高，使其开始着眼于对环境影响较小的可再生能源的使用。目前已有多种技术手段来达到这一目的。甲烷化技术以机废物作为原料来产热发电，并将这些废物转化为肥料加以利用，在欧洲被视为一条获得清洁能源的有效途径。在近十年中，这一技术在欧洲得到了极大的发展，其中以德国和北欧国家的发展最为迅速。由于支持系统（上网电价补贴、许可证、财政投入等）的不断完善，这一技术在法国等其他欧盟国家也得到了广泛应用。但目前，也有一些限制其推广的因素存在，高昂的初期投资以及监管负担就是下限制其发展的重要壁垒。本论文首先阐述了甲烷化技术的机能以及不同原料与产物之间的关联，以及该技术在经济与环境上的优势。甲烷化技术的输入原料包括来自工业或农业生产的干的或湿的有机废物，产出能源主要为热或电，沼渣可作为干的或湿的肥料使用，在经济上可为特定区域创造就业机会，提供稳定能源，在环境上可替代化石燃料并生产高品质有机肥。其次，本论文通过对比法国与德国之间沼气化的发展历程，重点分析该技术发展的促进因素和限制因素。因为起步较晚，法国只有不到200座甲烷化工厂，远落后于德国的6000余座。支持系统的差异也对沼气化发展造成较大影响。灵活的财政和管理是政府促进甲烷化发展的主要途径，而上网电价补贴是最为有效的扶持方式。第三，在上述信息基础上，本论文分析了甲烷化技术在气体利用与原料选择方面的创新潜力与风险，因为厌氧消化对环境较为敏感且沼气具有风险，该技术的发展必须在严格监管下进行。最后，本论文指出，由于中国等国家具有独特的能源和农业结构，甲烷化技术的发展具有一定优势，相关项目需分几个步骤推进实施。

关键词：沼气化可再生能源有机废物支持系统上网电价补贴