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Factors associated with DAA virological treatment failure and resistance-associated substitutions description in HIV/HCV coinfected patients

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World Journal of Hepatology 2018年第11期10卷 856-866页

作者： Dominique Salmon Pascale Trimoulet Camille Gilbert Caroline Solas Eva Lafourcade Julie Chas Lionel Piroth Karine Lacombe Christine Katlama Gilles Peytavin Hugues Aumaitre Laurent Alric Franoois Boué Philippe Morlat Isabelle Poizot-Martin Eric Billaud Eric Rosenthal Alissa Naqvi Patrick Miailhes Firouzé Bani-Sadr Laure Esterle Patrizia Carrieri Franoois Dabis Philippe Sogni Linda Wittkop 无 Assistance Publique des Hopitaux de Paris Hopitaux Universitaires Paris CentreHopital Hotel DieuUnitédes Maladies infectieuses et tropicalesParis 75004France université Paris Descartes Sorbonne Paris CitéParis 75006France Trimoulet CHU de BordeauxHopital PellegrinLaboratoire de VirologieBordeaux 33000France Trimoulet CNRS-UMR 5234Microbiologie fondamentale et PathogénicitéUniversitéde BordeauxBordeaux 3000France Philippe Morlat Laure EsterleFrancois DabisLinda WittkopUniv.BordeauxISPEDInsermBordeaux Population Health Research Centerteam MORPH3EUSUMR 1219CIC-EC 1401Bordeaux F-33000France APHM Hopital La TimoneLaboratoire de Pharmacocinétique et ToxicologieMarseille 13005France Centre Hospitalier universitaire de Dijon Département d'InfectiologieDijon cedex 21079France inserm-CIC 1342 universitéde Bourgogne Dijon 21000France Assistance Publique des Hopitaux de Paris GHUEP site Saint-AntoineServices Maladies infectieuses et tropicalesParis 75011France universitéPierre et Marie Curie UMR S1136Institut Pierre Louis d' Epidémiologie et de SantéPubliqueParis 75646France universitéParis-Sorbonne Paris 75005France Assistance Publique des Hopitaux de Paris Hopital PitiéSalpêtrière Services Maladies infectieuses et tropicalesParis 75013France Assistance Publique des Hopitaux de Paris Hopital Bichat-Claude BernardLaboratoire de PharmacologieParis 75877France IAME UMR 1137Sorbonne Paris CitéINSERMUniversitéParis DiderotParis 75890France Centre Hospitalier de Perpignan Service Maladies infectieuses et tropicalesPerpignan 66000Franc Centre Hospitalier universitaire de Toulouse Hopital PurpanService Médecine interne-Pole DigestifToulouse 31300France uMR 152 IRD universitéToulouseⅢ Paul SabatierToulouse 31330France Hopital Antoine-Béclère Assistance Publique des Hopitaux de ParisUniversitéParis SudService Médecine interne et immunologieClamart 92140France Centre Hospitalier universitaire de Bordeaux Service de médecine interneHopital Saint-AndréBordeaux 33000France uni

AIMTo describe factors associated with treatment failure and frequency of resistance-associated substitutions （RAS）.METHODSHuman immunodefciency virus （HIV）/hepatitis C virus （HCV） coinfected patients starting a first direct-acting antiviral （DAA） regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligible. Failure was defned as：（1） non-response [HCV-RNA remained detectable during treatment, at end of treatment （EOT）]; and （2） relapse （HCV-RNA suppressed at EOT but detectable thereafter）. Sequencing analysis was performed to describe prevalence of drug class-specifc RAS. Factors associated with failure were determined using logistic regression *** 559 patients, 77% had suppressed plasmaHIV-RNA 〈 50 copies/mL at DAA treatment initiation41% were cirrhotic, and 68% were HCV treatmentexperienced. Virological treatment failures occurred in22 patients and were mainly relapses （17, 77%） thenundefined failures （3, 14%） and non-responses （29%）. Mean treatment duration was 16 wk overall. Posttreatment NS3, NS5A or NS5B RAS were detected in10/14 patients with samples available for sequencinganalysis. After adjustment for age, sex, ribavirin useHCV genotype and treatment duration, low platelecount was the only factor signifcantly associated with ahigher risk of failure （OR： 6.5; 95%CI： 1.8-22.6）. CONCLuSIONOnly 3.9% HIV-HCV coinfected patients failed DAAregimens and RAS were found in 70% of those failingLow platelet count was independently associated withvirological failure.

关键词： Human immunodeficiency virus Hepatitis C virus Direct-acting antiviral Treatment virological failure Resistant associated mutations

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Multiscattering-enhanced absorbance to enable the sensitive analysis of extremely diluted biological samples: Determination of oxidative potential in exhaled air

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Medicine in Novel Technology and Devices 2022年第2期14卷 62-66页

作者： Sami Goekce Nicolas Concha-Lozano Jean-Jacques Sauvain Maud Hemmendinger Alejandro Portela Elise Sergent Pascal Andujar Jean-Claude Pairon Pascal Wild Guillaume Suarez Center for Primary Care and Public Health Lausanne UniversityLausanneSwitzerland Forensic Toxicology and Chemistry unit CURMLLausanne University HospitalGeneva University HospitalsSwitzerland International university of Catalonia Bioengineering Institute of TechnologyBarcelonaSpain CHI Creteil Service Pathologies Professionnelles et de L’EnvironnementCreteilFrance universite Paris-Est Creteil Faculte de SanteInstitut Sante Travail Paris-Est CreteilFrance inserm u955 Team 4CreteilFrance INRS Scientific ManagementVandoeuvre Les NancyFrance

Direct determination of the oxidative potential in exhaled air(OPEA)as a biological indicator of the redox balance status in airways requires an extremely sensitive sensing approach to counterbalance the high dilution of the exhaled air *** opposite to standard colorimetric assays based on Beer-Lambert Law,the use of simple multiscattering-enhanced absorbance(MEA)strategy results in an improved photonic sensing *** on this strategy and using the ferrous-xylenol orange assay,analytical performances allowing the detection of 3 pmol of H_(2)O_(2) could be *** comparative analysis of photometric configurations–standard vs MEA–highlights the large absorbance gain obtained for tiny H_(2)O_(2) amounts–from 0 to 30 pmol–whereas similar sensing trends are observed at higher concentration *** automated introduction of exhaled air sample into the reaction compartment via needle-impinger coupled with the MEA-based photonic cell enables ultrasensitive determination of OPEA in short time(udy conducted on healthy subjects(n=22)and chronic obstructive pulmonary disease(COPD)patients(n=23)volunteers shows a significant increase of the OPEA for COPD versus controls and strong negative correlation between OPEA and spirometry parameters(Tiffeneau index:FEV1/FVC)for ex-/*** perspectives to assess inflammatory episodes in obstructive lung diseases are thus made possible using this sensing approach.

关键词： Absorbance enhancement Photonic device Oxidative potential Exhaled air COPD Pilot study

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英国食品标准局的营养素度量法在法国食物成分数据库中的应用

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营养健康新观察 2014年第1期 36-37页

作者： Chantal Julia Emmanuelle Kesse-Guyot Mathilde Touvier Caroline Mejean Leopold Fezeu Serge Hercberg 刘轶群 universite Paris 13 Equipe de Recherche en Epidemiologie Nutritionnelle(EREN)Centre de Recherche en Epidemiologie et Biostatistiques Sorbonne Paris Cite(CRESS)UMR 1153 InsermU1125 InraCnam universite Paris 5 Universite Paris 774 rue Marcel CachinF-93017 Bobigny CedexFrance Departement de Sante Publique Hopital Avicenne(AP-HP)

营养素度量法对于公共卫生措施的建立是一个强有力的工具,它旨在以营养素含量为依据对食物进行分级评价。英国食品标准局(FSA)的营养素度量法(FSA score)已在英国食物数据库中得以验证。但是这个模型是否适用于其它国家食物数据库则还... 详细信息

营养素度量法对于公共卫生措施的建立是一个强有力的工具,它旨在以营养素含量为依据对食物进行分级评价。英国食品标准局(FSA)的营养素度量法(FSA score)已在英国食物数据库中得以验证。但是这个模型是否适用于其它国家食物数据库则还未被评价。本研究旨在评价英国FSA score在法国食物成分数据库中的应用。来源于法国NutriNet-Sante研究的食物成分表的食品根据英国FSA score进行分类,FSA score是以英国通讯署(OfCom)的切点值(‘健康的'总分≤4的食品和总分≤1的饮料;‘不健康的'总分>4的食品和总分>1的饮料)以及分布切点值(五分位的食物,四分位的饮料)。也可根据法国PNNS(Pro-gramme National Nutrition Sante)推荐的食物组对所采用的食品进行分类。从NutriNet-Sante研究(n=4225)具有法国人群中典型的食物中抽取样品,并根据其相对消耗量称量食品。根据OfCom切点值的食物分类与法国PNNS的食物组分类一致:97.8%的水果和蔬菜,90.4%的谷物和薯类以及仅3.8%的含糖零食被认为是健康的食物。此外,FSA score的可变性对于在同一食物组中子分类之间的区分,证实了使用FSA score作为多重分类体系的可行性,例如作为正面营养素标签的基础。英国FSA score在法国食物成分数据库中的应用更好的弥补了目前公共健康的推荐标准。

关键词：营养素度量体系应用食物成分

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人类慢性病毒性肝炎肝细胞的倍体变化与双核构象

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世界核心医学期刊文摘（胃肠病学分册） 2005年第6期1卷 48-48页

作者： Toyoda H. Bregerie O. Vallet A. C. Desdouets 雒向宁 inserm u370-Pasteur Institute CHU Necker 156 rue de Vaugirard 75015 Paris France Dr.

Background and aim: The importance of the hepatocyte ploidisation pattern to the control of cell proliferation and differentiation has been well established. However, there are no data that have characterised hepatocyte ploidy at various stages of chronic liver inflammation and fibrosis in vivo. Methods: We therefore investigated hepatocyte ploidy/binuclearity patterns in 57 patients with chronic hepatitis, using a recently developed methodology which allows simultaneous hepatocyte ploidy and binuclearity analyses on the same liver section. Results: The percentage of mononuclear diploid hepatocytes was significantly reduced in patients with high hepatitis activity and marked fibrosis (low activity: 75.1 (18.8)%v high activity: 61.8 (21.6)%, p = 0.0111, and low fibrosis: 77.3 (13.8)%v high fibrosis: 57.4 (23.3)%, p = 0.0002). Accordingly, the percentage of mononuclear polyploid hepatocytes increased in patients with high hepatitis activity and marked fibrosis (low activity: 11.9 (15.5)%v high activity: 22.2 (20.1)%, p = 0.0166, and low fibrosis: 9.4 (10.7)%v high fibrosis: 26.4 (21.6)%, p = 0.0001). In addition, the fraction of binuclear hepatocytes was significantly higher in patients with hepatitis B virus (HBV) than in those with hepatitis C virus (HCV) infections (HBV: 18.2 (7.6)%v HCV: 12.0 (4.8)%; p = 0.0020). under multivariate analysis, HBV infection was an independent factor accounting for the larger binuclear hepatocyte fraction (p = 0.0294). Conclusion: Our results revealed an increase in the polyploid hepatocyte fraction which correlates with the severity of chronic hepatitis; moreover, we demonstrated that HBV and HCV related chronic hepatitis exhibited distinctive hepatocyte ploidy patterns, thus allowing the suggestion that these two viral infections may modulate liver ploidy through different mechanisms.

关键词：慢性病毒性肝炎肝细胞慢性肝炎细胞增殖病毒感染同步分析肝脏细胞双倍体多变量分析

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DNA microarray unravels rapid changes in transcriptome of MK-801 treated rat brain

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World Journal of Biological Chemistry 2015年第4期6卷 389-408页

作者： Yuka Kobayashi Sofya P Kulikova Junko Shibato Randeep Rakwal Hiroyuki Satoh Didier Pinault Yoshinori Masuo Department of Biomolecular Science Faculty of ScienceToho University Health Technology Research Center National Institute of Advanced Industrial Science and Technology inserm u1114 Neuro-psychologie Cognitive et Physiopathologie de la SchizophrénieFMTS (Fédération de Médecine Translationnelle de Strasbourg)Faculté de MédecineUniversité de Strasbourg Department of Anatomy School of MedicineShowa University Laboratory of Exercise Biochemistry and Neuroendrocrinology Institute of Health and Sport SciencesUniversity of Tsukuba Global Research Center for Innovative Life Science Peptide Drug InnovationSchool of Pharmacy and Pharmaceutical SciencesHoshi University Organization for Educational Initiatives University of Tsukuba Faculty of Health and Sport Sciences and Tsukuba International Academy for Sport Studies University of Tsukuba Laboratory of Neuroscience Department of BiologyFaculty of ScienceToho University

AIM:To investigate the impact of MK-801 on gene expression patterns genome wide in rat brain regions. METHODS:Rats were treated with an intraperitoneal injection of MK-801 [0.08(low-dose) and 0.16(highdose) mg/kg] or NaC l(vehicle control). In a first series of experiment,the frontoparietal electrocorticogram was recorded 15 min before and 60 min after injection. In a second series of experiments,the whole brain of each animal was rapidly removed at 40 min post-injection,and different regions were separated:amygdala,cerebral cortex,hippocampus,hypothalamus,midbrain and ventral striatum on ice followed by DNA microarray(4 × 44 K whole rat genome chip) ***:Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline gamma frequency(30-80 Hz) oscillations in the frontoparietal electroencephalogram. DNA microarray analysis showed the largest number(up- and down- regulations) of gene expressions in the cerebral cortex(378),midbrain(376),hippocampus(375),ventral striatum(353),amygdala(301),and hypothalamus(201) under low-dose(0.08 mg/kg) of MK-801. under high-dose(0.16 mg/kg),ventral striatum(811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain ***:Acute MK-801 treatment increases synchrony of baseline gamma oscillations,and causes very early changes in gene expressions in six individual rat brain regions,a first report.

关键词： Dizocilpine Dye-swap Gene expression Microarray MK

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法国睡眠研究的历史

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世界睡眠医学杂志 2019年第5期

作者： Karen SPRuYT Lyon Neuroscience Research Center，inserm u1028-CNRS uMR 5292-Waking Team，university Claude Bernard，School of Medicine

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MRI有助于预测急性脑卒中病人的首发症状时间:对不明发病时间病人的意义

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国际医学放射学杂志 2011年第1期34卷 85-页

作者： M.Petkova S.Rodrigo C.Lamy G.Oppenheim E.Touzé J.L.Mas 韩鹏 Departments of Radiology Université Paris DescartesCentre de Psychiatrie et NeurosciencesINSERM U894Centre Hospitalier Sainte-Anne

目的探讨用MRI参数间接评价脑卒中发作时间的价值。材料与方法本研究经伦理委员会批准。

关键词：发病时间 MRI 病人急性脑卒中

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代谢综合征与双亲早发心血管疾病史之间的关系

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世界核心医学期刊文摘（心脏病学分册） 2006年第8期2卷 26-26页

作者： Dallongeville J. Grupposo M. - C. Cottel D. 王睿(译) 马超(校) inserm u508 Institut Pasteur de Lille 1 rue du Pr Calmette 59019 Lille Cedex France 不详

Aims: The goal of this study is to assess the association between the metabolic syndrome(MS) and parental history of cardiovascular disease(CVD). Methods and results: Participants were recruited in a population survey of 3441 men and women, aged 35-64. MS was defined with NCEP-III guidelines. Familial history of myocardial infarction(MI), angina, and stroke was assessed with a standardized questionnaire. Parental premature CVD was defined if CVD occurred before 55/65 years in the father/mother. A total of 390 men and 281 women had MS. Positive parental CVD was associated with MS in women(43.0 vs. 36.8% , Put not in men(36.9 vs. 31.8% , P=0.06). Similarly, parental premature CVD was associated with MS in women(19.2 vs. 11.8% , Put not in men(11.1 vs. 11.1% , ns). In women with MS, the age, centre, and educational level adjusted odds ratios [OR(95% CI)] of having a positive parental premature stroke was 1.84(1.0-3.38), P=0.049. This OR was 1.76(1.23-2.76), P=0.007 for combined parental premature MI and stroke and 1.67(1.17-2.38), P=0.004 for combined premature MI, stroke, and angina. After further adjustment on personal coronary heart disease and CVD risk factors, the ORs of having a positive parental history of combined premature MI and stroke [1.75(1.11-2.76), P=0.016] or MI, stroke, and angina [1.79(1.21-2.63), P=0.003], remained statistically significant, in women with MS. Conclusion: The MS is associated with parental premature CVD independently of classical CV risk factors, suggesting that MS is a contributor to the familial aggregation of premature CVD.

关键词：代谢综合征心血管疾病疾病史双亲危险因素脑卒中受试者心绞痛

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东亚钳蝎昆虫毒素BmK IT的初级结构研究

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中国科学（B辑） 1993年第1期23卷 46-52页

作者：吉永华 P. Mansuelle 徐科 C.Granier C.Kopeyan S. Terakawa H. Rochat 中国科学院上海生理研究所 Laboratorie de Biochime CNRS uRA 1455 inserm u 172 Faculte de Medecine Secteur Nord Bd Pierre Dramard 13326 Marseille Cedex 15 France 日本冈崎国立生理学研究所

从中国产东亚钳蝎(Buthus martensi Karsch)毒中纯化的一个昆虫毒素BmK IT经还原和羧甲基化处理后,分别用TPCK-胰蛋白酶和金黄色葡萄球菌蛋白酶进行用TLC-薄膜分离酶解的肽段并分别测定了它们的氨基酸顺序。将BmK IT及其酶解肽段的氨基... 详细信息

从中国产东亚钳蝎(Buthus martensi Karsch)毒中纯化的一个昆虫毒素BmK IT经还原和羧甲基化处理后,分别用TPCK-胰蛋白酶和金黄色葡萄球菌蛋白酶进行用TLC-薄膜分离酶解的肽段并分别测定了它们的氨基酸顺序。将BmK IT及其酶解肽段的氨基酸顺序的测定结果与由非洲产蝎Androctonus australis Hector毒中纯化的昆虫毒素AaH IT的初级结构进行参照对比,我们发现两种昆虫毒素的分子结构中仅有16个残基部位发生了变异,其同源性高达75％以上。这一结果为探讨蝎昆虫毒素的分子结构特征以及结构与功能的相互关系提供了重要资料,也为这类毒素的开发利用,如作为神经生物科学研究中的工具物或探讨作为生物杀虫剂的可能性等提供了必要的分子基础。

关键词：东亚钳蝎昆虫神经毒素初级结构

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p53 functional loss,stemness and hepatocellular carcinoma

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Hepatoma Research 2020年第11期6卷 67-84页

作者： Claude Caron de Fromentel Massimo Levrero Centre de Recherche en Cancérologie de Lyon INSERM U1052CNRS 5286UniversitéClaude Bernard Lyon 1Centre Léon BérardLyon 69008France Service d’Hépatologie et de Gastroentérologie Hôpital de la Croix-RousseHospices Civils de LyonLyon 69004France Dipartimento di Scienze Cliniche InternisticheAnestesiologiche e Cardiovascolari(SCIAC)Sapienza UniversityRome 00161Italy Center for Life Nano Science Istituto Italiano di TecnologiaSapienza UniversityRome 00161Italy

The tumor suppressor p53 is a key player in the control of genomic integrity and homeostasis in connection with p63 and p73,the two other members of the p53 *** of functional p53 leads to the proliferation and survival of mature cells and progenitor or stem cells that accumulate genetic alterations,thus favoring tumorigenesis.p53 loss of function,observed in a wide variety of human tumor types,is frequently caused by missense mutations more frequently found in the DNA binding domain,but can also be due to the expression of a plethora of viral and cellular negative *** hepatocellular carcinoma(HCC)represents a specific situation,first because the TP53 gene mutations pattern exhibits a“hot spot”rarely found in other tumor types that is linked to Aflatoxin B1 exposure and,second,because many HCCs do not exhibit any TP53 ***,we provide an overview of the current knowledge about the inhibition of p53 functions by the N-terminal(ΔN)truncated forms of the family,and their role in the emergence and maintenance of pre-malignant cells with stem cell characteristics and in HCC *** focus in particular on the Nanog-IGF1R-ΔNp73 axis that is associated with stem-like features in HCC cells and that may provide an attractive new therapeutic target and help to develop new biomarkers for HCC risk stratification,as well as preventive strategies.

关键词： p53 family p53 functional inactivation ΔNp73 hepatic progenitor cells cancer stem cells Nanog hepatocellular carcinoma

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