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Pathological evolution of hepatitis C virus-“Healthy carriers”

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World Journal of Gastroenterology 2008年第24期14卷 3861-3865页

作者： Rodolphe Sobesky Pascal Lebray Bertrand Nalpas Anas Vallet-Pichard Hélène Fontaine Jean-Luc Lagneau Stanislas Pol inserm u785 Centre Hépato-BiliaireHpital Paul Brousse united Hepatologie Hopital CochinUniversite Paris V-Rene Descartes

AIM： To determine factors associated with fibrosis progression in hepatitis C virus （HCV）-infected patients without significant initial pathological lesions. METHODS： Seventy six untreated HCV-infected patients with initially normal liver as defined by a Knodell score ≤ 3, with 2 liver biopsies and detectable HCVRNA were included. Markers of fibrosis progression were assessed. RESuLTS： Median duration of infection and time between paired biopsies was 13 （95% CI： 1-28） and 4 （95% CI： 2-16） years respectively. Alaninetransaminase （ALT） activity was normal in 43.4% of cases. 50% demonstrated progression of the necroinflammation and 34% of fibrosis after a median time evolution of 4 years （95% CI： 2-16）. The median difference in the necro-inflammation and fibrosis score between biopsies was low, 1.5 and 0.0 respectively. univariate analysis showed there was no difference between fibrosis activity or evolution according to genotype or viral load. A higher fibrosis progression （P = 0.03） was observed in patients with body mass index （BMI）〉 25. Fibrosis progression correlated with the time interval between biopsies （P = 0.01）. A significant progression of activity （1.7 vs 0.4, P 〈 0.05） or fibrosis （0.9 vs 0.0, P 〈 0.01） was observed in patients with elevated ALT. There was a significant correlation between activity progression and fibrosis progression（P = 0.003）. Multivariate analysis demonstrated that fibrosis progression was associated with elevated ALT, BMI 〉 25 and the time interval between 2 biopsies. CONCLuSION： There is no fibrosis progression in 66% of patients without significant initial histopathological lesion. Fibrosis progression is associated with elevated ALT and BMI 〉 25.

关键词： Hepatitis C virus Liver fibrosis Liver biopsy Alanine-transaminase Body mass index

From mouse to man——a bridge too far?

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National Science Review 2020年第7期7卷 1258-1259页

作者： Henry Kennedy Colette Dehay univ Lyon Université Claude Bernard Lyon 1 Inserm Stem Cell and Brain Research Institute U1208 Institute of Neuroscience Chinese Academy of Sciences

The contemplation of our demise, particularly via the loss of cognitive functions, is challenging for our species. While we seek to understand our brain and its action as a particularly intriguing manifestation of the physical universe, society also seeks solutions to concrete problems and, here, understanding the brain as an intellectual exercise must be extended to being able to maintain and repair its function. Just how difficult this is be-

关键词： VISuAL-CORTEX CIRCuIT BRAIN FEATuRES

Influence of hepatitis viruses on clinico-pathological profiles and long-term outcome in patients undergoing surgery for hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2014年第2期13卷 162-172页

作者： Anna-Maria Tanase Traian Dumitrascu Simona Dima Razvan Grigorie Agnes Marchio Pascal Pineau Irinel Popescu Center of General Surgery and Liver Transplant Fundeni Clinical Institute unité "Organisation nucléaire et oncogenèse" INSERM U993Institut

BACKGROuND: The global risk of hepatocellular carcinoma(HCC) is largely due to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. In recent years, however, an increased prevalence of non-viral HCC has been noted. The clinical impact of the presence/absence of viral infections in HCC remains controversial. The present study aimed to assess the effect of hepatitis viruses on demographics, clinical and pathological features and long-term outcome in a large cohort of Romanian patients who underwent surgery for HCC. METHODS: The study included 404 patients with HCC who had undergone resection, transplantation or radiofrequency ablation at a single institution between 2001 and 2010. The patients were divided into four groups: 85 patients with hepatitis B virus infection (HBV group), 164 patients with hepatitis C virus infection (HCV group), 39 patients with hepatitis B and C virus co-infection (HBCV group), and 116 patients without viral infection (non-BC group). RESuLTS: The patients of both HBV (56.0±11.3 years) and HBCV groups (56.0±9.9 years) were significantly younger than those of the HCV (61.0±8.5 years, P=0.001) and non-BC groups(61.0±13.0 years, P=0.002). Interestingly, the prevalence of liver cirrhosis was significantly lower in the non-BC group (47%)than in any other subsets (72%-90%, Purthermore, the non-BC patients were more advanced according to the Barcelona Clinic Liver Cancer stages than the patients of the HCV or HBCV groups (Puently assessed beyond the Milan criteria than any other groups (P=0.001). No significant differences in the disease-free or overall survival rates were observed among these groups. CONCLuSIONS: Patients with non-viral HCC are diagnosed at advanced ages and stages, a situation plausibly due to the poor effectiveness of cancer surveillance in community practice. The presence of viral infections does not appear to impair the longterm prognosis after surgical treatm

关键词： hepatitis B virus hepatitis Cvirus hepatocellular carcinoma recurrence prognosis

Silicone matrices for controlled dexamethasone release:toward a better understanding of the underlying mass transport mechanisms

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Regenerative Biomaterials 2023年第1期10卷 498-509页

作者： Thitiphorn Rongthong Adam Qnouch Maria Maue Gehrke Laurent Paccou Paulo Oliveira Florence Danede Jeremy Verin Christophe Vincent Jean-Francois Willart Florence Siepmann Juergen Siepmann univ.Lille INSERMCHU LilleU1008F-59000 LilleFrance univ.Lille UMR CNRS 8207UMETF-59655 Villeneuve d’AscqFrance

Dexamethasone-loaded silicone matrices offer an interesting potential as innovative drug delivery systems,*** the treatment of inner ear diseases or for ***,very long drug release periods are targeted:several years/*** renders the development and optimization of novel drug products cumbersome:experimental feedback on the impact of the device design is obtained very slowly.A better understanding of the underlying mass transport mechanisms can help facilitating research in this field.A variety of silicone films were prepared in this study,loaded with amorphous or crystalline *** polymorphic drug forms were investigated,the film thickness was altered and the drug optionally partially/completely exchanged by much more water-soluble dexamethasone‘phosphate’.Drug release studies in artificial perilymph,scanning electron microscopy,optical microscopy,differential scanning calorimetry,X-ray diffraction and Raman imaging were used to elucidate the physical states of the drugs and polymer,and of the systems’structure as well as dynamic changes thereof upon exposure to the release *** particles were initially homogeneously distributed throughout the *** hydrophobicity of the matrix former very much limits the amounts of water penetrating into the system,resulting in only partial drug *** mobile drug molecules diffuse out into the surrounding environment,due to concentration ***,Raman imaging revealed that even very thin silicone layers(ug for prolonged periods of *** physical state of the drug(amorphous,crystalline)did not affect the resulting drug release kinetics to a noteworthy extent.

关键词： silicone matrix drug release mechanism dexamethasone dexamethasone phosphate Raman imaging

Hepatitis C virus infection and apoptosis

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World Journal of Gastroenterology 2007年第36期13卷 4865-4872页

作者： Richard Fischer Thomas Baumert Hubert E Blum Department of InternalMedicine II University of Freiburg Germany inserm u748 Service d’Hépatogastro-entérologie Hpitaux Universitaires de Strasbourg Strasbourg France

Apoptosis is central for the control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death inducing ligands CD95/Fas, TRAIL and TNFα occur. Nevertheless, HCV infection persists in the majority of patients. The impact of apoptosis in chronic HCV infection is not well understood. It may be harmful by triggering liver fibrosis, or essential in interferon (IFN) induced HCV elimination. For virtually all HCV proteins, pro- and anti-apoptotic effects have been described, especially for the core and NS5A protein. To date, it is not known which HCV protein affects apoptosis in vivo and whether the infectious virions act pro- or anti- apoptotic. With the availability of an infectious tissue culture system, we now can address pathophysiologically relevant issues. This review focuses on the effect of HCV infection and different HCV proteins on apoptosis and of the corresponding signaling cascades.

关键词： Hepatitis C Spoptosis TRAIL CD95/Fas TNFα Perforin

Trends in incidence and management of cancer of the ampulla of Vater

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World Journal of Gastroenterology 2014年第29期20卷 10144-10150页

作者： Florian Rostain Samia Hamza Antoine Drouillard Jean Faivre Anne-Marie Bouvier C?me Lepage Registre Bourguignon des Cancers Digestifs INSERM U866CHU de DijonFaculté de Médecine21079 Dijon CedexFrance

AIM: To provide trends in incidence, management and survival of cancer of the ampulla of Vater in a well-defined French population.

关键词： Cancer of the ampulla of Vater Incidence Survival Treatment Epidemiology

Homozygosity for the CD1E★02 allele is associated with a resistance to Plasmodium falciparum malaria infection in Gabonese school children

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Asian Pacific Journal of Tropical Medicine 2017年第2期10卷 195-198页

作者： Landry-Erik Mombo Francine Ntoumi Cyrille Bisseye Rajendranath Ramasawmy Pascal Millet Ryad Tamouza Centre International de Recherches Medicales de Franceville(CIRMF) BP 769FrancevilleGabon inserm u458 Hopital Robert Debre48 Bd Serurier75019 ParisFrance Laboratoire d'Immunologie et d'Histocompatibilite AP-HP IUH and INSERM U662Hopital Saint-LouisParisFrance

Objective:To explore the possible association between polymorphisms in CD1 genes and both asymptomatic and mild Plasmodium falciparum ***:Two clusters of 85 school children,from the village of Dienga(Gabon) were *** first group was analysed for the prevalence and the multiplicity of asymptomatic Plasmodium falciparum infection,whereas the second group was screened for the frequency of malarial ***:Our findings showed that homozygosity for the CD1E★02 allele was associated with a low frequency of malarial ***,a strong association between CD1E★02 homozygotes and the resistance to multiple malarial attacks was *** CD1A★01 allele showed a weak association with a small number of malarial ***:Our results suggest a possible role of CD1E polymorphisms in malaria protection among school children and that CD1e molecules are involved in anti-malarial immunity.

关键词： CD1E CD1A Malaria GPI Gabon

Reproducing indolent B-cell lymphoma transformation with T-cell immunosuppression in LMP1/CD40-expressing mice

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Cellular & Molecular Immunology 2019年第4期16卷 412-414页

作者： Christelle Vincent-Fabert Alexis Saintamand Amandine David Mehdi Alizadeh François Boyer Nicolas Arnaud ursula Zimber-Strobl Jean Feuillard Nathalie Faumont CNRS-uMR 7276 inserm u1262 CRIBL University of Limogesand Hematology Laboratory of Dupuytren Hospital University Center(CHU)of LimogesLimogesFrance inserm u917 University of Rennes 1RennesFrance LNPRM EFS BretagneRennesFrance Research unit Gene Vectors Helmholtz Center MunichGerman Research Center for Environmental Health GmbHMunichGermany

Indolent B-cell lymphomas are a group of incurable cancers of the elderly that encompass various entities,such as chronic lymphocytic leukemia(CLL),follicular lymphoma(FL),and marginal zone lymphoma(MZL).All indolent lymphomas may evolve towards aggressive transformation with an increased proliferation index and decreased tumor doubling *** transformation,which is called Richter’s syndrome in CLL,is associated with an aggressive clinical course and poor *** least in CLL,transformation of an indolent B-cell clone is molecularly different from that of de novo diffuse large B-cell lymphomas.1 Aging is known to be associated with immune decline,with increased inflammation,decreased immune surveillance and increased onset of malignancies among the consequences.2 Progression of indolent B-cell lymphomas is likely to be associated with escape from immune surveillance.

关键词： lymphoma Richter transformation

Severe acute respiratory syndrome coronavirus-2-related and imputable deaths in children:results from the French pediatric national registry

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World Journal of Pediatrics 2024年第6期20卷 611-620页

作者： Marguerite Lockhart-Bouron Noemie Vanel Michael Levy Anais R.Briant Etienne Javouhey Sophie Breinig Julia Dina Marion Caseris Francois Angoulvant Stephane Leteurtre Morgan Recher David W.Brossier univ.Lille CHU LilleULR 2694-METRICS:Evaluation Des Technologies de Sante Et Des Pratiques Medicales59000LilleFrance Pediatric Intensive Care unit CHU de MarseilleMarseilleFrance Pediatric Intensive Care unit CHU Robert-DebreAssistance Publique Hopitaux de ParisParisFrance universitéParis-Cite ParisFrance Biostatistics and Clinical Research unit CHU de Caen Normandie14000CaenFrance Pediatric Intensive Care Hospices Civils de LyonLyonFrance Neonatal andPediatric IntensiveCare unit Children's HospitalToulouseFrance Virology Department INSERM U1311 DynamicureUniv CAEN NormandieCHU de Caen14000 CaenFrance Medical School Universite Caen Normandie14000 CaenFrance Department of Pediatrics CHU Robert-DebréAssistance Publique Hopitaux de ParisParisFrance Department Women-Mother-Child Service of PediatricsLausanne University Hospital(CHUV)LausanneSwitzerland Pediatric Intensive Care unit Réanimation Et Soins Intensifs PéediatriquesCHU de CAENAvenue de La Cote de Nacre14000 CaenFrance CHu Sainte Justine Research Center MontréalCanada

Background Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)is responsible for an important mortality rate *** aimed to evaluate the actual imputability of SARS-CoV-2 on the mortality rate associated with SARS-CoV-2-related illnesses in the pediatric intensive care unit(PICu).Secondary objectives were to identify risk factors for *** This national multicenter comparative study comprised all patients under 18 years old with positive SARS-CoV-2 polymerase chain reactions(PCRs)[acute corona virus disease 2019(COVID-19)or incidental SARS-CoV-2 infection]and/or pediatric inflammatory multisystem syndrome(PIMS)recorded in the French PICu registry(PICuRe)between September 1,2021,and August 31,*** patients were classified and compared according to their living status at the end of their PICu *** patients were evaluated by four experts in the field of pediatric infectiology and/or pediatric intensive *** imputability of SARS-CoV-2 as the cause of death was classified into four categories:certain,very probable,possible,or unlikely,and was defined by any of the first three *** There were 948 patients included of which 43 died(4.5%).From this,26 deaths(67%)could be attributed to SARS-CoV-2 infection,with an overall mortality rate of 2.8%.The imputability of death to SARS-CoV-2 was considered certain in only one case(O.1%).Deceased patients suffered more often from comorbidities,especially heart disease,neurological disorders,hematological disease,cancer,and *** of the deceased patients were admitted for pediatric inflam-matory multisystem syndrome(PIMS).Mortality risk factors were male gender,cardiac comorbidities,cancer,and acute respiratorydistress *** SARS-CoV-2 mortality in the French pediatric population was *** though the imputability of SARS-Cov-2 on mortality was considered in almost two-thirds of cases,this imputability was considered certain in only one case.

关键词： Death Pediatric intensive care unit SARS-CoV-2