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Severe asthma exacerbation:Changes in patient characteristics,management,and outcomes from 1997 to 2016 in 40 ICus in the greater Paris area

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Journal of Intensive Medicine 2024年第2期4卷 209-215页

作者： Romy Younan Jean Loup Augy Bertrand Hermann Bertrand Guidet Philippe Aegerter Emmanuel Guerot Ana Novara Caroline Hauw-Berlemont Amer Hamdan Clotilde Bailleul Francesca Santi Jean-Luc Diehl Nicolas Peron Nadia Aissaoui Intensive Care unit AP-HPGeorges Pompidou European HospitalUniversitéde ParisParisFrance Intensive Care unit AP-HPSaint Antoine HospitalUniversités de SorbonneUniversitéPierre et Marie CurieParisFrance inserm u1136 ParisFrance Versailles Saint-Quentin-en-Yvelines university INSERM U1018Groupe Interrégional de Recherche Clinique et d'InnovationÎle-de-FranceFrance Respiratory Medicine Department AP-HPGeorges Pompidou European HospitalUniversitéde ParisParisFrance Innovative Therapies in Hemostasis INSERM UMR-S1140Universitéde ParisParisFrance Intensive Care unit and Biosurgical Research Lab(Carpentier Foundation) AP-HPGeorges Pompidou European HospitalParisFrance Paris-Cardiovascular-Research-Center INSERM U970ParisFrance

Background Despite advances in asthma treatments,severe asthma exacerbation(SAE)remains a life-threatening condition in adults,and there is a lack of data derived from adult patients admitted to intensive care units(ICus)for *** current study investigated changes in adult patient characteristics,management,and outcomes of SAE over a 20-year period in 40 ICus in the greater Paris *** In this retrospective observational study,admissions to 40 ICus in the greater Paris area for SAE from January 1,1997,to December 31,2016 were *** primary outcome was the proportion of ICu admissions for SAE during 5-year *** outcomes were ICu and hospital mortality,and the use of mechanical ventilation and *** analysis was performed to assess factors associated with ICu *** A total of 7049 admissions for SAE were *** each 5-year period,the proportion decreased over time,with SAE accounting for 2.84%of total ICu admissions(n=2841)between 1997 and 2001,1.76%(n=1717)between 2002 and 2006,1.05%(n=965)between 2007 and 2011,and 1.05%(n=1526)between 2012 and *** median age was 46 years(interquartile range[IQR]:32–59 years),55.41%were female,the median Simplified Acute Physiology Score II was 20(IQR:13–28),and 19.76%had mechanical *** use of mechanical ventilation remained infrequent throughout the 20-year period,whereas the use of catecholamine *** and hospital mortality rates *** associated with ICu mortality were renal replacement therapy,catecholamine,cardiac arrest,pneumothorax,acute respiratory distress syndrome,sepsis,and invasive mechanical ventilation(IMV).Non-survivors were older,had more severe symptoms,and were more likely to have received *** ICu admission for SAE remains uncommon,and the proportion of cases decreased over *** a slight increase in symptom severity during a 20-year period,ICu and hospital mortality *** requirin

关键词： Epidemiology Intensive care unit Mechanical ventilation Severe asthma exacerbation

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Adult neurogenesis:a real hope or a delusion?

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Neural Regeneration Research 2024年第1期19卷 6-15页

作者： Ghulam Hussain Rabia Akram Haseeb Anwar Faiqa Sajid Tehreem Iman Hyung Soo Han Chand Raza Jose-Luis Gonzalez De Aguilar Neurochemicalbiology and Genetics Laboratory(NGL) Department of PhysiologyFaculty of Life SciencesGovernment College UniversityFaisalabadPunjabPakistan Department of Physiology School of MedicineClinical Omics InstituteKyungpook National UniversityDaeguKorea Department of Zoology Faculty of Chemistry and Life SciencesGovernment College UniversityLahorePakistan inserm U1118Mécanismes Centraux et Péripheriques de la NeurodégénérescenceStrasbourgFranceUniversitéde StrasbourgStrasbourgFrance

Adult neurogenesis,the process of creating new neurons,involves the coordinated division,migration,and differentiation of neural stem *** process is restricted to neurogenic niches located in two distinct areas of the brain:the subgranular zone of the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricle,where new neurons are generated and then migrate to the olfactory *** has been thought to occur only during the embryonic and early postnatal stages and to decline with age due to a continuous depletion of neural stem ***,recent years have seen tremendous progress in our understanding of adult brain neurogenesis,bridging the knowledge gap between embryonic and adult ***,we discuss the current status of adult brain neurogenesis in light of what we know about neural stem *** this notion,we talk about the importance of intra cellular signaling molecules in mobilizing endogenous neural stem cell prolife *** on the current understanding,we can declare that these molecules play a role in targeting neurogenesis in the mature ***,to achieve this goal,we need to avoid the undesired proliferation of neural stem cells by controlling the necessary checkpoints,which can lead to tumorigenesis and prove to be a curse instead of a blessing or hope.

关键词： adult neurogenesis aging brain-derived neurotrophic factor dentate gyrus hippocampus neural stem cells neurotrophic factors Notch oxidative stress stem cells subgranular zone

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Targeted therapy for capillary-venous malformations

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3024-3039页

作者： Lola Zerbib Sophia Ladraa Antoine Fraissenon Charles Bayard Marina Firpion Quitterie Venot Sanela Protic Clément Hoguin Amandine Thomas Sylvie Fraitag Jean-Paul Duong Sophie Kaltenbach Estelle Balducci Coline Lefevre Patrick Villarese Vahid Asnafi Christine Broissand Nicolas Goudin Ivan Nemazanyy Gwennhael Autret Bertrand Tavitian Christophe Legendre Nadia Arzouk Veronique Minard-Colin Caroline Chopinet Michael Dussiot Denise MAdams Tristan Mirault Laurent Guibaud Paul Isenring Guillaume Canaud universitéParis Cité ParisFrance inserm u1151 Institut Necker-Enfants MaladesParisFrance Service d’Imagerie Pédiatrique Hôpital Femme-Mère-EnfantHCLBronFrance CREATIS uMR 5220 Villeurbanne 69100France Service de Radiologie Mère-Enfant Hôpital NordSaint EtienneFrance Service d’Anatomie pathologique Hôpital Necker-Enfants MaladesAP-HPParisFrance Laboratoire d’Oncohématologie Hôpital Necker-Enfants MaladesAP-HPParisFrance Pharmacie Hôpital Necker-Enfants MaladesAP-HPParisFrance Necker Bio-Image Analysis INSERM US24/CNRS UMS 3633ParisFrance Platform for Metabolic Analyses Structure Fédérative de Recherche NeckerINSERM US24/CNRS UMS 3633ParisFrance Plateforme Imageries du Vivant Universitéde ParisPARCCINSERMParisFrance Service de Néphrologie Transplantation AdultesHôpital Necker-Enfants MaladesAP-HPParisFrance Service de Transplantation Hôpital La PitiéSalpétrièreAP-HPParisFrance Department of Pediatric and Adolescent Oncology INSERM 1015Gustave RoussyUniversitéParis-SaclayVillejuifFrance Service de Physiologie&Explorations Fonctionnelles Cardiovasculaires CHU de LilleLille 59000France inserm u1163 Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic ImplicationsLaboratoire d’Excellence GR-ExParisFrance Division of Oncology Comprehensive Vascular Anomalies ProgramChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA Service de Médecine Vasculaire hôpital Européen Georges-PompidouParisFrance Nephrology Research Group L’Hôtel-Dieu de Québec Research CenterDepartment of MedicineFaculty of MedicineLaval UniversityQuebecQC G1R2J6Canada unitéde médecine translationnelle et thérapies ciblées Hôpital Necker-Enfants MaladesAP-HPParisFrance CNRS uMR8253 Institut Necker-Enfants MaladesParisFrance

Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through *** malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening *** authorized medical treatment exists for patients with venous ***,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient *** showed that these malformations only partially signal through AKT *** compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse *** demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging *** these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous *** assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each *** demonstrated improvement in all 25 *** malformations previously considered intractable were reduced and clinical symptoms were *** showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on *** conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.

关键词： PIK3CA malformations venous

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Multi-Compartment SCFA Quantification in Human

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American Journal of Analytical Chemistry 2024年第6期15卷 177-200页

作者： Jérémy Monteiro Antoine Lefèvre Diane Dufour-Rainfray Adeline Oury Gabrielle Chicheri Laurent Galineau Hélène Blasco Lydie Nadal-Desbarats Patrick Emond Imaging Brain & Neuropsychiatry iBraiN u1253 Universit de Tours INSERM MetaboHub Tours Tours France CHRu de Tours Service de Mdecine Nuclaire in Vitro Tours France Service de Biochimie et Biologie Molculaire CHRU Tours France

Short-chain fatty acids (SCFA) play an important role in human biochemistry. They originate primarily from the digestive system through carbohydrates microbial fermentation. Most SCFA produced in the colon are absorbed by the intestinal wall and enter the bloodstream to be distributed throughout the body for multiple purposes. At the intestinal level, SCFA play a role in controlling fat storage and fatty acid metabolism. The effects of these beneficial compounds therefore concern overall health. They facilitate energy expenditure and are valuable allies in the fight against obesity and diabetes. SCFA are also involved in the regulation of the levels of several neurotransmitters such as GABA (γ-aminobutyric acid), glutamate, serotonin, dopamine, and norepinephrine. Their role is also highlighted in many inflammatory and neurodegenerative diseases such as Alzheimer’s disease (AD) or Parkinson’s disease (PD). To have a realistic picture of the distribution of SCFA in different biological compartments of the human body, we propose to study SCFA simultaneously in five human biological samples: feces, saliva, serum, cerebrospinal fluid (CSF), and urine, as well as in dried Blood Spot (DBS). To evaluate their concentration and repeatability, we used 10 aliquots from pooled samples, analyzed by 3-nitrophenylhydrazine (3-NPH) derivation and liquid chromatography coupled with high sensitivity mass spectrometry (LC-QqQ-MS). We also evaluated the SCFA assay on dried Blood Spot (DBS). In this work, we adapted the pre-analytical parts for each sample to be able to use a common calibration curve, thus facilitating multi-assay quantification studies and so being less time-consuming. Moreover, we proposed new daughter ions from the same neutral loss (43 Da) to quantify SCFAs, thus improving the sensitivity. In conclusion, our methodology, based on a unique calibration curve for all samples for each SCFA, is well-suited to quantified them in a clinical context.

关键词： LC-MS 3-Nitrophenylhydrazine Short-Chain Fatty Acids Human Biological Samples Quantification

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Rare dentin defects:understanding the pathophysiological mechanisms of COLXVA1 mutations

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Genes & Diseases 2024年第5期11卷 1-5页

作者： Isaac Maximiliano Bugueno Tristan Rey Alexandra Jimenez-Armijo Marzena Kawczynski Naji Kharouf Marie-Cecile Maniere Yann Herault Agnes Bloch-Zupan Virginie HaushalterLaugel Institute of Genetics and Molecular and Cellular Biology(IGBMC) CNRS-UMR7104INSERM U1258Universitede StrasbourgIllkirch 67400France Faculty of Dentistry Universitede StrasbourgStrasbourg 67000France Institute of Advanced Studies(uSIAS) Universitede StrasbourgStrasbourg 67045France Reference Center for Rare Oral and Dental Diseases(CRMR-O-Rares) Oral Medicine and Surgery DepartmentHopitaux Universitaires de Strasbourg(HUS)Strasbourg 67000France Rare Diseases Health Network“TETE COu”&European Reference Network ERN CRANIO Strasbourg 67000France “Institut de Genetique Medicale d’Alsace” Laboratory of Genetic DiagnosticHopitaux Universitaires de Strasbourg(HUS)Strasbourg 67000France Biomaterials and Bioengineering Laboratory Inserm UMR_S 1121Strasbourg 67000France Orofacial Development and Regeneration Faculty of MedicineInstitute of Oral BiologyCentre of Dental MedicineUniversity of ZurichZurich 8032Switzerland

Dentin is a mineralized tissue with a chemical composition similar to bone but with a higher mineralized density and *** constitutes the central structure of the tooth between the internal pulp and external enamel toward the oral cavity or cementum toward the underlying *** dentin defects occur in a variety of rare genetic *** can manifest as“isolated”occurrences such as in dentinogenesis imperfecta(DI)or dentin dysplasia(DD)or can be associated with other symptoms in diseases such as osteogenesis imperfecta,Goldblatt syndrome,microcephalic osteodysplastic primordial dwarfism type Ⅱ,among others.

关键词： diseases den rigidity

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一种连锁SPG27的新表型及其在10号染色体上的精确编码区域定位

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世界核心医学期刊文摘(神经病学分册) 2006年第12期 56-57页

作者： Ribai P. Stevanin G. Bouslam N. A.Brice 李青波 dr.inserm u679 Hpital de la Salpêtrière47 Bd de I'Hpital 75013 ParisFrance

Hereditary spastic paraplegias are genetically and clinically *** loci have been identified to ***27 was recently mapped to chromosome 10 in a single family with autosomal recessive hereditary spastic paraplegia(AR-HSP)and a pure *** describe a Tunisian family with a complicated form of AR-HSP also linked to *** parents are first cousins and 3 out of their 4 children manifest early onset progressive spastic paraparesis associated with sensorimotor *** addition,the eldest girl had facial dysmorphism and short stature(-3SD).Two of the three patients were mentally retarded,and one of these also had cerebellar *** ages at onset were 2,5 and 7 years.A genome-wide scan suggested linkage to SPG27 on the long arm of chromosome 10 with a multipoint lod score of *** addition,a recombination detected in this family by haplotype reconstruction reduced the SPG27 locus from 25 to 19.6 *** is the first clinical description of a complicated form of spastic paraplegia,characterized by great phenotypic variability among the sibs,associated with the SPG27 locus.

关键词：染色体 SPG27 遗传性痉挛性截瘫家族性痉挛性截瘫表型

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Compartmentalization of the inflammatory response during bacterial sepsis and severe COVID-19

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Journal of Intensive Medicine 2024年第3期4卷 326-340页

作者： Jean-Marc Cavaillon Benjamin G.Chousterman Tomasz Skirecki Institut Pasteur ParisFrance Department of Anesthesia and Critical Care Lariboisière University HospitalDMU ParabolAPHP NordParisFrance inserm u942 University of ParisParisFrance Department of Translational Immunology and Experimental Intensive Care Centre of Postgraduate Medical EducationWarsawPoland

Acute infections cause local and systemic disorders which can lead in the most severe forms to multi-organ failure and eventually to death. The host response to infection encompasses a large spectrum of reactions with a concomitant activation of the so-called inflammatory response aimed at fighting the infectious agent and removing damaged tissues or cells, and the anti-inflammatory response aimed at controlling inflammation and initiating the healing process. Fine-tuning at the local and systemic levels is key to preventing local and remote injury due to immune system activation. Thus, during bacterial sepsis and Coronavirus disease 2019 (COVID-19), concomitant systemic and compartmentalized pro-inflammatory and compensatory anti-inflammatory responses are occurring. Immune cells (e.g., macrophages, neutrophils, natural killer cells, and T-lymphocytes), as well as endothelial cells, differ from one compartment to another and contribute to specific organ responses to sterile and microbial insult. Furthermore, tissue-specific microbiota influences the local and systemic response. A better understanding of the tissue-specific immune status, the organ immunity crosstalk, and the role of specific mediators during sepsis and COVID-19 can foster the development of more accurate biomarkers for better diagnosis and prognosis and help to define appropriate host-targeted treatments and vaccines in the context of precision medicine.

关键词： Acute respiratory distress syndrome Bone marrow Cytokines Lungs Mucosa Vaccines

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use of longitudinal magnetic resonance imaging in preclinical models of spinal cord injury

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Neural Regeneration Research 2019年第5期14卷 771-772页

作者： Harun Najib Noristani Florence Evelyne Perrin inserm u1198 University of Montpellier

Spinal cord injury(SCI)is a distressing event with grave socio/economic consequences to our *** response following SCI involves blood-spinal cord barrier breakdown,neuroinflammation and formation of a glial scar that altogether govern the feasibility of spontaneous axonal re-growth and limited functional *** advances in understanding SCI pathophysiology have been achieved using numerous transgenic mouse lines developed in different ***,there are inherent strain differences that affect inflammation,gliosis,axon regeneration and ultimately functional recovery after SCI.

关键词： Spinal cord injury(SCI) spinal cord injury

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Hepatic arterial infusion of gemcitabine-oxaliplatin in a large metastasis from colon cancer

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World Journal of Gastroenterology 2010年第9期16卷 1150-1154页

作者： Boris Guiu Julie Vincent Séverine Guiu Sylvain Ladoire Pablo Ortega-Deballon Jean-Pierre Cercueil Bruno Chauffert Franois Ghiringhelli Department of Radiology INSERM U866University of BurgundyUniversity Hospital Department of Hepatology INSERM U866University of BurgundyUniversity Hospital Department of Oncology INSERM U866AVENIR TeamUniversity of Burgundy Department of Digestive Surgery INSERM U866University of BurgundyUniversity Hospital

Hepatic arterial infusion (HAI) of chemotherapy can be performed in cases of liver-confined metastatic disease,resulting in increased local drug *** we report the case of a 61-year-old man who presented with an isolated large unresectable liver metastasis of colon cancer after failure of surgery and multiple administration of systemic *** patient was treated with a combination of gemcitabine and oxaliplatin using *** tolerance was excellent and a radiological complete response was obtained after 8 cycles of *** rationale for the use of gemcitabine and oxaliplatin as well as that for the combination of the 2 drugs is discussed in this *** of gemcitabine-oxaliplatin should be evaluated in further clinical trials.

关键词： Hepatic artery Chemotherapy Colon cancer Liver metastasis Gemcitabine Oxaliplatin Contrast media Computed tomography

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Association of the immediate perioperative dynamics of circulating DNA levels and neutrophil extracellular traps formation in cancer patients

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Precision Clinical Medicine 2024年第2期7卷 93-108页

作者： Andrei Kudriavtsev Brice Pastor Alexia Mirandola Ekaterina Pisareva Yann Gricourt Xavier Capdevila Alain R.Thierry Philippe Cuvillon Institut de Recherche en Cancerologie de Montpellier INSERM U1194Universite de MontpellierMontpellier 34298France Institut regional du Cancer de Montpellier Montpellier 34298France Department of Anaesthesiology and Pain Management Centre Hospitalo-Universitaire(CHU)CaremeauPlace du Professeur DebreNimes 30400France university of Montpellier Montpellier 34298France Division of Anaesthesia Intensive Care Pain and Emergency MedicineMontpellier University HospitalMontpellier 34090France Montpellier NeuroSciences Institute INSERMU1298University of MontpellierMontpellier 34295Franc

Objectives:Elevated circulating DNA(cirDNA)concentrations were found to be associated with trauma or tissue damage which suggests involvement of inflammation or cell death in post-operative cirDNA *** carried out the first prospective,multicenter study of the dynamics of cirDNA and neutrophil extracellular trap(NETs)markers during the perioperative period from 24 h before surgery up to 72 h after curative surgery in cancer ***:We examined the plasma levels of two NETs protein markers[myeloperoxidase(MPO)and neutrophil elastase(NE)],as well as levels of cirDNA of nuclear(cir-nDNA)and mitochondrial(cir-mtDNA)origin in 29 colon,prostate,and breast cancer patients and in 114 healthy individuals(HI).Results:The synergistic analytical information provided by these markers revealed that:(i)NETs formation contributes to post-surgery conditions;(i)post-surgery cir-nDNA levels were highly associated with NE and MPO in colon cancer[r=0.60(Put not in prostate and breast cancer;(i)each tumor type shows a specific pattern of cir-nDNA and NETs marker dynamics,but overall the pre-and post-surgery median values of cir-nDNA,NE,and MPO were significantly higher in cancer patients than in ***:Taken as a whole,our work reveals the association of NETs formation with the elevated cir-nDNA release during a cancer patient's perioperative period,depending on surgical procedure or cancer *** contrast,cir-mtDNA is poorly associated with NETs formation in the studied perioperative period,which would appear to indicate a different mechanism of release or suggest mitochondrial dysfunction.

关键词： circulating DNA perioperative period neutrophil extracellular traps neutrophil elastase myeloperoxidase minimal residualdisease

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