The majority of individuals exposed to hepatitis C virus(HCV) establish a persistent infection,which is a leading cause of chronic liver disease,cirrhosis and hepatocellular carcinoma.Major progress has been made duri...The majority of individuals exposed to hepatitis C virus(HCV) establish a persistent infection,which is a leading cause of chronic liver disease,cirrhosis and hepatocellular carcinoma.Major progress has been made during the past twenty-five years in understanding the HCV life cycle and immune responses against HCV infection.Increasing evidence indicates that host genetic factors can significantly influence the outcome of HCV infection and the response to interferon alpha-based antiviral therapy.The arrival of highly effective and convenient treatment regimens for patients chronically infected with HCV has improved prospects for the eradication of HCV worldwide.Clinical trials are evaluating the best anti-viral drug combination,treatment doses and duration.The new treatments are better-tolerated and have shown success rates of more than 95%.However,the recent breakthrough in HCV treatment raises new questions and challenges,including the identification of HCVinfected patients and to link them to appropriate health care,the high pricing of HCV drugs,the emergence of drug resistance or naturally occurring polymorphism in HCV sequences which can compromise HCV treatment response.Finally,we still do not have a vaccine against HCV.In this concise review,we will highlight the progress made in understanding HCV infection and therapy.We will focus on the most significant unsolved problems and the key future challenges in the management of HCV infection.展开更多
Since the outbreak of coronavirus disease 2019(COVID-19)in December 2019 in China,various measures have been adopted in order to attenuate the impact of the virus on the population.With regard to spine surgery,French ...Since the outbreak of coronavirus disease 2019(COVID-19)in December 2019 in China,various measures have been adopted in order to attenuate the impact of the virus on the population.With regard to spine surgery,French physicians are devoted to take place in the national plan against COVID-19,the French Spine Surgery Society therefore decided to elaborate specific guidelines for management of spinal disorders during COVID-19 pandemic in order to prioritize management of patients.A three levels stratification was elaborated with Level I:Urgent surgical indications,Level II:Surgical indications associated to a potential loss of chance for the patient and Level III:Non-urgent surgical indications.We also report French experience in a COVID-19 cluster region illustrated by two clinical cases.We hope that the guidelines formulated by the French Spine Surgery Society and the experience of spine surgeons from a cluster region will be helpful in order optimizing the management of patients with urgent spinal conditions during the pandemic.展开更多
A 53-year-old woman underwent a 2-stage right hepatectomy for bilobar metastasis of an ileal neuroendocrine carcinoma. Preoperative three-dimensional computed tomography reconstruction helped to diagnose an intrahepat...A 53-year-old woman underwent a 2-stage right hepatectomy for bilobar metastasis of an ileal neuroendocrine carcinoma. Preoperative three-dimensional computed tomography reconstruction helped to diagnose an intrahepatic venovenous shunts from the right and middle hepatic veins to the left hepatic vein, which could cause a intraoperative bleeding. Hemostasis was performed by means of precoagulation with microwaveassisted coagulation.展开更多
Rheumatoid arthritis(RA) is an autoimmune disease affecting 1% of the world population and is characterized by chronic inflammation of the joints sometimes accompanied by extra-articular manifestations. K/Bx N mice, o...Rheumatoid arthritis(RA) is an autoimmune disease affecting 1% of the world population and is characterized by chronic inflammation of the joints sometimes accompanied by extra-articular manifestations. K/Bx N mice, originally described in 1996 as a model of polyarthritis, exhibit knee joint alterations. The aim of this study was to describe temporomandibular joint(TMJ)inflammation and damage in these mice. We used relevant imaging modalities, such as micro-magnetic resonance imaging(μMRI)and micro-computed tomography(μCT), as well as histology and immunofluorescence techniques to detect TMJ alterations in this mouse model. Histology and immunofluorescence for Col-I, Col-II, and aggrecan showed cartilage damage in the TMJ of K/Bx N animals, which was also evidenced by μCT but was less pronounced than that seen in the knee joints. μMRI observations suggested an increased volume of the upper articular cavity, an indicator of an inflammatory process. Fibroblast-like synoviocytes(FLSs)isolated from the TMJ of K/Bx N mice secreted inflammatory cytokines(IL-6 and IL-1β) and expressed degradative mediators such as matrix metalloproteinases(MMPs). K/Bx N mice represent an attractive model for describing and investigating spontaneous damage to the TMJ, a painful disorder in humans with an etiology that is still poorly understood.展开更多
Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients.Reliable and timely diagnosis is important to treat rejection as early as possible.Allograf...Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients.Reliable and timely diagnosis is important to treat rejection as early as possible.Allograft biopsies are not suitable for continuous monitoring of rejection.Thus,there is an unmet need for non-invasive methods to diagnose acute and chronic rejection.Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003.This review describes the different proteomic approaches and summarizes the results from the studies that examined proteomics for the rejection diagnoses.The potential limitations and open questions in establishing proteomic markers for rejection are discussed,including ongoing trials and future challenges to this topic.展开更多
Nanomechanical heterogeneity is expected to have an effect on elasticity, injury and bone remodelling. In normal bone, we have two types of cells (osteoclasts and osteoblasts) working together to maintain existing bon...Nanomechanical heterogeneity is expected to have an effect on elasticity, injury and bone remodelling. In normal bone, we have two types of cells (osteoclasts and osteoblasts) working together to maintain existing bone. Bone cancers can produce factors that make the osteoclasts work harder. This means that more bone is destroyed than rebuilt, and leads to weakening of the affected bone. We report here the first demonstration of the nanoscale stiffness distribution in bone metastases before and after treatment of animals with the bisphosphonate Risedronate, a drug which is currently used for the treatment of bone metastases in patients with advanced cancers. The strategy used here is applicable to a wide class of biological tissues and may serve as a new reflection for biologically inspired scaffolds technologies.展开更多
Background. Zolpidem, a hypnotic drug, is occasionally taken in high doses by some drug addicts for its hallucinogenic properties. Case report. We report the original observation of a young female addict who developed...Background. Zolpidem, a hypnotic drug, is occasionally taken in high doses by some drug addicts for its hallucinogenic properties. Case report. We report the original observation of a young female addict who developed aseptic cutaneous abscesses on the forearms and feet induced by self injection of powdered zolpidem. Histopathological analysis revealed birefringent vegetal structures. Discussion. The shape and size of the birefringent structures are those of microcrystalline cellulose, an excipient used in zolpidempills. The same structures have been identified by microscopic examination of a zolpidem tablet dissolved in water.展开更多
Objective Impaired hepatic expression of protein tyrosine phosphatase delta(PTPRD)is associated with increased STAT3 transcriptional activity and reduced survival from hepatocellular carcinoma in patients with chronic...Objective Impaired hepatic expression of protein tyrosine phosphatase delta(PTPRD)is associated with increased STAT3 transcriptional activity and reduced survival from hepatocellular carcinoma in patients with chronic hepatitis C virus infection.However,the PTPRD-expressing hepatic cell types,signalling pathways responsive to PTPRD and their role in non-viral liver disease are largely unknown.Methods We studied PTPRD expression in single-cell and bulk liver transcriptomic data from mice and humans,and established a Ptprd-deficient mouse model for metabolic dysfunction-associated steatohepatitis(MASH).Identified pathways were validated by perturbation studies in human hepatocytes and PTPRD substrates by pull-down assays.The clinical relevance was further explored in a cohort with metabolic disease by ranking patients according to PTPRD expression and analysing its association with metabolic disease markers.Results The analysis of individuals ranked according to PTPRD expression and Ptprd-deficient mice,showed that PTPRD levels were associated with hepatic glucose/lipid signalling and peroxisome function.Hepatic PTPRD expression is impaired in aetiologies of chronic liver diseases that are associated with metabolic disease.We further validated PTPRD as a STAT3 phosphatase in the liver,acting as a regulator of peroxisomal fatty acid metabolism.During MASH,low PTPRD led to increased liver steatosis in Ptprd+/−mice and a pronounced unfolded protein response,which impacts insulin signalling.Accordingly,silencing of PTPRD blunted insulin-induced AKT phosphorylation.Patients with obesity and low hepatic PTPRD expression exhibit increased levels of metabolic risk factors.Conclusion Our data revealed an important regulatory role of the hepatic PTPRD-STAT3 axis in maintaining glucose/lipid homeostasis,which is recapitulated in clinical manifestations of metabolic liver disease.展开更多
Dentin is a mineralized tissue with a chemical composition similar to bone but with a higher mineralized density and rigidity.It constitutes the central structure of the tooth between the internal pulp and external en...Dentin is a mineralized tissue with a chemical composition similar to bone but with a higher mineralized density and rigidity.It constitutes the central structure of the tooth between the internal pulp and external enamel toward the oral cavity or cementum toward the underlying roots.Inherited dentin defects occur in a variety of rare genetic diseases.They 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.展开更多
文摘The majority of individuals exposed to hepatitis C virus(HCV) establish a persistent infection,which is a leading cause of chronic liver disease,cirrhosis and hepatocellular carcinoma.Major progress has been made during the past twenty-five years in understanding the HCV life cycle and immune responses against HCV infection.Increasing evidence indicates that host genetic factors can significantly influence the outcome of HCV infection and the response to interferon alpha-based antiviral therapy.The arrival of highly effective and convenient treatment regimens for patients chronically infected with HCV has improved prospects for the eradication of HCV worldwide.Clinical trials are evaluating the best anti-viral drug combination,treatment doses and duration.The new treatments are better-tolerated and have shown success rates of more than 95%.However,the recent breakthrough in HCV treatment raises new questions and challenges,including the identification of HCVinfected patients and to link them to appropriate health care,the high pricing of HCV drugs,the emergence of drug resistance or naturally occurring polymorphism in HCV sequences which can compromise HCV treatment response.Finally,we still do not have a vaccine against HCV.In this concise review,we will highlight the progress made in understanding HCV infection and therapy.We will focus on the most significant unsolved problems and the key future challenges in the management of HCV infection.
文摘Since the outbreak of coronavirus disease 2019(COVID-19)in December 2019 in China,various measures have been adopted in order to attenuate the impact of the virus on the population.With regard to spine surgery,French physicians are devoted to take place in the national plan against COVID-19,the French Spine Surgery Society therefore decided to elaborate specific guidelines for management of spinal disorders during COVID-19 pandemic in order to prioritize management of patients.A three levels stratification was elaborated with Level I:Urgent surgical indications,Level II:Surgical indications associated to a potential loss of chance for the patient and Level III:Non-urgent surgical indications.We also report French experience in a COVID-19 cluster region illustrated by two clinical cases.We hope that the guidelines formulated by the French Spine Surgery Society and the experience of spine surgeons from a cluster region will be helpful in order optimizing the management of patients with urgent spinal conditions during the pandemic.
基金Institut Hospitalo-Universitaire de Strasbourg(IHU MixSurg),Strasbourg,France
文摘A 53-year-old woman underwent a 2-stage right hepatectomy for bilobar metastasis of an ileal neuroendocrine carcinoma. Preoperative three-dimensional computed tomography reconstruction helped to diagnose an intrahepatic venovenous shunts from the right and middle hepatic veins to the left hepatic vein, which could cause a intraoperative bleeding. Hemostasis was performed by means of precoagulation with microwaveassisted coagulation.
文摘Rheumatoid arthritis(RA) is an autoimmune disease affecting 1% of the world population and is characterized by chronic inflammation of the joints sometimes accompanied by extra-articular manifestations. K/Bx N mice, originally described in 1996 as a model of polyarthritis, exhibit knee joint alterations. The aim of this study was to describe temporomandibular joint(TMJ)inflammation and damage in these mice. We used relevant imaging modalities, such as micro-magnetic resonance imaging(μMRI)and micro-computed tomography(μCT), as well as histology and immunofluorescence techniques to detect TMJ alterations in this mouse model. Histology and immunofluorescence for Col-I, Col-II, and aggrecan showed cartilage damage in the TMJ of K/Bx N animals, which was also evidenced by μCT but was less pronounced than that seen in the knee joints. μMRI observations suggested an increased volume of the upper articular cavity, an indicator of an inflammatory process. Fibroblast-like synoviocytes(FLSs)isolated from the TMJ of K/Bx N mice secreted inflammatory cytokines(IL-6 and IL-1β) and expressed degradative mediators such as matrix metalloproteinases(MMPs). K/Bx N mice represent an attractive model for describing and investigating spontaneous damage to the TMJ, a painful disorder in humans with an etiology that is still poorly understood.
基金Supported by The Deutsche Forschungsgemeinschaft,No.GW 4/6-1
文摘Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients.Reliable and timely diagnosis is important to treat rejection as early as possible.Allograft biopsies are not suitable for continuous monitoring of rejection.Thus,there is an unmet need for non-invasive methods to diagnose acute and chronic rejection.Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003.This review describes the different proteomic approaches and summarizes the results from the studies that examined proteomics for the rejection diagnoses.The potential limitations and open questions in establishing proteomic markers for rejection are discussed,including ongoing trials and future challenges to this topic.
基金This work was supported by the NanoOSCAR ANR project from the“Agence Natiionale la Recherche”,the“Fondation Avenir”,the“Ligue contre le Cancer du Haut-Rhin,Région Alsace”and“Cancéropôle du Grand Est”.
文摘Nanomechanical heterogeneity is expected to have an effect on elasticity, injury and bone remodelling. In normal bone, we have two types of cells (osteoclasts and osteoblasts) working together to maintain existing bone. Bone cancers can produce factors that make the osteoclasts work harder. This means that more bone is destroyed than rebuilt, and leads to weakening of the affected bone. We report here the first demonstration of the nanoscale stiffness distribution in bone metastases before and after treatment of animals with the bisphosphonate Risedronate, a drug which is currently used for the treatment of bone metastases in patients with advanced cancers. The strategy used here is applicable to a wide class of biological tissues and may serve as a new reflection for biologically inspired scaffolds technologies.
文摘Background. Zolpidem, a hypnotic drug, is occasionally taken in high doses by some drug addicts for its hallucinogenic properties. Case report. We report the original observation of a young female addict who developed aseptic cutaneous abscesses on the forearms and feet induced by self injection of powdered zolpidem. Histopathological analysis revealed birefringent vegetal structures. Discussion. The shape and size of the birefringent structures are those of microcrystalline cellulose, an excipient used in zolpidempills. The same structures have been identified by microscopic examination of a zolpidem tablet dissolved in water.
基金supported by the European Union(ERC-AdG-2014 HEPCIR ERC POC PRELICAN 755460,ERC POC HEPCAN 862551 to TFB,EU H2020 HEPCAR 667273 to TFB and JL,HORIZON-HLTH-2021-DISEASE-04-07 D-SOLVE#101057917 to TFB and JL,IP-cure-B project#847939 to FZ,ERC-AdG-2020-101021417 to YH)the French Cancer Agency(TheraHCC2.0 IHU201901299 to TFB)+9 种基金the Agence Nationale de la Recherche(ANR-21-RHUS-001 to TFB)the ANRS Maladies infectieusesémergentes(ANRS-MIE)(ECTZ103701,ECTZ131760,ECTZ160436,ECTZ171594 to JL,ECTZ104017 and ECTZ75178 to TFB,ECTZ4446 and ECTZ206376 to AARS)the Fondation de l’Universitéde Strasbourg(HEPKIN)(TBA-DON-0002),SATT Conectus,University of Strasbourg(CANCLAU)(TFB)the Inserm Plan Cancer 2019-2023the US National Institutes of Health(CA233794,CA255621,CA282178,CA288375 and CA283935 to YH)the Cancer Prevention and Research Institute of Texas(RR180016,RP200554 to YH)The AEPIC animal facility platform is financially supported by the CoRTecS network of the University of StrasbourgThis work of the Interdisciplinary Thematic Institute IMCBio,as part of the ITI 2021-2028 programme of the University of Strasbourg,CNRS and Inserm,was supported by IdEx Unistra(ANR-10-IDEX-0002)SFRI-STRAT’US project(ANR 20-SFRI-0012)EUR IMCBio(ANR-17-EURE-0023)under the framework of the French Investments for the Future Programme,as well as state funds managed within the France 2030 programme(reference ANR-21-RHUS-0001).
文摘Objective Impaired hepatic expression of protein tyrosine phosphatase delta(PTPRD)is associated with increased STAT3 transcriptional activity and reduced survival from hepatocellular carcinoma in patients with chronic hepatitis C virus infection.However,the PTPRD-expressing hepatic cell types,signalling pathways responsive to PTPRD and their role in non-viral liver disease are largely unknown.Methods We studied PTPRD expression in single-cell and bulk liver transcriptomic data from mice and humans,and established a Ptprd-deficient mouse model for metabolic dysfunction-associated steatohepatitis(MASH).Identified pathways were validated by perturbation studies in human hepatocytes and PTPRD substrates by pull-down assays.The clinical relevance was further explored in a cohort with metabolic disease by ranking patients according to PTPRD expression and analysing its association with metabolic disease markers.Results The analysis of individuals ranked according to PTPRD expression and Ptprd-deficient mice,showed that PTPRD levels were associated with hepatic glucose/lipid signalling and peroxisome function.Hepatic PTPRD expression is impaired in aetiologies of chronic liver diseases that are associated with metabolic disease.We further validated PTPRD as a STAT3 phosphatase in the liver,acting as a regulator of peroxisomal fatty acid metabolism.During MASH,low PTPRD led to increased liver steatosis in Ptprd+/−mice and a pronounced unfolded protein response,which impacts insulin signalling.Accordingly,silencing of PTPRD blunted insulin-induced AKT phosphorylation.Patients with obesity and low hepatic PTPRD expression exhibit increased levels of metabolic risk factors.Conclusion Our data revealed an important regulatory role of the hepatic PTPRD-STAT3 axis in maintaining glucose/lipid homeostasis,which is recapitulated in clinical manifestations of metabolic liver disease.
基金the actions of the projects Offensives Sciences INTERREG IV A27 and“RARENET:No.1.7,a trinational network for education,research and management of complex and rare disorders in the Upper Rhine”co-financed by the European Regional Development Fund(ERDF)of the European Union in the framework of the INTERREG V Upper Rhine program as well as to the ERN(European reference network)CRANIO initiative.ABZ is a USIAS 2015 Fellow of the Institute of Advanced Studies(Institut d’Etudes Avancees)de l’Universite´de Strasbourg,France.It was also supported by the grant ANR10-LABX-0030-INRT,a French State fund managed by the Agence Nationale de la Recherche under the frame programme Investissements d’Avenir labelled ANR-10-IDEX0002-02.the Projet E-GENODENT financed by the Fonds d’Intervention Re´gionale(FIR)of the Agence Re´gionale de Sante´Grand Est(2019-2022)+1 种基金the“Impulsion Recherche”financial support of the“Filie`re de Sante´Maladies Rares TETECOU”2021 and 2022 and acknowledge the Fondation Force for supporting the DIAGNODENT project(2023-2026)the study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘Dentin is a mineralized tissue with a chemical composition similar to bone but with a higher mineralized density and rigidity.It constitutes the central structure of the tooth between the internal pulp and external enamel toward the oral cavity or cementum toward the underlying roots.Inherited dentin defects occur in a variety of rare genetic diseases.They 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.
