The purpose of this study was to investigate the repair of the osteoarthritis（OA）-induced car- tilage injury by transfecting the new TGF-β3 fusion protein （LAP-MMP-mTGF-β3） with targeted ther- apy function into ...The purpose of this study was to investigate the repair of the osteoarthritis（OA）-induced car- tilage injury by transfecting the new TGF-β3 fusion protein （LAP-MMP-mTGF-β3） with targeted ther- apy function into the bone marrow-derived mesenchymal stem cells （MSCs） in rats. The recombinant of plRES-EGFP-MMP was constructed by combination of DNA encoding MMP enzyme cutting site and eukaryotic expression vector plRES-EGFP. LAP and mTGF-β3 fragments were obtained from rat em- bryos by RT-PCR and inserted into the upstream and downstream of MMP from plRES-EGFP-MMP respectively, so as to construct the recombinant plasmid ofplRES-EGFP-LAP-MMP-mTGF-β3, plRES- EGFP-LAP-MMP-mTGF-β3 was transfected into rat MSCs. The genetically modified MSCs were cul- tured in medium with MMP-1 or not. The transfected MSCs were transplanted in the rat OA models. The OA animal models were surgically induced by anterior cruciate ligament transaction （ACLT）. The pathological changes were observed under a microscope by HE staining, Alcian blue, Safranin-fast Gre- en and graded by Mankin＇s scale, plRES-EGFP-LAP-MMP-mTGF-β3 was successfully constructed by means of enzyme cutting and sequencing, and the mTGF-β3 fusion protein （39 kD） was certified by Western blotting. Those genetically modified MSCs could differentiate into chondrocytes induced by MMP and secrete the relevant-matrix. The transfected MSCs could promote chondrogenesis and matrix production in rat OA models in vivo. It was concluded that a new fusion protein LAP-MMP-mTGF-β3 was constructed successfully by gene engineering, and could be used to repair the OA-induced cartilage injury.展开更多
Background: It is yet a controversy subject whether low birth weight and infant death are associated to human immunodeficiency virus-1 infection. Objective: To appreciate association between low birth weights, mother ...Background: It is yet a controversy subject whether low birth weight and infant death are associated to human immunodeficiency virus-1 infection. Objective: To appreciate association between low birth weights, mother to child HIV transmission and infant mortality in HIV-1 infected pregnant women delivering between 2011 and 2016. Materials: We conducted 6 years cohort study in urban Mali. Outcome included preterm delivery, small for gestational age, infant survival status and HIV transmission. Comparison concerned women clinical WHO stage, mother viro-immunological status, and newborn anthropometric parameters. Results: HIV-1 infected women who delivered low birth weight newborn were 20.9% (111/531) versus 16.5% (1910/11.546) in HIV negative patients (p = 0.016). CD4 T cell counts low than 350 T cells count were strongly associated to LBW (p = 0.000;RR = 3.03;95% CI [1.89 - 3.16]). There is no significant association between ART that was initiated during pregnancy (p = 0.061, RR = 0.02;CI 95% (1.02 - 1.99)) or during delivery (p = 0.571;RR = 1.01;CI 95% (0.10 - 3.02)) and LBW delivery. In multivariate analysis ART regimens containing protease inhibitor (PI) were lone regimens associated with LBW ((p = 0.030;RR = 1.001;95% confidence interval [1.28 - 3.80]). Very low birth weight was statistically associated to women HIV infection (adjusted relative risk, 2.02;p = 0.000;95% confidence interval (2.17 - 4.10)). There is no significant difference between mother to child HIV transmission rate in the two HIV-infected pregnant women (10 infected children in group 2: MTCT rate 4.5%) and 3 infected children in group 1 (MTCT rate: 2.7%) (p = 0.56;RR, 0.59;CI 95% (0.18 - 4.39)). In multivariate analysis, LBW was associated with infant death (p = 0.001;RR = 2.04;CI 95% [1.04 - 5.05]). The median weight of infant at the moment of death in group 1 was 851 g (IQR: 520 - 1833 g). Significant relationship was found between infant death among LBW newborn with mother WHO stage 2 (p = 0.004;adjusted RR = 3.22;CI 95% [2.25 - 6.00]), CD4 T cells count 3 (p = 0.005;RR = 2.81;CI 95% [1.20 - 4.11]), PI regimens (p = 0.030;RR = 1.00;CI 95% [1.28 - 3.80]). Conclusion: We confirm increased risk of low birth weight and mother HIV-1 infection and we identified strongest association between mortality in infant born to HIV-1 infected mother and LBW.展开更多
Kawasaki disease(KD)is an acute,self-limited systemic vasculitis that primarily affects children.Treating nonresponding KD with intravenous immunoglobulin(IVIG)presents numerous challenges.This article comprehensively...Kawasaki disease(KD)is an acute,self-limited systemic vasculitis that primarily affects children.Treating nonresponding KD with intravenous immunoglobulin(IVIG)presents numerous challenges.This article comprehensively reviews the basic theory,clinical manifestations and diagnosis,treatment strategies,disputes and challenges,historical evolution and current situation,and future research directions of immunoglobulin unresponsive KD.In terms of basic theory,the epidemiological characteristics of KD,the mechanism of IVIG action,and the pathophysiological mechanism of the nonresponsive type are elaborated.In the clinical manifestation and diagnosis section,symptoms,diagnostic criteria,and imaging applications are analyzed.The treatment strategy encompasses drug,nondrug and individualized therapy.Controversies and challenges focus on diagnostic difficulties,treatment disputes,and long-term prognosis research.The historical evolution and current situation review the changes in treatment strategies and the current state of affairs.Future research directions anticipate the role of new therapeutic drug research and development,breakthroughs in basic research,and international cooperation,aiming to provide a comprehensive reference for research and clinical practice in this field.展开更多
基金supported by the National Natural Science Foundation of China(No.81101376)
文摘The purpose of this study was to investigate the repair of the osteoarthritis（OA）-induced car- tilage injury by transfecting the new TGF-β3 fusion protein （LAP-MMP-mTGF-β3） with targeted ther- apy function into the bone marrow-derived mesenchymal stem cells （MSCs） in rats. The recombinant of plRES-EGFP-MMP was constructed by combination of DNA encoding MMP enzyme cutting site and eukaryotic expression vector plRES-EGFP. LAP and mTGF-β3 fragments were obtained from rat em- bryos by RT-PCR and inserted into the upstream and downstream of MMP from plRES-EGFP-MMP respectively, so as to construct the recombinant plasmid ofplRES-EGFP-LAP-MMP-mTGF-β3, plRES- EGFP-LAP-MMP-mTGF-β3 was transfected into rat MSCs. The genetically modified MSCs were cul- tured in medium with MMP-1 or not. The transfected MSCs were transplanted in the rat OA models. The OA animal models were surgically induced by anterior cruciate ligament transaction （ACLT）. The pathological changes were observed under a microscope by HE staining, Alcian blue, Safranin-fast Gre- en and graded by Mankin＇s scale, plRES-EGFP-LAP-MMP-mTGF-β3 was successfully constructed by means of enzyme cutting and sequencing, and the mTGF-β3 fusion protein （39 kD） was certified by Western blotting. Those genetically modified MSCs could differentiate into chondrocytes induced by MMP and secrete the relevant-matrix. The transfected MSCs could promote chondrogenesis and matrix production in rat OA models in vivo. It was concluded that a new fusion protein LAP-MMP-mTGF-β3 was constructed successfully by gene engineering, and could be used to repair the OA-induced cartilage injury.
文摘Background: It is yet a controversy subject whether low birth weight and infant death are associated to human immunodeficiency virus-1 infection. Objective: To appreciate association between low birth weights, mother to child HIV transmission and infant mortality in HIV-1 infected pregnant women delivering between 2011 and 2016. Materials: We conducted 6 years cohort study in urban Mali. Outcome included preterm delivery, small for gestational age, infant survival status and HIV transmission. Comparison concerned women clinical WHO stage, mother viro-immunological status, and newborn anthropometric parameters. Results: HIV-1 infected women who delivered low birth weight newborn were 20.9% (111/531) versus 16.5% (1910/11.546) in HIV negative patients (p = 0.016). CD4 T cell counts low than 350 T cells count were strongly associated to LBW (p = 0.000;RR = 3.03;95% CI [1.89 - 3.16]). There is no significant association between ART that was initiated during pregnancy (p = 0.061, RR = 0.02;CI 95% (1.02 - 1.99)) or during delivery (p = 0.571;RR = 1.01;CI 95% (0.10 - 3.02)) and LBW delivery. In multivariate analysis ART regimens containing protease inhibitor (PI) were lone regimens associated with LBW ((p = 0.030;RR = 1.001;95% confidence interval [1.28 - 3.80]). Very low birth weight was statistically associated to women HIV infection (adjusted relative risk, 2.02;p = 0.000;95% confidence interval (2.17 - 4.10)). There is no significant difference between mother to child HIV transmission rate in the two HIV-infected pregnant women (10 infected children in group 2: MTCT rate 4.5%) and 3 infected children in group 1 (MTCT rate: 2.7%) (p = 0.56;RR, 0.59;CI 95% (0.18 - 4.39)). In multivariate analysis, LBW was associated with infant death (p = 0.001;RR = 2.04;CI 95% [1.04 - 5.05]). The median weight of infant at the moment of death in group 1 was 851 g (IQR: 520 - 1833 g). Significant relationship was found between infant death among LBW newborn with mother WHO stage 2 (p = 0.004;adjusted RR = 3.22;CI 95% [2.25 - 6.00]), CD4 T cells count 3 (p = 0.005;RR = 2.81;CI 95% [1.20 - 4.11]), PI regimens (p = 0.030;RR = 1.00;CI 95% [1.28 - 3.80]). Conclusion: We confirm increased risk of low birth weight and mother HIV-1 infection and we identified strongest association between mortality in infant born to HIV-1 infected mother and LBW.
文摘Kawasaki disease(KD)is an acute,self-limited systemic vasculitis that primarily affects children.Treating nonresponding KD with intravenous immunoglobulin(IVIG)presents numerous challenges.This article comprehensively reviews the basic theory,clinical manifestations and diagnosis,treatment strategies,disputes and challenges,historical evolution and current situation,and future research directions of immunoglobulin unresponsive KD.In terms of basic theory,the epidemiological characteristics of KD,the mechanism of IVIG action,and the pathophysiological mechanism of the nonresponsive type are elaborated.In the clinical manifestation and diagnosis section,symptoms,diagnostic criteria,and imaging applications are analyzed.The treatment strategy encompasses drug,nondrug and individualized therapy.Controversies and challenges focus on diagnostic difficulties,treatment disputes,and long-term prognosis research.The historical evolution and current situation review the changes in treatment strategies and the current state of affairs.Future research directions anticipate the role of new therapeutic drug research and development,breakthroughs in basic research,and international cooperation,aiming to provide a comprehensive reference for research and clinical practice in this field.
