Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Objective To investigate the impact of inhibiting GATA binding protein 4(GATA4)on the susceptibility to atrial fibrillation in elderly individuals and to elucidate the underlying mecha-nisms.Methods Fifteen 3-month-old young SD rats and 45 18-month-old SD rats were selected.According to the age and the injection of adeno-associated virus,the rats were divided into young group,elderly group,negative control group and interfering GATA4 group,with 15 rats in each group.Based on age and AAV injection,the rats were categorized into four groups:young group,elderly group,negative control group,and GATA4 interference group,with 15 rats in each group.Left atrial anteroposterior diameter was assessed via echocardiography.The extent of atrial fibro-sis was evaluated using Masson staining.Western blot analysis was employed to examine the ex-pression levels of GATA4,calcium cycling-related proteins,and NOD-like receptor pyrin domain-containing protein 3(NLRP3).Mouse atrial myocytes(HL-1 cells)were divided into five groups according to viral infection:control group,knockdown negative control group,GATA4 knock-down group,overexpression negative control group,and GATA4 overexpression group.The expression of GATA4 and NLRP3 was analyzed using Western blotting.Results The incidence of atrial fibrillation in the elderly group was significantly higher than that in the young group(80.0％vs 11.1％,P＜0.01).Compared with the negative control group,the induction rate of atrial fibrillation in the GATA4 interference group was significantly decreased(22.2％vs 80.0％,P＜0.05).Compared with the young group,the left atrial diameter,percentage of collagen vol-ume,activation time,absolute value of conduction dispersion,and expression of NLPR3 in the aged group were significantly increased,and the expression of calcium cycling protein was disor-dered(P＜0.05,P＜0.01).Compared with the negative control group,the left atrial diameter,per-centage of collagen volume,activation time,absolute value of conduction dispersion,and expres-sion of NLPR3 in the GATA4 interference group were significantly decreased,and the disturbance of calcium circulation was alleviated(P＜0.05,P＜0.01).Compared with the negative group of knockdown and overexpression,the expression of GATA4 and NLRP3 in HL1 cells in GATA4 knockdown group was significantly decreased,and the expression of GATA4 and NLPR3 in HL-1 cells in GATA4 overexpression group was significantly increased(P＜0.01).Conclusion GATA4 inhibition decreases the susceptibility to atrial fibrillation and mitigates age-related structural remodeling,electrical remodeling,and inflammation in the atrium by regulating calcium cycling disorders and myocardial cell senescence via the NLRP3 pathway.

Objective To investigate the impact of inhibiting GATA binding protein 4(GATA4)on the susceptibility to atrial fibrillation in elderly individuals and to elucidate the underlying mecha-nisms.Methods Fifteen 3-month-old young SD rats and 45 18-month-old SD rats were selected.According to the age and the injection of adeno-associated virus,the rats were divided into young group,elderly group,negative control group and interfering GATA4 group,with 15 rats in each group.Based on age and AAV injection,the rats were categorized into four groups:young group,elderly group,negative control group,and GATA4 interference group,with 15 rats in each group.Left atrial anteroposterior diameter was assessed via echocardiography.The extent of atrial fibro-sis was evaluated using Masson staining.Western blot analysis was employed to examine the ex-pression levels of GATA4,calcium cycling-related proteins,and NOD-like receptor pyrin domain-containing protein 3(NLRP3).Mouse atrial myocytes(HL-1 cells)were divided into five groups according to viral infection:control group,knockdown negative control group,GATA4 knock-down group,overexpression negative control group,and GATA4 overexpression group.The expression of GATA4 and NLRP3 was analyzed using Western blotting.Results The incidence of atrial fibrillation in the elderly group was significantly higher than that in the young group(80.0％vs 11.1％,P＜0.01).Compared with the negative control group,the induction rate of atrial fibrillation in the GATA4 interference group was significantly decreased(22.2％vs 80.0％,P＜0.05).Compared with the young group,the left atrial diameter,percentage of collagen vol-ume,activation time,absolute value of conduction dispersion,and expression of NLPR3 in the aged group were significantly increased,and the expression of calcium cycling protein was disor-dered(P＜0.05,P＜0.01).Compared with the negative control group,the left atrial diameter,per-centage of collagen volume,activation time,absolute value of conduction dispersion,and expres-sion of NLPR3 in the GATA4 interference group were significantly decreased,and the disturbance of calcium circulation was alleviated(P＜0.05,P＜0.01).Compared with the negative group of knockdown and overexpression,the expression of GATA4 and NLRP3 in HL1 cells in GATA4 knockdown group was significantly decreased,and the expression of GATA4 and NLPR3 in HL-1 cells in GATA4 overexpression group was significantly increased(P＜0.01).Conclusion GATA4 inhibition decreases the susceptibility to atrial fibrillation and mitigates age-related structural remodeling,electrical remodeling,and inflammation in the atrium by regulating calcium cycling disorders and myocardial cell senescence via the NLRP3 pathway.

Objective To analyze the clinical features of patients with sporadic adult-onset neuronal intranuclear inclusion disease (NIID),and raise awareness of the disease among medical workers.Methods The clinical data of two patients with pathologically confirmed adult sporadic NIID,admitted to our hospital in February 2018 and October 2018,were collected.The clinical manifestations,head MR imaging,cutaneous pathological features,treatments and prognoses were retrospectively analyzed.Results Both patients were characterized with slow progressive dementia,accompanied with diverse clinical manifestations involving the central and autonomic nervous systems.Acute encephalopathic signs occurred in both patients.Head MR imaging showed extensive leukoencephalopathy mainly in the frontal and parietal lobes;these white matter abnormalities showed hyperintensity in T2-weighted imaging and liquid attenuated inversion recovery sequences,and equal or low signal in T1-weighted imaging.Remarkably,specific curve-like high-intensity signals along the corticomedullary junction in the bilateral frontal lobe were both observed in diffusion-weighted imaging.Patient 2 with seizures showed unilateral cerebral cortical edema on head MR imaging.In both patients,skin biopsy revealed specific eosinophilic inclusion bodies in the nucleus of some sweat gland cells,adipocytes and fibroblasts.Patient one was treated with dexamethasone intravenous drip to relieve headache and vision loss,and cognitive therapy was given.The acute encephalopathy of patient two was relieved by intravenous gamma globulin.Conclusions NIID has various clinical manifestations of central,peripheral,and autonomic nerve systems.Head MR imaging characteristic changes and skin pathological biopsy contribute to the diagnosis.Immunomodulatory therapy may be effective for acute encephalopathic symptoms in NIID.

[ ABSTRACT] AIM:To study the effect of idazoxan ( IDA) on the permeability of blood-brain barrier ( BBB) and the expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in mouse ex-perimental autoimmune encephalomyelitis (EAE).METHODS: Female C57BL/6 mice (n=36) were randomly divided into control group, EAE group and IDA group, with 12 mice in each group.EAE was induced by myelin oligodendrocyte glycoprotein 35-55 ( MOG35-55 ) .IDA (2 mg/kg, ip, bid) was administered for 15 d after immunization.The neurological defects of the mice were observed daily and scored.The pathological changes were observed under microscope with HE stai-ning and LFB myelin staining.The BBB permeability was detected by Evans blue extravasation.The expression of MMP-9 and TIMP-1 in the brain of EAE mice was determined by Western blotting.RESULTS: Compared with EAE group, the score of neurological defects in IDA group was decreased, the inflammation was relieved, the BBB permeability was re-duced, and the expression MMP-9 and the ratio of MMP-9/TIMP-1 were decreased ( P<0.05 ) .CONCLUSION: The neuroprotective effect of IDA on mouse EAE might be related to the down-regulation of MMP-9 and the ratio of MMP-9/TIMP-1, thus reducing the degradation of BBB and the permeability of BBB, and ameliorating the pathologic process of EAE.

Objective To evaluate the bone healing effect of vascularized tissue-engineered bone induced by endothelial progenitor cells(EPCs)in repair of large segmental radius defects in rabbits.Methods A total of 68 healthy New Zealand white rabbits were enrolled in the study and randomized into three groups,ie,experimental group(EPCs group):EPCs plus bone marrow mesenchymal stem cells (BMSCs)plus decalcified bone matrix(DBM);control group:BMSCs plus DBM;sham control group:pure DBM.Materials mentioned above were implanted into middle radius defects for 15 mm.At 12 and 16 weeks post-operatively,X-ray test,bone mineral density test,histological light microscopic test,osteocalcin immunohistochemical staining test and biomechanical test were carried out.Results Growth and plasticity of callus,speed of medullary cavity recanalization,bone healing speed and biomechanical intensity in the experimental group were all significantly better than those of control group.Conclusions Vascularized tissue-engineered bone induced by EPCs has strong osteegenic ability,can accelerate bone healing and hence is an effective method for repair of large segmental bone defects.

Objective: To find out the relation factors of hyperuricemia in cadres. Methods: The cadres who had health check on 2008 were analyzed. Results: The rate hyperuricemia in cadres of Zhuhai city was 35.42%. Conclusion: The rate of hyperuricemia in cadres is increasing by ages. It has the relations with sexual distinction, overweight or obesity, abnormal triglyceride and high purine-food.