Cardiomyopathy, Dilated ; Cardiomyopathy, Hypertrophic ; genetics ; Humans ; Mutation

Arrhythmias, Cardiac ; Humans ; Potassium Channels, Voltage-Gated ; genetics

Arrhythmogenic Right Ventricular Dysplasia ; complications ; Autopsy ; Cardiomyopathy, Hypertrophic ; complications ; Cause of Death ; Coronary Disease ; complications ; Coronary Vessel Anomalies ; complications ; Death, Sudden, Cardiac ; etiology ; pathology ; Humans

Cardiomyopathy, Dilated ; genetics ; Lamin Type A ; genetics

Objective To investigate the epidemiologic factors associated with the age of natural menopause and menopausal symptoms in a large population at age of 40 to 65 years in Jiangsu Province.Methods From May 2010 to Oct.2011,a total of 20 275 women (40 to 65 years) attending health examination in Jiangsu Province were enrolled in this cross-sectional study.A structured questionnaire was used to collect data of demographics,menopausal status,chronic diseases,reproductive history.Also the menopausal symptoms were evaluated by Kupperman menopause index (KMI).Cox proportional hazards regression model and Logistic regression were performed to identify risk factors for earlier age of natural menopause and menopausal symptoms,respectively.Results The overall median age at natural menopause in Jiangsu women was 50 years.Lower educational level,poor economic status,lower body mass index (BMI),age at menarche less than 14 years,nulliparity and smoking were associated with earlier onset of natural menopause (P ＜ 0.05).The most frequently symptoms in perimenopausal women were fatigue (46.84％,1880/4014),insomnia (44.67％,1793/4014) and muscle/joint pain (43.80％,1758/ 4014),while sexual problems (57.06％,3463/6070),muscle/joint pain (53.30％,3235/6070) and insomnia (51.03％,3097/6070) were predominant symptoms in postmenopausal women.After adjusting for confounding factors,it was revealed that women with poor educational background,low income,divorce,higher BMI,higher parity,and smoking presented positive correlation with menopausal symptoms (P ＜ 0.05).Conclusions The study suggested that an estimate of median age at natural menopause were 50 years in Jiangsu women.The main factors contributing to earlier onset of menopause and menopausal symptoms were lower educational level,poor economic status,and smoking.Moreover,there were different menopausal symptoms between perimenopausal and postmenopausal women,which provided the important insights for physicians to prevent and treat menopause symptoms in their clinical practice.

Objective To evaluate the embolic effect on rabbits arteries using self-made copper plated platinum coil.Methods 1 7 New Zealand Big Ear Rabbits were selected.Unilateral subclavian artery or carotid artery was embolized with self-made secondary level copper plated platinum micro-coils (experimental group)through 3F-catheter.Contralateral subclavian artery or carotid artery was also embolized using secondary level platinum micro-coils (control group)as a control.The level of serum copper ions and the liver and renal function were recorded during different intervals before and after embolization.The arteriography and the tissue his-tology were observed respectively during different intervals after the embolization.Results 1 5 of 1 7 rabbits were embolized success-fully.After embolization,the level of serum copper ions increased in 2 weeks(P <0.05).However,it returned to preoperative level after 4 weeks (P >0.05).The liver and renal function was similar to that of the preoperation after 2 weeks.After embolization,an-giography showed that vascular embolization effect between two groups was not significantly different at 10 min and 30 min;howev-er,the embolization effect of experimental group was superior to that of control one (P <0.01)at 3 days and 1 week,2 weeks,4 weeks,6 weeks and 12 weeks.Pathological results showed that there were a lot of thromboses inside,outside and around the copper coil.Few thromboses appeared around platinum coil in control group.The thrombosis situation in experiment group was better than that in control one (P <0.01).However,no significant difference in inflammatory cell infiltration between two groups was found. Conclusion Self-made secondary level copper plated platinum coil has good physical property,rememorability,flexibility and con-trollability.

BACKGROUNDMutations in the lamin A/C gene (LMNA) may cause familial dilated cardiomyopathy (dilated cardiomyopathy) characterized by early onset atrio-ventricular block (A-V block) before the manifestation of dilated cardiomyopathy and high risk of sudden death due to ventricular arrhythmia, which is very similar to the phenotype of gap junction related heart disease. This study aimed to determine the expression and localization of connexins in neonatal myocytes transfected with wild-type (WT) or mutant LMNA to elucidate how these mutations cause heart diseases.

METHODSWe studied the connexin 43 (Cx43) and connexin 40 (Cx40) expression in cultured neonatal myocytes transfected with wild-type (WT) or mutant LMNA (Glu82Lys (E82K) and Arg644Cys (R644C)) using confocal imaging and Western blotting analysis.

RESULTSCx43 protein expression was reduced by 40% in cells transfected with LMNA E82K than that in cells transfected with WT LMNA cDNA. Confocal imaging showed that the Cx43 located inside the cells by LMNA E82K. By contrast, LMNA E82K mutation had no effect on expression and localization of Cx40. LMNA R644C transfection did not show any significant effects on gap junctions at all.

CONCLUSIONSOur findings suggest that LMNA E82K significantly reduced the Cx43 expression and altered its localization which may be one of the pathological mechanisms underlying LMNA-related heart disease.

Animals ; Atrioventricular Node ; pathology ; Blotting, Western ; Cardiomyopathy, Dilated ; metabolism ; pathology ; Cells, Cultured ; Connexin 43 ; metabolism ; Connexins ; metabolism ; Fluorescent Antibody Technique ; Gap Junctions ; metabolism ; Humans ; Lamin Type A ; genetics ; physiology ; Mutation ; Rats ; Transfection

OBJECTIVETo identify the electrophysiological properties of long-QT syndrome (LQTS) associated missense mutations in the outer mouth of the HERG potassium channel in vitro.

METHODSMutations V630A and N633S were constructed by Megaprimer PCR method and cRNA were produced by T7 RNA polymerase. The electrophysiological properties of the mutation were investigated in the Xenopus oocyte heterologous expression system.

RESULTSCoexpression of mutant and wild-type HERG subunits caused a dominant-negative effect, and the currents were significantly decreased. Compared with wild-type HERG channels, V630A and N633S mutations were related to decreased time constants for inactivation for V630A/WT and N633S/WT at all potentials, reduced slope conductance and the voltage dependence of steady-state inactivation was shifted to negative potentials for V630A/WT and N633S/WT.

CONCLUSIONPresent study shows that LQTS associated missense mutations located in the outer mouth of HERG cause a dominant-negative effect and alterations in steady-state voltage dependence of channel gating of heteromultimeric channels suggesting a reduction in expressional current might be one of the pathophysiologic mechanisms of LQTS.

Animals ; DNA Mutational Analysis ; ERG1 Potassium Channel ; Electrocardiography ; Ether-A-Go-Go Potassium Channels ; genetics ; Humans ; Long QT Syndrome ; genetics ; Mutation, Missense ; Oocytes ; Patch-Clamp Techniques ; RNA, Complementary ; Xenopus

Age Factors ; Animals ; Atrial Fibrillation ; etiology ; Atrial Function ; physiology ; Dogs ; Female ; Male ; Refractory Period, Electrophysiological ; physiology

OBJECTIVETo investigate effect of CD4(+) CD25(+) Foxp3(+) Tregs in the treatment of autoimmune myositis (EAM) in mice and explore the possible mechanisms.

METHODSMouse models of EAM were divided randomly into model group and treatment group, and the latter received infusion of CD4(+) CD25(+) Foxp3(+) Tregs separated from normal mouse spleen by magnetic activated cell sorting. The changes of muscle pathology was observed, and the expression of PD-1 and CTLA-4 in spleen CD4(+) CD25(+) Foxp3(+) Tregs was analyzed using flow cytometry; peripheral blood IL-10 and TGF-β levels were tested using double antibody sandwich ELISA.

RESULTSCompare with the model group, the mice in the treatment group showed significantly reduced muscular inflammatory cell infiltration, increased blood levels of IL-10 and TGF-β (P<0.05), and increased expression of PD-1 and CTLA-4 in spleen CD4(+) CD25(+) Foxp3(+) Tregs (P<0.05).

CONCLUSIONCD4(+) CD25(+) Foxp3(+) Tregs reinfusion produces therapeutic effect in mice with EAM by increasing peripheral blood IL-10 and TGF-β levels and PD-1 and CTLA-4 expressions in spleen CD4(+) CD25(+) Foxp3(+) Tregs.

Animals ; Autoimmune Diseases ; immunology ; CTLA-4 Antigen ; metabolism ; Cell Separation ; Cell- and Tissue-Based Therapy ; Disease Models, Animal ; Flow Cytometry ; Interleukin-10 ; blood ; Mice ; Myositis ; immunology ; Programmed Cell Death 1 Receptor ; metabolism ; Spleen ; immunology ; T-Lymphocytes, Regulatory ; immunology ; Transforming Growth Factor beta1 ; blood