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Objective To observe the therapeutic effect of porcine myocardium against porcine myocardial infarction (MI) by porcine myocardial infarction model with connexin-43/zonula occludens-1 (CX43/ZO-1) double gene induced pluripotent stem cells (iPS) transplantation.Methods Porcine myocardial infarction model was established by balloon occlusion.One week later,1640 culture medium,CX43 gene ips cells and CX43/ZO-1 gene ips cells were injected into the different coronary arteries.After 3 months,electron microscopy and color Doppler ultrasonography were used to evaluate the curative effect.Results Compared to ips group of CX43 and 1640 culture group,in CX43/ZO-1 gene ips group,electron microscope showed a large number of island-like cardiomyocytes,blood vessels and intact intercalated discs in the infarct area and normal myocardial junction area structure,color Doppler echocardiography showed left ventricular end diastolic diameter reduced,and ejection fraction was significantly increased (P ＜ 0.05).Conclusions Transfection of CX43/ZO-1 double gene ips cells can promote cardiomyocyte regeneration and cardiac function recovery in porcine myocardial infarction model.
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OBJECTIVE To explore the genetic mechanism for a family affected with cardiac conduction block. METHODS Affected family members were screened for potential mutations of known candidate genes. As no pathogenic mutation was found, two patients and one healthy member from the family were further analyzed by exomic sequencing followed by Sanger sequencing. The pathogenicity of suspected mutation was analyzed using bioinformatics software. RESULTS Sequencing of the full exome has identified a c.G1725T mutation in the CLCA2 gene. Sanger sequencing has detected the same mutation in all five patients, but not in the normal member from the family. Bioinformatics analysis indicated that the mutation has resulted in substitution of the 575th amino acid cysteine (C) by tryptophan (W). The site is highly conserved and becomes pathogenic with the mutation. CONCLUSION The heterozygous c.G1725T mutation in exon 11 of the CLCA2 gene probably underlies the disease and fit the autosomal dominant pattern of inheritance.
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Female , Humans , Male , Middle Aged , Amino Acid Sequence , Chloride Channels , Genetics , Computational Biology , Heart Block , Genetics , Molecular Sequence Data , MutationABSTRACT
Objective:To observe and compare the therapeutic effect of metoprolol by routine increasing dose method and rapid titration method on acute myocardial infarction (AMI).Methods:A total of 60 inpatients,who were di-agnosed with AMI within 24h and without contraindications for metoprolol,were randomly divided into two groups:routine therapy group (received metoprolol using routine methods,the dose was added in seven days)and rapid ti-tration group (metoprolol was added in three days using titration).The dosage maintained with 190 mg/d after both groups reaching the target dose of 190mg/d;then therapeutic effects were observed in both groups.Results: ①There were no re-myocardial infarction,rehospitalization caused by heart failure and sudden death etc.in both groups;② Patients received echocardiography in outpatients after three months.Compared with routine increasing dose group,there was significant reduction in left ventricular end-diastolic diameter [LVEDd,(55.00±7.56)mm vs.(50.00± 5.81)mm]and significant rise in left ventricular ejection fraction [LVEF,(49.13 ± 10.18)% vs. (57.84±10.34)%]in rapid titration group,P <0.01 both.Conclusion:Rapid titration method could make the pa-tients rapidly reach the targeted dose of metoprolol and inhibit renin release earlier,block the renin-angiotensin sys-tem,and improve myocardial remodeling and cardiac function.
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ObjectiveTo investigate the effects of bone marrow stem cells autologous transplantation after acute myocardial infarction on local mRNA expression of SDF-1,Kit ligand,E-selectin,ICAM-1and VCAM-1.Methods Acute myocardial infarction models were established in 10 swine,which were randomized divided into placebo group (5 swine) and transplantation group (5 swine).After six months,hearts of placebo group and early transplantation group were harvested and mRNA expression of SDF-1,Kit ligand,E-selectin,ICAM-1 and VCAM-1 in infarcted myocardial region was detected.Results The mRNAs of SDF-1,Kit ligand,E-selection,ICAM-1 and VCAM-1 were expressed in the infarcted myocardial region of transplantation group six months after myocardial infarction,but it was not found in the placebo group.ConclusionsBone marrow autologous transplantation after acute myocardial infarction can promote local mRNA expression of SDF-1,Kit ligand,E-selectin,ICAM-1 and VCAM-1,which may be due to the paracrine effects of stem cells.
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Objective To investigate the effects of established swine acute myocardial infarction and following ventricular remodeling model by occluding Coronary with balloon. Methods Ten healthy Domestic swine are enrolled. Each swine's left anterior descending coronary artery was occluded for three hours by dilated balloon, and then reperfusion was performed. During the whole course of operation, the electro-cardiogram was monitored. B-ultrasound and single -photon emission computed tomography examination (SPECT) were performed to detect left ventricular end diastolic dimension, left ventricular tip wall thickness, left ventricular end diastolic volume and left ventricula ejection fraction before operation and one week, three month, six month after acute myocardial infarction. Results Five swine died during the period of opera-tion for lack of experience, the remains survived. Electrocardiogram revealed significant ST-elevation and Q-wave formation. B-untrasound and SPECT witnessed deteriorating left ventricular end diastolic dimension expansion, left ventricular tip wall thickness thinning, left ventricular end diastolic volume expansion and left ventricular ejection fraction depression. Conclusions Coronary artery occlusion by balloon can successfully establish acute myocardial infarction and following left ventricular remodeling models.
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Objective To investigate the effects of bone marrow stem cells autologous transplantation on left ventricular remodeling after acute myocardial infarction. Methods Acute myocardial infarction models were successfully established in 10 swines, which were ran-dom divided into two groups, placebo group and trasplantation group. One week after operation, bone marrow stem cells autologous transplan-tation was performed, and control group was administrated with placebo. B-ultrasound and emission computed tomography aexaminations were performed to assess the left ventrieular end diastolic dimension, left ventricular tip wall thickness, left ventricular end diastolic volume and left ventricula ejection fraction before operation, one week, three months after acute myocardial infarction. Results Compared with that of control group, three months after acute myocardial infarction, transplantation group witnessed smaller left ventricular end diastolic dimension, thicker left ventricular tip wall, smaller left ventricular end diastolic volume and higher left ventricular ejection fraction. Conclusions Bone marrow autologous transplantation after acute myocardial infarction can alleviate left ventricular remodeling.
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Background Neointima formation plays an important role in the pathogenesis of atherosclerosis and restenosis after angioplasty.We hypothesized if atorvastatin inhibits neointima formation mediating decreases in cathepsin S (Cat S) and nuclear factor-?B(NF-?B) expression.Objective The study was aimed to explore the effect of atorvastatin on the neointima formation,Cat S and NF-?B expression in rats after balloon-injured carotid artery.Methods Twenty-four male Sprague-Dawley rats were randomly one of three arms:control group(n=8),surgery group(n=8) and atorvastatin group[10 mg/(kg?d),n=8] for 4 weeks.Surgery and atorvastatin group were performed with balloon angioplasty to the left common carotid artery.The serum levels of IL-1? were measured using enzyme-link-immunosorbent assay(ELISA).Carotid arteries were excised and examined with pathomorphology.The expression of Cat S and NF-?B was measured using using the RT-PCR and immunohistochemistry techniques.Results Compared with surgery group,atorvastatin decreased intima area and intima media ratio(I/M)[intima area:(148.6?8.8)?103 vs (64.8?5.1)?103 ?m2;I/M:(2.1?0.2) vs (0.9?0.1),all P