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Although great progress has been made in the treatment of heart failure,refractory heart failure is still a difficult problem.It has high incidence and poor prognosis,which brings huge financial burden to patients, families and society. Recently,the clinical application of sacubitril/ valsartan and ivabradine,mechanical circulatory support,and heart transplantation have been greatly improved.This article reviews current treatments of refractory heart failure from aspects of new breakthroughs in drug treatment,mechanical circulatory support,and heart transplantation.
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Hypertension is closely related to the formation of aortic dissection.Long-term effects of hypertension on the vessel wall can cause lesions of the aortic wall.Under the influence of various factors, the vascular structure is easy to be affected by hypertension, leading to tearing injury.This article mainly discuss the pathogenesis of aortic dissection by hypertension from three aspect:the hemodynamics, histopathology and inflammatory immunology.
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Objective To investigate the effect of psychological intervention, combined with Concentrated Tinidazole Gargles on dental plaque and gingivitis inflammation and influence factor of life quality in elder patients. Methods The control group was given Concentrated Tinidazole Gargles treatment, the research group was given psychological intervention on the basis of Concentrated Tinidazole Gargles (as control group). Plaque index, gingivitis index and SF-36 scale changes before and after treatment were recorded between two groups of elderly patients with gingivitis. Results There was no significant difference in plaque index, gingival indexand SF-36 score compared with before treatment between two groups; Plaque index, gingivitis index and the SF-36 score were improved in the research group better than the control group after treatment (P<0.05). Conclusion There is positive significance in improving the clinical efficacy of Concentrated Tinidazole Gargles plus psychological intervention and assurance of the quality of life on gingivitis in elder patients.
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During percutaneous coronary intervention,thrombotic storm which is mediated by hypercoagulable state,mechanical distension induced-plaque rupture,platelet activation and adhesion is still the main cause of cardiovascular adverse events.The mortality rate is extremely high if not treated properly.Thrombotic storm can be diagnosed quickly through coronary artery angiography and myocardial blush grades.Once coronary thrombosis occurs,medicine including platelet Ⅱ b/Ⅲ a receptor antagonist tirofiban or vasodilators can rapidly improve coronary flow and effectively treat it.
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Objective To compare the effect of intracoronary versus intravenous administration of tiroifban for acute coronary syndrome (ACS) patients during percutaneous coronary intervention (PCI). Methods A search was retrieved from Pubmed, EMbase, Chinese Biomedical Literature Database (CBM), Chinese Journal Full-text Database (CNKI), Chinese Science and Technology Periodical Database (VIP), Cochrane Library to systematically collect the randomized controlled trials of intracoronary versus intravenous administration of tirofiban for the patients with ACS undergoing PCI. The data was extracted from the included studies and analyzed by Cochrane Collaboration's RevMan5.2 software. Results Twenty-five studies involving 2516 patients met the inclusion criteria. The results of meta-analysis showed that thrombolysis in myocardial infarction (TIMI) grade 3 lfow (RR 1.15, 95%CI 1.07-1.23, P=0.0001) were signiifcantly more often achieved in the patients by intracoronary administration of tiroifban (IC group) than those by intravenous strategy (IV group). Left ventricular ejection fraction (LVEF) values in a week after PCI which were evaluated by Cardiac Ultrasound were statistically significant between the two groups (WMD 2.69, 95%CI 0.14-5.25, P=0.04). LVEF values in IC group were increased by an average of 2.69% compared with group IV. Intracoronary administration resulted in a reduced incidence of major adverse cardiovascular events (MACE) at 30-day follow-up (RR 0.51, 95%CI 0.38-0.69, P < 0.0001). However, the incidence of bleeding complications was not statistically signiifcant between the two groups (RR 0.95, 95% CI 0.76-1.19, P=0.64). Conclusions Compared with intravenous strategy, intracoronary administration of tiroifban can be more effective in increasing coronary blood lfow and microvascular perfusion, more signiifcantly in reducing the incidence of MACE at 30-day follow-up and improving the prognosis after PCI without increasing the risk of bleeding.
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Objective To investigate the effect and underlying mechanism of nocodazole on the inhibition of rVSMCs proliferation. Methods rVSMCs were divided into four groups, group A (normal culture), group B (serum-free culture for 24 h) , group C ( 18 h normal culture after 48 h of serum-free culture ) , and group D ( nocodazole treatment for 12 h after thymidine treatment for 12 h) . Flow cytometry, transmission electron microscopy, and metabolism measurements were performed and mitofusin-2 ( Mfn-2 ) expression was detected. Results Flow cytometry analysis showed rVSMCs of group B、C、D were arrested to G0/G1 , S and G2/M phases, respectively. Less and smaller mitochondria were observed in group D by transmission electron microscopy in nocodazole-treated rVSMCs. Compared with groups A and C, there were significant decreases in glucose and L-amino acid metabolism, levels of ATP, and marked increase in NADH in group D(P<0. 05). Western Blot showed that G2/M cell cycle arrest and nocodazole could induce up-regulation of Mfn-2 in rVSMCs(P<0. 05). Conclusion Nocodazole can block the energy metabolism and proliferation in rVSMCs, which is probably associated with the role of Mfn-2 on anti-atherosclerosis.
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Angiotensin II (ANGII) plays an important role in the pathogenesis of atherosclerosis by inducing proliferation of vascular smooth muscle cells (VSMCs). In our study, we observed the effects of valsartan on proliferation of cultured VSMCs treated with or without ANGII by cell counting and methyl thiazolyl tetrazolium (MTT) assay, and detected the expression of mitofusin 2 (Mfn2), a newly discovered cell proliferation inhibitor and a related cell proliferation signaling pathway protein by Western blotting. ANGII at a concentration of 10(-6) mol/L significantly stimulated VSMCs proliferation, down-regulated the expression of Mfn2 and up-regulated the expression of Raf and ERK1/2. Valsartan inhibited such effects of ANGII at concentrations of 10(-5) and 10(-6) mol/L, but not at 10(-7) mol/L. Valsartan had no significant effect on the proliferation of untreated VSMCs. These results suggest that valsartan inhibits ANGII-induced proliferation of VSMCs in vitro via Mfn2-Ras-Raf-ERK/MAPK signaling pathway.
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Objective To study the effects of protein kinase A (PKA) phosphorylation site' s mutation of mitofusin-2 (Mfn2) on intimal proliferation after balloon injury of carotid artery of rats. Method Rat model of carotid artery balloon injury was established and infected with Adv-LacZ, Adv-Mfn2, AdvMfn2-S442A or Adv-Mfn2-S442D from the peri-arterial sheathes of vessels, while phosphate buffered solution (PBS) used instead of above infectious adenovirus as uninfected group and sham operation as control group. The rats were sacrificed 14 days after balloon injury of carotid artery in order to measure the level of Mfn2 protein and the prol9iferation cell nuclear antigen (PCNA) with immunohistochemistry staining. The morphology of vessels was observed with HE staining. All data were statistically analyzed with ANOVA and Dunnett-t test. Results Fourteen days after surgery, the levels of Mfn2 protein significantly increased in arteries infected with Adv-Mfn2, Adv-Mfn2-S4442A and Adv-Mfn2-S442D compared with those in control group, sham operation group and Adv-LacZ infected group. The ratio of intimal area/medial area (I/M) and percentage of PCNA positive cells in both Adv-Mfn2 and Adv-Mfn2-S442A groups markedly decreased compared with control group (P ＜0. 01 ) . Compared with the Adv-Mfn2 group, the I/M and the percentage of PCNA positive cells reduced more significantly in Adv-S442A group (P ＜ 0. 01 ) . However,the I/M and the percentage of PCNA positive cells in Adv-LacZ and Adv-S442D groups were not significantly different from those found in the control group. Conclusions The over-expression of Mfn2 gene may effectively inhibit intimal proliferation after balloon injury of carotid artery of rats. The inhibitory effects of Mfn2-S442A are more obvious than those of Mfn2. However, the Mfn2-S442D is out of the inhibitory effect on neo-intimal proliferation.
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BACKGROUND: The mitofusin 2 (Mfn2) may affects vascular smooth muscle cell Ras protein and suppress cellular proliferation through inhibition of extracellular signal-regulated protein kinase signaling pathway, which plays an important role in pathogenesis of vascular disorders such as hypertension, atherosclerosis and post-angioplasty restenosis. Mfn-2 gene amino acid sequence of the first 442 serine serves as protein kinase A (PKA) phosphorylation site, which is closely related to its phosphorylation status and may be involved in its functional regulation.OBJECTIVE: To investigate the effect of Mfn2 gene with PKA phosphorylation site deletion[Mfn2-PKA (△)] on inhibiting the proliferation of vascular smooth muscle cells and related signaling pathway.METHODS: Vascular smooth muscle cells of rats infected by recombinational adenovirus carrying green fluorescent protein,Mfn2 gane and Mfn2-PKA (△), were subcultured for 3-10 passages and randomly divided into 4 groups: ① Control group without intervention. ② Control group infected with adenovirus carrying green fluorescent protein. ③ Experiment group infected with adenovirus carrying Mfn-2 gene.④ Experiment group infected with adenovirus carrying Mfn2-PKA (△). Laser confocal microscopy was used to observe the locations of Mfn2 gene with and without PKA in cells. The expressions of extracallular signal-regulated protein kinase, Mfn2 gone and Mfn2-PKA (△) were determined by Western blot analysis. The growth curve of the vascular smooth muscle cells was explored by MTT.RESULTS AND CONCLUSION: The Mfn-2 and Mfn2-PKA (△) both expressed protein-specific bands in vascular smooth muscle cells. Two kinds of gone expression products were mainly located at the out membrane of mitochondria. Compared with the control group and adenovirus carrying green fluorescent protein group, the absorbance values at 3, 4, 5, 6 days were significantly reduced in adenovirus carrying Mfn2 group (P ＜ 0.01), and no obvious changes were observed in adenovirus carrying Mfn2-PKA (△) group. Compared with the control group and adenovirus carrying green fluorescent protein group, the extracellular signal-regulated protein kinase expression was significantly reduced in adenovirus carrying Mfn2 group (P ＜ 0.01), and no obvious changes were observed in adenovirus carrying Mfn2-PKA (△) group. Mfn2-PKA (△) located at the out membrane of mitochondria, has no effect on suppressing the proliferation of vascular smooth muscle cells, and no inhibition effect on extracellular signal-regulated protein kinase signaling pathway.
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BACKGROUND: Mitofusin2 (Mfn2) profoundly inhibits proliferation and induces apoptosis of vascular smooth muscle cells (VSMCs) through phosphatidylinositol 3 kinase/protein kinase B. Notably, tMfn2, with the transmembrane domain deleted, has a 41%-reduced molecular weight, which possibly exhibits a stronger effect on inducing apoptosis.OBJECTIVE: To investigate the effect of rat tMfn2 gene, with the transmembrane domain deleted, on promoting the apoptosis of VSMCs, and to determine related signal pathway.DESIGN, SETTING AND TIME: A controlled observational study at a gene level was performed in the central laboratory, Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology between January and October in 2008.MATERIALS: Rat VSMCs and the recombinant adenovirus containing LacZ, Mfn2 or tMfn2 was offered by Professor Chen as a gift.METHODS: The rat VSMCs cultured at 3-10 passages were divided into 4 groups. ①Blank control group: No interventions. ② VSMCs were infected by adenovirus-mediated LacZ, Mfn2, and tMfn2, respectively.MAIN OUTCOME MEASURES: ①Expressions of Mfn2 and tMfn2 following the VSMCs were infected with recombinant adenovirus for 24 hours. ②The apoptosis of VSMCs was determined with flow cytometry and enzyme linked immunosorbent assay at 24, 48 and 72 hours following infection. ③Western blot was used to analyze the expression of phosphorylated AKT following the VSMCs were infected with recombinant adenovirus for 24 hours.RESULTS: ①Both Mfn2 and tMfn2 were expressed in the VSMCs. ②The tMfn2 was superior to Mfn2 in promoting the apoptosis of VSMCs in a time-dependent manner (P<0.01). ③The protein expression of phosphorylated AKT remarkably decreased two groups, especially significant in tMfn2-infected group (P<0,01).CONCLUSION: The tMfn2 can induce the apoptosis of VSMCs more effectively via the inhibition of phosphorylated AKT signaling pathway.
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Objective To develop an oligonucleotide array to detect single nucleotide mutations in 23S rRNA gene.Methods Primers and probes targeting A2142G.A2143G and C2182T mutations in 23S rRNA gene were designed tp develop an oligonucleotide array.Samples were performed by an asymmetric PCR and the PCR products were hybridized with the specific DNA microarray chips.Non fluorescence-labeled PCR products were cloned into T vectors.The results of oligonucleofide array were confirmed by direct DNA sequencing and evaluated by minimal inhibitory concentration (MIC).Results The results obtained from oligonucleotide microarray were identical to those of direct sequencing.In 54 Helicobacter pylori samples,oligonucleotide microarray indicated that no A-to-C transition at 2142 was found,and the mutant rate of A2143G was 11.11 % (6/54),the mutant rate of C2182T was 12.96% (7/54).A2143C,A2143T,C2182A and C2182G mutations were not found.The other specimens were wild-type.All the above results were the same as that of MIC tests.Conclusions The oligonucleofide microarray is a reliable and accurate genotyping assay for clarithromycin-resistance of Helieobaeter pylofi.It is high-throughput screening method for gastric mucosa and improve the application of strategy for personalized therapy.
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Objective To investigate the effect of tMfn2 gene on inhibiting the proliferation of vascular smooth muscle cells (VSMCs) and related mechanism. Method VSMCs were transfected with adenovirus vector encoding tMfn2 or Mfn2 (Adv-tMfn2, Adv-Mfn2). The abundance of tMfn2 protein and Mfn2 protein were deter-mined by Western blot analysis using Mfn2 N-term antibody. The effect of tMfn2 on the proliferation of VSMCs was explored by cell counting and MTT assay. The cell cycle was analyzed using flow cytometry. Western blot were used to detect the expression of p-ERK1/2 and p-Raf-1. Results The results of cell counting and MTT both indi-cated that tMfn2 gene displayed more remarkable effect on inhibiting the proliferation of VSMCs than Mfn2 (P <0.01). Flow cytometry showed that most of the cells infected with Adv-tMfn2 or Adv-Mfn2 were blocked in the stage of G0/G1 and few entered into the S phase. Western blot indicated that overexpression of tMfn2 gene resulted in downregulation of phosphorylated ERK1/2 and Raf-1 protein (P < 0.01). These results demonstrated tMfn2 had stronger effect than Mfn2 (P < 0.01). Conclusions tMfn2 gene is superior to Mfn2 gene in attenuating the proliferation of VSMCs via the Ras-Raf-ERK1/2 signaling pathway.
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Heart fatty acid-binding protein (H-FABP) is supposed to be the most sensitive biomarker of early acute myocardial infarction (AMI). To evaluate the diagnostic value of H-FABP for AMI in the early stage, the plasma levels of H-FABP were measured by sandwich ELISA in 93 patients with suspected AMI at admission within 6 h after onset of chest pain and 69 normal healthy subjects. The plasma concentrations of cardiac troponin-I (cTnI), creatine kinase-MB (CK-MB) and myoglobin (Mb) were assayed at the same time by using corpuscle chemiluminescence for those patients. The patients were classified as AMI group (n=32) and non-AMI group (n=61) retrospectively. The diagnostic validity was evaluated in terms of sensitivity, specificity and receiver operating characteristic (ROC) curve analysis. The results showed the cutoff value of H-FABP for AMI was 16.8 ng/ml, and its diagnostic sensitivity for AMI was 64.29% within 3 h and 84.38% within 6 h after onset of chest pain, and the diagnostic specificity for non-AMI was 100% within 3 h and 91.8% within 6 h. H-FABP had higher sensitivity than that of cTnI and CK-MB at all time points (P<0.05), whereas there was no significant difference in specificity among the four markers. But the area under the ROC curve of H-FABP was significantly greater than that of cTnI, CK-MB and Mb within 3 h. These results revealed that H-FABP possessed high diagnostic sensitivity and specificity for AMI in early stage, especially within 3 h after onset of persistent angina pectoris. In conclusion, H-FABP can be used as a sensitive marker for AMI in the early stage.
Subject(s)
Female , Humans , Male , Angina Pectoris , Blood , Diagnosis , Biomarkers , Blood , Creatine Kinase, MB Form , Blood , Fatty Acid-Binding Proteins , Blood , Myocardial Infarction , Blood , Diagnosis , Myoglobin , Blood , Sensitivity and Specificity , Time Factors , Troponin I , BloodABSTRACT
uring last 16 years we have successfully developed the computer-assisted vectorcardiogram analysis systems: model TJ-Ⅰ, TJ-Ⅱ, and TJ-Ⅲ, but some technical problems remained unresolved, such as the recognition accuracy for vectorcardiograms, measurement of the parameters of complicated QRS waves, the ratio of T loop length to width, and the area of spatial vectors etc. A new system, model TJ-Ⅳ was designed to resolve these technical problems. The system was equipped with a 586 computer with a CPU of 120 MHz. Special new low-noise amplifier was employed and C language was used for programming. Three graph recognition techniques were used to enhance the accuracy of VCG recognition. 32 orthogonal electrocardiograms and vectorcardiograms were displayed and printed, and 566 parameters of vectorcardiograms were calculated. Our results with 150 cases showed that the system had high accuracy of graph recognition, and parameter calculation and the results were essentially consistent with those of manipulative methods. We were led to concluded when compared with TJ-Ⅲ system, the new version has higher accuracy of processing and measurement for vectorcardiograms, is able to process more vectorcardiographic parameters, with higher processing speed.
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uring last 16 years we have successfully developed the computer-assisted vectorcardiogram analysis systems: model TJ-Ⅰ, TJ-Ⅱ, and TJ-Ⅲ, but some technical problems remained unresolved, such as the recognition accuracy for vectorcardiograms, measurement of the parameters of complicated QRS waves, the ratio of T loop length to width, and the area of spatial vectors etc. A new system, model TJ-Ⅳ was designed to resolve these technical problems. The system was equipped with a 586 computer with a CPU of 120 MHz. Special new low-noise amplifier was employed and C language was used for programming. Three graph recognition techniques were used to enhance the accuracy of VCG recognition. 32 orthogonal electrocardiograms and vectorcardiograms were displayed and printed, and 566 parameters of vectorcardiograms were calculated. Our results with 150 cases showed that the system had high accuracy of graph recognition, and parameter calculation and the results were essentially consistent with those of manipulative methods. We were led to concluded when compared with TJ-Ⅲ system, the new version has higher accuracy of processing and measurement for vectorcardiograms, is able to process more vectorcardiographic parameters, with higher processing speed.
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The role of lipid-regulating capsule in the regulation of experimental dislipidemia was studied in SD rats. The SD rats were divided into 6 groups: group A (normal control)，group B to F (experimental hyperlipidemia). The rats in the groups C，D and E received the capsule in a daily dose of 2.5 g，5 g and 10 g/kg respectively for 3 weeks，while the rats in the group F received Simvastatin in a daily dose of 7.5 mg/kg for 3 weeks. By comparison with the group B after 3 weeks，the levels of plasma total cholesterol (TC) and low density lipoprotein (LDL-C) were very significantly decreased in the groups C，D，E and F(P<0.01)，the value of plasma total triglyceride (TG) was very significantly decreased in the groups D，E and F (<0.01)，and the level of high density lipoprotein was significantly increased in the groups C，D and E (P<0.05)，but very significantly increased in the group F (P<0.01). It was suggested that the therapeutic efficiency of the lipid-regulating capsule in low，middle and high dosage was the same as that in high dose of simvastatin for the SD rats with high plasma TC and LDL-C，and middle and high doses of the capsule had the same effect of simvastatin on the plasma TG.