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Objective@#To evaluate the efficacy and safety of ivabradine for the treatment of Chinese patients with chronic heart failure based on the Chinese subgroup data of the systolic heart failure treatment with the If inhibitor ivabradine trial (SHIFT).@*Method@#A total of 6 558 stable outpatients who presented symptoms of heart failure, with a left ventricular ejection fraction (LVEF) ≤35%, sinus rhythms with a heart rate ≥70 bpm participated in the randomized, double-blind, placebo-controlled, international multicenter clinical study.The subset of Chinese patients with heart rate ≥75 bpm was enrolled in the post-hoc subgroup analyses.Patients were randomly allocated by computer-generated assignment through a telephone interactive voice response system to ivabradine group (starting dose 5 mg bid, which was then uptitrated to the maximum 7.5 mg bid) or matched placebo group.The clinical baseline characteristics of participants were obtained and analyzed.The primary outcome endpoint was a composite endpoint of cardiovascular death or hospitalization resulting from worsening HF.The primary safety endpoint included total incidence of adverse events during the study, bradycardia, and adverse visual reaction (phosphenes).@*Results@#A total of 49 Chinese centers enrolled a total of 225 patients with chronic heart failure, of whom, 106 patients were randomized to the ivabradine group and the other 119 patients to the placebo group, and the mean follow-up time was (15.6±5.1) months.By the end of the study, mean heart rate (71.0 bpm vs. 80.3 bpm, P<0.05) and incidence of the primary endpoint events (18.9% (20/106) vs. 31.9%(38/119), HR=0.56, 95%CI 0.33-0.97, P=0.039) were significantly lower, while the percentage of patients with improvement in heart functional class NYHA (53.8% (56/106) vs. 34.5% (41/119), P=0.006 1) was significantly higher in the ivabradine group than in the placebo group.The total number of adverse events (129 events, 49.6% PY) in the ivabradine group was lower than that in the placebo group (203 events, 50.8% PY). In the ivabradine group and the placebo group, there were respectively 2 patients (1.9%) and 0 patients experienced bradycardia, 3 patients (2.9%) and 1 patient (0.8%) experienced adverse visual reaction (phosphenes).@*Conclusions@#Ivabradine significantly reduced heart rate and improved the clinical outcomes and NYHA function class in Chinese patients with chronic heart failure, these beneficial effects are achieved without inducing remarkable adverse reactions.The results of Chinese subgroup analysis were thus consistent with the overall results of the SHIFT study.@*Clinical Trial Registry@#International standard randomized controlled trials registry, ISRCTN 70429960.
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AIM: To investigate the effect oferythropoietin (EPO) on the rats with heart failure (HF) in hypothermia and to explore its underlying mechanism.METHODS: The Sprague-Dawley rats (n=80) were randomly divided into five groups: control group (CON group), HF in low-temperature group (HFLT group), HF in normal temperature group (HFNT group), HF with EPO in low temperature group (HFLT+EPO group), and HF with EPO and LY2940002 in low temperature group (HFLT+EPO+LY group).All rats were housed in artifitial climate chamber.The animals in CON, HFLT, HFLT+EPO and HFLT+EPO+LY groups were under the low-temperature environment, while those in HFNT group were under normal temperature.The heart function was evaluated by echocardiography.The rats were then executed and the hearts were harvested.The apoptosis of myocytes was assessed by TUNEL method.The mRNA expression of Fas and PI3K was detected by fluorescence quantitative PCR (qPCR) and the protein levels of HSP70, Akt and p-Akt in the myocardial tissues were determined by Western blot.RESULTS: The rat cardiac functions in HFLT group were significantly deteriorated compared with HFNT group.The cardiac functions in HFLT+EPO group were improved compared with HFLT group.The cardiac functions in HFLT+EPO+LY group were significantly pejorated compared with HFLT+EPO group.The apoptotic index of the myocardium in HFLT group and HFNT group was significantly higher than that in CON group (P<0.01).The apoptotic index of the myocardium in HFLT group was significantly higher than that in HFNT group (P<0.05).The apoptotic index of the myocardium in HFLT+EPO group was significantly lower than that in HFLT group (P<0.01).The mRNA expression of Fas in HFLT group was significantly higher than that in HFNT group, and no obvious difference of the mRNA expression level of PI3K between HFLT group and HFNT group was observed.The mRNA expression of PI3K in HFLT+EPO group was significantly lower than that in HFLT group and HFLT+EPO+LY group (P<0.05), and that in HFLT+EPO group was significantly higher than that in HFLT group and HFLT+EPO+LY group (P<0.05).The protein levels of p-Akt and HSP70 in HFLT+EPO group was also higher than those in HFLT group and HFLT+EPO+LY group (P<0.05), and no obvious difference of the protein levels of p-Akt and HSP70 in CON, HFLT and HFNT groups was found.The protein level of Akt had no significant difference in each group.CONCLUSION: The pathway of PI3K/Akt may be one of the cardioprotective ways of EPO.EPO activates the PI3K/Akt pathway, upregulates the experssion of HSP70 (an endogenous protective factor) and inhibits the apoptosis, thus protecting the cardiac functions in the rats with HF in hypothermia.
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Pulse waves contain abundant physiological and pathological information of human body. Research of the relationship between pulse wave and human cardiovascular physiological parameters can not only help clinical diagnosis and treatment of cardiovascular diseases, but also contribute to develop many new medical instruments. Based on the traditional double elastic cavity model, the human cardiovascular system was established by using the electric network model in this paper. The change of wall pressure and blood flow in artery was simulated. And the influence of the peripheral resistance and vessel compliance to the distribution of blood flow in artery was analyzed. The simulation results were compared with the clinical monitoring results to predict the physiological and pathological state of human body. The result showed that the simulation waveform of arterial wall pressure and blood flow was stabile after the second cardiac cycle. With the increasing of peripheral resistance, the systolic blood pressure of artery increased, the diastolic blood pressure had no significant change, and the pulse pressure of artery increased gradually. With the decreasing of vessel compliance, the vasoactivity became worse and the pulse pressure increased correspondingly. The simulation results were consistent with the clinical monitoring results. The increasing of peripheral resistance and decreasing of vascular compliance indicated that the incidence of hypertension and atherosclerosis was increased.
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Humanos , Aorta , Artérias , Fisiologia , Aterosclerose , Pressão Sanguínea , Doenças Cardiovasculares , Eletricidade , Coração , Fisiologia , Hemodinâmica , Hipertensão , Modelos Cardiovasculares , Resistência VascularRESUMO
[ABSTRACT]AIM:Tostudytherelationshipbetweenhuman8-oxoguanineglycosylase1(hOGG1)gene Ser326Cys polymorphism and severity of coronary artery lesions in the patients with diabetes mellitus .METHODS: We retrospectively analyzed 323 patients with diabetic mellitus receiving coronary angiography .These patients underwent the test of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and were divided into Cys/Cys genotype (n=85), Ser/Ser genotype (n=121) and Ser/Cys genotype (n=117) according to the results of PCR-RFLP. All clinical data including history of diseases , complications and biochemical markers , such as blood glucose , blood lipids and so on, were recorded.hOGG1 mRNA and 8-hydroxydeoxyguanosine (8-OHdG) were measured by RT-PCR and ELISA, respectively.The results of coronary angiography such as number and severity of coronary artery with lesions were analyzed by 2 cardiovascular physicians .Gensini score and SYNTAX score were also detected by the unitary criteria .RE-SULTS:(1)8-OHdG in Cys/Cys genotype was higher than that in Ser /Ser genotype and Ser/Cys genotype (P0.05).(2)hOGG1 mRNA ex-pression in Cys/Cys genotype was lower than that in Ser/Ser genotype and Ser/Cys genotype (P0.05) was observed.(3)The probability of triple vessel lesions in Cys/Cys genotype was high and the probability of single vessel lesions in Ser /Cys genotype was low , but the difference among 3 genotypes was not statistically significant (P>0.05).(4)Gensini score and SYNTAX score in Cys/Cys genotype were 48.7 ±15.3 and 39.5 ±17.2, respectively, and the ratio of complex lesions in Cys/Cys genotype was 73.0%.These scores and the ratio of complex lesions were higher than the other 2 genotypes (P0.05).CONCLUSION:hOGG1 gene Ser326Cys polymorphism has relationship with coronary artery lesions in the patients with diabetes mellitus and Cys /Cys genotype might have some impacts on the severity of lesions .The mRNA expression of hOGG1 in the patients with diabetes mellitus carrying Cys/Cys genotype is lower than that in the patients carrying the other 2 genotypes , then decreases the abil-ity of identification and removal of 8-OHdG and the capacity of repairing DNA oxidative damage , and accelerates the devel-opment of atherosclerosis .
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<p><b>OBJECTIVE</b>To examine the oral health status among the orphan children and adolescents of Chongqing and assist in planning of the oral health programs.</p><p><b>METHODS</b>According to the third national oral health investigation of epidemiology, the dental caries, gingival bleeding and calculus was examined among 317 orphan living in Chongqing, by cluster sampling. The statistical software SPSS 17.0 was used for the data analysis.</p><p><b>RESULTS</b>In primary and permanent teeth, the prevalence of dental caries and mean DMFT (dmft) were found to be 50.00%, 1.94 +/- 2.81 and 39.53%, 0.90 +/- 1.38. There were no significant difference between female and male (P>0.05). But there was significant difference of the prevalence of permanent tooth caries between the age group under 12 (include 12) and above 12 (P < 0.05). It was also found that 35.25% of the orphan children and adolescents had caries in the first permanent molar, and there was significant difference between female and male (P < 0.05). Neither of the caries teeth above was treated nor the healthy teeth were sealed. The prevalence rate of gingival bleeding was 78.22%, and the calculus rate was 67.66%.</p><p><b>CONCLUSION</b>The oral status of the orphan is poor, and this community has experienced a low utilization of preventive or therapeutic oral health services. In the future work, orphans should be considered as a priority group when make plans for oral health care.</p>
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Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , China , Índice CPO , Cárie Dentária , Dentição Permanente , Nível de Saúde , Dente Molar , Saúde Bucal , PrevalênciaRESUMO
Objective To investigate the association between plasma lipoprotein (a) [LP (a)] concentra-tion and in-stent restenosis after coronary stent implantation. Methods 152 patients with successful elective coro-nary stont implantation and percutancous transluminal coronary angioplasty (PICA) undergoing foUow-up angiogra-phy were retrospectively analyzed. These patients were divided into restenosis group( n = 29) and no-restenosis group (n = 123 ). The serum LP (a) levels of all patients were also investigated. The general clinical data were analyzed. Multivariate logistic regression was used for statistical analysis. Results We compared the serum Lap (a) levels, smoking and diabet in the two groups, and there was a statisticaLly significant difference between the restenosis group and no-restenosis group(P<0.05). Multivariate logistic regression showed that the elevation of Lap (a) level re-mained as an independent predictor of restenosis (RR =2. 648,95% CI 1. 066-6. 575,P <0. 05). Other risk fac-tors,such as smoking(P =0.023) ,diabet(P =0. 036) and the type of stent(P = 0.011 ) were also correlated with restenosis. Conclusions High plasma LP (a) concentration is an independent predictor of stent restenosis after stent implantation.
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AIM: To investigate the effect and the mechanism of apolipoprotein (a) [apo (a) ] on proliferation of vascular smooth muscle cells ( VSMCs). METHODS: All VSMCs used in experiments were serial subcultured from primary cells and were identified by immunohistochemistry staining of a - actin. Cell growth assay was observed as cell counting and MTT assay. Western blotting was also employed to detect the related mechanism. RESULTS: All cells used in experiments were confirmed as VSMCs. Although apo (a) enhanced VSMCs proliferation, this effect was attenuated by anti -integrin α_vβ_3, LM609.Use these reagents alone had no effect on VSMCs growth. The results of Western blotting demonstrated that focal adhesion kinase (FAK) was activated by apo (a) and the expression of total or phosphorylated transforming growth factor β_1 (TGF -β_1) was also decreased. However, these effects described above were all blocked by LM609.CONCLUSION: Apolipoprotein (a) enhances VSMCs proliferation and this effect is mediated by integrin α_vβ_3, which activates FAK and attenuates TGF - β_1 and phospho -TGF - β_1 expression.
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BACKGROUND:The benefit of cell therapy may be partly due to the secretion of angiogenic and antiapoptotic growth factors.Whether amniotic fluid stem cells (AFS) could secrete some growth factors requires further studies.OBJECTIVE:To isolate and culture AFS cells,and explore the angiogenic or antiapoptotic effect of cytokines secreted by AFS on endothelial cells.DESIGN,TIME AND SETTING:A in vitro cytological experiment was performed at the Institute of Hypertensive Disease,First Affiliated Hospital,Nanchang University from December 2008 to June 2009.MATERIALS:Term amniotic fluid of ten samples,50 mL/case,was obtained following caesarean delivery.The umbilical vein was used to isolate endothelial cells.Written informed content was obtained from all women.METHODS:AFS isolated from human amniotic fluid was cultured and digested by trypsin at confluence of 80%.The third passage of cells at a density of 5×10~8/L were divided into two groups:hypoxia group:the cells were cultured in 2% O_2 + 5% CO_2 +93% N_2;normal group:the cells were cultured in 5% CO_2 + 95% air.Two groups were cultured at 37 ℃ for 24 hours.The supematant of two groups was collected.The second passage of human umbilical vein endothelial cells cultured in vitro was collected and seeded onto 12-well culture plate at a density of 2×10~4 cells/well,and divided into 3 groups:control group was cultured in 2 mL EBM-2 containing 5% fetal bovine serum (FBS);normal group was cultured in 1 mL EBM-2 containing 5% FBS and 1 mL AFS cell culture solution;hypoxia group was cultured in 1 mL EBM-2 containing 5% FBS and 1 mL hypoxia AFS cell culture solution for 3 days,followed by incubation with 10 μg/L tumor necrosis factor (TNF)-α.MAIN OUTCOME MEASURES:AFS surface phenotype was examined by flow cytometry;the secretion level and mRNA expression of vascular endothelial cell growth factor (VEGF) and hepatocyte growth factor (HGF) were examined by ELISA or RT-PCR.The proliferation and apoptotic rates of endothelial cells were examined.RESULTS:AFS cells were long fusiform-shaped and arranged radially after 7 days of culture.The third passage of AFS cells expressed CD29 and CD105 while did not express CD34.AFS cells of normal culture secreted VEGF and HGF;AFS cells of hypoxia condition significantly increased secrete of VEGF (P＜0.01),and VEGF mRNA expression was significantly upregulated (P＜0.05),while HGF and mRNA expression remained unchanged (P＞0.05).Compared with control group,the number of endothelial cells was significantly increased in normal and hypoxia AFS cell groups after 3 days of culture (P＜0.05).After cocultured with TNF-α for 24 hours,the apoptosis rates of endothelial cells in AFS-conditioned medium was significantly decreased (P ＜ 0.05),and the change degree of hypoxia AFS cell group was greater than normal AFS cell group (P ＜ 0.05).CONCLUSION:AFS can secrete cytokines such as VEGF and HGF.Moreover,it significantly promotes endothelial cells proliferation and inhibits apoptosis.Under hypoxia condition,the secretion of VEGF from AFS cells is increased,and the effects on endothelial cells proliferation and apeptosis are enhanced.
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Objective To investigate the effect of the Senlm of patients with congestive heart failure(CHF) on the apoptosis of endothelial progentior eelts(EPCs)and protective role of carvedil01.Method Totally 20 patientswithCHF、