Objective:To study the causality relationship between diastolic blood pressure(DBP)and hypertensive renal disease with renal failure(HRDRF)and the mediating role of hear t failure(HF)in the causality relationship by n...Objective:To study the causality relationship between diastolic blood pressure(DBP)and hypertensive renal disease with renal failure(HRDRF)and the mediating role of hear t failure(HF)in the causality relationship by network Mendelian randomization(MR).Methods:Genome-wide analysis of DBP,HRDRF,and HF was downloaded from the public database(Genome-Wide Analysis Study[GWAS])and was used to analyze the results and to conduct mediated MR analysis.Results:Analysis showed that DBP was positively correlated with HRDRF(OR=1.0002,95%CI:1.0001–1.0003,P=1.8076e-05)and DBP was positively correlated with HF(OR=1.0295,95%CI:1.0221–1.0370,P=2.5292e-15).HF and HRDRF had a positive causal effect(OR=1.0001,95%CI:1.0000–1.0001,P=0.0152).Mediation analysis showed that the contribution ratio of HF to the combined effect of DBP and HRDRF was 24.69%.Conclusions:DBP can increase the risk of renal disease with renal failure,and HF may play an impor tant role in mediating this causal relationship.展开更多
OBJECTIVE To investigate the synergistic effect on dilating blood vessels and anti-hypertension of GYS combined with metoprolol.METHODS ① Spontaneously hypertensive rats(SHR)were administered orally with the vehicle,...OBJECTIVE To investigate the synergistic effect on dilating blood vessels and anti-hypertension of GYS combined with metoprolol.METHODS ① Spontaneously hypertensive rats(SHR)were administered orally with the vehicle,GSY,metoprolol or GSY combined with metoprolol for 4weeks.Blood pressure,which included SBP,DBP and MBP was measured by a noninvasive method every week.At the end of4 weeks,blood was drawn from the ophthalmic venous plexus to determine blood fat levels(serum TC,TG,LDL-c,HDL-c),liver function(serum ALT,AST),and kidney function(serum BUN,UA and Cr)by the ACCUTE(TBA-40FR)automatic.② The aortae of normal SD rats were prepared and cleaned from periadventitial fat and surrounding connective tissue and cut transversely into 4-mm width rings.To observe different concentration of GYS,metoprolol or GSY combined with metoprolol causing relaxation of the isolated aortic rings precontracted until a stable plateau by noradrenaline(NA)directly or in the presence of eNOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin(INDO)respectively.③ The concentrations of plasma GSY was determined by the HPLC after rats administered orally with GSY or GSY combined with metoprolol for single-dose.DAS data processing software calculated the pharmacokinetic parameters of GSY.RESULTS There was a significant synergism between GYS and metoprolol in lowering blood pressure and the concentrations of serum TC and LDL-c of SHR.The relaxant effect of GYS combined with metoprolol on the aortic rings precontracted by NA could be attenuated by L-NAME or INDO.The AUC0-tof GSY significantly increased after in conjunction with metoprolol.CONCLUSION GYS combined with metoprolol increases the concentrations of plasma GSY and synergistically lowers blood pressure based on endothelium-dependent vasodilatation function(EDVF).展开更多
BACKGROUND: This study aimed to observe the effect of recruitment maneuver (RM) and post-RM ventilation at different tidal volume on lung vascular diastole endothelial function in rats with acute lung injury (ALI...BACKGROUND: This study aimed to observe the effect of recruitment maneuver (RM) and post-RM ventilation at different tidal volume on lung vascular diastole endothelial function in rats with acute lung injury (ALI).METHODS: A ALl rat model was produced by intravenous infusion of lipopolysaccharide (6 mg/ kg). Twenty-five rats were randomly divided into five groups: control group (n=5), ALl group (n=5), low tidal volume group (LV group, VT 6 mL/kg, n=5), sustained inflation (SI) with low tidal volume group (SI+LV group, VT 6 mL/kg, n=5), and SI with moderate tidal volume group (SI+MV group, VT 12 mL/ kg, n=5). RM was performed with SI, airway pressure 30 cmH2O for 30 seconds, and positive end- expiratory pressure (PEEP) was set to 5 cmH2O. Lung tissue was taken after 5 hours of mechanical ventilation. Mean arterial blood pressure (MAP) was monitored during the experiment. Endothelin-1 (ET-1), endothelial nitricoxide synthase (eNOS), Ach-induced endothelium-dependent relaxation response of isolated pulmonary artery rings were determined at 5 hours. RESULTS:LPS increased ET-1 level, decreased the expression of eNOS in lung tissue, impaired the Ach-induced endothelium-dependent relaxation response in the pulmonary artery, without obvious effect on systemic hemodynamics. SI+LV significantly reduced LPS-induced elevation of ET-1 level, increased the expression of eNOS, significantly improved endothelial dysfunction, and improved the dysfunction of endothelium-dependent relaxation in the pulmonary artery. CONCLUSIONS:RM with a high or low tidal volume ventilation could improve the lung vascular endothelial function of rats with acute lung injury, and RM with low tidal volume ventilation could lower significantly the injury of lung vascular endothelial diastole function in rats with acute lung injury.展开更多
Aim: The aim of this study was to determine the effect of training on endothelium-dependent vasodilatation in patients with coronary artery disease (CAD) after revascularization and healthy young men. Background: Impa...Aim: The aim of this study was to determine the effect of training on endothelium-dependent vasodilatation in patients with coronary artery disease (CAD) after revascularization and healthy young men. Background: Impaired endothelial function has been observed in patients with CAD and those with CAD risk factors. Studies have shown that exercise can enhance endothelial function. Methods: This experimental cross-sectional study was conducted on patients with CAD (3 months after CABG and PCI) and students of medical school in 2011. Endothelium dependent dilation of the brachial artery was determined by using high-resolution vascular ultrasonography through flow-mediated vasodilatation (FMD) after induction of ischemia, and the data were analyzed using SPSS, dependent t-test and ANCOVA. Findings: The findings showed that at baseline, FMD was reduced in revascularized patients, when compared with healthy young men, after 8 weeks, and exercise training significantly improved FMD in patients underwent training group [from 4.31 ± 1.45 (SD)% to 6.15 ± 0.773 (SD)%, p p ed unchanged, and even after aerobic training, it did not significantly modify the brachial artery diameter in these groups. Conclusion: Our study demonstrates that endothelial dysfunction persisting in CAD patients after revascularization and aerobic training can improve endothelial function in different vascular beds in CAD patients and healthy young men. This may contribute to the benefit of regular exercise in preventing and restricting cardiovascular disease.展开更多
Objective Anthracycline chemotherapeutic agents have significant cardiotoxicity.The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular(LV)myocardial stiffness in breast cancer ...Objective Anthracycline chemotherapeutic agents have significant cardiotoxicity.The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular(LV)myocardial stiffness in breast cancer patients by measuring the intrinsic wave velocity propagation(IVP),and evaluating the potential clinical value of IVP in detecting early LV diastolic function impairment.Methods A total of 68 newly diagnosed breast cancer patients,who were treated with anthracycline-based chemotherapy,were analyzed.Transthoracic echocardiography was performed at baseline(T0),and after 1,2,3,4 and 8 chemotherapeutic cycles(T1,T2,T3,T4 and T5,respectively).Then,the IVP,LV strain parameters[global longitudinal strain(GLS),longitudinal peak strain rate at systole(LSRs),longitudinal peak strain rate at early diastole(LSRe),longitudinal peak strain rate at late diastole(LSRa),and the E/LSRe ratio],and conventional echocardiographic parameters were obtained and further analyzed.A relative reduction of>15%in GLS was considered a marker of early LV subclinical dysfunction.Results Compared to the T0 stage,IVP significantly increased at the T1 stage.However,there were no significant changes in GLS,LSRs,or LSRe between the T0 and T1 stages.These parameters significantly decreased from the T2 stage.LSRa started to significantly decrease at the T5 stage,and the E/LSRe ratio started to significantly increase at the T3 stage(all P<0.05).At the T0 stage,IVP(AUC=0.752,P<0.001)had a good predictive value for LV subclinical dysfunction after chemotherapy.Conclusions IVP is a potentially sensitive parameter for the early clinical assessment of anthracycline-related cardiac diastolic impairment.展开更多
基金supported by the scientific research project of Shanxi Provincial Health Commission(No.2022073)。
文摘Objective:To study the causality relationship between diastolic blood pressure(DBP)and hypertensive renal disease with renal failure(HRDRF)and the mediating role of hear t failure(HF)in the causality relationship by network Mendelian randomization(MR).Methods:Genome-wide analysis of DBP,HRDRF,and HF was downloaded from the public database(Genome-Wide Analysis Study[GWAS])and was used to analyze the results and to conduct mediated MR analysis.Results:Analysis showed that DBP was positively correlated with HRDRF(OR=1.0002,95%CI:1.0001–1.0003,P=1.8076e-05)and DBP was positively correlated with HF(OR=1.0295,95%CI:1.0221–1.0370,P=2.5292e-15).HF and HRDRF had a positive causal effect(OR=1.0001,95%CI:1.0000–1.0001,P=0.0152).Mediation analysis showed that the contribution ratio of HF to the combined effect of DBP and HRDRF was 24.69%.Conclusions:DBP can increase the risk of renal disease with renal failure,and HF may play an impor tant role in mediating this causal relationship.
基金The project supported by National Natural Science Foundation of China(81374003)National Major Scientific and Technological Specialized Project for the Significant Formulation of New Drugs,China(2011ZX09101-002-07)Zhejiang province health high-level innovative talents training project
文摘OBJECTIVE To investigate the synergistic effect on dilating blood vessels and anti-hypertension of GYS combined with metoprolol.METHODS ① Spontaneously hypertensive rats(SHR)were administered orally with the vehicle,GSY,metoprolol or GSY combined with metoprolol for 4weeks.Blood pressure,which included SBP,DBP and MBP was measured by a noninvasive method every week.At the end of4 weeks,blood was drawn from the ophthalmic venous plexus to determine blood fat levels(serum TC,TG,LDL-c,HDL-c),liver function(serum ALT,AST),and kidney function(serum BUN,UA and Cr)by the ACCUTE(TBA-40FR)automatic.② The aortae of normal SD rats were prepared and cleaned from periadventitial fat and surrounding connective tissue and cut transversely into 4-mm width rings.To observe different concentration of GYS,metoprolol or GSY combined with metoprolol causing relaxation of the isolated aortic rings precontracted until a stable plateau by noradrenaline(NA)directly or in the presence of eNOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin(INDO)respectively.③ The concentrations of plasma GSY was determined by the HPLC after rats administered orally with GSY or GSY combined with metoprolol for single-dose.DAS data processing software calculated the pharmacokinetic parameters of GSY.RESULTS There was a significant synergism between GYS and metoprolol in lowering blood pressure and the concentrations of serum TC and LDL-c of SHR.The relaxant effect of GYS combined with metoprolol on the aortic rings precontracted by NA could be attenuated by L-NAME or INDO.The AUC0-tof GSY significantly increased after in conjunction with metoprolol.CONCLUSION GYS combined with metoprolol increases the concentrations of plasma GSY and synergistically lowers blood pressure based on endothelium-dependent vasodilatation function(EDVF).
文摘BACKGROUND: This study aimed to observe the effect of recruitment maneuver (RM) and post-RM ventilation at different tidal volume on lung vascular diastole endothelial function in rats with acute lung injury (ALI).METHODS: A ALl rat model was produced by intravenous infusion of lipopolysaccharide (6 mg/ kg). Twenty-five rats were randomly divided into five groups: control group (n=5), ALl group (n=5), low tidal volume group (LV group, VT 6 mL/kg, n=5), sustained inflation (SI) with low tidal volume group (SI+LV group, VT 6 mL/kg, n=5), and SI with moderate tidal volume group (SI+MV group, VT 12 mL/ kg, n=5). RM was performed with SI, airway pressure 30 cmH2O for 30 seconds, and positive end- expiratory pressure (PEEP) was set to 5 cmH2O. Lung tissue was taken after 5 hours of mechanical ventilation. Mean arterial blood pressure (MAP) was monitored during the experiment. Endothelin-1 (ET-1), endothelial nitricoxide synthase (eNOS), Ach-induced endothelium-dependent relaxation response of isolated pulmonary artery rings were determined at 5 hours. RESULTS:LPS increased ET-1 level, decreased the expression of eNOS in lung tissue, impaired the Ach-induced endothelium-dependent relaxation response in the pulmonary artery, without obvious effect on systemic hemodynamics. SI+LV significantly reduced LPS-induced elevation of ET-1 level, increased the expression of eNOS, significantly improved endothelial dysfunction, and improved the dysfunction of endothelium-dependent relaxation in the pulmonary artery. CONCLUSIONS:RM with a high or low tidal volume ventilation could improve the lung vascular endothelial function of rats with acute lung injury, and RM with low tidal volume ventilation could lower significantly the injury of lung vascular endothelial diastole function in rats with acute lung injury.
文摘Aim: The aim of this study was to determine the effect of training on endothelium-dependent vasodilatation in patients with coronary artery disease (CAD) after revascularization and healthy young men. Background: Impaired endothelial function has been observed in patients with CAD and those with CAD risk factors. Studies have shown that exercise can enhance endothelial function. Methods: This experimental cross-sectional study was conducted on patients with CAD (3 months after CABG and PCI) and students of medical school in 2011. Endothelium dependent dilation of the brachial artery was determined by using high-resolution vascular ultrasonography through flow-mediated vasodilatation (FMD) after induction of ischemia, and the data were analyzed using SPSS, dependent t-test and ANCOVA. Findings: The findings showed that at baseline, FMD was reduced in revascularized patients, when compared with healthy young men, after 8 weeks, and exercise training significantly improved FMD in patients underwent training group [from 4.31 ± 1.45 (SD)% to 6.15 ± 0.773 (SD)%, p p ed unchanged, and even after aerobic training, it did not significantly modify the brachial artery diameter in these groups. Conclusion: Our study demonstrates that endothelial dysfunction persisting in CAD patients after revascularization and aerobic training can improve endothelial function in different vascular beds in CAD patients and healthy young men. This may contribute to the benefit of regular exercise in preventing and restricting cardiovascular disease.
基金the Hubei Province Health and Famliy Planning Scientific Research Project(No.WJ2023M011)the Department of Finance of Hubei Province(No.3890750).
文摘Objective Anthracycline chemotherapeutic agents have significant cardiotoxicity.The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular(LV)myocardial stiffness in breast cancer patients by measuring the intrinsic wave velocity propagation(IVP),and evaluating the potential clinical value of IVP in detecting early LV diastolic function impairment.Methods A total of 68 newly diagnosed breast cancer patients,who were treated with anthracycline-based chemotherapy,were analyzed.Transthoracic echocardiography was performed at baseline(T0),and after 1,2,3,4 and 8 chemotherapeutic cycles(T1,T2,T3,T4 and T5,respectively).Then,the IVP,LV strain parameters[global longitudinal strain(GLS),longitudinal peak strain rate at systole(LSRs),longitudinal peak strain rate at early diastole(LSRe),longitudinal peak strain rate at late diastole(LSRa),and the E/LSRe ratio],and conventional echocardiographic parameters were obtained and further analyzed.A relative reduction of>15%in GLS was considered a marker of early LV subclinical dysfunction.Results Compared to the T0 stage,IVP significantly increased at the T1 stage.However,there were no significant changes in GLS,LSRs,or LSRe between the T0 and T1 stages.These parameters significantly decreased from the T2 stage.LSRa started to significantly decrease at the T5 stage,and the E/LSRe ratio started to significantly increase at the T3 stage(all P<0.05).At the T0 stage,IVP(AUC=0.752,P<0.001)had a good predictive value for LV subclinical dysfunction after chemotherapy.Conclusions IVP is a potentially sensitive parameter for the early clinical assessment of anthracycline-related cardiac diastolic impairment.