Myocardial infarction accompanied by diabetes mellitus is accepted as the most seri-ous type of coronary heart disease,and among the current treatment strategies,the precise delivery of protective drugs for inhibiting...Myocardial infarction accompanied by diabetes mellitus is accepted as the most seri-ous type of coronary heart disease,and among the current treatment strategies,the precise delivery of protective drugs for inhibiting cardiomyocyte apoptosis is still a challenge.In this study,we developed a biodegradable nanoparticles-based delivery system with excellent macrophage escape,cardiac targeting,and drug release prop-erties to achieve targeted therapy of myocardial infarction.Specifically,a copolymer of p(DMA–MPC–CD)combining self-adhesion,hydration lubrication,and targeting peptide binding site was successfully prepared by free radical copolymerization,and it was self-assembled on the surface of melatonin-loaded dendritic mesoporous silica nanoparticles(bMSNs)following the integration of adamantane-modified cardiac homing peptide(CHP)based on supramolecular host–guest interaction.Importantly,a hydration layer formed around the zwitterionic phosphorylcholine groups of the multifunctional nanoparticles,which was confirmed by the enhancement in hydra-tion lubrication and reduction in coefficient of friction,prevented the nanoparticles from phagocytosis by the macrophages.The in vivo bioluminescence imaging test indicated that the nanoparticles were endowed with satisfied cardiac targeting capa-bility,and the in vivo mice study demonstrated that the intravenous injection of drug-loaded nanoparticles(namely bMSNs–Mel@PDMC–CHP)effectively reduced cardiomyocyte apoptosis,alleviated myocardial interstitialfibrosis,and enhanced cardiac function.展开更多
Objective:This study evaluated the prognostic power of serum uric acid(UA)in predicting adverse events in elderly acute coronary syndrome(ACS)patients with diabetes mellitus(DM).Methods:The analysis involved 718 ACS p...Objective:This study evaluated the prognostic power of serum uric acid(UA)in predicting adverse events in elderly acute coronary syndrome(ACS)patients with diabetes mellitus(DM).Methods:The analysis involved 718 ACS patients>80 years old whose general clinical data and baseline blood biochemical indicators were collected prospectively from January 2006 to December 2012.These patients were classified into two groups based on DM status,and then followed up after discharge.The Kaplan-Meier method was used for major adverse cardiac event(MACE)rates and all-cause mortality.Multivariate Cox regression was performed to analyze the relationship between UA level and long-term clinical prognosis.Receiver operating characteristic(ROC)curves were analyzed to predict the cutoff value of UA in elderly ACS patients with DM.There were 242 and 476 patients in the DM and non-DM(NDM)groups,respectively,and the follow-up time after discharge was 40‒120 months(median,63 months;interquartile range,51‒74 months).Results:The all-cause mortality,cardiac mortality,and MACE rates in both DM and NDM patients were higher than those in the control group(P=0.001).All-cause mortalities,cardiac mortalities,and MACE rates in DM patients with moderate and high UA levels were significantly higher than those in the NDM group(P=0.001).Long-term survival rates decreased significantly with increased UA levels in the ACS groups(P=0.001).UA(odds ratio(OR)=2.106,95%confidence interval(CI)=1.244‒3.568,P=0.006)was found to be an independent risk factor for all-cause mortality and MACE in elderly ACS patients with DM.The cutoff value of UA was 353.6μmol/L(sensitivity,67.4%;specificity,65.7%).Conclusions:Serum UA level is a strong independent predictor of long-term all-cause death and MACE in elderly ACS patients with DM.展开更多
基金National Natural Science Foundation of China,Grant/Award Numbers:52275199,82073833,52335004,52022043Beijing-Tianjin-Hebei Fundamental Research Cooperation Project,Grant/Award Number:J230001+1 种基金Hainan Provincial Social Development Fund,Grant/Award Number:ZDYF2023SHFZ145National Key Research and Development Program of China,Grant/Award Numbers:2022YFC3600500,2022YFC3600502。
文摘Myocardial infarction accompanied by diabetes mellitus is accepted as the most seri-ous type of coronary heart disease,and among the current treatment strategies,the precise delivery of protective drugs for inhibiting cardiomyocyte apoptosis is still a challenge.In this study,we developed a biodegradable nanoparticles-based delivery system with excellent macrophage escape,cardiac targeting,and drug release prop-erties to achieve targeted therapy of myocardial infarction.Specifically,a copolymer of p(DMA–MPC–CD)combining self-adhesion,hydration lubrication,and targeting peptide binding site was successfully prepared by free radical copolymerization,and it was self-assembled on the surface of melatonin-loaded dendritic mesoporous silica nanoparticles(bMSNs)following the integration of adamantane-modified cardiac homing peptide(CHP)based on supramolecular host–guest interaction.Importantly,a hydration layer formed around the zwitterionic phosphorylcholine groups of the multifunctional nanoparticles,which was confirmed by the enhancement in hydra-tion lubrication and reduction in coefficient of friction,prevented the nanoparticles from phagocytosis by the macrophages.The in vivo bioluminescence imaging test indicated that the nanoparticles were endowed with satisfied cardiac targeting capa-bility,and the in vivo mice study demonstrated that the intravenous injection of drug-loaded nanoparticles(namely bMSNs–Mel@PDMC–CHP)effectively reduced cardiomyocyte apoptosis,alleviated myocardial interstitialfibrosis,and enhanced cardiac function.
文摘Objective:This study evaluated the prognostic power of serum uric acid(UA)in predicting adverse events in elderly acute coronary syndrome(ACS)patients with diabetes mellitus(DM).Methods:The analysis involved 718 ACS patients>80 years old whose general clinical data and baseline blood biochemical indicators were collected prospectively from January 2006 to December 2012.These patients were classified into two groups based on DM status,and then followed up after discharge.The Kaplan-Meier method was used for major adverse cardiac event(MACE)rates and all-cause mortality.Multivariate Cox regression was performed to analyze the relationship between UA level and long-term clinical prognosis.Receiver operating characteristic(ROC)curves were analyzed to predict the cutoff value of UA in elderly ACS patients with DM.There were 242 and 476 patients in the DM and non-DM(NDM)groups,respectively,and the follow-up time after discharge was 40‒120 months(median,63 months;interquartile range,51‒74 months).Results:The all-cause mortality,cardiac mortality,and MACE rates in both DM and NDM patients were higher than those in the control group(P=0.001).All-cause mortalities,cardiac mortalities,and MACE rates in DM patients with moderate and high UA levels were significantly higher than those in the NDM group(P=0.001).Long-term survival rates decreased significantly with increased UA levels in the ACS groups(P=0.001).UA(odds ratio(OR)=2.106,95%confidence interval(CI)=1.244‒3.568,P=0.006)was found to be an independent risk factor for all-cause mortality and MACE in elderly ACS patients with DM.The cutoff value of UA was 353.6μmol/L(sensitivity,67.4%;specificity,65.7%).Conclusions:Serum UA level is a strong independent predictor of long-term all-cause death and MACE in elderly ACS patients with DM.
