The neuroprotective effect against spinal cord ischemia/reperfusion injury in rats exerted by delayed xenon post-conditioning is stronger than that produced by immediate xenon post-conditioning. However, the mechanism...The neuroprotective effect against spinal cord ischemia/reperfusion injury in rats exerted by delayed xenon post-conditioning is stronger than that produced by immediate xenon post-conditioning. However, the mechanisms underlying this process remain unclear. Activated microglia are the main inflammatory cell type in the nervous system. The release of pro-inflammatory factors following microglial activation can lead to spinal cord damage, and inhibition of microglial activation can relieve spinal cord ischemia/reperfusion injury. To investigate how xenon regulates microglial activation and the release of inflammatory factors, a rabbit model of spinal cord ischemia/reperfusion injury was induced by balloon occlusion of the infrarenal aorta. After establishment of the model, two interventions were given： （1） immediate xenon post-conditioning—after reperfusion, inhalation of 50% xenon for 1 hour, 50% N2/50%O2 for 2 hours; （2） delayed xenon post-conditioning—after reperfusion, inhalation of 50% N2/50%O2 for 2 hours, 50% xenon for 1 hour. At 4, 8, 24, 48 and 72 hours after reperfusion, hindlimb locomotor function was scored using the Jacobs locomotor scale. At 72 hours after reperfusion, interleukin 6 and interleukin 10 levels in the spinal cord of each group were measured using western blot assays. Iba1 levels were determined using immunohistochemistry and a western blot assay. The number of normal neurons at the injury site was quantified using hematoxylin-eosin staining. At 72 hours after reperfusion, delayed xenon post-conditioning remarkably enhanced hindlimb motor function, increased the number of normal neurons at the injury site, decreased Iba1 levels, and inhibited interleukin-6 and interleukin-10 levels in the spinal cord.Immediate xenon post-conditioning did not noticeably affect the above-mentioned indexes. These findings indicate that delayed xenon post-conditioning after spinal cord injury improves the recovery of neurological function by reducing microglial activation and the release of interleukin-6 and interleukin-10.展开更多
Background In patients with acute ST-segment elevation myocardial infarction(STEMI)who undergo primary percutaneous coronary intervention(PCI),approximately 10%are concomitant with a chronic total occlusion(CTO)in a n...Background In patients with acute ST-segment elevation myocardial infarction(STEMI)who undergo primary percutaneous coronary intervention(PCI),approximately 10%are concomitant with a chronic total occlusion(CTO)in a non-culprit vessel.However,the impact of staged CTO recanalization on prognosis in this cohort remains disputable.This study aimed to compare the long-term outcomes of staged CTO recanalization versus medical therapy in patients with STEMI after primary PCI.Methods Between January 2005 and December 2016,a total of 287 patients were treated with staged CTO-PCI(n=91)or medical therapy(n=196)after primary PCI in our center.The primary endpoint was major adverse cardiovascular and cerebrovascular event(MACCE),defined as a composite of all-cause death,nonfatal myocardial infarction(MI),stroke or unplanned revascularization.After propensity-score matching,77 pairs of well-balanced patients were identified.Results The mean follow-up period was 6.06 years.Overall,the incidence of the primary endpoint of MACCE was significantly lower in staged CTO-PCI group than that in medical therapy group in both overall population(22.0%vs.46.9%;hazard ratio(HR)=0.48,95%CI:0.29-0.77)and propensity-matched cohorts(22.1%vs.42.9%;HR:0.48,95%CI:0.27-0.86).In addition,staged CTO-PCI was also associated with reduced risk of the composite of cardiac death,nonfatal MI or stroke compared with medical therapy in both overall population(9.9%vs.26.5%;hazard ratio(HR)=0.39,95%CI:0.19-0.79)and propensity-matched cohorts(9.1%vs.22.1%;HR:0.40,95%CI:0.16-0.96).After correction of the possible confounders,staged CTO-PCI was independently associated with reduced risks of MACCE(adjusted HR:0.46,95%CI:0.28-0.75),the composite of cardiac death,nonfatal MI or stroke(adjusted HR:0.45,95%CI:0.22-0.94)and all-cause mortality(adjusted HR:0.32,95%CI:0.13-0.83).Moreover,the results of sensitivity analysis were almost concordant with the overall analysis.Conclusions In patients with STEMI and a concurrent CTO who undergo primary PCI,successful staged recanalization of CTO in the non-culprit vessels is associated with better clinical outcomes during long-term follow-up.展开更多
基金supported by the National Natural Science Foundation of China,No.81271387the Research Special Fund of Public Welfare and Health Department of China,No.201402009a grant form the National Key Technology R&D Program in China,No.Z141107002514031
文摘The neuroprotective effect against spinal cord ischemia/reperfusion injury in rats exerted by delayed xenon post-conditioning is stronger than that produced by immediate xenon post-conditioning. However, the mechanisms underlying this process remain unclear. Activated microglia are the main inflammatory cell type in the nervous system. The release of pro-inflammatory factors following microglial activation can lead to spinal cord damage, and inhibition of microglial activation can relieve spinal cord ischemia/reperfusion injury. To investigate how xenon regulates microglial activation and the release of inflammatory factors, a rabbit model of spinal cord ischemia/reperfusion injury was induced by balloon occlusion of the infrarenal aorta. After establishment of the model, two interventions were given： （1） immediate xenon post-conditioning—after reperfusion, inhalation of 50% xenon for 1 hour, 50% N2/50%O2 for 2 hours; （2） delayed xenon post-conditioning—after reperfusion, inhalation of 50% N2/50%O2 for 2 hours, 50% xenon for 1 hour. At 4, 8, 24, 48 and 72 hours after reperfusion, hindlimb locomotor function was scored using the Jacobs locomotor scale. At 72 hours after reperfusion, interleukin 6 and interleukin 10 levels in the spinal cord of each group were measured using western blot assays. Iba1 levels were determined using immunohistochemistry and a western blot assay. The number of normal neurons at the injury site was quantified using hematoxylin-eosin staining. At 72 hours after reperfusion, delayed xenon post-conditioning remarkably enhanced hindlimb motor function, increased the number of normal neurons at the injury site, decreased Iba1 levels, and inhibited interleukin-6 and interleukin-10 levels in the spinal cord.Immediate xenon post-conditioning did not noticeably affect the above-mentioned indexes. These findings indicate that delayed xenon post-conditioning after spinal cord injury improves the recovery of neurological function by reducing microglial activation and the release of interleukin-6 and interleukin-10.
基金funded by the Ministry of Science and Technology of the People’s Republic of China,State Science and Technology Support Program (No.2011BAI11B05)Beijing Lab for Cardiovascular Precision Medicine, Beijing, China (PXM2019_014226_000023)
文摘Background In patients with acute ST-segment elevation myocardial infarction(STEMI)who undergo primary percutaneous coronary intervention(PCI),approximately 10%are concomitant with a chronic total occlusion(CTO)in a non-culprit vessel.However,the impact of staged CTO recanalization on prognosis in this cohort remains disputable.This study aimed to compare the long-term outcomes of staged CTO recanalization versus medical therapy in patients with STEMI after primary PCI.Methods Between January 2005 and December 2016,a total of 287 patients were treated with staged CTO-PCI(n=91)or medical therapy(n=196)after primary PCI in our center.The primary endpoint was major adverse cardiovascular and cerebrovascular event(MACCE),defined as a composite of all-cause death,nonfatal myocardial infarction(MI),stroke or unplanned revascularization.After propensity-score matching,77 pairs of well-balanced patients were identified.Results The mean follow-up period was 6.06 years.Overall,the incidence of the primary endpoint of MACCE was significantly lower in staged CTO-PCI group than that in medical therapy group in both overall population(22.0%vs.46.9%;hazard ratio(HR)=0.48,95%CI:0.29-0.77)and propensity-matched cohorts(22.1%vs.42.9%;HR:0.48,95%CI:0.27-0.86).In addition,staged CTO-PCI was also associated with reduced risk of the composite of cardiac death,nonfatal MI or stroke compared with medical therapy in both overall population(9.9%vs.26.5%;hazard ratio(HR)=0.39,95%CI:0.19-0.79)and propensity-matched cohorts(9.1%vs.22.1%;HR:0.40,95%CI:0.16-0.96).After correction of the possible confounders,staged CTO-PCI was independently associated with reduced risks of MACCE(adjusted HR:0.46,95%CI:0.28-0.75),the composite of cardiac death,nonfatal MI or stroke(adjusted HR:0.45,95%CI:0.22-0.94)and all-cause mortality(adjusted HR:0.32,95%CI:0.13-0.83).Moreover,the results of sensitivity analysis were almost concordant with the overall analysis.Conclusions In patients with STEMI and a concurrent CTO who undergo primary PCI,successful staged recanalization of CTO in the non-culprit vessels is associated with better clinical outcomes during long-term follow-up.
