Central nervous system(CNS)degenerative disorders refer to a spectrum of pathological alterations triggered by struc-tural damage to cerebral neural tissues,clinically manifested as diverse neurological dysfunction syndromes,including multiple sclerosis(MS),neurodegenerative diseases(NDs),and ische-mic stroke.The hallmark pathological features of these disorders involve irreversible neuronal damage and decompensation of functional neural networks,ultimately leading to progressive neurological deficits.Notably,with the accelerating global popu-lation aging,the incidence of these diseases has surged signifi-cantly.According to WHO statistics,they now rank among the top three global causes of disability and mortality.Current re-search has confirmed that the pathogenesis of CNS degenerative disorders exhibits high heterogeneity,encompassing multifaceted pathophysiological processes such as genetic predisposition,oxi-dative stress,protein misfolding,and metabolic dysregulation.This intricate pathogenic network not only complicates clinical differential diagnosis but also poses substantial challenges to the development of precision therapeutic strategies.Importantly,re-cent studies have revealed that mitochondrial homeostasis disrup-tion-induced inflammatory cascades(termed mitochondrial in-flammation)play a pivotal regulatory role in neurodegenerative progression.Key molecular mechanisms include impaired mito-phagy,aberrant mitochondrial DNA(mtDNA)release and NL-RP3 inflammasome activation.This review systematically deci-phers the molecular regulatory network of mitochondrial inflam-mation,with a focus on its biological effects in critical pathologi-cal events such as blood-brain barrier disruption,microglial hy-peractivation and neuronal apoptosis.The overarching aim is to provide a theoretical foundation for developing innovative thera-peutic strategies targeting mitochondrial homeostasis restoration.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Cannabidiol(CBD),a major pharmacologically active phytocannabinoid found in cannabis,exhibits potent anti-inflam-matory activity through its multi-target actions.Furthermore,CBD derivatives with enhanced activity through structural modifi-cations are gaining increasing attention for their potential thera-peutic benefits.While reviews have explored the targets and pharmacological effects of CBD and its derivatives,and the struc-ture-activity relationship(SAR)of cannabinoid quinones regard-ing anticancer activity,a systematic summary of the SAR of CBD and its derivatives concerning anti-inflammatory activity is cur-rently lacking.This review therefore summarizes the research progress on the anti-inflammatory activity of CBD and its deriva-tives,focusing on their mechanisms of action,the impact of dif-ferent structural modifications on anti-inflammatory activity,and their potential applications in the treatment of inflammatory dis-eases.

Aim To generate a dual-reporter mouse model for tracing microglia and neurons to analyze their dynamic changes in real-time and to investigate the functional role of microglia-neuron interactions through microglial depletion.Methods Mi-croglia reporter mice were crossed with neuron reporter mice to generate Tmem119-e(2A-tdTomato-2A-DTR);Thy1-GFP dual-reporter mice.Genotyping was performed using tail DNA.Con-focal and two-photon microscopy were used to examine neuronal morphology.In vivo two-photon imaging was employed to observe the distribution of microglia and neurons in the brain.Diphtheria toxin(DT)was intraperitoneally injected to deplete microglia.Results The dual-reporter mice were successfully generated with the correct genotype.Both microglia and neurons were visu-alized,and microglia were specifically depleted by DT.Conclu-sions The successful establishment of a dual-reporter mouse model for tracing neurons and microglia will facilitate real-time in vivo observation of microglial and neuronal changes under physiological or pathological conditions,elucidating their specific roles in brain homeostasis.

Aim To generate a dual-reporter mouse model for tracing microglia and neurons to analyze their dynamic changes in real-time and to investigate the functional role of microglia-neuron interactions through microglial depletion.Methods Mi-croglia reporter mice were crossed with neuron reporter mice to generate Tmem119-e(2A-tdTomato-2A-DTR);Thy1-GFP dual-reporter mice.Genotyping was performed using tail DNA.Con-focal and two-photon microscopy were used to examine neuronal morphology.In vivo two-photon imaging was employed to observe the distribution of microglia and neurons in the brain.Diphtheria toxin(DT)was intraperitoneally injected to deplete microglia.Results The dual-reporter mice were successfully generated with the correct genotype.Both microglia and neurons were visu-alized,and microglia were specifically depleted by DT.Conclu-sions The successful establishment of a dual-reporter mouse model for tracing neurons and microglia will facilitate real-time in vivo observation of microglial and neuronal changes under physiological or pathological conditions,elucidating their specific roles in brain homeostasis.

Central nervous system(CNS)degenerative disorders refer to a spectrum of pathological alterations triggered by struc-tural damage to cerebral neural tissues,clinically manifested as diverse neurological dysfunction syndromes,including multiple sclerosis(MS),neurodegenerative diseases(NDs),and ische-mic stroke.The hallmark pathological features of these disorders involve irreversible neuronal damage and decompensation of functional neural networks,ultimately leading to progressive neurological deficits.Notably,with the accelerating global popu-lation aging,the incidence of these diseases has surged signifi-cantly.According to WHO statistics,they now rank among the top three global causes of disability and mortality.Current re-search has confirmed that the pathogenesis of CNS degenerative disorders exhibits high heterogeneity,encompassing multifaceted pathophysiological processes such as genetic predisposition,oxi-dative stress,protein misfolding,and metabolic dysregulation.This intricate pathogenic network not only complicates clinical differential diagnosis but also poses substantial challenges to the development of precision therapeutic strategies.Importantly,re-cent studies have revealed that mitochondrial homeostasis disrup-tion-induced inflammatory cascades(termed mitochondrial in-flammation)play a pivotal regulatory role in neurodegenerative progression.Key molecular mechanisms include impaired mito-phagy,aberrant mitochondrial DNA(mtDNA)release and NL-RP3 inflammasome activation.This review systematically deci-phers the molecular regulatory network of mitochondrial inflam-mation,with a focus on its biological effects in critical pathologi-cal events such as blood-brain barrier disruption,microglial hy-peractivation and neuronal apoptosis.The overarching aim is to provide a theoretical foundation for developing innovative thera-peutic strategies targeting mitochondrial homeostasis restoration.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Cannabidiol(CBD),a major pharmacologically active phytocannabinoid found in cannabis,exhibits potent anti-inflam-matory activity through its multi-target actions.Furthermore,CBD derivatives with enhanced activity through structural modifi-cations are gaining increasing attention for their potential thera-peutic benefits.While reviews have explored the targets and pharmacological effects of CBD and its derivatives,and the struc-ture-activity relationship(SAR)of cannabinoid quinones regard-ing anticancer activity,a systematic summary of the SAR of CBD and its derivatives concerning anti-inflammatory activity is cur-rently lacking.This review therefore summarizes the research progress on the anti-inflammatory activity of CBD and its deriva-tives,focusing on their mechanisms of action,the impact of dif-ferent structural modifications on anti-inflammatory activity,and their potential applications in the treatment of inflammatory dis-eases.

Once ischemic stroke occurs,severely insufficient blood supply causes massive neuronal apoptosis and necrosis,leading to the release of damage-associated molecular patterns(DAMPs)that exacerbate neuroinflammation and worsen brain damage.As the resident efferocytes in central nervous system,microglia possess the capability to phagocytose and eliminate ap-optotic cells by efferocytosis before necrosis occurs,thereby mit-igating the release of DAMPs and the accumulation of cellular debris.This process is crucial for neuroinflammation reduction and neurorestoration.Hence,a comprehensive understanding of the regulatory mechanism of microglial efferocytosis post-ische-mia,as well as its impact on neuroinflammation and cerebral damage,has the potential to advance diagnostic and therapeutic approaches for ischemic stroke.Here,we outline the molecular mechanisms and signaling pathways involved in microglial effero-cytosis following ischemic stroke,and summarize the research progress on drugs targeting microglial efferocytosis to enhance stroke prognosis.

Aim To study the inhibitory effect of ginsenoside Rgl on neuronal ferroptosis after ischemic stroke and its mechanism. Methods A model of oxygen glucose deprivation/reoxygenation (OGD/R) was established in HT22 cells, and the effect of Rgl on the viability of HT22 cells after OGD/R injury was detected by CCK-8. The effect of Rgl on ferroptosis in HT22 cells after OGD/R injury was detected by the test of ferroptosis markers GSH/GSSG, SOD, MDA, and Fe