OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

Aim To investigate the im-munomodulatory effects of Ononin on Th17/Treg bal-ance and inflammatory responses,and to evaluate its neuroinmune regulatory role in ischemic stroke.Methods A Foxp3 promoter-driven luciferase reporter assay was used to assess the effect of Ononin on Foxp3 transcriptional activity.The effect of Ononin on the dif-ferentiation of na?ve CD4+T cells into Th 17 and Treg subsets was evaluated by flow cytometry.A transient middle cerebral artery occlusion(tMCAO)model was established in mice to evaluate the effects of Ononin on infarct size,neurological recovery,body weight resto-ration,and survival rate.Flow cytometry and RT-PCR were conducted to elucidate the immunological mechanisms underlying Ononin's effects.Results On-onin significantly enhanced Foxp3 promoter activity,promoted the differentiation of na?ve CD4+T cells into Treg cells,and suppressed Th17 polarization.In the tMCAO model,Ononin significantly reduced acute in-farct size,improved survival,ameliorated long-term neurological deficits,and increased Treg cell propor-tions in ischemic brain tissue.Conclusions Ononin modulates peripheral and central inflammation by resto-ring the Th17/Treg immune balance,thereby exerting significant immunomodulatory effects.Its therapeutic benefit in ischemic stroke is closely linked to immune balance restoration.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

Objective:To investigate the neuroprotective efficacy of scutellarin(Scu)against cerebral ischemia-reperfusion(CIRI)injury in rats,with a focus on its regulatory mechanisms involving the CX3CL1/CX3CR1-PI3K/AKT signaling axis.Methods:The rat CIRI model was established using Longa's intraluminal suture method.The experimental design comprised four groups(n=15 per group):Sham operation group,CIRI model group,Scu treat-ment(40 mg/kg/d Scu gavage)group,and Scu+LY294002(Scu combined with PI3K inhibitor LY294002)group.Following 4 weeks of intervention,neurological function,pathological changes,and pathway protein expression were evaluated using Longa scoring,TTC staining,HE staining,transmission electron microscopy,immunofluorescence,or Western blot analysis.Results:Compared to the CIRI model group,Scu treatment significantly improved neurological function,reduced cerebral infarct volume and attenuated neuronal damage(P<0.05).Furthermore,Scu downregulat-ed CX3CL1/CX3CR1 expression,increased p-PI3K/PI3K and p-AKT/AKT ratios,elevated Bcl-2/Bax ratio,and de-creased IL-17A expression(P<0.05).These protective effects were partially reversed by LY294002.Conclusion:Scu exerts neuroprotective effects in cerebral CIRI injury by downregulating CX3CL1/CX3CR1 expression and activating the PI3K/AKT pathway,thereby attenuating inflammation and apoptosis.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

Objective To analyze the changing trends and epidemiological characteristics of the disease burden of blindness caused by type 2 diabetes mellitus(T2DM)in China from 1990 to 2021,and to predict the trends up to 2035.Methods Based on the standardized methodology of the Global Burden of Disease Study 2021,the age-standardized rates(ASRs)and their corresponding 95％uncertainty intervals(UI)for prevalence and years lived with disability(YLDs)rate were used to systematically describe the disease burden of blindness caused by T2DM in China.The temporal trends[esti-mated annual percentage change(EAPC)]and epidemiological characteristics were assessed,with attention to age and sex differences,to predict the trends in the disease burden up to 2035.Results From 1990 to 2021,the age-standardized prevalence rate increased from 6.03 per 100 000(95％UI:4.46-8.18)to 10.35 per 100 000(7.60-13.69),and the age-standardized YLDs rate increased from 1.09 per 100 000(95％UI:0.67-1.70)to 1.88 per 100 000(95％UI:1.21-2.90),with an EAPC of 2.18(95％CI:1.73-2.64).The disease burden was relatively heavier in females and the elderly population.Epidemiological changes,population growth,and aging collectively drove the increase in the burden of blind-ness caused by T2DM.The disease burden of blindness caused by T2DM is projected to continue rising by 2035.Conclu-sion The disease burden of blindness caused by T2DM in China continues to increase,with a relatively heavier burden on females and the elderly population.Future research should optimize the equity of medical resource allocation and conduct studies on the mechanisms of sex differences to enable precise interventions with evidence-based strategies.

Objective To compare the clinical outcomes of patients with coronary in-stent restenosis(ISR)who underwent drug-coated balloon(DCB)treatment,based on different clinical presentations.Methods This prospective study included 508 patients diagnosed with coronary ISR at Anzhen Hospital,Capital Medical University,between May 2020 and May 2022.All patients received DCB treatment.According to clinical presentation,the patients were divided into an acute coronary syndrome(ACS)group(185 patients)and a non-acute coronary syndrome(non-ACS)group(323 patients).All patients were followed for two years,primarily comparing the incidence of myocardial infarction(MI),target lesion revascularization(TLR),death,and major adverse cardiovascular events(MACE)between the two groups.Results Baseline data showed that the ACS group had a significantly higher proportion of hypertension,diabetes,and smoking compared to the non-ACS group(all P＜0.05).Additionally,the ACS group had a higher proportion of B2/C-type lesions,long lesions,and moderate to severe calcified lesions(all P＜0.05).The number,length,and diameter of stents implanted were also significantly larger in the ACS group(all P＞0.05).At the 1-year follow-up,the ACS group had a significantly higher incidence of TLR(8.1％vs.2.5％,P=0.007)and MACE(10.3％vs.5.3％,P=0.047)than the non-ACS group.By the end of the 2-year follow-up,the ACS group still had higher rates of TLR(18.9％vs.10.2％,P=0.007)and MACE(22.7％vs.14.9％,P=0.030).Conclusions ISR patients with ACS have higher cardiovascular risk and more complex lesions.They also experience a higher incidence of adverse events after DCB treatment.

Objective:To investigate the neuroprotective efficacy of scutellarin(Scu)against cerebral ischemia-reperfusion(CIRI)injury in rats,with a focus on its regulatory mechanisms involving the CX3CL1/CX3CR1-PI3K/AKT signaling axis.Methods:The rat CIRI model was established using Longa's intraluminal suture method.The experimental design comprised four groups(n=15 per group):Sham operation group,CIRI model group,Scu treat-ment(40 mg/kg/d Scu gavage)group,and Scu+LY294002(Scu combined with PI3K inhibitor LY294002)group.Following 4 weeks of intervention,neurological function,pathological changes,and pathway protein expression were evaluated using Longa scoring,TTC staining,HE staining,transmission electron microscopy,immunofluorescence,or Western blot analysis.Results:Compared to the CIRI model group,Scu treatment significantly improved neurological function,reduced cerebral infarct volume and attenuated neuronal damage(P<0.05).Furthermore,Scu downregulat-ed CX3CL1/CX3CR1 expression,increased p-PI3K/PI3K and p-AKT/AKT ratios,elevated Bcl-2/Bax ratio,and de-creased IL-17A expression(P<0.05).These protective effects were partially reversed by LY294002.Conclusion:Scu exerts neuroprotective effects in cerebral CIRI injury by downregulating CX3CL1/CX3CR1 expression and activating the PI3K/AKT pathway,thereby attenuating inflammation and apoptosis.

The plants of the genus Caragana Fabr. are desert plants of the Leguminosae family, which are widely used in traditional ethnomedicine, with the effects of nourishing Yin and nourishing blood, dispelling wind and removing dampness, clearing heat and detoxifying toxins. The anti-inflammatory effect of Caragana Fabr. has attracted much attention, the research on the related mechanism has made some progress, but it lacks systematic collation. By summarising the anti-inflammatory effects of the active ingredients of Caragana Fabr., the authors found that they have good anti-inflammatory activities on different inflammatory cell models in vitro, and have good improvement effects on rheumatoid arthritis, colitis, complex nephritis, and acute lung injury and other disease models. The anti-inflammatory effects of the active components of this genus mainly include the reduction of the levels of a variety of pro-inflammatory factors, and the signalling pathways involved mainly include TLR4/NF-κB, TLR4/MAPK, TLR4/NF-κB/IRF3, JAK/STAT-1, ERK/STAT-1 and so on. Therefore, the paper mainly reviews the research progress on the anti-inflammatory effects and mechanisms of the Caragana Fabr. plants and their active components according to disease types, with a view to providing reference for the in-depth study of their anti-inflammatory activities and the development of new products with related functions.

Aim To investigate the im-munomodulatory effects of Ononin on Th17/Treg bal-ance and inflammatory responses,and to evaluate its neuroinmune regulatory role in ischemic stroke.Methods A Foxp3 promoter-driven luciferase reporter assay was used to assess the effect of Ononin on Foxp3 transcriptional activity.The effect of Ononin on the dif-ferentiation of na?ve CD4+T cells into Th 17 and Treg subsets was evaluated by flow cytometry.A transient middle cerebral artery occlusion(tMCAO)model was established in mice to evaluate the effects of Ononin on infarct size,neurological recovery,body weight resto-ration,and survival rate.Flow cytometry and RT-PCR were conducted to elucidate the immunological mechanisms underlying Ononin's effects.Results On-onin significantly enhanced Foxp3 promoter activity,promoted the differentiation of na?ve CD4+T cells into Treg cells,and suppressed Th17 polarization.In the tMCAO model,Ononin significantly reduced acute in-farct size,improved survival,ameliorated long-term neurological deficits,and increased Treg cell propor-tions in ischemic brain tissue.Conclusions Ononin modulates peripheral and central inflammation by resto-ring the Th17/Treg immune balance,thereby exerting significant immunomodulatory effects.Its therapeutic benefit in ischemic stroke is closely linked to immune balance restoration.