BACKGROUND:Peripheral nerve axon rupture seriously affects patients' physical function and mental health.Microsurgery,nerve autograft,nerve allograft,fibrin glue and catheter technology are the main treatments for peripheral nerve injury,each of which has its own advantages and disadvantages,but the overall treatment effect is not satisfactory.Despite the clinical success of Schwann cells in promoting axonal regeneration,there are still many challenges in the treatment with Schwann cells,such as slow expansion of Schwann cells,immune rejection,and low survival rate of transplanted cells.OBJECTIVE:To summarize the role and mechanism of Schwann cells in promoting the regeneration of peripheral nerve axons,and the difficulties and challenges of Schwann cells in the process of nerve regeneration treatment.METHODS:PubMed,Medline,WanFang,VIP,and CNKI were searched by computer using the search terms of"Schwann cells,synaptic Schwann cell,macrophage,peripheral nerve axon rupture,Wallerian degeneration,Peripheral nerve axon regeneration,Central nervous system repair"in English and Chinese.Literature related to Schwann cell proliferation and differentiation,promotion of peripheral nerve regeneration,and clinical applications was retrieved from database inception to October 2024,and a total of 95 articles were finally included for review.RESULTS AND CONCLUSION:Schwann cells interact with macrophages,T cells and other cells,to initiate the regeneration process through signaling pathways,including Krox20/C-Jun,NRG-1/ErbB,Notch,MAPK,and PI3K/Akt/mTOR,synthesize and release nerve growth factors,and thus promote regeneration of the peripheral nervous system.Schwann cells have been experimentally demonstrated to have great potential in peripheral nerve repair and are expected to become the key target of therapeutic intervention.However,there are still problems such as difficulties in cell harvest and culture,as well as the occurrence of other diseases during the treatment process.

ObjectiveTo explore the mechanism of ventricular remodeling mediated by the p38 mitogen-activated protein kinase （MAPK）/nuclear factor kappa B （NF-κB） signaling pathway in the rat model of chronic heart failure （CHF） with heart-blood stasis syndrome， as well as the intervention effect of Danhong injection. MethodsIn vivo experiment： SPF-grade male SD rats were assigned via the random number table method into 4 groups： Sham operation， model， captopril （8.8 mg·kg^-1）， and Danhong injection （6.0 mL·kg^-1）. The model of CHF with heart-blood stasis syndrome was established by abdominal aortic constriction， and the sham operation group only underwent laparotomy without constriction. All the groups were treated continuously for 15 days. The tongue color of rats was observed. Echocardiography， hemorheology， heart mass index （HMI）， and left ventricular mass index （LVMI） were measured. Hematoxylin-eosin （HE） staining and Masson staining were performed to observe the pathological and fibrotic changes of the myocardial tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify the levels of N-terminal pro-B-type natriuretic peptide （NT-proBNP）， interleukin-6 （IL-6）， angiotensin Ⅱ （AngⅡ）， tumor necrosis factor-α （TNF-α）， and Creactive protein （CRP） in the serum， as well as the levels of matrix metalloproteinase-2 （MMP-2） and matrix metalloproteinase-9 （MMP-9） in the myocardial tissue. Western blot was used to quantify the protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the myocardial tissue. In vitro experiment： H9C2 cardiomyocytes were treated with 1×10^-6 mol·L^-1 AngⅡ to establish a model of myocardial hypertrophy. H9C2 cardiomyocytes were allocated into normal， model， inhibitor + Danhong injection， Danhong injection （20 mL·L^-1）， and inhibitor （SB203580， 5 μmol·L^-1） groups. CCK-8 assay was used to detect the viability of H9C2 cardiomyocytes. Rhodamine-labeled phalloidin staining was used to reveal the area of cardiomyocytes. Real-time PCR was performed to determine the mRNA levels of atrial natriuretic peptide （ANP） and brain natriuretic peptide （BNP）. Western blot was used to assess the protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65. ResultsIn vivo experiment： Compared with the sham operation group， the model group showed purplish-dark tongue with decreased R， G， B values of the tongue surface （P<0.01）， increased whole blood viscosity （at low， medium， and high shear rates） （P<0.01）， decreased left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01）， increased left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， and left ventricular posterior wall thickness at end-diastole （LVPWd） （P<0.01）， raised LVMI and HMI （P<0.01）， and elevated levels of NT-proBNP， TNF-α， IL-6， and CRP in the serum and MMP-2 and MMP-9 in the myocardial tissue （P<0.01）. The HE and Masson staining of the myocardial tissue showed compensatory myocardial hypertrophy， fibrosis， and massive inflammatory cell infiltration in the model group. Additionally， the model group presented up-regulated protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the myocardial tissue （P<0.01）. Compared with the model group， each administration group showed increased R， G， B values of the tongue surface （P<0.05， P<0.01）， decreased whole blood viscosity （at low， medium， and high shear rates） （P<0.05， P<0.01）， increased LVEF and LVFS （P<0.01）， decreased LVIDd， LVIDs， and LVPWd （P<0.05， P<0.01）， declined LVMI and HMI （P<0.05， P<0.01）， and lowered levels of NT-proBNP， TNF-α， IL-6， and CRP in the serum and MMP-2 and MMP-9 in the myocardial tissue （P<0.01）. HE and Masson staining showed alleviated compensatory myocardial hypertrophy， reduced fibrosis， and decreased expression of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the myocardial tissue （P<0.01）. In vitro experiment： When the concentration of Danhong injection reached 20 mL·L^-1， the survival rate of H9C2 cardiomyocytes was the highest （P<0.01）. Compared with the normal group， the model group showed up-regulated mRNA levels of ANP and BNP （P<0.01）， increased relative cell surface area （P<0.01）， and raised protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 （P<0.01）. Compared with the model group， each administration group showed down-regulated mRNA levels of ANP and BNP （P<0.01）， reduced relative cell surface area （P<0.05， P<0.01）， and down-regulated protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 （P<0.05， P<0.01）. ConclusionDanhong injection can regulate ventricular remodeling through the p38 MAPK/NF-κB pathway， thereby exerting a protective effect on the rat model of CHF with heart-blood stasis syndrome.

Chronic heart failure （CHF） is a major global public health problem， and myocardial infarction is one of its main causes. The mouse model of heart failure induced by coronary artery ligation is widely used in the study of CHF， while the TCM syndrome attributes of this model have not yet been clarified. According to the theory of correspondence between prescriptions and syndromes， the method of syndrome identification by prescription efficacy is an important means of current syndrome research of animal models. This method deduces the syndrome characteristics of animal models through prescription efficacy. Taking the four basic syndrome elements of Qi， blood， Yin and Yang as the classification reference， this study used coronary artery ligation to construct a mouse model of CHF and treated the model with four representative TCM injections with the effects of replenishing Qi， warming Yang， nourishing Yin， and activating blood and enalapril. Echocardiography， tongue color parameters， histopathology， serum N-terminal pro-brain natriuretic peptide （NT-proBNP） and cardiac troponin Ⅰ （cTnⅠ） levels， and systematically explored the TCM syndrome attributes of this model. The results showed that the coronary ligation model presented an obvious cardiac function decline， myocardial fibrosis， infarct size expansion， and purple dark tongue， which were consistent with the basic syndrome characteristics of blood stasis in CHF. Danhong injection had significant effects of improving the cardiac function， alleviating myocardial fibrosis， and reducing serum NT-proBNP and cTnⅠ levels. Huangqi Injection and Shenfu injection can improve the cardiac function and tongue color parameters， with limited effects. The effect of Shenmai injection group was not obvious. This study verifies that the established model conforms to blood stasis syndrome through the method of syndrome identification by prescription efficacy， which provides an experimental basis for the study of TCM syndrome mechanism of CHF.

BACKGROUND:Peripheral nerve axon rupture seriously affects patients' physical function and mental health.Microsurgery,nerve autograft,nerve allograft,fibrin glue and catheter technology are the main treatments for peripheral nerve injury,each of which has its own advantages and disadvantages,but the overall treatment effect is not satisfactory.Despite the clinical success of Schwann cells in promoting axonal regeneration,there are still many challenges in the treatment with Schwann cells,such as slow expansion of Schwann cells,immune rejection,and low survival rate of transplanted cells.OBJECTIVE:To summarize the role and mechanism of Schwann cells in promoting the regeneration of peripheral nerve axons,and the difficulties and challenges of Schwann cells in the process of nerve regeneration treatment.METHODS:PubMed,Medline,WanFang,VIP,and CNKI were searched by computer using the search terms of"Schwann cells,synaptic Schwann cell,macrophage,peripheral nerve axon rupture,Wallerian degeneration,Peripheral nerve axon regeneration,Central nervous system repair"in English and Chinese.Literature related to Schwann cell proliferation and differentiation,promotion of peripheral nerve regeneration,and clinical applications was retrieved from database inception to October 2024,and a total of 95 articles were finally included for review.RESULTS AND CONCLUSION:Schwann cells interact with macrophages,T cells and other cells,to initiate the regeneration process through signaling pathways,including Krox20/C-Jun,NRG-1/ErbB,Notch,MAPK,and PI3K/Akt/mTOR,synthesize and release nerve growth factors,and thus promote regeneration of the peripheral nervous system.Schwann cells have been experimentally demonstrated to have great potential in peripheral nerve repair and are expected to become the key target of therapeutic intervention.However,there are still problems such as difficulties in cell harvest and culture,as well as the occurrence of other diseases during the treatment process.

BACKGROUND:Previous studies have demonstrated that acupuncture at the governor meridian has precise efficacy in the treatment of ischemic stroke and can improve cerebral ischemia-reperfusion injury by attenuating pyroptosis,but the upstream regulatory mechanisms are not yet fully clarified.OBJECTIVE:To observe the neuroprotective effect of electroacupuncture in model rats of cerebral ischemia-reperfusion injury.METHODS:Twenty-seven Sprague-Dawley rats were randomly divided into sham surgery,model,and electroacupuncture groups,with nine rats in each group.Modified suture method was used to establish cerebral ischemia-reperfusion model rats in the model and electroacupuncture groups.The electroacupuncture group was subjected to electroacupuncture at"Baihui,""Fengfu,"and"Dazhui"acupoints,20 minutes each,once a day,for 7 consecutive days.After treatment,neurological deficit scoring and pole test were performed to assess behavioral changes.Tri-phenyl tetrazolium chloride staining was used to assess cerebral infarction size in rats.Hematoxylin-eosin staining was performed to observe morphological changes in cerebral cortex tissue on the infarcted side of rats.Immunofluorescence analysis was used to determine Iba-1 and reactive oxygen species levels in cerebral cortex tissue on the infarcted side of rats,ELISA method was used for measuring interleukin-1β,interleukin-6 and tumor necrosis factor α levels in cerebral cortex tissue on the infarcted side of rats.Real-time fluorescence quantitative PCR and western blot were used to detect mRNA and protein expression levels of thioredoxin interaction protein,nod-like receptor associated protein 3(NLRP3),Caspase-1 and interleukin-1β in cerebral cortex tissue on the infarcted side of rats respectively,and the interaction between thioredoxin interaction protein and NLRP3 was analyzed by immunoprecipitation.RESULTS AND CONCLUSION:(1)Compared with the sham surgery group,rats in the model group showed an increase in neurological deficit score,pole test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining in the model group showed neuronal degeneration and necrosis,with fragmented and dissolved nuclei and cellular vacuoles.(2)Compared with the model group,rats in the electroacupuncture group showed a reduction in neurological deficit score,pole climbing test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining showed that the pathological damage of neurons in cerebral cortex tissue on the infarcted side of rats in the electroacupuncture group was significantly attenuated,with significantly reduced cell necrosis and vacuolation.(3)Immunoprecipitation assay showed an interaction between thioredoxin interaction proteins and NLRP3 in the cerebral cortical tissues on the infarcted side of rats in the model group.To conclude,electroacupuncture has a significant therapeutic effect against cerebral ischemia-reperfusion injury,possibly by inhibiting the reactive oxygen species/thioredoxin interaction protein/NLRP3 cell pyroptosis signaling pathway and activation of microglia to reduce the release of inflammatory factors.

BACKGROUND:Previous studies have demonstrated that acupuncture at the governor meridian has precise efficacy in the treatment of ischemic stroke and can improve cerebral ischemia-reperfusion injury by attenuating pyroptosis,but the upstream regulatory mechanisms are not yet fully clarified.OBJECTIVE:To observe the neuroprotective effect of electroacupuncture in model rats of cerebral ischemia-reperfusion injury.METHODS:Twenty-seven Sprague-Dawley rats were randomly divided into sham surgery,model,and electroacupuncture groups,with nine rats in each group.Modified suture method was used to establish cerebral ischemia-reperfusion model rats in the model and electroacupuncture groups.The electroacupuncture group was subjected to electroacupuncture at"Baihui,""Fengfu,"and"Dazhui"acupoints,20 minutes each,once a day,for 7 consecutive days.After treatment,neurological deficit scoring and pole test were performed to assess behavioral changes.Tri-phenyl tetrazolium chloride staining was used to assess cerebral infarction size in rats.Hematoxylin-eosin staining was performed to observe morphological changes in cerebral cortex tissue on the infarcted side of rats.Immunofluorescence analysis was used to determine Iba-1 and reactive oxygen species levels in cerebral cortex tissue on the infarcted side of rats,ELISA method was used for measuring interleukin-1β,interleukin-6 and tumor necrosis factor α levels in cerebral cortex tissue on the infarcted side of rats.Real-time fluorescence quantitative PCR and western blot were used to detect mRNA and protein expression levels of thioredoxin interaction protein,nod-like receptor associated protein 3(NLRP3),Caspase-1 and interleukin-1β in cerebral cortex tissue on the infarcted side of rats respectively,and the interaction between thioredoxin interaction protein and NLRP3 was analyzed by immunoprecipitation.RESULTS AND CONCLUSION:(1)Compared with the sham surgery group,rats in the model group showed an increase in neurological deficit score,pole test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining in the model group showed neuronal degeneration and necrosis,with fragmented and dissolved nuclei and cellular vacuoles.(2)Compared with the model group,rats in the electroacupuncture group showed a reduction in neurological deficit score,pole climbing test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining showed that the pathological damage of neurons in cerebral cortex tissue on the infarcted side of rats in the electroacupuncture group was significantly attenuated,with significantly reduced cell necrosis and vacuolation.(3)Immunoprecipitation assay showed an interaction between thioredoxin interaction proteins and NLRP3 in the cerebral cortical tissues on the infarcted side of rats in the model group.To conclude,electroacupuncture has a significant therapeutic effect against cerebral ischemia-reperfusion injury,possibly by inhibiting the reactive oxygen species/thioredoxin interaction protein/NLRP3 cell pyroptosis signaling pathway and activation of microglia to reduce the release of inflammatory factors.

This study was aimed atanalyzing the epidemic characteristics of dengue fever in Ruili City atthe China-Myanmar bor-der in late 2023,to provide evidence for local dengue fever prevention and control measures.Adult Aedes mosquitoes were collected from Ruili City with a backpack type mosquito sucking machine in October of 2023.Serum samples frompatients with suspected den-gue were collected in acutephase,in November of 2023.Detection ofdengue virus(DENV)nucleic acids in Aedesmosquitoes and acute phase serum samples from suspected dengue fever patients using reverse transcription-polymerase chain reaction,and nucleic acid positive samples were inoculated into Vero cells for viral culture.After three consecutive blind passage,samples with cytopathic effect(CPE)were collected for be sequencingand analysisof genetic and evolutionary information.Dengue case characteristics were analyzed through descriptive epidemiological methods.Among the 109 cases of dengue fever,the ratio of males to females was 1.27∶1.The youngest patient was 1 year old,the oldest patient was 84 years old,the age group of 20～59 years accounted for 73.39%,and the major-ity of occupations were freelancer(40.37%).A total of 827 female Aedes albopictus and 312 Aedes aegypti were collected,all of which tested negative for DENV nucleic acid.109 serum samples tested positive for DENV nucleic acid,including 49 DENV-1 and 60 DENV-2.Moreover,five DENV-1 and nine DENV-2 samples were obtainedthrough third-generation blind passaging with CPE.The E gene sequences of these five DENV-1 strains were detected,all were found to belong to DENV-1 genotype I,and had same evolu-tionary branch as the 2023 Guangzhou,China(PP563911),the 2019 Myanmar(MW793710),and 2019 Attapeu,Laos(MW559046).The nucleotide and amino acid sequence similarityamong the five DENV-1 genotype was 99.4%-99.9%and 99.8%-100.0%.Compared with the aforementioned epidemic strains,their nucleotide similarities were 99.5%-100.0%,99.4%-99.6%and 99.3%-99.5%,respec-tively,and amino acid similarity was 99.8%-100.0%.Nine DENV-2 E gene sequences were of Asian genotype I and belonged to the same evolutionary branch as the 2018 Myanmar(MW788982),2019 Hangzhou(OP684212)and 2019 Ruili(OQ928150).The nucleotide and amino acid similarities of the nine samples were 99.5%-100.0%and 99.8%-100.0%,respectively.Compared with the aforementioned epidemic strains,their nucleotide similarities were 99.7%-100.0%,99.3%-99.7%and 99.3%-99.7%,respectively,and the amino acid similarity was 99.8%-100%,99.8%-100.0%and 99.4%-99.6%,respectively.Two dengue vectors,Aedes albopictus and Aedes aegypti,were present in Ruili city,and the dengue outbreak was caused primarily by DENV-1 genotype I and DENV-2 Asian genotype I in later 2023.The sources of DENV-1 were probably the same as those of DENV-1 with Guangzhou(2023),and the sources of DENV-2 were probably from Myanmar.Dengue cases were found primarilyin the 20-59 year age group and freelancers,thus suggesting that relevant local departments should strengthen surveillance of dengue imported case and vector.

Objective To investigate how dietary supplementation with tetrahydrocurcumin(THC)improves kidney injury in type 2 dia-betic mellitus(T2DM)and its mechanism of action using transcriptome sequencing(RNA-seq).Methods C57BL/6J mice were randomly assigned to the control,T2DM,and T2DM+THC groups.After a high-fat meal and streptozotocin injection,the body weights and fasting blood glucose levels of each mouse with T2DM were measured.Hematoxylin and eosin staining,Oil red O staining,and RNA-seq were performed to examine kidney pathology,lipid deposition,and differentially expressed genes,respectively,in the mice.Results Mice in T2DM group exhibited significantly higher fasting blood glucose levels(P＜0.001),renal tubule degeneration,glomeruli enlargement,disordered epithelial cells,and increased kidney lipid deposition after 12 weeks compared with those of the control group.THC adminis-tration alleviated all these conditions(P＜0.001).RNA-seq analysis revealed significant gene expression variations among the control,T2DM,and T2DM+THC groups.THC may protect against T2DM-induced kidney injury and lipid deposition by regulating the cell cycle(apoptosis),P53 signaling pathway,and PPARγ signaling path way,as indicated by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.In mice with T2DM,THC intervention may upregulate the expression of Cd36,Lpl,PPARγ,and Plin4 genes in renal tissues,while downregulating Ccnb1,Ccnb2,Cdk1,Bub1,and Cdc25c gene expressions.The proteins encoded by the four upregulated genes interact,as do those encoded by the five downregulated genes.Conclusion THC administration improves fasting blood glucose levels,reduces renal damage,and decreases fat deposition in mice with T2DM.The processes may involve decreasing apoptosis,blocking the P53 signaling pathway,and activating the PPARγ signaling pathway.

Objective This study aims to explore the efficacy of tetrahydrocurcumin(THC),the major active metabolite of curcumin,on high glucose(HG)-induced human platelet aggregation and activation as well as to clarify the underlying mechanisms in vitro.Methods Purified platelets prepared from healthy subjects were pre-incubated with various concentrations of THC(0.5 μmol/L,1 μmol/L or 10 μmol/L)or vehicle control(0.05％DMSO)for 40 min at 37℃,followed by the stimulation of normal glucose(NG,5 mmol/L)or HG(25 mmol/L)for additional 90 min.The maximal aggregation rate was determined by an aggregometer.Flow cytometry was used to measure platelet surface expression of CD62P(a typical marker of platelet activation)and generation of total intraplatelet reactive oxygen species(ROS).Meanwhile,the phosphorylation level of platelet p53 was detected by Western blot assay.Results Compared with NG group,HG intervention significantly increased platelet aggrega-tion(P<0.05)and CD62P expression(P<0.001),which were greatly inhibited by different concentrations of THC(P<0.05).Mechanistically,when compared with solvent control,THC significantly decreased the level of total ROS production(P<0.001)and p53 phosphorylation(P<0.05).In addition,HG-induced total intraplatelet ROS generation(P<0.001)and p53 phosphorylation(P<0.05)were greatly attenuated by adding a ROS scavenger N-acetyl-L-cysteine(NAC).The combination of NAC with THC(10 μmol/L)showed no additive inhibitory effects(P>0.05).Moreover,platelet aggregation and activation induced by HG were greatly decreased by NAC and a p53 specific inhibitor PFT-μ(P<0.05).The combination of THC(10 μmol/L)and NAC resulted no additive inhibitory effects on HG-increased platelet aggregation and activation(P>0.05).THC(10 μmol/L)exhibited additive inhibitory effects on platelet aggregation(P<0.05)but no additive inhibitory effects on platelet activation when combined with PFT-μ(P>0.05).Conclusions THC exerts a protective effect on HG-induced platelet aggregation and activation possibly through down-regulating ROS/p53 signaling pathway in human platelets in vitro.The current study may provide potential value for THC to improve thrombosis in diabetes mellitus and the related chronic metabolic diseases.

BACKGROUND:Synovitis is involved in all stages of osteoarthritis and is a key factor contributing to the development of osteoarthritis.Studies have shown that circular RNA(circRNA)plays an important role in the proliferation,apoptosis and extracellular matrix degradation of synovial cells and chondrocytes.OBJECTIVE:To observe the effects of circRNA SEC24A on the interleukin-1β-induced proliferation,apoptosis,and expression of inflammatory factors in human synovial fibroblasts.METHODS:Human synovial fibroblasts were divided into four groups,including control group,interleukin-1β group,empty vector group,and sh-circSEC24A group.Except for the control group,the other three groups were induced with 10 ng/mL interleukin-1β for 24 hours to establish inflammatory cell models;the empty vector group and sh-circSEC24A group were infected with empty vector virus and lentiviral vector knocking down circSEC24A.CCK-8 assay was used to detect cell proliferation.Flow cytometry was used to detect cell apoptosis.ELISA was used to detect the levels of matrix metalloproteinase-9,matrix metalloproteinase-13,interleukin-6,and tumor necrosis factor-α in cell supernatant.Western blot assay was used to detect the relative expression levels of Bax,Bcl-2,matrix metalloproteinase-9,matrix metalloproteinase-13,casepase3,cleaved-casepase3,casepase8,and cleaved-casepase8 proteins in cells.RESULTS AND CONCLUSION:(1)qRT-PCR results showed that compared with the normal group,the expression of circSEC24A in human synovial fibroblasts induced by interleukin 1β was significantly up-regulated.(2)The absorbance value of cells in the sh-circSEC24A group detected by CCK-8 assay was significantly higher than that of interleukin 1β group and empty vector group(P＜0.05).The apoptosis rate of sh-circSEC24A group detected by flow cytometry was significantly lower than that of interleukin 1β group and empty vector group(P＜0.05).(3)The levels of tumor necrosis factor α and interleukin 6 in the supernatant of human synovial fibroblasts in the sh-circSEC24A group detected by ELISA were significantly lower than those in the interleukin 1β group and the empty vector group(P＜0.01,P＜0.001).(4)Western blot assay results showed that compared with the interleukin 1β group and the empty vector group,the expression of the pro-apoptotic factor Bax protein in the sh-circSEC24A group significantly decreased,and the expression of the anti-apoptotic factor Bcl-2 protein increased significantly(P＜0.05);apoptosis and related activating factors cleaved-casepase3 and cleaved-casepase8 protein expressions were both reduced(P＜0.05).(5)ELISA and western blot assay results showed that compared with the interleukin 1β group and the empty vector group,the sh-circSEC24A group had lower levels of matrix metalloproteinase 9 and matrix metalloproteinase 13 protein(P＜0.05).These findings indicated that the expression of circSEC24A was abnormally increased in human synovial fibroblasts induced by interleukin 1β.Knocking down circSEC24A expression could promote the proliferation of human synovial fibroblasts and inhibit apoptosis,inflammatory factor release,and extracellular matrix degradation,suggesting that circSEC24A may be an important intervention target for early osteoarthritis.