ObjectiveTo investigate whether Carthamus tinctorius L.-derived nanovesicles （CDNVs） can alleviate angiotensin Ⅱ （ANGⅡ）-induced cardiomyocyte （H9C2） hypertrophy by inhibiting the NF-κB signaling pathway and to elucidate the underlying molecular mechanisms. MethodsCDNVs were isolated and purified by ultracentrifugation combined with sucrose density gradient centrifugation， and their morphology and particle size distribution were identified by transmission electron microscopy and nanoparticle tracking analysis. Rat H9C2 cardiomyocytes were cultured in vitro and randomly divided into the normal control group （NC）， ANGⅡ （1.0 μmol/L） group， ANGⅡ+CDNVs group， and ANGⅡ+CDNVs+NF-κB activator 1 group. After 24 h of intervention， cell viability was detected by the CCK-8 assay， the expression of myocardial hypertrophy-related genes （ANP， BNP） was determined by qPCR， the relative cell area was measured by phalloidin staining， the expression of hypertrophy marker proteins and NF-κB pathway proteins （P-p65/p65， P-IκBα/IκBα） was examined by Western blot， and nuclear translocation of p65 was observed by immunofluorescence. Subsequently， NF-κB signaling pathway agonist activator 1 was added， and the expression of myocardial hypertrophy marker proteins and NF-κB pathway proteins was detected. ResultsCDNVs exhibited a typical round-like vesicle structure with an average particle size of 140.4 nm， which was consistent with the morphological characteristics of exosomes. ANGⅡ at concentrations of 0.1-1.0 μmol/L had no significant effect on cardiomyocyte viability. Compared with the NC group， ANGⅡ significantly upregulated the gene expression of ANP and BNP， increased the relative surface area of cardiomyocytes， elevated the levels of myocardial hypertrophy marker proteins and NF‑κB pathway proteins， and promoted the nuclear translocation of p65 （P<0.05）. Following treatment with CDNVs， all the above indicators were markedly reduced in comparison with the ANGⅡ group （all P<0.05）. However， all these experimental results were reversed after the addition of an NF‑κB agonist. ConclusionCDNVs alleviate ANGⅡ-induced H9C2 cell hypertrophy by inhibiting the NF-κB signaling pathway.

ObjectiveTo investigate the protective effect of Astragaloside Ⅳ （AS-Ⅳ） on D-galactose （D-gal）-induced cardiomyocytes senescence and its potential mechanisms. MethodsUsing H9C2 cardiomyocytes as a model， D-gal was used to induce cardiomyocyte senescence. Cell viability was assessed using the CCK-8 assay， senescenceextent was evaluated via β-galactosidase （SA-β-Gal） staining， reactive oxygen species （ROS） levels were measured to assess intracellular oxidative stress， apoptosis extent was determined using the TUNEL assay， and qRT-PCR and Western blot analyses were conducted to examine the expression levels of senescence-related genes and proteins （p21、p53） and key genes （STING， CXCL10， and MX-1） and proteins （STING， cGAS， p-IRF3/IRF3） of the stimulator of interferon genes （STING） pathway. ResultsThe 50 g/L D-gal significantly reduced myocardial cell viability， increased SA-β-Gal positivity， apoptosis rate， and intracellular reactive oxygen species levels， and upregulated the expression of p16， p21， and STING， cGAS， p-IRF3/IRF3 pathway proteins （P< 0.05）； After intervention with 200 μmol/L of AS-Ⅳ， cell viability was significantly enhanced， the SA-β-Gal-positive rate decreased， intracellular reactive oxygen species levels decreased， oxidative stress damage was alleviated， myocardial cell apoptosis was inhibited， and the mRNA and protein levels of aging-related p21 and p53 were downregulated （P＜0.05）. Further detection of STING pathway-related molecules showed that 200 μmol/L of AS-IV inhibited D-galactose-induced STING mRNA and protein expression and reduced p-IRF3/IRF3 protein expression levels， as demonstrated by qRT-PCR and Western blot results. However， the SA-β-Gal positivity rate， intracellular reactive oxygen species （ROS） levels， DNA damage results， and Western blot findings suggested that the STING agonist （STING agonist-7） could reverse the ameliorative effects of AS-Ⅳ on D-galactose-induced cardiomyocytes senescence. ConclusionAS-Ⅳ may mitigate D-gal-induced cardiomyocytes senescence by inhibiting STING pathway activation， providinga new strategy for the prevention and treatment of cardiovascular senescence-related diseases.

Objective To analyze the efficacy and safety of denosumab(DEN)in the treatment of type 2 diabetes mellius(T2DM)complicated with osteoporosis(OP).Methods The DEN's efficacy on bone metabolism and glucose metabolism in patients with T2DM and OP was retrospectively analyzed through a before-and-after self-controlled design.Forty-one T2DM patients combined with OP who were treated in The First Hospital of Changsha from January 2022 to December 2022 were selected.All patients were observed with subcutaneous injection of DEN 60 mg every 6 months for 12 months.The changes of HbA1c,FPG,bone metabolism indexes,25-hydroxyvitamin D[25(OH)D]and bone mineral density(BMD)of patients before and after DEN treatment were compared.The adverse reactions of DEN were recorded.Results After 12 months of treatment,25(OH)D,the BMD oflumbar vertebra(L1～4),left femoral neck and left hip were higher than before treatment(P<0.05),while the osteocalcin,β-collagen special series,parathyroid hormone and alkaline phosphatase were lower than before treatment(P<0.05),and the adverse reactions were reduced.Conclusions DEN can significantly improve bone metabolism in patients with T2DM and osteoporosis,increase BMD of lumbar spine and whole hip with fewer adverse reactions.

Objective To analyze the efficacy and safety of denosumab(DEN)in the treatment of type 2 diabetes mellius(T2DM)complicated with osteoporosis(OP).Methods The DEN's efficacy on bone metabolism and glucose metabolism in patients with T2DM and OP was retrospectively analyzed through a before-and-after self-controlled design.Forty-one T2DM patients combined with OP who were treated in The First Hospital of Changsha from January 2022 to December 2022 were selected.All patients were observed with subcutaneous injection of DEN 60 mg every 6 months for 12 months.The changes of HbA1c,FPG,bone metabolism indexes,25-hydroxyvitamin D[25(OH)D]and bone mineral density(BMD)of patients before and after DEN treatment were compared.The adverse reactions of DEN were recorded.Results After 12 months of treatment,25(OH)D,the BMD oflumbar vertebra(L1～4),left femoral neck and left hip were higher than before treatment(P<0.05),while the osteocalcin,β-collagen special series,parathyroid hormone and alkaline phosphatase were lower than before treatment(P<0.05),and the adverse reactions were reduced.Conclusions DEN can significantly improve bone metabolism in patients with T2DM and osteoporosis,increase BMD of lumbar spine and whole hip with fewer adverse reactions.