ObjectiveTo investigate the protective effect of genistein （Gen） on etoposide-induced chondrocyte senescence and its underlying mechanism. MethodsThe C28/I2 cell line was treated with different concentrations of Gen and etoposide， and the cell viability was detected by the CCK-8 assay. The senescence model of C28/I2 chondrocytes was induced by etoposide， with Gen intervention. Senescence-associated β-galactosidase （SA-β-gal） staining was performed to detect the senescence-positive rate and staining characteristics of chondrocytes. The expressions of peroxiredoxin 6 （Prdx6）， cyclin-dependent kinaseto clarify the functional necessity of Prdx6. ResultsCompared with the etoposide group， the C28/I2 chondrocyte viability significantly increased （P<0.01）， the expression ofsenescence-associated proteins p21 and p16 decreased （P<0.01， P<0.05）， the expression of senescence-associated genes p21 and p16 reduced （both P<0.01）， the fluorescence intensity of senescence-associated proteins p21 and p16 was diminished （P<0.05， P<0.01）， and the proportion of SA-β-gal-positive cells decreased （P<0.01） in the Gen+etoposide group. Compared with the Control group， the expression of Prdx6 was downregulated in the etoposide group （P<0.05）. Compared with the etoposide group， the expression of Prdx6 was upregulated in the Gen+etoposide group （P<0.01）. Compared with the Control group， the GPx activity significantly decreased in the si-Prdx6 group （P<0.01）. Furthermore， compared with the si-Prdx6 group， the GPx activity increased in the si-Prdx6+Gen group （P<0.05）. Molecular docking results revealed that Gen formed hydrogen bond interactions with the active site of Prdx6. After Prdx6 knockdown， the expression of senescence-associated genes p21 and p16 and the fluorescence intensity of senescence-associated proteins p21 and p16 both increased in the Gen+etoposide+si-Prdx6 group （both P<0.01）. ConclusionGen can inhibit etoposide-induced senescence of C28/I2 chondrocytes by upregulating the expression of Prdx6. This study provides potential drug targets and experimental basis for the prevention and treatment of chondrocyte senescence-related diseases.

Objective To analyze the trends in the disease burden of tracheal, bronchus, and lung cancer (TBL) in China and in low-, middle-, and high-socio-demographic index (SDI) countries and regions from 1990 to 2021, with the aim of providing evidence for the formulation of targeted prevention and control strategies. Methods Utilizing data from the Global Burden of Disease (GBD) Study 2021, we extracted TBL-related data from 1990 to 2021, stratified by sex, age group, and year. We assessed the disease burden and trends of TBL across different groups, conducted a decomposition analysis to identify the leading contributors to the change in disease burden, and examined the relationship between disability-adjusted life years (DALYs) and SDI. Results In 2021, the overall burden of TBL in China was substantially higher than that in other groups. The fold-increase in the number of prevalent cases, deaths, and DALYs was significantly greater in China. Moreover, the growth rates of the age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR) in China were higher than the overall levels in other SDI countries. In all groups, the ASPR of TBL generally followed a pattern of increasing and then decreasing with age; however, for males in China and middle-SDI countries, the ASPR exhibited a decline in the 80-84 age group. Decomposition analysis revealed that the primary drivers of the increasing TBL burden varied among groups: the rise in DALYs in China and middle-SDI countries was mainly driven by population aging, in low-SDI countries by population growth, and in high-SDI countries by epidemiological transition. While global health inequality in TBL showed some improvement, low-SDI countries continued to bear a disproportionately heavy health burden. Conclusion The disease burden of TBL in China has progressively increased from 1990 to 2021, now ranking among the highest globally. Multiple factors, predominantly driven by population aging, are exacerbating this burden. The burden of TBL is influenced by advancing age, sex differences, and SDI levels. China, along with low- and middle-SDI countries, should implement targeted intervention strategies based on epidemiological findings, including expanding investment in public health services and strengthening healthcare systems, to mitigate the growing burden of TBL.

ObjectiveTo investigate the effects and mechanisms of pulchinenoside A （PSA） on tumor necrosis factor-α （TNF-α） -induced abnormal proliferation， migration， and invasion of synovial fibroblasts. MethodsA synovitis model was established by stimulating SW982 synovial cells with TNF-α. The low-density lipoprotein receptor-related protein 1 （LRP1） was knocked down using LRP1-specific siRNA or inhibited by the receptor-associated protein （RAP）. Cells were treated with various concentrations of PSA， and cell viability was assessed by CCK-8 assay. Protein levels of LRP1， matrix metalloproteinase-3 （MMP3）， and N-cadherin were measured by Western blotting. Proliferation was evaluated using an EdU incorporation assay. Migration and invasion capacities were examined by Transwell and wound-healing assays. mRNA expression of LRP1， MMP3， N-cadherin， IL-1β， IL-6， and TNF-α was detected by reverse transcription quantitative real-time PCR （RT-qPCR）. Immunofluorescence staining was used to visualize the expression of MMP3 and N-cadherin. The involvement of LRP1 was further verified with the inhibitor RAP. ResultsCompared with the TNF-α-treated model group， PSA treatment significantly reduced SW982 cell viability （P<0.05）， downregulated MMP3 and N-cadherin expression （both P<0.01）， and decreased the proportion of EdU-positive cells （P<0.05）. Moreover， TNF-α stimulation upregulated LRP1 expression compared with normal controls （P<0.01）， whereas PSA treatment reversed this increase （P<0.05）. LRP1 knockdown or inhibition markedly decreased MMP3 and N-cadherin levels compared with the model group （both P<0.01）. Similarly， the combination of PSA and RAP led to significant reductions in MMP3 and N-cadherin expression compared with the model group （both P<0.01）. ConclusionPSA inhibits TNF-α-induced abnormal proliferation， migration， and invasion of synovial， at least in part， by downregulating LRP1 expression.

Objective To compare the safety and efficacy of directional atherectomy with anti-restenosis therapy(DAART,drug-coated balloon)versus conventional balloon angioplasty(bare-metal stent,BMS)in elderly patients with femoropopliteal artery disease.Methods A retrospec-tive cohort study was conducted on 116 elderly patients undergoing endovascular intervention due to femoropopliteal artery disease in our hospital between May 2016 and September 2019,divided into DAART group(57 cases)and BMS group(59 cases).Results No statistical differences were observed between the DAART and BMS groups in terms of age,risk factors,distribution of Ruth-erford classification,lesion length,lesion type,lesion location,Global Limb Anatomic Staging Sys-tem grade,infra-popliteal runoff status,or preoperative ankle-brachial index(P＞0.05).However,the BMS group had significantly larger proportion of chronic limb-threatening ischemia than the other group(P＜0.05).Both groups achieved a 100％success rate of surgery.The DAART group obtained obviously higher primary patency rates at 1 and 2 years than the BMS group(90.4％vs 75.0％,76.3％vs 57.3％;P＜0.045).There were no significant differences in the rate of freedom from target lesion revascularization at 1 and 2 years between the two group(96.1％vs 88.8％,91.6％vs 77.7％;P＞0.05).In 2 years of follow-up,the incidence of major adverse events was 10.0％(5 cases)in the DAART group and 20.8％(12 cases)in the BMS group,but no obvious difference(P＞0.05).Conclusion DAART demonstrates superior mid-term efficacy than BMS in treating femoropopliteal artery disease in elderly patients.However,comprehensive preoperative assessment is essential to optimize individualized treatment strategies for this population.

Objective To investigate the efficacy and safety of transcutaneous electrical acupoint stimulation(TEAS)in reducing the consumption of analgesics after total knee arthroplasty(TKA).Methods Totally 124 patients undergoing unilateral TKA were included and divided into an intervention group and a control group according to random number table method,with 62 cases in each group.Both groups received routine postoperative analgesic protocols,with the intervention group additionally receiving TEAS treatment,30 min per time,twice a day.The additional doses of intravenous patient-controlled analgesia pumps and opioid analgesic consumption in two groups of patients after surgery were analyzed,as well as the adverse events and laboratory test results(WBC,PLT,SCr,BUN,ALT and AST)in both groups.Results The number of additional doses in the intervention group with the patient-controlled analgesia pump and the consumption of opioid analgesic were both lower than those in the control group(P<0.05);the incidence of postoperative nausea symptoms in the intervention group was lower than that in the control group,while other adverse reactions showed no significant difference(P>0.05).There was no significant difference in laboratory test results(WBC,PLT,SCr,BUN,ALT and AST)between the two groups on the day before surgery and on the 1st and 7th days after surgery(P>0.05).Conclusion TEAS can reduce the consumption of analgesics after TKA,decrease some adverse reactions associated with the use of analgesics,and has good safety.

Objective : To explore the effects and mechanisms of Kobophenol A ( KPA) on lipopolysaccharide ( LPS) -induced M1 macrophage polarization，and to provide a theoretical basis for the treatment of inflammatory immune diseases and the development of new drugs． Methods: The M1 macrophage polarization model of RAW264. 7 was established by LPS induction，and the peroxiredoxin 6 ( Prdx6) knockdown model was constructed using the Prdx6 inhibitor MJ33 and Prdx6-siRNA．RAW264. 7 cells，a mouse macrophage cell line，were treated with various concentrations of KPA． Cell viability was assessed using the CCK-8 assay．The expression levels of Prdx6 and M1 macrophage polarization-related proteins，including inducible nitric oxide synthase ( iNOS) and cyclooxygenase-2 ( COX-2) ，were detected by Western blot and immunofluorescence staining．The expression levels of Prdx6 and M1 macrophage polarization-related genes iNOS，interleukin-6 ( IL-6) ，and tumor necrosis factor α ( TNF-α) ，were measured by RT-qPCR. Flow cytometry was employed to detect the expression of cluster of differentiation 86 ( CD86) ，a marker of M1 macrophages． Results: Compared with the LPS-induced M1 macrophage polarization model ， KPA significantly reversed the morphological changes of M1 macrophage polarization in RAW264. 7 macrophages and decreased the expression of M1 macrophage polarization-related proteins iNOS，COX- 2，CD86 and related genes iNOS，IL-6，TNF-α ( all P＜0. 05) ．In addition，LPS significantly downregulated the expression of Prdx6 in RAW264. 7 macrophages，while KPA upregulated the expression of Prdx6．Moreover，treatment with the Prdx6 inhibitor MJ33 significantly upregulated the expression of iNOS，a marker of M1 macrophage polarization，in RAW264. 7 macrophages，whereas treatment with KPA significantly downregulated the expression of iNOS ( all P＜0. 05) ． Conclusion KPA inhibits LPS-induced M1 polarization of RAW264. 7 macrophages by upregulating the expression of Prdx6．

Objective To investigate the efficacy and safety of transcutaneous electrical acupoint stimulation(TEAS)in reducing the consumption of analgesics after total knee arthroplasty(TKA).Methods Totally 124 patients undergoing unilateral TKA were included and divided into an intervention group and a control group according to random number table method,with 62 cases in each group.Both groups received routine postoperative analgesic protocols,with the intervention group additionally receiving TEAS treatment,30 min per time,twice a day.The additional doses of intravenous patient-controlled analgesia pumps and opioid analgesic consumption in two groups of patients after surgery were analyzed,as well as the adverse events and laboratory test results(WBC,PLT,SCr,BUN,ALT and AST)in both groups.Results The number of additional doses in the intervention group with the patient-controlled analgesia pump and the consumption of opioid analgesic were both lower than those in the control group(P<0.05);the incidence of postoperative nausea symptoms in the intervention group was lower than that in the control group,while other adverse reactions showed no significant difference(P>0.05).There was no significant difference in laboratory test results(WBC,PLT,SCr,BUN,ALT and AST)between the two groups on the day before surgery and on the 1st and 7th days after surgery(P>0.05).Conclusion TEAS can reduce the consumption of analgesics after TKA,decrease some adverse reactions associated with the use of analgesics,and has good safety.

Objective To compare the safety and efficacy of directional atherectomy with anti-restenosis therapy(DAART,drug-coated balloon)versus conventional balloon angioplasty(bare-metal stent,BMS)in elderly patients with femoropopliteal artery disease.Methods A retrospec-tive cohort study was conducted on 116 elderly patients undergoing endovascular intervention due to femoropopliteal artery disease in our hospital between May 2016 and September 2019,divided into DAART group(57 cases)and BMS group(59 cases).Results No statistical differences were observed between the DAART and BMS groups in terms of age,risk factors,distribution of Ruth-erford classification,lesion length,lesion type,lesion location,Global Limb Anatomic Staging Sys-tem grade,infra-popliteal runoff status,or preoperative ankle-brachial index(P＞0.05).However,the BMS group had significantly larger proportion of chronic limb-threatening ischemia than the other group(P＜0.05).Both groups achieved a 100％success rate of surgery.The DAART group obtained obviously higher primary patency rates at 1 and 2 years than the BMS group(90.4％vs 75.0％,76.3％vs 57.3％;P＜0.045).There were no significant differences in the rate of freedom from target lesion revascularization at 1 and 2 years between the two group(96.1％vs 88.8％,91.6％vs 77.7％;P＞0.05).In 2 years of follow-up,the incidence of major adverse events was 10.0％(5 cases)in the DAART group and 20.8％(12 cases)in the BMS group,but no obvious difference(P＞0.05).Conclusion DAART demonstrates superior mid-term efficacy than BMS in treating femoropopliteal artery disease in elderly patients.However,comprehensive preoperative assessment is essential to optimize individualized treatment strategies for this population.

Objective:To evaluate the relationship between the mechanism of buprenorphine in attenuating neuroinflammation in microglia and the MAM domain-containing glycosylphosphatidylinositol anchor gene 1 ( MDGA1). Methods:The human microglial cell line HMC-3 was cultured in vitro and divided into 4 groups ( n=6 each) using a table of random numbers: control group (Con group), lipopolysaccharide(LPS)group, buprenorphine + LPS group (Bup+ LPS group) and buprenorphine + LPS + MDGA1 knockdown group (Bup+ LPS+ shMDGA1 group). LPS group was incubated with LPS at a final concentration of 1 μg/ml for 4 h. Bup+ LPS group was incubated with buprenorphine at a final concentration of 100 ng/ml for 1 h, followed by incubation with LPS at a final concentration of 1 μg/ml for 4 h. Bup+ LPS+ shMDGA1 group was transfected with MDGA1-specific shorthairpin RNA for knockdown, and the remaining treatment was similar to those previously described in Bup+ LPS group. The expression of MDGA1 in microglia was detected using real-time quantitative polymerase chain reaction, and the concentrations of interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) in the supernatant were measured using enzyme-linked immunosorbent assay. Results:Compared with Con group, the concentrations of IL-6, IL-1β, TNF-α and iNOS in the supernatant were significantly increased, and the expression of MDGA1 in microglia was down-regulated in LPS group ( P<0.05). Compared with LPS group, the concentrations of IL-6, IL-1β, TNF-α and iNOS in the supernatant were significantly decreased, and the expression of MDGA1 in microglia was up-regulated in Bup+ LPS group ( P<0.05). Compared with Bup+ LPS group, the concentrations of IL-6, IL-1β, TNF-α and iNOS in the supernatant were significantly increased, and the expression of MDGA1 in microglia was down-regulated in Bup+ LPS+ sh MDGA1 group ( P<0.05). Conclusions:The mechanism by which buprenorphine alleviates neuroinflammation in microglia may be related to the up-regulation of the expression of MDGA1.