BACKGROUND:Radiotherapy significantly improves survival rates in patients with various malignant tumors.However,with prolonged post-treatment survival,many patients face the risk of radiation-related cardiac toxicity.This is especially true after chest radiotherapy,where the risk of radiation-induced heart disease significantly increases,becoming one of the most severe complications affecting prognosis survival.OBJECTIVE:To identify diagnostic markers of endothelial cellular senescence in radiation-induced heart disease through systematic transcriptomic analysis.METHODS:Firstly,genes associated with cellular senescence were screened from the CellAge database and intersected with the transcriptomic training dataset of a mouse model of radiation-induced heart disease to identify differentially expressed senescence-related genes.Secondly,weighted gene co-expression network analysis and machine learning were used to identify key hub genes that play critical roles in radiation-induced heart disease.The expression of these genes was validated using a dataset of radiation-induced endothelial injury.Additionally,the quanTlseq method was employed to assess the immune infiltration status related to radiation-induced heart disease.The expression levels of key genes and their association with survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy were explored through the analysis of The Cancer Genome Atlas database.RESULTS AND CONCLUSION:(1)Systematic transcriptomic analysis identified CCND1 as the core gene of endothelial cellular senescence in radiation-induced heart disease,and this finding was validated in the mouse model of radiation-induced heart disease.(2)The diagnostic model constructed from these data indicated that CCND1 had high specificity and sensitivity for diagnosing radiation-induced heart disease.(3)Immune infiltration analysis revealed significant immune response dysregulation in the mouse model of radiation-induced heart disease,and CCND1 was closely related to various immune cells.(4)Kaplan-Meier survival analysis showed that CCND1 was associated with poorer disease-specific survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy.This study systematically uncovers,for the first time,the pivotal role of CCND1 in endothelial cell senescence associated with radiation-induced heart disease.CCND1,a gene integral to cell cycle regulation,can induce cellular senescence when abnormally expressed.Furthermore,the findings highlight its potential as an early diagnostic marker.

BACKGROUND:Radiotherapy significantly improves survival rates in patients with various malignant tumors.However,with prolonged post-treatment survival,many patients face the risk of radiation-related cardiac toxicity.This is especially true after chest radiotherapy,where the risk of radiation-induced heart disease significantly increases,becoming one of the most severe complications affecting prognosis survival.OBJECTIVE:To identify diagnostic markers of endothelial cellular senescence in radiation-induced heart disease through systematic transcriptomic analysis.METHODS:Firstly,genes associated with cellular senescence were screened from the CellAge database and intersected with the transcriptomic training dataset of a mouse model of radiation-induced heart disease to identify differentially expressed senescence-related genes.Secondly,weighted gene co-expression network analysis and machine learning were used to identify key hub genes that play critical roles in radiation-induced heart disease.The expression of these genes was validated using a dataset of radiation-induced endothelial injury.Additionally,the quanTlseq method was employed to assess the immune infiltration status related to radiation-induced heart disease.The expression levels of key genes and their association with survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy were explored through the analysis of The Cancer Genome Atlas database.RESULTS AND CONCLUSION:(1)Systematic transcriptomic analysis identified CCND1 as the core gene of endothelial cellular senescence in radiation-induced heart disease,and this finding was validated in the mouse model of radiation-induced heart disease.(2)The diagnostic model constructed from these data indicated that CCND1 had high specificity and sensitivity for diagnosing radiation-induced heart disease.(3)Immune infiltration analysis revealed significant immune response dysregulation in the mouse model of radiation-induced heart disease,and CCND1 was closely related to various immune cells.(4)Kaplan-Meier survival analysis showed that CCND1 was associated with poorer disease-specific survival in esophageal squamous cell carcinoma patients receiving chest radiotherapy.This study systematically uncovers,for the first time,the pivotal role of CCND1 in endothelial cell senescence associated with radiation-induced heart disease.CCND1,a gene integral to cell cycle regulation,can induce cellular senescence when abnormally expressed.Furthermore,the findings highlight its potential as an early diagnostic marker.

Objective To investigate whether the PI3K/AKT/Cdkn1a/GPX4 signaling axis participates in the pathogenesis of radiation-induced heart disease (RIHD) through the ferroptosis pathway. Methods An RIHD mouse model was established by irradiating C57BL/6J mice with 20 Gy X-rays. Transcriptomic sequencing, the FerrDb ferroptosis-related gene set, and weighted gene co-expression network analysis were used to identify hub genes associated with ferroptosis in RIHD. KEGG enrichment analysis was employed to determine key signaling pathways. An AC16 cardiomyocyte model of RIHD was constructed, and the optimal modeling conditions were determined using CCK-8 assays and flow cytometry. Reverse transcription-quantitative PCR and Western blotting were applied to validate the expression changes of key genes and pathways in cardiomyocytes. Results Compared with the control group, myocardial tissues from irradiated mice exhibited typical RIHD pathological alterations, including structural disorganization and degeneration. Bioinformatics analysis identified Cdkn1a and Ddit4 as potential hub genes, with the PI3K/AKT pathway as the key signaling pathway. The optimal conditions for establishing the RIHD cell model were determined to be 10 Gy irradiation and 48 hours of incubation. Cellular experiments confirmed that, compared with the control group (0 Gy), irradiated cardiomyocytes (10 Gy) showed significantly elevated CDKN1A expression (P < 0.01), inhibited phosphorylation of the PI3K/AKT signaling pathway (P < 0.05), downregulated GPX4 expression (P < 0.05), and induction of ferroptosis. Conclusion This study preliminarily clarifies the potential role of the PI3K/AKT/Cdkn1a/GPX4 signaling axis in regulating ferroptosis in RIHD cardiomyocytes, providing new therapeutic targets and strategies for the prevention and treatment of RIHD.

Objective:To identify the main components of Huanglian Jiedu Decoction(HLJDD)using ultra-high-performance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS),and to explore the potential mechanism of action of HLJDD in the treatment of gouty arthritis(GA)using network pharmacology and molecular docking methods.Methods:We identi-fied the chemical components of HLJDD by combining UPLC-Q-TOF-MS data acquired in both positive and negative ion modes with reference standards,relevant literature,and database searches.We analyzed the potential therapeutic mechanism of HLJDD for GA by using network pharmacology to determine the intersection targets between the active ingredients of HLJDD and GA for further enrich-ment analysis and visual network mapping.The binding affinity of the active ingredients with the intersection targets was validated through molecular docking.Results:A total of 47 components were identified by UPLC-Q-TOF-MS;54 key components of HLJDD for GA treatment and 37 intersection targets were determined by net-work pharmacology;and the top 10 key targets by Degree value were obtained by protein-protein interaction analysis.The Gene On-tology functional enrichment analysis revealed 20 biological pro-cesses,7 cellular components,and 8 molecular functions.The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis demonstrated 96 GA-related intervention pathways,in which inflammatory signaling pathways such as interleukin-17(IL-17)and tu-mor necrosis factor(TNF)were involved.Molecular docking verified that the key components of HLJDD had high binding affinity with the core targets.Conclusion:The identified key components in HLJDD,such as phellodendrine,coptisine,wogonin,and β-sitosterol,may alleviate GA by regulating multiple core targets in the IL-17 and TNF pathways,such as PTSG2,which provides a theoretical ba-sis for future investigation into the mechanism of action of HLJDD.

Objective:To explore the short- and medium-term clinical outcomes of covered stent implantation in the treatment of transplant renal artery stenosis (TRAS).Methods:A retrospective analysis was conducted on the clinical data of 12 consecutive patients with TRAS (transplant renal artery stenosis) who underwent covered stent implantation in Henan Provincial People′s Hospital from January 2021 to December 2024. The changes in indicators such as serum creatinine (Cr), blood urea nitrogen (BUN), mean arterial pressure (MAP), peak systolic velocity (PSV), intrarenal resistance index (RI), and the diameter of the stenotic site were analyzed before the operation, one week after the operation, six months after the operation, and 12 months after the operation. Repeated measures analysis of variance was used to investigate the changes of each observation index over time.Results:The surgery was successfully performed on all 12 patients, with a technical success rate of 100%. Among them, 8 cases used self-expanding covered stents, and 4 cases used balloon-expandable covered stents. One week, six months and twelve months after the surgery, the levels of Cr, BUN, PSV and MAP were all lower than those before the surgery. The RI and the diameter of the stenotic site were significantly increased compared with those before the surgery, the difference was statistically significant ( P<0.05). During the perioperative period and the postoperative follow-up period, no surgery-related complications were found. Conclusion:The implantation of the covered stent can effectively relieve the stenosis of the transplant renal artery, significantly improve renal function, and reduce blood pressure levels in TRAS patients, while maintaining excellent short-to medium-term clinical outcomes.

Objective:To explore the short- and medium-term clinical outcomes of covered stent implantation in the treatment of transplant renal artery stenosis (TRAS).Methods:A retrospective analysis was conducted on the clinical data of 12 consecutive patients with TRAS (transplant renal artery stenosis) who underwent covered stent implantation in Henan Provincial People′s Hospital from January 2021 to December 2024. The changes in indicators such as serum creatinine (Cr), blood urea nitrogen (BUN), mean arterial pressure (MAP), peak systolic velocity (PSV), intrarenal resistance index (RI), and the diameter of the stenotic site were analyzed before the operation, one week after the operation, six months after the operation, and 12 months after the operation. Repeated measures analysis of variance was used to investigate the changes of each observation index over time.Results:The surgery was successfully performed on all 12 patients, with a technical success rate of 100%. Among them, 8 cases used self-expanding covered stents, and 4 cases used balloon-expandable covered stents. One week, six months and twelve months after the surgery, the levels of Cr, BUN, PSV and MAP were all lower than those before the surgery. The RI and the diameter of the stenotic site were significantly increased compared with those before the surgery, the difference was statistically significant ( P<0.05). During the perioperative period and the postoperative follow-up period, no surgery-related complications were found. Conclusion:The implantation of the covered stent can effectively relieve the stenosis of the transplant renal artery, significantly improve renal function, and reduce blood pressure levels in TRAS patients, while maintaining excellent short-to medium-term clinical outcomes.

Objective To evaluate the efficacy and safety of laser-assisted balloon angioplasty(LABA)in treating patients with infrapopliteal arterial occlusion complicated by critical limb ischemia(CLI).Methods The clinical data of patients with infrapopliteal artery occlusion complicated by CLI,who were admitted to the Fuwai Central China Cardiovascular Hospital to receive LABA(LABA group)or balloon angioplasty alone(BA group)between January 2019 and December 2021,were retrospectively analyzed.The incidence of perioperative complications and postoperative clinical efficacy were compared between the two groups.Results A total of 32 patients received LABA therapy and 40 patients received BA alone.The technical success rate,the postoperative ankle-brachial index(ABI),the numerical value of postoperative ABI value deducting preoperative ABI value,the postoperative 24-month continuous improvement rate of clinical symptoms and the primary patency rate of target vessels in the LABA group were remarkably higher than those in the BA group(all P＜0.05).No procedure-related target vessel perforation,amputation,or death occurred in both groups.No statistically significant differences in the target vessel dissection,distal embolism,remedial stenting,and postoperative 24-month amputation-free survival existed between the groups(all P＞0.05).Conclusion For the infrapopliteal arterial occlusion complicated by CLI,LABA therapy is clinically safe and effective,and its mid-term efficacy is superior to BA alone.

Objective:To investigate the efficacy of excimer laser atherectomy (ELA) combined with drug-coated balloon (DCB) in the treatment of femoropopliteal arteriosclerosis obliterans (ASO) and its influencing factors.Methods:The clinical data of patients with femoropopliteal ASO treated by ELA combined with DCB from July 2019 to March 2022 were retrospectively analyzed, including technical success rate, ankle-brachial index(ABI), primary patency rate and freedom from target lesion revascularization (TLR) rate. Cox regression was applied to analyze the risk factors affecting the decline in the rate of primary patency and freedom from TLR.Results:All 82 patients were treated with ELA+DCB. The technical success was 91.5%. The post-operative ABI (0.73±0.13) was significantly higher than preoperative ABI (0.39±0.11) ( t=35.26, P<0.001). The 24-month cumulative primary patency and TLR-free rates were 64.1% and 76.8%, respectively. Lesion length>15 cm ( HR=2.57, P=0.047) and severe calcification ( HR=3.26, P=0.021) were associated with loss of primary patency. Having diabetes ( HR=5.24, P=0.010) and a single postoperative outflow tract ( HR=4.18, P=0.008) were associated with a decrease in TLR-free rates. Conclusions:ELA combined with DCB for femoropopliteal ASO is safe and has good intermediate efficacy. Lesion length>15 cm and severe calcification were independent risk factors for primary patency rate, and diabetes and a single postoperative outflow tract were independent risk factors for TLR-free rate.

Objective To investigate the effect and mechanism of methyltransferase-like 3(METTL3)on the pro-liferation,migration,and secretion of inflammatory factors by synovial fibroblasts from rheumatoid arthritis(RA).Methods The expression of METTL3 in synovial tissue(SF)from 25 patients with rheumatoid arthritis and 25 pa-tients with osteoarthritis was detected by RT-qPCR and immunohistochemistry,respectively.The concentration of RNA m6A was detected by ELISA.RA synovial fibroblasts were isolated and cultured,and divided into NC(nor-mal control)group,hi-METTL3(overexpression of METTL3)group,si-METTL3(knock-down METTL3)group,and STM2457(METTL3 specific inhibitor)intervention group.Cell proliferation was detected by CCK-8 method.Apoptosis was detected by flow cytometry.And the concentrations of interleukin-6(IL-6),interleukin-17A(IL-17A),receptor activator of nuclear factor-kappa B ligand(RANKL),and osteoprotegerin(OPG)in the superna-tant of cell culture were detected by ELISA.Results Compared with synovial tissue of osteoarthritis,the expres-sion of mRNA m6A and METTL3 in synovial tissue of RA significantly increased(P<0.05).After overexpression of METTL3,the expression of m6A in synovial fibroblasts increased.The proliferation and migration abilities of SF in hi-METTL3 group were significantly improved,and their apoptosis did not change significantly.The secretion of cytokines IL-6 and RANKL of SF in hi-METTL3 group significantly increased,while the OPG significantly de-creased(P<0.05).After interfering with METTL3 expression,the expression of m6A in synovial fibroblasts de-creased.Cell proliferation and migration of SF in siMETTL3 group significantly decreased.The secretion of cyto-kines IL-6 and RANKL significantly decreased,and OPG significantly increased(P<0.05).After intervention with METTL3 inhibitor STM2457,the proliferation and migration of synovial fibroblasts were significantly reduced,and the secretion of cytokines IL-6 and RANKL significantly reduced,and OPG significantly increased(P<0.05).There was no significant difference in the expression of IL-17A among each group.Conclusion METTL3 may promote the proliferation and migration of RA synovial fibroblasts,enhance the expression of IL-6 and RANKL,and inhibit the expression of OPG through RNA m6A methylation modification.

Objective:To study the role and preliminary molecular mechanism of TRIM24 regulating macrophage polarization in viral myocarditis(VM).Methods:VM mouse model was established by Coxsackie virus B3(CVB3),and expression of TRIM24 in myocardial tissue was detected.Cardiac inflammation level and polarization phenotype of cardiac infiltrating macrophages in a murine model of cardiac TRIM24 inhibition were detected in vivo.A polarization model of mouse bone marrow-derived macrophages(BMDMs)in vitro was established to observe the role of TRIM24 inhibition in polarizing BMDMs to M1 and M2,as well as its effects on phagocy-tosis and bactericidal function of BMDMs.Effects of TRIM24 inhibition on total STAT6 protein level and phosphorylation were investi-gated.Results:TRIM24 was significantly highly expressed in myocardial tissue of VM mice(P<0.001).Inhibition of TRIM24 expres-sion in myocardium had an attenuating effect on VM and promoted polarization of cardiac infiltrating macrophages to M2.TRIM24 was significantly down-regulated in vitro during the polarization of BMDMs toward M2(P<0.01).Inhibition of TRIM24 expression signifi-cantly promoted macrophage polarization toward M2 type and inhibited polarization toward M1 type,accompanied by a significant increase in STAT6 phosphorylation levels(P<0.01).Conclusion:TRIM24 regulates macrophage M2 polarization via activation of STAT6 signaling pathway to attenuate VM.