Objective To investigate the diagnositic performance of cardiac myosin-binding protein C (cMyBP-C) in cardiovascular immune-related adverse events (CV-irAE), and to evaluate its potential as a novel biomarker of myocardial injury. Methods Cancer patients receiving immune checkpoint inhibitors (ICI) therapy at Zhongshan Hospital, Fudan University, from January 2025 to September 2025 were enrolled. Patients were divided into the positive group (high-sensitivity cardiac troponin T [hs-cTnT]≥99th percentile [14 pg/mL], n＝78) and the negative group (hs-cTnT＜99th percentile, n＝56). A control group (n＝231) consisted of cancer patients without prior anti-tumor therapy and healthy individuals. Levels of cMyBP-C, hs-cTnT, creatine kinase isoenzyme-MB (CK-MB), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured. The screening reference value of cMyBP-C was established using the 99th percentile method. Diagnositic performance was evaluated by receiver operating characteristic (ROC) curves and area under the curve (AUC). The association between cMyBP-C level and myocardial edema assessed by cardiac magnetic resonance (CMR) was analyzed using Spearman correlation. Results The difference in cMyBP-C levels among the three groups was statistically significant (P＜0.001). Based on the 99th percentile of the control group, the screening reference value of cMyBP-C was determined to be 5.86 pg/mL. ROC curves showed that cMyBP-C achieved an AUC of 0.919 (95%CI 0.898–0.939) for detecting the risk of CV-irAE, comparable to CK-MB (AUC＝0.917, 95%CI 0.896–0.939, P＝0.682) and superior to NT-proBNP (AUC＝0.876, 95%CI 0.850–0.902, P＜0.001). After excluding non-cardiovascular adverse events, the AUC of cMyBP-C increased to 0.934, CK-MB was 0.893, and NT-proBNP was 0.877. Spearman correlation analysis revealed that among patients with ICI-associated myocarditis (n＝21), cMyBP-C level was positively correlated with the extent of myocardial edema assessed by CMR ( ρ＝0.64, P＝0.002). Conclusions cMyBP-C is significantly elevated in patients with CV-irAEs, demonstrating diagnositic performance comparable to or better than conventional biomarkers, and reflecting the burden of myocardial inflammation. These findings suggest that cMyBP-C may serve as a valuable complementary diagnositic biomarker for CV-irAEs.

Objective To develop a risk assessment scale for immune checkpoint inhibitor (ICI)-associated myocarditis based on multidisciplinary collaboration, and to evaluate its diagnostic performance. Methods Based on multidisciplinary cooperation, integrating clinical experience from oncology and cardiology, literature data, and patient conditions, a risk assessment scale for ICI-associated myocarditis was developed. A total of 101 patients with malignancies who received immunotherapy at Zhongshan Hospital, Fudan University, from October 2020 to October 2024 were included as the validation cohort. Patients were stratified into low-risk (0-1 point), medium-risk (2-4 points), and high-risk (≥5 points) groups based on their scale scores. The association between pretictive risk stratifications and actual assessment results was assessed using the Cox proportional hazards regression model. The predictive value of the scale for ICI-associated myocarditis was evaluated using receiver operating characteristic (ROC) curve. Agreement between the scale scores and actual assessment results was assessed using Cohen’s Kappa coefficient. Results Based on the scale pretictive results, 28(27.7%), 8(7.9%), 65(64.4%) patients were at low risk, medium risk, and high risk for ICI-related myocarditis, respectively; however, 46(45.5%), 8(7.9%), 47(46.5%) were at low risk, medium risk, and high risk actually. Kaplan-Meier survival analysis showed that the cumulative incidence of ICI-related myocarditis in the high-risk group was significantly higher than that in the medium- and low-risk groups (P＜0.05). In the multivariable-adjusted Cox proportional hazards model, the ICI-related myocarditis risk in high-risk group was about 4 times that in the low-risk group. ROC curve analysis demonstrated that the average area under the curve (AUC) for predicting ICI-related myocarditis was 0.81, with an accuracy of 0.74. The Cohen’s Kappa coefficient was 0.55, indicating moderate agreement. In the actual high-risk group, no patient was predicted to be at low risk; in the actual low-risk group, 16 patients were predicted to be at high risk. Conclusions This risk assessment scale for ICI-associated myocarditis shows high predictive performance. It provides oncologists with a simple yet effective multidisciplinary diagnostic reference tool, potentially enhancing early identification of ICI-associated myocarditis.

Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

Objective:To summarize and analyze the clinical efficacy and experience of ultrasound-guided radiofrequency ablation (RFA) in the treatment of Kasabach-Merritt syndrome (KMS).Methods:A retrospective analysis was conducted on the data of pediatric patients with KMS who underwent ultrasound-guided RFA in Department of Hemangioma Surgery, the Third Affiliated Hospital of Zhengzhou University, between March 2018 and March 2024. Preoperative laboratory tests and imageological examination were performed. Under general anesthesia, the working tip of the RFA electrode needle was precisely reached the bottom of the lesion under ultrasound guidance. The electrode needle was then gradually withdrawn until the entire lesion area was covered by hyperechoic signals, indicating complete ablation. Postoperative symptomatic and supportive treatments, such as ice pack application and dressing changes, were administered to the surgical area. Platelet detection was performed immediately after the operation. Complications were closely monitored and regular follow-ups were carried out.Results:A total of 30 pediatric patients were included, comprising 14 males and 16 females, from 10 min to 5 months and 29 d after birth, with a median time of 6 d. Lesions were located in the limbs and trunk in 27 cases, and head and neck region in 3 cases, with lesion volumes ranged from 2.4 cm×2.3 cm×1.2 cm to 14.4 cm×9.3 cm×3.3 cm. The mean preoperative platelet count was 43×10 9/L, among them, the platelet values of 11 cases were (10-30) ×10 9/L, and those of 6 cases were lower than 10×10 9/L, other 13 cases with progressive thrombocytopenia. All patients successfully underwent RFA, achieving complete lesion ablation and normalization of platelet counts postoperatively. Platelet counts recovered to above 300×10 9/L in 15 patients, with no severe complications observed. The RFA area became slightly hardened within 7 d postoperatively but gradually returned to normal after consistent dressing changes for 2 weeks. During the follow-up period of 6 months to 2 years, complete lesion ablation was confirmed, with disappearance of the mass, no recurrence, good local function, mild local scar formation, and satisfactory cosmetic appearance. Conclusion:Ultrasound-guided RFA for KMS has advantages of favorable therapeutic outcomes, minimal tissue damage, no significant complications, and satisfactory cosmetic result.

Objective:To summarize and analyze the clinical efficacy and experience of ultrasound-guided radiofrequency ablation (RFA) in the treatment of Kasabach-Merritt syndrome (KMS).Methods:A retrospective analysis was conducted on the data of pediatric patients with KMS who underwent ultrasound-guided RFA in Department of Hemangioma Surgery, the Third Affiliated Hospital of Zhengzhou University, between March 2018 and March 2024. Preoperative laboratory tests and imageological examination were performed. Under general anesthesia, the working tip of the RFA electrode needle was precisely reached the bottom of the lesion under ultrasound guidance. The electrode needle was then gradually withdrawn until the entire lesion area was covered by hyperechoic signals, indicating complete ablation. Postoperative symptomatic and supportive treatments, such as ice pack application and dressing changes, were administered to the surgical area. Platelet detection was performed immediately after the operation. Complications were closely monitored and regular follow-ups were carried out.Results:A total of 30 pediatric patients were included, comprising 14 males and 16 females, from 10 min to 5 months and 29 d after birth, with a median time of 6 d. Lesions were located in the limbs and trunk in 27 cases, and head and neck region in 3 cases, with lesion volumes ranged from 2.4 cm×2.3 cm×1.2 cm to 14.4 cm×9.3 cm×3.3 cm. The mean preoperative platelet count was 43×10 9/L, among them, the platelet values of 11 cases were (10-30) ×10 9/L, and those of 6 cases were lower than 10×10 9/L, other 13 cases with progressive thrombocytopenia. All patients successfully underwent RFA, achieving complete lesion ablation and normalization of platelet counts postoperatively. Platelet counts recovered to above 300×10 9/L in 15 patients, with no severe complications observed. The RFA area became slightly hardened within 7 d postoperatively but gradually returned to normal after consistent dressing changes for 2 weeks. During the follow-up period of 6 months to 2 years, complete lesion ablation was confirmed, with disappearance of the mass, no recurrence, good local function, mild local scar formation, and satisfactory cosmetic appearance. Conclusion:Ultrasound-guided RFA for KMS has advantages of favorable therapeutic outcomes, minimal tissue damage, no significant complications, and satisfactory cosmetic result.

Objective:This study aimed to identify key genes in endothelial cell (EC) associated with the pathogenesis and progression of human venous malformations (VMs) through bioinformatics analysis, providing potential biomarkers for early screening and targeted therapy of VMs.Methods:A case-control study was conducted using surgically resected tissue specimens from VMs patients at the Third Affiliated Hospital of Zhengzhou University (from September 2021 to September 2023), with malformed venous tissues as the experimental group and distal normal venous tissues as controls. Single-nucleus RNA sequencing (snRNA-seq) was performed on paired experimental and control samples from four VM patients. High-dimensional weighted gene co-expression network analysis (hdWGCNA), combined with gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and protein-protein interaction (PPI) network analysis, identified critical genes. Validation experiments included 15 additional VM cases and controls using reverse transcription quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC), and Western blot.Results:A total of 55 430 nuclei were captured using snRNA-seq, with 30 391 nuclei from the experimental group and 25 039 nuclei from the control group. Cluster analysis identified 22 distinct cell populations, which were annotated into 8 cell types. hdWGCNA revealed four modules associated with invasion, which were enriched in angiogenesis, integrin signaling, and cell adhesion according to GO analysis. KEGG pathway analysis indicated that the PI3K-AKT signaling pathway and focal adhesion are key regulatory mechanisms. PPI network analysis combined with cytoscape identified EGFL7, TEK, and FLT1 as key genes. RT-qPCR results demonstrated that the relative mRNA expression levels of these three genes in the experimental group (6.66±2.31, 1.86±0.62, 3.49±0.58) were significantly higher than those in the control group (1.05±0.14, 1.00±0.14, 1.06±0.25), with statistically significant differences ( t=9.37, 4.27, 11.20, P<0.05). Immunohistochemical analysis showed that the relative protein expression levels of these three genes in the cytoplasm of the experimental group (0.84±0.15, 0.68±0.14, 0.85±0.12) were also significantly higher than those in the control group (0.19±0.05, 0.23±0.06, 0.30±0.05), with statistically significant differences ( t=16.62, 5.93, 11.68, P<0.05). Western blot analysis confirmed that the relative protein expression levels of these three genes in the experimental group (0.35±0.04, 0.36±0.09, 0.31±0.04) were significantly higher than those in the control group (0.19±0.01, 0.13±0.02, 0.14±0.04), with statistically significant differences ( t=7.05, 4.61, 5.93, P<0.05). Conclusion:EGFL7, FLT1, and TEK in EC may play crucial roles in the occurrence and invasion of VMs.

Objective:This study aimed to identify key genes in endothelial cell (EC) associated with the pathogenesis and progression of human venous malformations (VMs) through bioinformatics analysis, providing potential biomarkers for early screening and targeted therapy of VMs.Methods:A case-control study was conducted using surgically resected tissue specimens from VMs patients at the Third Affiliated Hospital of Zhengzhou University (from September 2021 to September 2023), with malformed venous tissues as the experimental group and distal normal venous tissues as controls. Single-nucleus RNA sequencing (snRNA-seq) was performed on paired experimental and control samples from four VM patients. High-dimensional weighted gene co-expression network analysis (hdWGCNA), combined with gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and protein-protein interaction (PPI) network analysis, identified critical genes. Validation experiments included 15 additional VM cases and controls using reverse transcription quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC), and Western blot.Results:A total of 55 430 nuclei were captured using snRNA-seq, with 30 391 nuclei from the experimental group and 25 039 nuclei from the control group. Cluster analysis identified 22 distinct cell populations, which were annotated into 8 cell types. hdWGCNA revealed four modules associated with invasion, which were enriched in angiogenesis, integrin signaling, and cell adhesion according to GO analysis. KEGG pathway analysis indicated that the PI3K-AKT signaling pathway and focal adhesion are key regulatory mechanisms. PPI network analysis combined with cytoscape identified EGFL7, TEK, and FLT1 as key genes. RT-qPCR results demonstrated that the relative mRNA expression levels of these three genes in the experimental group (6.66±2.31, 1.86±0.62, 3.49±0.58) were significantly higher than those in the control group (1.05±0.14, 1.00±0.14, 1.06±0.25), with statistically significant differences ( t=9.37, 4.27, 11.20, P<0.05). Immunohistochemical analysis showed that the relative protein expression levels of these three genes in the cytoplasm of the experimental group (0.84±0.15, 0.68±0.14, 0.85±0.12) were also significantly higher than those in the control group (0.19±0.05, 0.23±0.06, 0.30±0.05), with statistically significant differences ( t=16.62, 5.93, 11.68, P<0.05). Western blot analysis confirmed that the relative protein expression levels of these three genes in the experimental group (0.35±0.04, 0.36±0.09, 0.31±0.04) were significantly higher than those in the control group (0.19±0.01, 0.13±0.02, 0.14±0.04), with statistically significant differences ( t=7.05, 4.61, 5.93, P<0.05). Conclusion:EGFL7, FLT1, and TEK in EC may play crucial roles in the occurrence and invasion of VMs.

Objective To investigate the serum tumor necrosis factor like weak inducer of apoptosis(TWE AK),sterol regulatory element-binding protein 1(SREBP-1)levels in patients with prostate cancer(PC)and their relationship with clinical pathological characteristics and progression free survival prognosis.Method A total of 94 PC patients who underwent PC radical surgery in Wuhan Dongxihu District People's Hospital from January 2018 to January 2020 were selected as the PC group.Meanwhile,50 patients with benign prostatic hyperplasia(BPH)during the same period were selected as the BPH group,and 50 healthy individuals who underwent physical examination during the same period were selected as the control group.Enzyme linked immunosorbent assay(ELISA)was used to detect the expression levels of serum TWEAK and SREBP-1.Kaplan-Meier survival analysis was used to analyze the effects of serum TWEAK and SREBP-1 on the progression free survival in prostate cancer patients.Multivariate COX regression analysis was used to analyze factors affecting the prognosis of progression free survival in prostate cancer patients.Results The serum TWEAK(77.14±15.46 ng/L)and SREBP-1(334.14±33.81 ng/L)levels in the PC group were higher than those in the BPH group(38.69±10.58 ng/L,201.69±28.74 ng/L)and control group(36.26±10.27 ng/L,189.51±27.65 ng/L),with significant differences(t=23.752,25.249;34.636,37.821,all P＜0.05).There was a positive correlation between serum TWEAK and SREBP-1 expression in PC patients(r=0.668,P=0.001).The serum TWEAK and SREBP-1 levels in PC patients with Gleason score＞7,TNM stage Ⅲ,and preoperative prostate specific antigen(PSA)level ≥ 20 ng/ml were higher than those with Gleason score≤7,TNM stage Ⅰ～Ⅱ,and preoperative PSA level＜20ng/ml,with significance differences(t=8.465～16.597,all P＜0.05).The 3-year overall progression free survival rates of the TWEAK high expression and low expression groups were 60.42％(29/48)and 86.96％(40/46),respectively.The 3-year overall progression free survival rates of the SREBP-1 high expression and low expression groups were 57.78％(26/45)and 87.76％(43/49),respectively.The 3-year cumulative progression free survival rates of the TWEAK high expression group and the SREBP-1 high expression group were lower than those of the TWEAK low expression group and the SREBP-1 low expression group,and the differences were significant(Log rankx2=8.125,9.547,P=0.004,0.002).TNM stage Ⅲ(OR=1.448,P＜0.001),Gleason score＞7(OR=1.401,P＜0.001),preoperative PSA ≥ 20 ng/ml(OR=1.353,P＜0.001),serum TWEAK(OR=1.338,P＜0.001),and SREBP-1(OR=1.293,P＜0.001)were independent risk factors affecting the progression free survival prognosis of PC patients.Conclusion Serum TWEAK and SREBP-1 in prostate cancer patients were increased,and they were correlated with the clinical pathological characteristics of PC.They could be serum biomarkers for evaluating the prognosis of progression free survival.

Background::Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.Methods::This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. Results::The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.Conclusions::The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Objective:To investigate effect of vitexin on macrophage polarization and its impact on tumor growth in a mouse model of prostate cancer.Methods:C57BL/6J male mice were used to establish RM-1 prostate cancer xenograft model.Mice were ran-domly divided into model group,vitexin-low,medium and high doses groups(40,80,160 mg/kg),and cisplatin group as positive control.After continuous administration for 16 days,mice were euthanized and tumor mass was measured.HE staining was performed to observe tumor morphology.Immunohistochemistry was used to detect Ki67 positive rate.Flow cytometry was conducted to measure expressions of CD86+CD11b and CD206+CD11b in tumor-associated macrophages.CCK8 assay was performed to assess cytotoxic effect of vitexin on RAW264.7 macrophages to determine suitable concentrations.RT-qPCR was used to measure mRNA expressions of M2 macrophage markers,including arginase-1(ARG-1),Fizz1 and Ym1.Results:Vitexin inhibited tumor volume and weight,induced tumor tissue necrosis,suppressed Ki67 protein expression,increased expression of CD86+CD11b+M1 macrophages,and inhibited CD206+CD11b+M2 macrophage expression in mouse tumor tissues in vivo.Vitexin at concentrations of 10～20 μmol/L showed no cyto-toxicity on RAW264.7 macrophages in vitro,and promoted expression of iNOS in IL-4-induced M2 macrophages while inhibiting CD206 expression,as well as suppressed mRNA expressions of ARG-1,Fizz1 and Ym1.Conclusion:Vitexin effectively inhibits tumor growth in a mouse model of prostate cancer,possibly by regulating M2 macrophages towards an M1 phenotype and exerting immunomodulatory effects.