Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.
Ferroptosis/drug effects* ; Humans ; Iron/metabolism* ; Glioblastoma/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Homeostasis/physiology* ; Ferritins/metabolism* ; Brain Neoplasms/genetics* ; Mutation ; Astrocytes/drug effects* ; Cell Line, Tumor ; Piperazines/pharmacology* ; Quaternary Ammonium Compounds/pharmacology* ; Ferric Compounds

Objective:To investigate the expression and clinical relevance of MicroRNA(miRNA)-21 and miRNA-22 in urine exosomes of patients diagnosed with contrast-induced nephropathy(CIN).Methods:A total of 258 patients who underwent coronary intervention at our hospital's Department of Cardiology between July 2020 and July 2023 were retrospectively selected.These patients were divided into a CIN group( n=68)and a non-CIN group( n=190)based on the occurrence of contrast-induced nephropathy(CIN)post-coronary intervention.Clinical data from both groups were collected and compared, and levels of miRNA-21 and miRNA-22 in urinary exosomes were detected using polymerase chain reaction.Binary logistic regression was then utilized to analyze the risk factors associated with CIN.Furthermore, the diagnostic accuracy of urine exosomal miRNA-21 and miRNA-22 in detecting CIN was assessed through a receiver operating characteristic(ROC)curve. Results:Various risk factors were identified for contrast-induced nephropathy(CIN)in the study, including age(≥70 years old, 48.5%), diabetes(52.9%), myocardial infarction(11.8%), hypotension(17.7%), reduced glomerular filtration rate(GFR)[≤60 ml·min -1·1.73(m -1) 2, 32.4%], decreased left ventricular ejection fraction(LVEF)(≤0.45, 16.2%), high contrast agent dosage(>200 ml, 17.7%), elevated serum creatinine(Scr)levels 24 hours post-coronary intervention in the CIN group[(76.5±4.5)μmol/L], as well as higher levels of urine exosomal miRNA-21(0.9±0.2)and miRNA-22(5.9±1.1)between CIN group and non-CIN group[32.6%, 32.1%, 2.6%, 5.8%, 18.9%, 5.8%, 5.3%, (68.4±3.3)mol/L, (0.8±0.2), (3.1±0.90]( t=5.441, 9.266, 8.730, 8.671, 5.164, 6.927, 9.846, 8.707, 3.040, 11.233, all P<0.05).Logistic regression analysis showed that age ≥70 years( OR: 3.611, 95% CI: 1.235-10.561), diabetes( OR: 5.886, 95% CI: 1.601-21.641), myocardial infarction( OR: 3.600, 95% CI: 1.204-10.763), hypertension( OR: 6.672, 95% CI: 1.761-25.281), GFR≤60 ml·min -1·1.73(m -1) 2( OR: 3.413, 95% CI: 1.086-10.732), LVEF≤0.45( OR: 5.008, 95% CI: 1.380-18.178), dosage of contrast agent >200mL( OR: 3.389, 95% CI: 1.016-11.299), elevated Scr 24 hours after operation( OR: 0.597, 95% CI: 0.478-0.746)and high expression of miRNA-21( OR: 0.014, 95% CI: 0.001-0.292)and miRNA-22( OR: 0.017, 95% CI: 0.001-0.294)in urine exosomes were the risk factors for CIN(all P<0.05).The AUC of urinary exocrine miRNA-21 and miRNA-22 in the diagnosis of CIN were 0.694 and 0.950, respectively, and the AUC of combined diagnosis was 0.967. Conclusions:The expression levels of miRNA-21 and miRNA-22 in urinary exosomes of patients with contrast-induced nephropathy(CIN)are significantly elevated, indicating their potential clinical relevance in predicting CIN.Simultaneous assessment of both miRNAs can enhance the precision of CIN identification.

Objective:To develop and evaluate a medical visual question answering (VQA) model for neonatal lung ultrasound (LUS) images to enhance intelligent auxiliary diagnosis of neonatal pulmonary diseases.Methods:Using data from neonates admitted to Beijing Obstetrics and Gynecology Hospital, Capital Medical University (January 2023 to December 2024), an image-question-answer dataset comprising 251 LUS images was constructed [43 pneumonia (17.1%), 42 neonatal respiratory distress syndrome (16.7%), 83 transient tachypnea (33.1%), and 83 normal (33.1%) images] with a four-tier medical question-answer framework. Building upon the Qwen2.5-VL-7B base model and integrating LoRA fine-tuning with chain-of-thought prompting, we developed the NLUS-VQA model to enhance visual-language semantic alignment and enable stepwise clinical reasoning, achieving efficient small-sample adaptation. Model performance was comprehensively assessed through natural language generation metrics (BLEU-4, ROUGE-1/2/L), qualitative evaluation of characteristic recognition, and clinical consistency analysis.Results:(1) Quantitative evaluation demonstrated that NLUS-VQA achieved scores of 22.38 (BLEU-4), 48.26 (ROUGE-1), 22.40 (ROUGE-2), and 37.20 (ROUGE-L), representing significant improvements over baseline models. (2) Qualitatively, the model exhibited strong performance in identifying lung consolidation, coalescent B-lines, and snowflake signs, with its chain-of-thought strategy enhancing clinical interpretability and answer accuracy. (3) Clinically, NLUS-VQA achieved a Cohen's Kappa coefficient of 0.78 and diagnostic accuracy of 80.8% (21/26), indicating substantial agreement with clinical experts.Conclusion:The NLUS-VQA model demonstrates robust interpretability in recognizing key sonographic patterns (e.g. lung consolidation, confluent B-lines, and snowflake signs), providing a scalable framework for small-sample medical image analysis, though diagnostic performance on complex conditions remains limited by dataset scale and minority class representation.

Objective To analyze the clinical efficacy of valve surgeries for infective endocarditis and the affecting factors, and compare the early- and long-term postoperative outcomes of different surgery approaches. Methods The patients with infective endocarditis who underwent valve replacement/valvuloplasty in our hospital from 2010 to 2022 were retrospectively collected. The clinical data of the patients were analyzed. Results A total of 343 patients were enrolled, including 197 patients with mechanical valve replacement, 62 patients with bioprosthetic valve replacement, and 84 patients with valvuloplasty. There were 238 males and 105 females with an average age of (44.2±14.8) years. Single-valve endocarditis was present in 200 (58.3%) patients, and multivalve involvement was present in 143 (41.7%) patients. Sixty (17.5%) patients had suffered thrombosis before surgery, including cerebral embolisms in 32 patients. The mean follow-up time was (60.6±43.8) months. Early mortality within one month after the surgery occurred in 17 (5.0%) patients, while later mortality occurred in 19 (5.5%) patients. Eight (2.3%) patients underwent postoperative dialysis, 13 (3.8%) patients suffered postoperative stroke, 6 patients underwent reoperation, and 3 patients suffered recurrence of infective endocarditis. Smoking (P=0.002), preoperative embolisms (P=0.001), duration of surgery (P=0.001), and postoperative dialysis (P=0.001) were risk factors for early mortality, and left ventricular ejection fraction ≥60% (P=0.022) was protective factor for early mortality. New York Heart Association classification Ⅲ-Ⅳ (P=0.010) and ≥3 valve procedures (P=0.028) were risk factors for late mortality. The rate of composite endpoint events was significantly lower in the valvuloplasty group than that in the valve replacement group. Conclusion For patients with infective endocarditis, smoking and preoperative embolisms are associated with high postoperative mortality, multiple-valve surgery is associated with a poorer prognosis, and valvuloplasty has advantages over valve replacement and should be attempted in the surgical management of patients with infective endocarditis.

Objective:To investigate the expression and clinical relevance of MicroRNA(miRNA)-21 and miRNA-22 in urine exosomes of patients diagnosed with contrast-induced nephropathy(CIN).Methods:A total of 258 patients who underwent coronary intervention at our hospital's Department of Cardiology between July 2020 and July 2023 were retrospectively selected.These patients were divided into a CIN group( n=68)and a non-CIN group( n=190)based on the occurrence of contrast-induced nephropathy(CIN)post-coronary intervention.Clinical data from both groups were collected and compared, and levels of miRNA-21 and miRNA-22 in urinary exosomes were detected using polymerase chain reaction.Binary logistic regression was then utilized to analyze the risk factors associated with CIN.Furthermore, the diagnostic accuracy of urine exosomal miRNA-21 and miRNA-22 in detecting CIN was assessed through a receiver operating characteristic(ROC)curve. Results:Various risk factors were identified for contrast-induced nephropathy(CIN)in the study, including age(≥70 years old, 48.5%), diabetes(52.9%), myocardial infarction(11.8%), hypotension(17.7%), reduced glomerular filtration rate(GFR)[≤60 ml·min -1·1.73(m -1) 2, 32.4%], decreased left ventricular ejection fraction(LVEF)(≤0.45, 16.2%), high contrast agent dosage(>200 ml, 17.7%), elevated serum creatinine(Scr)levels 24 hours post-coronary intervention in the CIN group[(76.5±4.5)μmol/L], as well as higher levels of urine exosomal miRNA-21(0.9±0.2)and miRNA-22(5.9±1.1)between CIN group and non-CIN group[32.6%, 32.1%, 2.6%, 5.8%, 18.9%, 5.8%, 5.3%, (68.4±3.3)mol/L, (0.8±0.2), (3.1±0.90]( t=5.441, 9.266, 8.730, 8.671, 5.164, 6.927, 9.846, 8.707, 3.040, 11.233, all P<0.05).Logistic regression analysis showed that age ≥70 years( OR: 3.611, 95% CI: 1.235-10.561), diabetes( OR: 5.886, 95% CI: 1.601-21.641), myocardial infarction( OR: 3.600, 95% CI: 1.204-10.763), hypertension( OR: 6.672, 95% CI: 1.761-25.281), GFR≤60 ml·min -1·1.73(m -1) 2( OR: 3.413, 95% CI: 1.086-10.732), LVEF≤0.45( OR: 5.008, 95% CI: 1.380-18.178), dosage of contrast agent >200mL( OR: 3.389, 95% CI: 1.016-11.299), elevated Scr 24 hours after operation( OR: 0.597, 95% CI: 0.478-0.746)and high expression of miRNA-21( OR: 0.014, 95% CI: 0.001-0.292)and miRNA-22( OR: 0.017, 95% CI: 0.001-0.294)in urine exosomes were the risk factors for CIN(all P<0.05).The AUC of urinary exocrine miRNA-21 and miRNA-22 in the diagnosis of CIN were 0.694 and 0.950, respectively, and the AUC of combined diagnosis was 0.967. Conclusions:The expression levels of miRNA-21 and miRNA-22 in urinary exosomes of patients with contrast-induced nephropathy(CIN)are significantly elevated, indicating their potential clinical relevance in predicting CIN.Simultaneous assessment of both miRNAs can enhance the precision of CIN identification.

Objective:To develop and evaluate a medical visual question answering (VQA) model for neonatal lung ultrasound (LUS) images to enhance intelligent auxiliary diagnosis of neonatal pulmonary diseases.Methods:Using data from neonates admitted to Beijing Obstetrics and Gynecology Hospital, Capital Medical University (January 2023 to December 2024), an image-question-answer dataset comprising 251 LUS images was constructed [43 pneumonia (17.1%), 42 neonatal respiratory distress syndrome (16.7%), 83 transient tachypnea (33.1%), and 83 normal (33.1%) images] with a four-tier medical question-answer framework. Building upon the Qwen2.5-VL-7B base model and integrating LoRA fine-tuning with chain-of-thought prompting, we developed the NLUS-VQA model to enhance visual-language semantic alignment and enable stepwise clinical reasoning, achieving efficient small-sample adaptation. Model performance was comprehensively assessed through natural language generation metrics (BLEU-4, ROUGE-1/2/L), qualitative evaluation of characteristic recognition, and clinical consistency analysis.Results:(1) Quantitative evaluation demonstrated that NLUS-VQA achieved scores of 22.38 (BLEU-4), 48.26 (ROUGE-1), 22.40 (ROUGE-2), and 37.20 (ROUGE-L), representing significant improvements over baseline models. (2) Qualitatively, the model exhibited strong performance in identifying lung consolidation, coalescent B-lines, and snowflake signs, with its chain-of-thought strategy enhancing clinical interpretability and answer accuracy. (3) Clinically, NLUS-VQA achieved a Cohen's Kappa coefficient of 0.78 and diagnostic accuracy of 80.8% (21/26), indicating substantial agreement with clinical experts.Conclusion:The NLUS-VQA model demonstrates robust interpretability in recognizing key sonographic patterns (e.g. lung consolidation, confluent B-lines, and snowflake signs), providing a scalable framework for small-sample medical image analysis, though diagnostic performance on complex conditions remains limited by dataset scale and minority class representation.

Objective:To compare and discuss the mid-to-long-term outcomes of mitral valve repair (MVP) versus biological mitral valve replacement (bMVR) in patients aged 60 years and above with rheumatic mitral valve disease.Methods:This is a retrospective cohort study. A total of 765 patients aged 60 years and older, diagnosed with rheumatic mitral valve disease and who underwent MVP or bMVR at Beijing Anzhen Hospital from January 2010 to January 2023, were retrospectively included. Among them, 186 were male and 579 were female, with an age of (66.1±4.5) years (range: 60 to 82 years). Patients were divided into two groups based on the surgical method: the mitral valve repair group (MVP group, n=256) and the bioprosthetic mitral valve replacement group (bMVR group, n=509). A 1∶1 propensity score matching was performed using a caliper value of 0.2 based on preoperative data. Paired sample t-tests, χ2 tests, or Fisher′s exact tests were used for intergroup comparisons. Kaplan-Meier method was employed to plot survival curves and valve-related reoperation rate curves for both groups before and after matching, and Log-rank tests were used to compare the mid-to long-term survival rates and valve-related reoperation rates between the two groups. Results:A total of 765 patients who completed follow-up were ultimately included, with a follow-up period ( M(IQR)) of 5.1(5.0) years (range: 1.0 to 12.9 years). After matching, each group consisted of 256 patients. The incidence of early postoperative atrial fibrillation (39.1% vs. 49.2%, χ2=4.95, P=0.026) and early mortality rates (2.0% vs. 6.2%, χ2=4.97, P=0.026) were lower in the MVP group. Unadjusted Kaplan-Meier analysis showed significantly higher 5-year and 10-year survival rates for the MVP group (92.54% vs. 83.02%, 86.22% vs. 70.19%, Log-rank: P=0.001). After adjustment with propensity scores, the Kaplan-Meier analysis still indicated higher 5-year and 10-year survival rates in the MVP group compared to the bMVR group (92.54% vs. 85.89%, 86.22% vs. 74.83%, Log-rank: P=0.024). There were no significant differences in the rates of valve-related reoperation between the two groups before and after matching (5-year and 10-year reoperation rates pre-matching: 1.75% vs. 0.57%, 5.39% vs. 7.54%, Log-rank: P=0.207; post-matching: 1.75% vs. 0, 5.39% vs. 9.27%, Log-rank: P=0.157). Conclusion:For patients aged 60 years and above with rheumatic mitral valve disease, mitral valve repair offers better mid-to-long-term survival compared to biological valve replacement.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Objective To investigate the clinical effect of ginkgo leaf extract and armillariella mellea powders oral solution on the treatment of coronary heart disease complicated with depression and its impact on immune function.Methods A total of 124 patients with coronary heart disease combined with depression admitted to Jinhua Hospital of Traditional Chinese Medicine and Cixi Seventh People's Hospital from July 2019 to July 2023 were randomly divided into control group and observation group,with 62 cases in each group.The control group received conventional treatment,while the observation group received additional treatment with ginkgo leaf extract and armillariella mellea powders oral solution on this basis.After 8 weeks of treatment,inflammatory factors,immune function,quality of life and depression scores were compared between two groups.Results After treatment,the levels of C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin-8(IL-8)and CD8+in two groups were significantly lower than before treatment,while the levels of CD3+,CD4+and CD4+/CD8+were significantly higher than before treatment(P<0.05).The levels of CRP,TNF-α,IL-8 and CD8+in observation group were significantly lower than those in control group,while the levels of CD3+,CD4+and CD4+/CD8+were significantly higher than those in control group(P<0.05).After treatment,the scores of Seattle angina questionnair(SAQ)in all dimensions in both groups were significantly higher than before treatment(P<0.05),and the scores of SAQ in all dimensions in observation group were significantly higher than those in control group(P<0.05).After treatment,the Hamilton depression scale score of observation group was significantly lower than that of control group[(9.26±1.58)points vs.(12.87±1.89)points,t=11.538,P<0.001].Conclusion Ginkgo leaf extract and armillariella mellea powders oral solution can inhibit the inflammatory response and improve the symptoms of depression in patients with coronary heart disease and improve the immune function and quality of life.

Objective:To compare and discuss the mid-to-long-term outcomes of mitral valve repair (MVP) versus biological mitral valve replacement (bMVR) in patients aged 60 years and above with rheumatic mitral valve disease.Methods:This is a retrospective cohort study. A total of 765 patients aged 60 years and older, diagnosed with rheumatic mitral valve disease and who underwent MVP or bMVR at Beijing Anzhen Hospital from January 2010 to January 2023, were retrospectively included. Among them, 186 were male and 579 were female, with an age of (66.1±4.5) years (range: 60 to 82 years). Patients were divided into two groups based on the surgical method: the mitral valve repair group (MVP group, n=256) and the bioprosthetic mitral valve replacement group (bMVR group, n=509). A 1∶1 propensity score matching was performed using a caliper value of 0.2 based on preoperative data. Paired sample t-tests, χ2 tests, or Fisher′s exact tests were used for intergroup comparisons. Kaplan-Meier method was employed to plot survival curves and valve-related reoperation rate curves for both groups before and after matching, and Log-rank tests were used to compare the mid-to long-term survival rates and valve-related reoperation rates between the two groups. Results:A total of 765 patients who completed follow-up were ultimately included, with a follow-up period ( M(IQR)) of 5.1(5.0) years (range: 1.0 to 12.9 years). After matching, each group consisted of 256 patients. The incidence of early postoperative atrial fibrillation (39.1% vs. 49.2%, χ2=4.95, P=0.026) and early mortality rates (2.0% vs. 6.2%, χ2=4.97, P=0.026) were lower in the MVP group. Unadjusted Kaplan-Meier analysis showed significantly higher 5-year and 10-year survival rates for the MVP group (92.54% vs. 83.02%, 86.22% vs. 70.19%, Log-rank: P=0.001). After adjustment with propensity scores, the Kaplan-Meier analysis still indicated higher 5-year and 10-year survival rates in the MVP group compared to the bMVR group (92.54% vs. 85.89%, 86.22% vs. 74.83%, Log-rank: P=0.024). There were no significant differences in the rates of valve-related reoperation between the two groups before and after matching (5-year and 10-year reoperation rates pre-matching: 1.75% vs. 0.57%, 5.39% vs. 7.54%, Log-rank: P=0.207; post-matching: 1.75% vs. 0, 5.39% vs. 9.27%, Log-rank: P=0.157). Conclusion:For patients aged 60 years and above with rheumatic mitral valve disease, mitral valve repair offers better mid-to-long-term survival compared to biological valve replacement.