To investigate the role of quercetin （QUE） in ferroptosis during intestinal ischemia-reperfusion （IR） injury and elucidate its underlying mechanisms.

① Potential target genes of QUE were predicted using the TCMSP，PharmMapper，and SwissTargetPredictive databases. Target genes associated with intestinal IR injury and ferroptosis were collected from GeneCards，PharmGKB，and OMIM databases. After overlapping genes were identified and analyzed，protein-protein interaction （PPI） networks were constructed using the STRING database and then visualized with Cytoscape 3.10.0. Molecular docking was performed to validate the binding conformations between QUE and key targets. ② In vivo experiments were conducted to verify QUE’s protective effects against intestinal IR injury. Thirty-six SPF-grade male C57BL/6J mice （6~8 weeks old，body weight：22±2 g） were randomly divided into Sham，Sham+QUE，IR，IR+QUE，IR+QUE+erastin （IR+QUE+Era），and IR+QUE+ kevetrin hydrochloride （IR+QUE+KH） groups，with 6 mice in each group. Mouse model of intestinal IR injury was induced by 45 min ischemia of the superior mesenteric artery followed by 60 min reperfusion. HE staining was used to observe histopathological changes in the intestinal tissues. ELISA was employed to the serum or intestinal contents of diamine oxidase （DAO），pro-inflammatory cytokines （TNF-α，IL-6，IL-1β），and ferroptosis markers ［glutathione （GSH） and Fe²⁺］. Western blotting was utilized to detect the protein expression of glutathione peroxidase 4 （GPX4），acyl-CoA synthetase long-chain family member 4 （ACSL4），and tumor protein 53 （p53）.

① Network pharmacology identified 460 QUE targets，1 552 intestinal IR injury targets，and 1 967 ferroptosis-related targets，and 92 overlapping genes were identified as potential therapeutic targets. Molecular docking revealed a strong binding affinity between QUE and p53 （binding energy：-6.8 kcal/mol）. ② In vivo experiments demonstrated that the IR+QUE group exhibited reduced intestinal damage and lower Chiu’s score （P<0.05），decreased serum DAO content but elevated intestinal DAO content （P<0.05），decreased levels of TNF-α，IL-6，and IL-1β in the serum and intestinal tissues （P<0.05），reduced Fe²⁺ accumulation，and increased GSH content （P<0.05），and up-regulated GPX4 （P<0.05） and down-regulated ACSL4 and p53 expression （P<0.05） at protein level when compared with the IR group. While，the administration of ferroptosis agonist Era，or p53 agonist KH resulted in diminished therapeutic effects of QUE （P<0.05） when compared with the IR+QUE group.

QUE alleviates intestinal IR injury by inhibiting ferroptosis，which may be associated with its down-regulating p53 expression.

To analyze the expression patterns of immunohistochemical markers CK20, CD10, PHLDA1, CD34, AR, Ber-EP4, and Ki-67 in cutaneous trichoblastoma (TB) and basal cell carcinoma (BCC), and validate their diagnostic value in differentiating TB from BCC.

Pathological specimens were harvested from 35 TB patients and 35 BCC patients diagnosed with histopathological biopsy in our department between January 2013 and December 2023. Their clinical data were collected, and the expression levels of CK20, CD10, PHLDA1, CD34, AR, Ber-EP4, and Ki-67 in TB and BCC tissues were detected with immunohistochemical staining. The staining patterns and proportions of positive cells in basaloid tumor nests and peritumoral stroma were analyzed. χ² test was used to screen statistically significant variables, and then multivariate logistic regression analysis was utilized to evaluate the diagnostic efficacy of each marker. Based on the significance of the markers, stepwise combinations of immunohistochemical markers were analyzed to determine their collective diagnostic performance.

Peripheral CD10 positivity in basaloid cell nests (P<0.001) and diffuse CD10 positivity in basaloid cells (P<0.001) strongly supported BCC diagnosis. In contrast, CK20 positivity in basaloid cells (P=0.028), CD10 positivity in stromal cells (P<0.001), and PHLDA1 positivity in basaloid cells (P<0.001) favored TB. Stromal CD34 positivity (P=0.247), AR positivity in basaloid cells (P=0.794), Ber-EP4 positivity in basaloid cells (P=0.156), Ki-67 proliferation index (P=0.280), and Ki-67 staining patterns (P=0.897) showed no significant differences between TB and BCC. Multivariate logistic regression analysis identified stromal CD10 positivity (P<0.001) and PHLDA1 positivity (P=0.042) as independent predictors of TB, showing negative correlations with BCC. CK20 positivity in basaloid cells (P=0.340) showed no statistically significant difference in expression between TB and BCC. The combination of stromal CD10, PHLDA1, and CK20 demonstrated the highest diagnostic performance (Youden index=0.74).

Stromal CD10 and basaloid PHLDA1 positivity serve as reliable markers for distinguishing TB from BCC.

To investigate the relationship of aberrant SMAD family member 7 (SMAD7) signaling pathway and ferroptosis in myelodysplastic syndromes (MDS) and evaluate the effect of asiaticoside (AC)-modulating SMAD7 up-regulation to suppress ferroptosis in MDS cell lines.

Publicly available MDS-related datasets from the Gene Expression Omnibus (GEO) database were analyzed to identify differentially expressed genes (DEGs) between MDS patients and healthy controls. These DEGs were cross-referenced with ferroptosis-associated genes from the Ferroptosis Database (FerrDb) to identify potential ferroptosis-related targets in MDS. Bone marrow mononuclear cells (BMMNCs) were isolated from 18 MDS patients freshly diagnosed in the First Medical Center of Chinese PLA General Hospitaland and from 16 healthy donors during October 2022 and November 2024. RT-qPCR was employed to detect the expression of SMAD7 and ferroptosis-related genes. Immunomagnetic bead sorting was applied to purify CD33⁺ cells, and then qPCR and Western blotting were utilized to measure the expression of SMAD7 and ferroptosis-related biomarkers at mRNA and protein levels. Human normal bone marrow cells (HS-5) and MDS cell lines (MUTZ-1, SKM-1) were treated with gradient concentrations of AC (SMAD7 activator) and ferrostatin-1 (Fer-1, ferroptosis inhibitor), and SMAD7 overexpression plasmids were transfected into MDS cells. qPCR and Western blotting were utilized to measure the expression of SMAD7 and ferroptosis-related biomarkers at mRNA and protein levels, and the contents of glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were detected. Flow cytometry of CD11b⁺ was performed to measure cellular differentiation.

‍①Bioinformatics analysis revealed significant down-regulation of SMAD7 in MDS patients, correlating with ferroptosis activation. Compared to the healthy controls, MDS patients exhibited decreased SMAD7 expression (P<0. 05), reduced levels of negative regulators of ferroptosis, glutathione peroxidase 4 (GPX4) and ferritin heavy chain (FTH1) (P<0.05), and elevated expression of its positive regulator transferrin receptor protein 1 (TFRC) (P<0.05). Consistent with this, when compared with the normal human bone marrow stromal cell line HS-5, the MDS cell lines MUTZ-1 and SKM-1 exhibited declined expression of SMAD7, GPX4, and FTH1, alongside elevated expression of TFRC (P<0.05). ② Treatment with gradient concentrations of the ferroptosis inhibitors ferrostatin-1 (Fer-1), the expression levels of GPX4 and FTH1 in MDS cell lines were significantly upregulated in a concentration-dependent manner (P<0.05), while TFRC was markedly downregulated (P<0.05). Additionally, GSH content and SOD activity were enhanced, whereas ROS levels and MDA content were significantly reduced (P<0.05). These results suggest that Fer-1 effectively suppresses ferroptosis in MDS cells.③SMAD7 overexpression led to up-regulation of GPX4 and FTH1 ih MDS cell lines, while downregulation of TFRC, improved anti-oxidative ability and reduced ferroptosis, with enhanced CD11b⁺ expression and myeloid differentiation. ④ Following AC treatment, the expression levels of GPX4 and FTH1 in MDS cell lines were significantly upregulated in a concentration-dependent manner (P<0.05), whereas the downregulation of TFRC did not reach statistical significance. Additionally, AC treatment effectively enhanced the antioxidant capacity of the cells, increased the proportion of CD11b⁺ cells (P<0.05), and facilitated cellular differentiation.

AC activates SMAD7 in MDS cell lines, up-regulating GPX4 and FTH1 while suppressing TFRC expression. This mechanism alleviates oxidative damage and lipid peroxidation, thereby inhibiting ferroptosis in MDS cells. Concurrently, SMAD7 activation promotes cellular differentiation.

To explore the roles of transcription factor E26 transformation-specific 1 (ETS1) and F-box protein 45 (FBXO45) in invasion and metastasis in hepatocellular carcinoma cells and the potential molecular mechanism.

Jaspar, hTFtarget and Cistrome transcription factor database prediction websites were used to predict the transcription factors of FBXO45. According to the intersection of the predicted results of each database, the expression of FBXO45 was detected after the candidate transcription factors were knockdown in HCCLM3 and Huh7 liver cancer cells, respectively. The most significant influence on FBXO45 expression was selected for further analysis, and chromatin immunoprecipitation assay (ChIP) was used to verify the binding to the FBXO45 promoter. Finally, the potential transcription factor of FBXO45 was identified. The effect of ETS1 overexpression on invasion and migration in HCCLM3 and Huh7 cells was detected by Transwell assay, and the expression levels of epithelial-mesenchymal transition (EMT) pathway proteins were detected by Western blot assay. The effects of FBXO45 knockdown on the invasion and migration under the condition of overexpression of ETS1 were also studied.

Intersection of FBXO45 transcription factors identified 3 candidate transcription factors, ETS1, SPI1 and YY1. When the 3 transcription factors were knocked down in HCCLM3 and Huh7 cells, respectively, ETS1 knockdown significantly reduced the expression of FBXO45. According to the analysis of The Cancer Genome Atlas (TCGA) data and the Gene Expression Omnibus (GEO) data, the expression levels of ETS1 and FBXO45 were significantly positively correlated (R=0.31, P<0.000 1; R=0.40, P=0.021 9). ChIP suggested that ETS1 could specifically bind to FBXO45 promoter sequence to regulate its expression, confirming that ETS1 was a potential transcription factor of FBXO45. After overexpression of ETS1 in HCCLM3 and Huh7 cells, the invasion and migration abilities of cells were significantly enhanced, and the expression of N-cadherin and Snail was up-regulated(P<0.01). In addition, in the case of ETS1 overexpression, FBXO45 knockdown significantly inhibited the invasion and migration(P<0.01).

ETS1 activates the transcription of FBXO45 and leads its high expression, which enhances the invasion and migration of HCC cells via EMT pathway and promotes the progression of hepatocellular carcinoma.

To systematic analyze the risk factors for new-onset urethral stricture after transurethral holmium laser enucleation of the prostate （HoLEP） in the treatment of benign prostatic hyperplasia （BPH）.

A case-control study was conducted on 746 BPH patients undergoing HoLEP treatment in Department of Urology of the Third Medical Center of Chinese PLA General Hospital from November 2021 to August 2024. After 23 cases were excluded because of complication of prostate cancer，finally 723 patients were included. General clinical data such as age，height，weight，history of smoking and drinking，perioperative parameters，and follow-up data at 1，3 and 6 months after operation were collected. Univariate and multivariate logistic regression analyses were used to identify the clinical risk factors for new-onset urethral stricture after HoLEP.

The subjected patients had a median age of 66.5 （64.0，75.0） years，and a preoperative median prostate volume of 66 （45，92） mL，and a median indwelling catheter time of 4 （4，5） d. The incidence of new urethral stricture after operation was 5.8% （42/723），with membranous part of the urethra （61.9%） the most common site，followed by the external urethral orifice （21.4%） and the bladder neck （7.1%）. Risk factor analysis indicated that low BMI （<18.5 kg/m²） （OR=4.682，P=0.037），young age （OR=0.946，P=0.005），and postoperative urinary tract infection （OR=4.513，P=0.001） were independent risk factors for new-onset urethral stricture after surgery. Prostate volume and indwelling time of urinary catheter had no significant association with the occurrence of new urethral stricture after surgery.

The occurrence of new-onset urethral stricture after HoLEP is significantly correlated with BMI，age and urinary tract infection. The above 3 factors can be used as better predictors of new-onset urethral stricture after HoLEP.

To explore the relationship between postoperative defecation dysfunction and quality of life in children with anorectal malformation (ARM) complicated with spinal cord anomalies (SCA) and analyze the impact of different types of SCA on ARM patients in order to provide a reference for the early clinical identification of high-risk children with poor prognosis.

A retrospective analysis was conducted on 282 ARM neonates admitted to our department between June 2015 and April 2021. Radiological examinations were applied to evaluate the development of the spinal cord, and Rintala score and the PedsQL 4.0 scale were employed to assess postoperative defecation function and quality of life, respectively. According to their SCA types and other complications, the patients were grouped. The relationship between these factors and defecation function as well as quality of life was then analyzed.

Among the 282 subjected children, 104 (36.9%) had SCA. The incidence of SCA varied significantly across different types of ARM (P=0.002), with the highest incidence observed in vaginal fistula patients (100.0%) and the lowest in children without fistula (13.6%). Radiological findings revealed that sacral bone anomalies were common, with absent coccyx (62.7%) and vertebral anomalies (69.8%) being the most prevalent. The SCA group had significantly lower Rintala bowel function score (12.70±3.24) and PedsQL 4.0 quality of life score (81.42±5.03) than the non-SCA group (P<0.001). As the increment of SCA types, both the Rintala score and PedsQL 4.0 score were in a significant downward trend (P<0.001). Among the children with different types of SCA, those with tethered cord syndrome had the statistically lowest Rintala score (8.05±2.35, P<0.05). Meanwhile, their PedsQL 4.0 score (75.90±3.35) was significantly lower than those of other types except syrinx (P<0.05). Multiple linear regression analysis indicated that both SCA and sacral bone anomalies exerted notably negative impacts on the Rintala score and PedsQL 4.0 score (P≤0.001), with SCA having the most pronounced effect.

SCA is closely associated with postoperative defecation dysfunction and diminished quality of life in ARM children. The greater the type and number of SCAs, the worse the postoperative defecation function and quality of life. Early identification of concomitant SCAs holds significant clinical value for predicting postoperative outcomes in ARM patients.

To construct and validate an interpretable machine learning model integrating contrast-enhanced venous phase CT radiomics and clinical features for preoperative prediction of central lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC).

A case-control study was conducted on 243 histologically confirmed PTC patients. Among them, 196 patients from the First Affiliated Hospital of Army Medical University were randomly allocated into a training set (n=137) and an internal validation set (n=59) at a 7:3 ratio, while the left 47 patients from No. 958 Hospital of PLA Army were assigned into an external validation set. All participants completed standardized preoperative contrast-enhanced neck CT scanning. Quantitative radiomic features were systematically extracted from venous phase CT images through an open-source big data AI platform. Six machine learning classifiers, eXtreme Gradient Boosting (XGBoost), Support Vector Machine (SVM), Random Forest (RF), Logistic Regression (LR), k-Nearest Neighbors (KNN), and Decision Tree (DT) were implemented to construct clinical-radiomics integration models. The predictive performance was quantitatively assessed through receiver operating characteristic (ROC) curve analysis, with area under the curve (AUC) values calculated for training, internal validation, and external validation sets. Model interpretability was achieved using Shapley additive explanations (SHAP) framework, with particular focus on elucidating feature contributions in the best-performing model.

The XGBoost model had an AUC value of 0.936 (95%CI: 0.895~0.976), 0.832 (95%CI: 0.724~0.941), and 0.772 (95%CI: 0.632~0.912) in training, internal and external validation sets, respectively. SHAP analysis revealed age as the most influential clinical predictor, with younger patients showing higher CLNM risk (OR=0.968, P=0.042).

Our machine learning-based clinic-radiomic prediction model demonstrates satisfactory performance in predicting CLNM of PTC, providing valuable references for clinical decision-making.

To construct 5 machine-learning models and compare their performance in predicting the associations between pre-pregnancy socio-psycho-behavioral exposures of both spouses and preconception outcomes.

Based on Chongqing Preconception Reproductive Health and Birth Outcome Cohort of volunteers recruited from Chongqing Health Center for Women and Children during January 2019 and March 2022, 5 447 couples were recruited and surveyed through interviewer-interview for the demographic and social-psychological-behavioral data of both spouses (221 variables). According to the inclusion and exclusion criteria, 4 097 couples were finally included, and randomly assigned into a training set (n=2 867 spouses) and a validation set (n=1 230 spouses) at a ratio of 7∶3. Feature analysis and collinear screening were applied to select the potential exposure factors. In consideration of difficulty to carry out semen parameters analysis in primary healthcare institutions, feature Set 1 including sperm parameters and feature Set 2 excluding semen parameters were constructed by including or excluding sperm quality simultaneously in the training set and the validation set. Five algorithms, that is, Logistic Regression, Naive Bayes, Random Forest, Gradient Boosting Machine, and Support Vector Machine, were used to construct preconception outcome prediction models, and the parameters of each model were optimized using random search combined with grid search. The predictive performance of each model was compared using precision, recall, F1 score, area under the receiver operating characteristic curve (AUC), and calibration curve. The optimal model was then selected by comparing the changes in the predictive ability of the questionnaire data for fertility outcomes with or without semen parameters.

There were 24 variables screened out in feature Set 1, and 16 variables in feature Set 2. In feature Set 1, the gradient boosting machine performed better, with a relatively higher AUC value (0.651) and better F1 score (0.61). The logistic regression model performed stably (AUC value =0.647) and was suitable as the reference model. The random forest (AUC value=0.641), Naive Bayes (AUC value=0.641), and support vector machine (AUC value=0.634) performed second-best. By utilizing the gradient boosting machine, comparable results were found between the predictions from feature sets with or without semen parameters, as in feature Set 1, the AUC value of its validation set was 0.651 (95%CI: 0.629~0.681), the prediction accuracy was 0.63, the recall rate was 0.65, and the average precision value F1 was 0.61; and in feature Set 2, the AUC value of its validation set was 0.649 (95%CI: 0.624~0.663), and both the calibration curves were close to the ideal curve. The prediction results indicated that in feature Set 1, the features highly negatively correlated with preconception outcomes were female age, male age, and no pregnancy within 1 year without contraception, while the features highly positively correlated with preconception outcomes were female pregnancy history, total sperm vitality, and use of contraceptive measures before enrollment.

Among the 5 machine-learning algorithms performed in this cohort data, the gradient boosting machine shows slightly better performance. There are 24 factors being associated with preconception outcomes in both spouses, and the performance of the simplified model excluding semen parameters is not significantly declined. It is feasible to use machine-learning methods to predict human preconception outcomes through social-psychological-behavioral questionnaires.

To systematically assess the spatiotemporal distribution，risk factors，and future trends of chronic obstructive pulmonary disease （COPD） among individuals under 50 years of age globally from 1990 to 2021 based on Global Burden of Disease （GBD） data in order to provide support for the formulation of prevention and control strategies of the disease.

The GBD data from 1990 to 2021 were analyzed for the incidence，mortality，disability-adjusted life years （DALYs），and estimated annual percentage change （EAPC） of COPD in <50-year-old individuals across 204 countries and regions. The data were stratified by age，sex，region，country，and sociodemographic index （SDI）. The COPD trends until 2035 were predicted.

In 2021，the global incidence of early-onset COPD was estimated at 2.5 million cases （95% uncertainty interval：2.09~2.96 million），representing a 50.55% increase compared to 1990. Significant regional heterogeneity was observed，with low SDI regions experiencing a 134.08% increase，whereas high SDI regions exhibited a rise-then-fall trend. Risk factor analysis identified environmental and occupational exposures （air pollution，ambient ozone pollution，household air pollution from solid fuels， etc.） and smoking as the primary etiological factors. Notably，household solid fuel exposure accounted for 50.90% of COPD-related deaths in low SDI regions，compared to only 0.03% in high SDI regions. Projections indicated that by 2035，the global burden of early-onset COPD will increase to 2.59 million cases.

The global disease burden of COPD among people under 50 years increased significantly from 1990 to 2021，with pronounced disparities across regions and socioeconomic levels. COPD deaths in low-SDI regions are strongly associated with solid fuel exposure and particulate matter pollution，and these regions are expected to remain the main drivers of global COPD incidence growth through 2035.

To investigate the role and underlying mechanisms of oxoglutarate dehydrogenase-L (OGDHL) in renal fibrosis.

Twelve male wild-type C57BL/6J mice (8 weeks old, weighting about 25 g) were randomly divided into control group and model group (n=6). A mouse model of renal fibrosis was established by unilateral ureteral obstruction (UUO). HE staining, immunofluorescence assay, and immunohistochemical and Masson staining were applied to assess the extent of renal fibrosis. Human kidney-2 proximal tubule cell line (HK-2) were randomly divided into blank plasmid group (Vector), OGDHL overexpression group (OGDHL OE), blank plasmid + TGF-β1 treatment group (TGF-β1+Vector), TGF-β1 treatment and OGDHL overexpression group (TGF-β1+OGDHL OE). Transmission electron microscopy (TEM) was employed to observe mitochondrial morphology. RT-qPCR, Western blotting and immunofluorescence assay were used to detect the expression levels of OGDHL and mitochondrial metabolism-related genes. Adenosine triphosphate (ATP) level, oxygen consumption rate (OCR), extracellular acidification rate (ECAR) and other mitochondrial metabolism-related indicators were detected with corresponding reagent kits and Agilent Seahorse.

UUO operation resulted in obvious thinning of the renal cortex, significant hydronephrosis. HE staining revealed that tubular atrophy accompanied by dilated tubular lumens in the kidneys. Immunofluorescence, immunohistochemical and Masson staining showed obvious renal fibrosis after UUO operation. In the mouse model of renal fibrosis, the expression of OGDHL was decreased by 82.9% at mRNA level (P<0.001) and 81.9% at protein level (P<0.001), the production of mitochondrial ATP was reduced by 0.970±0.151 µmol/L (P<0.01), and notable damaged mitochondrial structure was observed, with maximum breathing capacity decreased by 25.260±1.920 pmol/min (P<0.001), expression levels of fatty acid oxidation-related genes were declined by 50.2% (P<0.05), while glycolysis was enhanced, with the genes related to glycolysis increased by 2.5 times when compared with those in the control group (P<0.05). After OGDHL overexpression, mitochondrial morphological damage was significantly improved, ATP production was increased by 0.980±0.090 µmol/L (P<0.05), with significantly alleviated energy metabolism disorder and renal fibrosis (P<0.05).

OGDHL regulates mitochondrial metabolic reprogramming of renal tubular epithelial cells to alleviate fibrosis, suggesting that OGDHL may be a new therapeutic target for renal fibrosis.