Determine whether a modified macroscopic on-site evaluation （MOSE) technique, by enhancing visualization of the macroscopic visible core (MVC) in 22G/25G fine needle aspiration (FNA) specimens, improves specimen adequacy and pathological diagnostic accuracy.

This single-center, prospective, randomized crossover trial enrolled 90 consecutive patients with solid pancreatic lesions scheduled for EUS-FNA from the Department of Gastroenterology at the Third People’s Hospital of Chengdu between February 2023 and August 2024. Patients were randomly assigned (1∶1) via a computer-generated sequence to Group A (first pass using traditional MOSE, second pass using modified MOSE) or Group B (first pass using modified MOSE, second pass using traditional MOSE). The core modification was the use of an adjustable white light source from 35 to 1 700 LUX at a fixed distance (37.2 mm) from the slide. Specimen adequacy was defined as MVC≥4 mm. The primary outcome was the specimen adequacy rate between groups. Secondary outcomes included the diagnostic accuracy of cytopathology and histopathology. Bias was controlled through blinded assessment (pathologists and data analysts were unaware of group allocation) and standardized operating procedures.

The specimen adequacy rate was significantly higher in the modified MOSE group (70.0%, 95%CI: 59.9 to 78.5%) than in the traditional MOSE group (43.3%, 95%CI: 33.6 to 54.6%; χ²=13.714, P<0.001). The modified MOSE group also demonstrated superior diagnostic accuracy for both cytopathology ［94.4%(95%CI: 87.7%~97.6%) vs 85.6%(95%CI: 76.8%~91.4%),χ²=4.9, P=0.021) and histopathology of tissue strips ［95.6%(95%CI: 89.1%~98.3%) vs 83.3%(95%CI: 76.8%~91.4%),χ²=7.69, P=0.003]. Subgroup analysis based on needle gauge demonstrated that for the 22G needle, which constituted 87.8% (79/90) of cases, the modified MOSE demonstrated statistically significant advantages over the traditional MOSE in the following outcomes: specimen adequacy rate [65.8% (95%CI: 55.1% to 76.5%) vs 41.8% (95%CI: 30.7% to 52.9%), P=0.003], cytological diagnostic accuracy [93.7% (95%CI: 88.1% to 99.2%) vs 84.8% (95%CI: 76.7% to 92.9%), P=0.039], and histological diagnostic accuracy [94.9% (95%CI: 90.0% to 99.9%) vs 82.3% (95%CI: 73.7% to 90.9%), P=0.013].

Modified MOSE can enhance the visualization of the MVC in specimens obtained by 22G/25G FNA, thereby improving the specimen adequacy rate and pathological diagnostic accuracy.

To investigate the restoration of near stereopsis following corrective surgery for concomitant exotropia and analyze its influencing factors.

This retrospective case series included 246 patients with concomitant exotropia who underwent strabismus surgery between February 2022 and June 2025. The patients were stratified into a pediatric group (6~<18 years, n=147) and an adult group (≥18 years, n=99). Preoperative and postoperative clinical data were analyzed to assess near stereopsis restoration and its predictors.

A total of 147 pediatric patients with concomitant exotropia were included. The preoperative presence rate of near stereopsis was 83.0%, increasing to 95.9% postoperatively. Postoperative outcomes for near stereoscopic function were cure (60.5%), improvement (19.7%), and no improvement (19.7%). Ninety-nine adult patients with concomitant exotropia were also included. The preoperative presence rate of near stereopsis was 43.4%, increasing to 85.9% postoperatively; Postoperative outcomes were cure (27.3%), improvement (43.4%), and no improvement (29.3%). Near stereoscopic function significantly improved postoperatively in both groups (P<0.001). The postoperative restoration rate was significantly higher in pediatric patients than in adults (80.3% vs 70.7%, χ² = 27.543, P<0.001). Univariate analysis showed that in the pediatric group, age at surgery, type of exotropia, preoperative near stereopsis, preoperative near and distance deviation, surgical approach, and follow-up time were significant predictors (P<0.05). In adults, only the type of exotropia and preoperative near stereopsis were significantly associated with stereopsis restoration (P<0.05). Multivariate logistic regression analysis revealed that preoperative near stereopsis and exotropia type were independent predictors of stereopsis restoration in both groups (P<0.05). Additionally, in pediatric patients, age at surgery, surgical approach, and follow-up time were significant factors, while in adults, age at onset was significant (P<0.05).

Near stereopsis restoration is superior in pediatric patients versus adults. Key determinants differ: pediatric outcomes are influenced by surgical age, approach, follow-up, exotropia type, and preoperative stereopsis; adult outcomes by age at onset, exotropia type, and preoperative stereopsis. These differences should be taken into account in clinical practice.

To construct a machine learning-based prediction model for chronic kidney disease(CKD) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and to develop a diagnostic nomogram for guiding clinical management.

This study was based on the National Health and Nutrition Examination Survey (NHANES) database (2007 to 2018). Patients with MASLD, defined as hepatic steatosis with at least one cardiometabolic risk factor, were selected as the analysis sample. After excluding patients with chronic renal failure and other conditions, a total of 2 144 MASLD patients were included, and 34 variables (including demographics, clinical characteristics, and laboratory indicators) were collected. Patients were stratified into a chronic kidney disease (CKD) group (n=347) and a non-CKD group (n=1 797) based on CKD status. The total participants were randomly divided into a training set (n=1 501) and an internal validation set (n=643) using stratified sampling at a 7∶3 ratio. A prospective external validation cohort comprising 110 eligible fatty liver disease patients was recruited from our department during January 2024 and October 2025, adhering strictly to predefined inclusion and exclusion criteria Variables were screened using Least Absolute Shrinkage and Selection Operator (Lasso) regression. Eight machine learning algorithms were then employed to construct the CKD risk prediction models: decision trees (DT), extreme gradient boosting (XGBoost), K-nearest neighbors (KNN), Naive Bayes (NB), support vector machine (SVM), single hidden layer neural networks (NNET), light gradient boosting machine (LightGBM), and random forest (RF). Model performance was comprehensively evaluated using receiver operating characteristic (ROC) curves area under the curve (AUC), sensitivity, specificity, calibration curves, and clinical decision curves. Based on key biomarkers identified through SHAP analysis, a diagnostic nomogram was constructed, and its diagnostic accuracy was assessed using ROC curves.

Using interpretable machine learning algorithms, we identified 10 key biomarkers: SBP, age, diabetes, BUN, BMI, globulin, HDL-C, neutrophil count, uric acid, and gamma-glutamyl transferase. These biomarkers were utilized to construct predictive models through 8 distinct machine learning algorithms. Comprehensive evaluation revealed that the LightGBM model achieved optimal performance, with an AUC of 0.871, a sensitivity of 0.838, a specificity of 0.756, an accuracy of 0.825, an F1 score of 0.889, and a Brier score of 0.091. Calibration curve analysis demonstrated good consistency of the LightGBM-based predictive model across both training and validation sets. Clinical decision curve analysis indicated significant clinical utility of this model in predicting kidney damage risk in patients with MASLD. Based on SHAP values, we developed a diagnostic nomogram with a risk cutoff score of 81.7. This nomogram enabled categorization of patients into high-risk and low-risk subsets for MASLD-related CKD, and exhibited favorable accuracy and robust predictive reliability with an AUC value of 0.816.

The LightGBM model significantly outperforms other models and demonstrates potential for application in early clinical prediction of CKD risk among MASLD patients.

This study proposes a multi-omics integration model, EGWO-GAT, based on graph attention network (GAT) and enhanced-grey wolf optimizer (EGWO), for staging prediction of bladder urothelial carcinoma (BLCA) samples.

A total of 404 BLCA samples from The Cancer Genome Atlas (TCGA) were collected from the University of California, Santa Cruz Xena (UCSC Xena) functional genomics explorer, including mRNA, DNA methylation, and microRNA (miRNA) data. After separate preprocessing and differential analysis of the 3 omics datasets, node features and edge features were extracted. Using GAT as the backbone framework, EGWO was employed for hyperparameter optimization, and multilayer perceptron (MLP) was applied for cancer staging prediction. Through 5-fold cross-validation, the performance of EGWO-GAT was compared with classical machine learning models, along with omics contribution analysis and performance conparison of models retaining different numbers of similar edges. Accuracy, precision, recall, F1 score, and area under the curve (AUC) were used as core evaluation metrics.

Differential feature screening identified 534 differentially expressed genes in mRNA, 3 108 differential probes in DNA methylation, and 114 differential miRNAs. Model comparisons showed that EGWO-GAT achieved optimal performance when integrating all omics data and retaining edges from the top 3 similar patients, with an AUC value of 0.744, an accuracy of 0.711, a precision of 0.792, a recall of 0.782, and an F1 score of 0.785. Its performance significantly surpassed other classical methods and outperformed the GS-GAT model across all metrics. Omics contribution analysis confirmed that full integration (mRNA+DNA methylation+miRNA) outperformed all other combinations. Result of the similarity edge number performance comparison demonstrated that retaining the top 3 similar edges yielded the highest AUC, accuracy, precision, and F1 score compared to the top 5 or 7 edges.

The EGWO-GAT model exhibits excellent performance in BLCA staging, providing reliable technical support for precise diagnosis. It addresses clinical challenges caused by sample heterogeneity and holds significant potential for guiding individualized treatment and improving patient prognosis.

To explore the mediating roles of positive and negative rumination in the relationship between depressive symptoms and executive function and its subdomains (inhibitory control, working memory, and cognitive flexibility) among college students.

During September and October 2024, an electronic questionnaire was distributed using convenience sampling through the “Wenjuanxing” platform to universities in 30 provinces and municipalities across China, such as Chongqing and Sichuan.A total of 699 college students were surveyed online using patient health questionnaire-9 (PHQ-9), positive and negative rumination scale (PANRS), and behavior rating inventory of executive function-adult version (BRIEF-A). The participants were divided into depressive symptom group (n=466, 66.67%) and a non-depressive symptom group (n=233, 33.33%) based on PHQ-9 score. Differences in scores between the 2 groups were compared, and the relationships between variables as well as the mediating effects were analyzed.

① Scores of negative rumination were significantly higher in the depressive symptom group than in the non-depressive symptom group [(30.27±4.93） vs （26.42±3.81）， t=-10.451，P<0.001], while executive function and its subdomains, as well as positive rumination, were significantly lower (r=0.394，P<0.01). ② Depressive symptoms showed a significant positive correlation with negative rumination and a significant negative correlation with executive function and its subdomains (P<0.01), but no significant correlation with positive rumination (P>0.05).③ Negative rumination exhibited a mediating effect in the relationship between depressive symptoms and executive function, accounting for 10.85% of the total effect, whereas positive rumination served as a positive predictor of executive function (β=0.086， P<0.05).④ The mediating effect of negative rumination between depressive symptoms and executive function subdomains demonstrated domain specificity, reaching statistical significance only for inhibitory control and working memory, with indirect effect ratios of 8.11% and 16.94% respectively, but not for cognitive flexibility. No significant mediating effect was observed for positive rumination.

Negative rumination plays a partial mediating role between depressive symptoms and executive function (particularly in inhibitory control and working memory) among college students, and it can be regarded as a core modifiable target for interventions to improve executive dysfunction in depressed college students.

To investigate the role and mechanism of CD4⁺ T-cell-derived IFN-γ in host defense against blood-stage Plasmodium berghei (P. berghei) infection.

A tamoxifen-inducible conditional knockout strategy was performed to generate mice lacking IFN-γ specifically in CD4⁺T cells (Ifng^fl/flCD4-CreER^T2). Then after the mice were infected intravenously with luciferase-expressing P. berghei ANKA (P. berghei ANKA-luciferase) strain, parasite burden, survival, and intra-erythrocytic developmental rhythm were monitored dynamically. Flow cytometry and ELISA were carried out respectively to quantify the splenic myeloid subsets and the titers of P. berghei-specific IgG and IgG2c.

CD4⁺T-cell-specific IFN-γ deficiency significantly reduced peripheral parasitemia on day 5 post-infection (P<0.05), showing no effect on survival or 24-hour intra-erythrocytic cycle of the parasite. Ifng^fl/fl CD4-CreER^T2 mice exhibited obviously decreased P. berghei-specific IgG2c (P<0.01) but increased total IgG (P<0.05). Frequencies and absolute numbers of neutrophils, monocytes, and macrophages remained unchanged.

During the process of P. berghei infection, IFN-γ secreted by CD4⁺T cells may decrease total serum IgG level by promoting class switching to IgG2c, and then enhance parasite burden after blood-stage P. berghei infection.

To investigate the effect and underlying mechanisms of curcumin (CUR) on small intestinal injuries associated with severe traumatic infections after combined treatment of ciprofloxacin (CIP) and indomethacin (IND).

Adult male C57BL/6 mice (8 weeks old) were randomly divided into (10 animals for survival rate observation, 10 for other indicators) control group, model group [hemorrhage+ fracture+Pseudomonas aeruginosa (PA) infection], IND+CIP treatment group, and IND+ CIP+CUR treatment group. The survival rates within 72 h post-modelling were observed across all groups. At 24 h post-modelling, peripheral blood samples, small intestinal tissues and mesenteric lymph nodes (MLN) were harvested. Small intestinal length, hemorrhagic status, and adhesions were also observed grossly in each group. Bacterial load was determined via dilute plating. HE staining was used to observe histopathological alterations in intestinal tissues across groups. ELISA was employed to measure the contents of inflammatory cytokines, IL-1β, IL-6, IL-10 and TNF-α in the serum and small intestinal homogenate of each group. Liver, renal, and cardiac functions were evaluated by measuring key biochemical indicators. Flow cytometry was applied to measure the percentages of IFN-γ, IL-4, TGF-β, and IL-17 positive cells within CD4⁺ T cells in the MLN. Real-time quantitative polymerase chain reaction (qPCR) was performed to detect the mRNA expression of forkhead box protein P3(FOXP3) and retinoic acid receptor-related orphan receptor gamma (RORγ)-t in each group.

Both the IND+CIP treatment group and the IND+CIP+CUR treatment group significantly improved survival rates in mice with severe traumatic infections (P<0.05). CUR addition reduced bacterial load in the mice (P<0.01). The IND+CIP treatment group exhibited small intestinal injury, which worsened over time, manifested by elevated contents of TNF-α (P<0.01), IL-6 (P<0.05), and IL-1β (P<0.05) and decreased IL-10 (P<0.01) in the small intestine tissues, accompanied with pathological damage in the small intestine. The IND+CIP+CUR treatment group had significantly reversed small intestinal injury, reduced inflammatory factor levels (P<0.01), and restored normal small intestinal structure, showing no significant differences in relevant blood biochemical indicators when compared to the IND+CIP treatment group. The expression of FOXP3 was increased and that of RORγ-t was decreasedin CD4⁺ T cells from the IND+CIP+CUR treatment group than the IND+CIP treatment group (both P<0.01).

The combination of CUR with IND and CIP can effectively alleviate severe traumatic infections, while antagonize small intestinal damage observed in IND and CIP therapy, with no significant adverse effects on vital organ functions. This mechanism may be related to the balance between regulatory T (Treg) cells and T helper 17 (Th17) cells.

TTo explore the role of circ-gabra5 in the pathogenesis of Alzheimer’s disease (AD) in mice.

APP/PS1 double transgenic AD mice (6 months old) were selected as the experimental group, and C57BL/6 wild-type (WT) mice were enrolled as the control group. The mice were divided into an AD group and an AD mice with circ-gabra5 knockout (AD+circ-gabra5 knockout) group, with 5 mice in each group. After total RNA was extracted from mouse brain, differential expression of circRNA was detected, and real-time quantitative PCR (RT-qPCR) was used to validate the top 6 circRNA genes with differences. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Using hippocampal stereo injection of lentivirus to knock out the circ-gabra5 gene, the learning and memory function of mice was detected with Morris water maze test, and the number of Aβ plaques in mouse brain tissue was observed through immunohistochemistry. Transmission electron microscopy was utilized to observe the mitochondrial damage and synaptic count in mouse neurons. Dual luciferase reporter assay and RNA binding protein immunoprecipitation (RIP) assay were employed to verify the interaction between circ-gabra5 and miR-455-3p. Western blotting was apllied to detect the expression level of AKT protein.

There were 273 differentially expressed genes screened between AD mice and WT mice, including 163 up-regulated and 110 down-regulated genes. Circ-gabra5 had the largest fold difference of 1.39 (P<0.05). GO and KEGG analyses suggested that the functional expression differences between AD mice and WT mice were enriched in thyroid hormone, PI3K/AKT, RNA metabolism and other signaling pathways. Knocking out of circ-gabra5 gene in AD mice resulted in obvious improvement in cognitive impairment in Morris water maze test, decreased Aβ plaques by immunohistochemistry, and attenuated neuronal mitochondrial damage and more cortical synapses in AD mice by transmission electron microscopy (P<0.05). According to the starBase database prediction, circ-gabra5 and miR-455-3p have complementary sequences. Dual luciferase reporter assay and RIP assay confirmed the interaction between circ-gabra5 and miR-455-3p. Database bioinformatics analysis predicted that miR-455-3p and AKT have complementary sequences. qPCR indicated that knocking down the circ-gabra5 gene in primary cultured neurons of AD mice resulted in a decrease in miR-455-3p expression, and subsequent Western blot analysis showed a decrease in AKT protein level (P<0.01).

Circ-gabra5 exacerbates cognitive impairment in AD mice by regulating AKT protein through miR-455-3p, increases Aβ deposition in brain tissue, aggravates neuronal mitochondrial damage, and reduces the number of neural synapses.

To investigate the effect of prenatal estriol (E3) exposure on autism spectrum disorders (ASD) and the role of the Notch signaling pathway in the process.

Untargeted metabolomics was performed on plasma samples from 44 mothers of ASD children and 44 matched controls in the Guangxi Zhuang birth cohort. Then E3 was identified as main differential metabolite during pregnancy. SH-SY5Y cells were subjected and divided into a control group and study groups (10, 30, 50 and 100 μmol/L E3), and proteomics was performed to screen the main pathway involved in the process. CCK-8 assay was employed to detect cell proliferation. Western blotting and RT-qPCR were performed to verify the obtained pathway.

Metabolomics analysis for plasma metabolite levels in pregnant women showed that the E3 level in the case group was significantly down-regulated than that of the control group (P<0.01). KEGG enrichment analysis indicated that the Notch signaling pathway was a significantly enriched pathway (P<0.01). CCK-8 assay suggested that the concentration of 100 μmol/L was identified as the most significant dose for E3 in the proliferation inhibition of SH-SY5Y cells (P<0.01). Both qPCR and Western blotting indicated that 100 μmol/L E3 treatment resulted in obvious down-regulation in Jagged1 (P<0.01), Notch1 (P<0.01), and Hes1 (P<0.05) at mRNA and protein levels in SH-SY5Y cells.

Prenatal E3 exposure may be associated with ASD, and its mechanism may be through inhibiting the Notch signaling pathway, and thereby inhibiting neural cell proliferation.

To construct an Escherichia coli (E. coli)-specific reporter phage, T6::Nluc, and evaluate its performance in the rapid diagnosis of E. coli-induced urinary tract infections.

T6::Nluc was constructed by the CRISPR/Cas9 system combined with homologous recombination technology. Then biological characteristics of T6 and T6::Nluc were systematically compared in terms of optimal multiplicity of infection (MOI), one-step growth curves, and lysis efficiency. Time-luminescence curves were plotted to determine the limit of detection (LOD) and the impact of urine matrix. Luminescence quantification was performed to detect the specificity of the phage after being co-cultured with non-E.coli pathogens. In addition, 104 strains of E. coli isolated from clinical urine samples were collected to analyze the detection coverage of T6::Nluc. Finally, 437 clinical urine samples were obtained for clinical validation.

The successful construction of reporter phage T6::Nluc was validated by Sanger sequencing. Its one-step growth curve and optimal MOI differed from those of T6, and the lysis efficiency remained comparable. T6::Nluc exhibited outstanding diagnostic performance, enabling the detection of ≥10⁴ CFU/mL E. coli within 40 min, with complete resistance to interference from urine matrix and excellent pathogen-specific recognition. Additionally, T6::Nluc successfully detected 51 out of 104 clinical E. coli isolates (49.04%). And the results of the detection in clinical urine samples indicated that the phage had a sensitivity of 48.84% and a specificity of 100.00 in the detection.

Reporter phage T6::Nluc is successfully constructed, and can sensitively and specifically detect E. coli causing urinary tract infections, significantly reducing detection time and enhancing efficiency and accuracy.