To screen novel molecular glues targeting ovarian tumor domain deubiquitinase with linear linkage specificity (OTULIN) and provide a new therapeutic strategy for gastric cancer.

Gastric cancer cell lines with high OTULIN expression (AGS-NC, SNU601-NC) and OTULIN-knockout cells (AGS-sgOTULIN, SNU601-sgOTULIN) were used. Experimental groups included: control (DMSO), LTL-04-061 concentration gradients (0.1, 0.3, 1.0, 3.0, 5.0, 7.0, 10.0 μmol/L), and proteasome inhibitor intervention (MG-132/MLN4924+5 μmol/L LTL-04-061). OTULIN protein expression was analyzed by Western blotting, while mRNA levels were quantified by qPCR. Protein interactions were validated by co-immunoprecipitation (Co-IP). Molecular docking and 100 ns molecular dynamics (MD) simulations were performed to analyze complex conformations. Anti-proliferative effects were assessed using CCK-8, cell proliferation, and colony formation assays.

LTL-04-061 degraded OTULIN protein in a concentration-dependent manner (0.1 to 10.0 μmol/L), with significant degradation at 5 μmol/L. At this concentration, OTULIN mRNA levels remained unchanged (P>0.05). Degradation was blocked by MG-132/MLN4924, indicating dependence on the CRBN-mediated ubiquitin-proteasome pathway. Co-IP confirmed LTL-04-061-induced OTULIN-CRBN ternary complex formation. Key interactions involved OTULIN HIS339 and CRBN TRP378/HIS380. MD simulations showed stable complex conformation after 50 ns (RMSD fluctuation <0.1 nm), sustained hydrogen bonds (80 to 100 ns), and stable radius of gyration (Rg) and solvent-accessible surface area (SASA), indicating no structural expansion/collapse. LTL-04-061 concentration-dependently suppressed gastric cancer cell proliferation and colony formation. CCK-8 assays revealed IC₅₀ values of 8.95 μmol/L (AGS) and 11.70 μmol/L (SNU601). OTULIN knockout significantly attenuated this inhibition (P<0.01).

OTULIN exerts pro-oncogenic effects in gastric cancer. The molecular glue LTL-04-061 targets OTULIN for CRBN-dependent ubiquitin-proteasomal degradation, thereby suppressing malignant proliferation. This identifies LTL-04-061 as a promising precursor for molecularly targeted gastric cancer therapy.

To investigate the mechanism of bone marrow-derived mesenchymal stem cells (MSCs) in alleviating severe acute pancreatitis (SAP) by inhibiting the pyroptosis pathway in a rat model.

Bone marrow-derived MSCs were isolated from 4-week-old male SPF SD rats [body weight, (100±20) g] using the bone marrow flush technique, followed by culture and characterization. Twenty-four male SPF SD rats [body weight (200±20) g] were randomly assigned to four groups (n=6 per group) using a random number table: a sham-operated group, an SAP model group, an ulinastatin-treated group, and an MSCs-treated group. SAP was induced in the latter three groups via retrograde injection of 5%sodium taurocholate into the biliopancreatic duct. The SAP model group received an injection of 100 μL PBS at 12 h post-modeling. The ulinastatin-treated group received an intraperitoneal injection of ulinastatin solution (5×10⁴ U/kg) immediately after model induction. The MSCs-treated group received an injection of MSC suspension (5×10⁶ cells/kg) at 12 h post-modeling. Sham-operated rats underwent laparotomy with gentle pancreatic manipulation before abdominal closure. Pancreatic histopathology was assessed by HE staining and pathological scoring. Serum amylase and lipase activities were measured using commercial assay kits. Serum levels of IL-10, IL-1β, and TNF-α were determined by ELISA. The ultrastructural changes of pancreatic acinar cells were observed under transmission electron microscopy (TEM). Protein expression of NLRP3, GSDMD, and caspase-1 in pancreatic tissue was evaluated by immunofluorescence. The mRNA levels of NLRP3, GSDMD, and caspase-1 were quantified by qRT-PCR. The relative protein expression levels of NLRP3, GSDMD, GSDMD-N, caspase-1, cleaved caspase-1, and IL-1β were analyzed by Western blotting.

The isolated cells exhibited a typical adherent, spindle-shaped, fibroblast-like morphology. Flow cytometry confirmed they were highly positive for the mesenchymal marker CD29 (99.22%) and nearly negative for the hematopoietic marker CD45 (0.42%). These cells also demonstrated osteogenic and adipogenic differentiation potential and were maintained in good condition. Compared with the sham-operated group, the SAP model group showed significantly increased pancreatic histopathological scores, elevated serum amylase and lipase activities, higher levels of pro-inflammatory cytokines (IL-1β and TNF-α), and a lower level of IL-10 (all P<0.000 1). Both ulinastatin and MSCs treatment significantly attenuated these changes, reducing histopathological scores, serum enzyme activities, IL-1β, and TNF-α (P<0.001), while increasing IL-10 (P<0.05). Importantly, the MSCs-treated group showed significantly greater improvement in all these metrics compared to the ulinastatin-treated group (P<0.05). TEM analysis revealed that MSCs treatment promoted the recovery of mitochondrial cristae structure, improved overall organelle morphology, and reduced endoplasmic reticulum swelling in acinar cells, with these restorative effects being more pronounced than in the ulinastatin group. The immunofluorescence results showed that compared with the SAP model group, the expression levels of NLRP3, GSDMD, and caspase-1 in pancreatic tissue were decreased in both the MSCs-treated group and the ulinastatin-treated group (P<0.000 1). Western blot results indicated that, compared with the SAP model group, the relative protein expression levels of NLRP3, GSDMD, GSDMD-N, caspase-1, cleaved caspase-1, and IL-1β in pancreatic tissue were reduced to varying degrees in both the MSCs-treated group and the ulinastatin-treated group (P<0.000 1). qPR-PCR results demonstrated that, compared with the SAP model group, the mRNA expression levels of NLRP3, GSDMD, and caspase-1 in pancreatic tissue were significantly decreased in both the MSCs-treated group and the ulinastatin-treated group (P<0.01). Moreover, compared with the ulinastatin-treated group, the MSCs-treated group exhibited a more significant decrease in all the aforementioned indicators (P<0.001).

Mesenchymal stem cells alleviate inflammation and tissue damage in severe acute pancreatitis. Their protective mechanism involves inhibiting the NLRP3/GSDMD/IL-1β signaling axis, thereby suppressing acinar cell pyroptosis.

To systematically characterize tumor microenvironmental features and spatial cellular interactomes associated with distinct transcriptional meta-program (MP) in gastric cancer, and explore their clinical implications.

We integrated 2 gastric cancer single-cell RNA sequencing (scRNA-seq) datasets to identify malignant cell-derived transcriptional MP. The prognostic value was validated in 3 independent bulk transcriptomic cohorts: The Cancer Genome Atlas (TCGA), GSE15459, and GSE66229. Using scRNA-seq, we dissected MP-specific shifts in microenvironmental cell composition and inferred dominant ligand-receptor interactions. Spatial transcriptomics confirmed the co-localization of implicated cell subsets and signaling pairs. Survival analyses were used to access the associations between key cellular signatures/interaction signatures and patient outcomes.

Four MP from MP1 to MP4 were identified in malignant cells. High expression of MP2 and MP4 significantly correlated with worse overall survival (P<0.05). In MP2-high tumors, SPP1⁺ macrophages were enriched and predicted to interact with T3 neutrophils via the SPP1-CD44 ligand-receptor pair, with spatial co-localization validated. Both SPP1⁺ macrophage signature (P=0.007) and SPP1-CD44 interaction signature (P=0.008) predicted adverse prognosis. In MP4-high tumors, myofibroblastic cancer-associated fibroblast (myCAF) were expanded and showed interaction with exhausted CD8⁺ T cells through the COL6A family-ITGB1 signaling axis, which was also spatially validated. The myCAF signature (P=0.001) and COL6A family-ITGB1 interaction signature (P<0.001) correlated with poorer survival.

MP2 and MP4 delineate 2 distinct immunosuppressive spatial niches in gastric cancer: SPP1⁺ macrophage-T3 neutrophil and myCAF-exhausted CD8⁺ T cell. These niches likely drive tumor progression via SPP1-CD44 and COL6A family-ITGB1 axes, respectively, providing potential targets for precision immunotherapy.

To investigate whether the MHC-Ⅰ humanized mouse model (AAD mice) combined with the Plasmodium berghei transgenic strain expressing Plasmodium falciparum circumsporozoite protein (PfCSP,Pb-PfCSP) can be used to establish an evaluation model for PfCSP-based vaccines.

AAD mice and C57BL/6J mice (6 to 8 weeks old, body weight 20 to 35 g, 4 mice per group) were challenged with graded doses (200, 500, and 1 000) of Pb-PfCSPsporozoites and wild-type P.berghei (Pb) sporozoites via tail vein injection. The susceptibility of the 2 mouse strains to Pb and Pb-PfCSP infection was compared by monitoring the onset time of erythrocytic-stage parasitemia and the dynamic changes in parasitemia levels. Flow cytometry was performed to analyze the frequency and absolute number of major hepatic immune cell subsets in the 2 mouse strains, so as to preliminarily explore the potential mechanisms underlying the differential susceptibility to malaria parasites. For vaccine efficacy evaluation, 4 AAD mice per group were immunized with either CI-679-attenuated Pb-PfCSP sporozoite vaccine or LNP-encapsulated mRNA vaccine encoding PfCSP (PfCSP@LNP), with unimmunized AAD mice as the control group. After immunization, all mice were challenged with Pb-PfCSP sporozoites, and the protective efficacy was evaluated. The frequency and number of CSP-specific tissue-resident memory T cells (Trm) in the liver were detected by flow cytometry, and CSP-specific antibody titers in serum were measured by enzyme-linked immunosorbent assay (ELISA).

Pb-PfCSP sporozoites at all tested doses successfully infected both AAD and C57BL/6J mice. Compared with C57BL/6J mice, AAD mice exhibited higher susceptibility to both Pb and Pb-PfCSP infection, as evidenced by earlier onset of erythrocytic-stage parasitemia and significantly higher parasitemia levels in the mid-stage of infection (P<0.05). Regardless of infection status, the frequency and absolute number of hepatic natural killer T (NKT) cells in AAD mice were significantly lower than those in C57BL/6J mice (P<0.05), which might be one of the reasons for the increased susceptibility of AAD mice to malaria parasite infection. After challenge with Pb-PfCSP sporozoites, PfCSP@LNP-immunized AAD mice exhibited delayed erythrocytic-stage parasitemia onset compared with the control group, and detectable titers of CSP-specific antibodies were observed in their serum; however, PfCSP-specific Trm cells were not detected in the liver. Similarly, AAD mice immunized with the nitroquine-attenuated Pb-PfCSP sporozoite vaccine only achieved a protective efficacy of 16.6%, and PfCSP-specific Trm cells were not detected either.

The Pb-PfCSP-infected AAD mouse model can be used for evaluating the efficacy of PfCSP-based vaccines in inducing CSP-specific antibody responses. However, this model requires further optimization for assessing PfCSP-specific CD8⁺ T cell response induction.

To investigate the effects of autologous fecal microbiota transplantation (AFMT) on immune regulation and tumor suppression in a murine model of colitis-associated colorectal cancer (CAC) induced by azoxymethane (AOM)/dextran sulfate sodium (DSS), with mechanistic emphasis on NF-κB pathway inhibition and CD8⁺ T cell/regulatory T cell (Treg) balance modulation.

Six-week-old female BALB/c mice [SPF grade, body weight (20±2) g] were randomly divided into 3 groups (n=5 per group): control group (Con), CAC model group (Mod), and AFMT intervention group (AFMT). The CAC model was established by a single intraperitoneal injection of AOM (10 mg/kg) followed by three cycles of DSS treatment (each cycle: 3.5%DSS in drinking water for 7 d plus 14 d of recovery with sterile water). Starting from day 7 post-modeling, the AFMT group received 0.1 mL of autologous fecal microbiota suspension via oral gavage every other day until the end of the experiment; control groups received equal volumes of sterile saline. At endpoint, colorectal tissues, spleen, serum, and fecal samples were collected. Colonic pathological injury and inflammatory cell infiltration were assessed by hematoxylin-eosin (HE) staining. NF-κB p65 and p-NF-κB p65 protein expression in colon tissue was detected by Western blot. Serum TNF-α levels were measured by ELISA. Flow cytometry was used to analyze the proportions of CD8⁺ T cells and regulatory T cells (Treg, defined as CD4⁺CD25⁺Foxp3⁺) in the spleen. Gut microbiota composition and diversity (α- and β-diversity) were analyzed by 16S rRNA sequencing.

Compared with the Con group, the Mod group showed a reduction in goblet cells and significant inflammatory cell infiltration in HE-stained colon sections, an increased ratio of p-NF-κB p65 to NF-κB p65 in colon tissue (P<0.05), elevated serum TNF-α levels (P<0.001), a decreased proportion of CD8⁺ T cells in the spleen (P<0.001), an increased proportion of Treg cells (P<0.05), an increased relative abundance of Bacteroidales (P<0.05), and a decreased relative abundance of Lactobacillales (P<0.05). Compared with the Mod group, the AFMT group showed milder structural damage and reduced inflammatory cell infiltration in the colon, a decreased ratio of p-NF-κB p65 to NF-κB p65 in colon tissue (P<0.01), reduced serum TNF-α levels (P<0.01), an increased proportion of CD8⁺ T cells in the spleen (P<0.05), a decreased proportion of Treg cells (P<0.05), a decreased relative abundance of Bacteroidales (P<0.05), and an increased relative abundance of Lactobacillales (P<0.05).

AFMT intervention may alleviate disease progression in CAC model mice through multiple mechanisms: restoring the abundance of Lactobacillales, enhancing the intestinal barrier function and promoting short-chain fatty acid production, inhibiting the NF-κB inflammatory pathway, reducing TNF-α levels, and regulating T-cell immune balance.

To investigate CXCL12 therapeutic potential in endometrial repair post intrauterine adhesion (IUA) surgery.

A murine model of IUA was established using mechanical curettage. A total of 48 healthy female C57BL/6 mice (aged 7 to 8 weeks, weighing 18 to 20 g) were randomly allocated to 4 groups (n=12 per group): the sham-operated group (Sham), the model group (Model), the umbilical cord mesenchymal stem cell treatment group (UC-MSCs treatment group), and the CXCL12 treatment group. In the Sham group, only the abdominal wall was incised without intrauterine manipulation. In the Model group, after mechanical curettage, 100 μL of normal saline was infused into the uterine cavity. In the UC-MSCs treatment group, after curettage, 100 μL of UC-MSCs suspension (1×10⁶ cells) was infused into the uterine cavity. In the CXCL12 treatment group, after curettage, 100 μL of CXCL12 solution (containing 200 ng CXCL12) was infused into the uterine cavity. At 7 d post-modeling, histological examination was performed to confirm model establishment, and immunofluorescence staining was used to assess the chemotactic effect of CXCL12 on MSCs. At 21 d post-modeling, hematoxylin and eosin (HE) staining was used to evaluate endometrial thickness and gland number; Masson’s trichrome staining assessed the extent of endometrial fibrosis. Immunohistochemical staining was employed to determine the microvessel density (MVD) and the expression levels of VEGF, Ki-67, and Sirt1. Spearman correlation coefficient was used to assess the correlation between Sirt1 expression levels and endometrial fibrosis.

At 7 d post-modeling, histological examination confirmed the successful establishment of the IUA mouse model. Immunofluorescence staining demonstrated significantly increased MSC homing to the endometrium in both the CXCL12 and UC-MSCs treatment groups versus the Sham and Model groups (P<0.001), with no significant difference between the 2 treatment groups. At 21 d post-modeling, both the CXCL12 and UC-MSCs treatment groups exhibited significantly greater endometrial thickness (P<0.001) and gland number (P<0.05) relative to the Model group. Endometrial fibrosis was significantly reduced in the treatment groups compared with the Model group (P<0.001). Microvessel density (MVD) was significantly higher in the CXCL12 and UC-MSCs groups than in the Model group (P<0.05). Immunohistochemical analysis revealed significantly elevated expression of VEGF (P<0.001), Ki-67 (P<0.001), and Sirt1 (P<0.001) in both treatment groups versus the Model group. After controlling for group allocation, Sirt1 expression showed a significant negative correlation with endometrial fibrosis area (r_s=-0.73, P<0.05, t=-3.86).

Through enhancing MSC homing to the endometrium in IUA mice, CXCL12 exerts therapeutic effects comparable to UC-MSCs therapy, effectively promoting endometrial regeneration and reducing stromal fibrosis, with upregulated Sirt1 expression potentially mediating these effects.

To investigate the mechanism of stigmasterol, an extract from Coicis Semen, in treating rats with a chronic obstructive pulmonary disease (COPD) model.

Forty healthy male SD rats (body weight:120±10 g) were randomly divided into four groups (n=10) using a random number table: blank control (NC) group, model (Mock) group, Stigmasterol group (stigmasterol 20 mg/kg), and stigmasterol+GW9662 group (stigmasterol 20 mg/kg+peroxisome proliferator-activated receptor γ (PPARγ) antagonist GW9662 1 mg/kg). The COPD rat model was established by smoke exposure combined with intratracheal instillation of lipopolysaccharide (LPS, 1 mg/kg). After 14 d of intervention, alveolar macrophages were isolated. M1/M2 polarization was analyzed by flow cytometry; PPARγ expression was detected using qRT-PCR, Western blot, and ELISA; macrophage oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured with a Seahorse XF Analyzer; and lung tissue pathology and macrophage infiltration were observed via HE staining and immunohistochemistry.

Compared with the NC group, the Mock group exhibited a significantly increased M1/M2 ratio (P<0.01), markedly reduced PPARγ expression at both mRNA and protein levels (P<0.001), and decreased mitochondrial basal OCR, maximal OCR, and glycolytic ECAR in alveolar macrophages (P<0.01). Lung tissues showed typical histopathological damage, including alveolar destruction and inflammatory cell infiltration. Stigmasterol intervention reversed these abnormalities by decreasing the M1/M2 ratio (P<0.01), upregulating PPARγ expression (P<0.01), improving mitochondrial respiration and glycolytic capacity (as indicated by OCR and ECAR), and alleviating lung tissue histopathological damage (P<0.05). However, co-administration of the PPARγ antagonist GW9662 significantly attenuated stigmasterol’s beneficial effects on promoting M2 macrophage polarization, upregulating PPARγ expression, improving cellular metabolic reprogramming (OCR and ECAR), and protecting against lung tissue damage.

Stigmasterol from Coicis Semen ameliorates lung injury in COPD rats by activating PPARγ, which reprograms alveolar macrophage metabolism and drives M2 polarization.

To evaluate the clinical characteristics and their associations with treatment response and prognosis in multiple myeloma (MM) patients with positive autoantibody profiles (PA).

This single-center retrospective cohort study enrolled 189 MM patients who had undergone the autoantibody profile tests at the Gansu Provincial Clinical Medical Research Center for Molecular Diagnosis and Treatment of Hematological Diseases, the First Hospital, Lanzhou University, from April 2015 to April 2025. Follow-up data were collected until August 1, 2025. Based on the autoantibody profile results, patients were categorized into a negative autoantibody profiles group (NA) and a PA group for comparison of baseline characteristics and treatment responses between the two groups. The assessment of treatment response included the overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, non-response rate, and the utilization rates of key therapeutic strategies, such as anti-CD38 monoclonal antibody therapy and autologous hematopoietic stem cell transplantation (auto-HSCT). Furthermore, the PA group patients were stratified into three subtypes based on antibody profiles: antinuclear antibody (ANA)-positive, anti-extractable nuclear antigen (ENA) antibody-positive, and antineutrophil cytoplasmic antibody (ANCA)-positive, to analyze prognostic differences. The Kaplan-Meier survival curve was used to calculate median survival time, and Cox regression analysis was performed to evaluate prognostic factors.

A total of 189 patients with MM were included, with 57 (30.16%) in the PA group and 132 (69.84%) in the NA group. All patients received treatment; 58 (30.69%) received anti-CD38 monoclonal antibody therapy, and 57 (30.16%) underwent auto-HSCT. After induction therapy, the ORR was 75.66% (143/189), comprising a PR in 43.39% (82/189) and a CR in 32.28% (61/189). The CR rate was significantly lower in the PA group than in the NA group (21.05% vs 37.12%, P=0.031). At a median follow-up of 39 months (IQR 16 to 59), the median progression-free survival (PFS) was 37 months (IQR 16 to 58) for the entire cohort, while the median overall survival (OS) was not reached. Kaplan-Meier analysis showed significantly shorter median PFS in the PA group versus the NA group (31 vs 43 months, P=0.048). Subgroup analysis based on specific autoantibodies revealed that patients with anti-ENA antibody positivity had significantly shorter median OS (41 vs 61 months, P=0.038) and PFS (28 vs 41 months, P=0.001) than those without. No significant differences in OS or PFS were observed between ANA/ANCA-positive and -negative groups. Cox regression identified anti-ENA antibody positivity (P=0.004) and male sex (P<0.001) as independent risk factors for OS, whereas achievement of CR post-induction (P=0.002) and anti-CD38 therapy (P=0.008) were protective factors. For PFS, independent risk factors were male sex (P<0.001) and anti-ENA positivity (P<0.001), with protective factors including elevated fibrinogen (P=0.011), achievement of CR (P=0.009), and anti-CD38 therapy (P=0.011).

MM patients with positive autoantibodies exhibit inferior responses to induction therapy and poor long-term outcomes. Anti-ENA antibody positivity is an independent risk factor for both OS and PFS in MM.

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.