The progression of chronic kidney disease (CKD) is closely associated with the disruption of renal spatial immune microenvironment. This study aimed to develop an integrated experimental and analytical system for dissecting the immune microenvironment of CKD using imaging mass cytometry (IMC), thereby enabling panoramic analysis of single-cell spatial immune microenvironment in CKD renal tissues.

① Antigenic markers targeting renal structural units, stromal cells, and immune cells were screened to construct a mass cytometry imaging antibody panel; all metal-conjugated antibodies were validated for specificity by immunohistochemistry. ②Two normal kidney biopsy specimens adjacent to ureteral carcinoma, 2 diabetic nephropathy (DN), and 2 IgA nephropathy (IgAN) renal biopsy specimens were collected, stained with the aforementioned antibodies, and subjected to image data acquisition using the Hyperion imaging system to obtain multiplexed spatial data. ③ An integrated Ilastik and CellProfiler workflow was established for single-cell segmentation pipeline tailored for renal tissues, and cell identity annotation was achieved using a combination of manual gating and Phenograph unsupervised clustering. ④ Spatial proximity relationships between cells were defined, and permutation testing was employed to simulate random distribution models to examine spatial relationships between tissue cells and immune cells. ⑤ k-nearest neighbors (kNN) algorithm was applied for spatial clustering, and cellular neighborhoods (CNs) were used to delineate the spatial functional units within renal tissue, followed by analysis of the immunological characteristics and relative abundance of these units.

①A 37-color antibody panel was constructed and optimized, with all antibodies demonstrating high specificity and low background noise; this panel enabled accurate identification of renal structural cells, stromal cells, and infiltrating immune cells. ② High-dimensional IMC imaging data were successfully obtained from normal and CKD renal tissues using the Hyperion imaging system. ③ With the aid of the single-cell segmentation pipeline, a high-resolution single-cell atlas of human kidney was systematically mapped, comprising 21 structural cell types and 17 immune cell subtypes. Immune cell populations such as CD15⁺ macrophages, GzmK⁺ CD4⁺ effector T cells, and 3 distinct double-positive renal tubular cells were identified, revealing differential infiltration of immune cells in DN and IgAN tissues. ④ A single-cell spatial interaction analysis framework was established, demonstrating a disease-specific spatial interaction network of immune cells in CKD tissues, and identifying myofibroblasts as a critical spatial hub connecting tissue injury and immune cell infiltration.⑤ Spatial neighborhood analysis delineated 9 functional units of renal tissue, including glomerular, proximal tubular, ascending limb of the loop of Henle, vascular and fibrotic, and immune cell-enriched regions. In diseased tissues, the proportion of normal functional regions was decreased, whereas the proportions of fibrotic and immune-enriched regions were increased significantly. Moreover, immune cell-enriched zones maintained close colocalization with various functional regions, while vascular and fibrotic regions were predominantly adjacent to collecting duct and ascending limb of the loop of Henle.

An IMC methodology tailored for the spatial analysis of renal tissue is successfully developed. This platform enables high-resolution, panoramic visualization of spatial distribution of immune cells in chronic renal tissues, dissecting spatial interactions between immune and structural cells and characteristics of local immune microenvironment. This technology holds promise to advance the development of spatially informed precision diagnostics and targeted therapeutic strategies for renal diseases.

To investigate the molecular mechanisms by which branched-chain amino acids (BCAAs) catabolic disorder induces glomerular podocyte injury, and to elucidate its role and mechanism in promoting the pathogenesis of diabetic nephropathy (DN) in a high-fat diet (HFD)-induced mouse model of obesity.

(1) Cellular Experiments: ① Primary glomerular podocytes were isolated from 6- to 8-week-old male C57BL/6J mice (weight 20 to 25 g) and cultured, and then were randomly divided into 3 groups (n=4): low-glucose (LG, 5.5 mmol/L) group, high-glucose (HG, 25 mmol/L) group, and HG+3 mmol/L BCAA group. Western blotting was used to detect the expression of BCAA metabolism-related molecules (PPM1K, BCKD, and BCKD pSer293), podocyte functional markers (Nephrin, Synaptopodin, and WT1), and the apoptotic molecule Cleaved Caspase-3. Immunohistochemistry staining and Western blotting were performed to detect the expression levels of mTOR signaling pathway molecules (p70s6K pThr389, p70s6K, ATF4 pSer166, and ATF4) and apoptotic pathway molecules (Chop and Trib3). ② ATF4-knockout fibroblast cells were randomly divided into control (n=4) and BCAA (n=4) groups. Western blotting was used to detect the expression levels of apoptosis pathway molecules. ③ Primary glomerular podocytes isolated from 6- to 8-week-old C57BL/6J mice were randomly divided into 3 groups (n=4): HG (25 mmol/L) group, HG + 3 mmol/L BCAA group, and HG + 3 mmol/L BCAA + rapamycin (HG + BCAA + Rap) group. Western blotting was performed to assess the expression levels of mTOR signaling pathway and apoptotic pathway molecules. (2) Animal Experiments: An HFD-induced mouse model of obesity was established. Male C57BL/6J mice aged 6 to 8 weeks were randomly divided into an HFD group, an HFD/Paired group (food intake matched to the HFD/BCAA group), an HFD/BCAA group (4% BCAAs supplemented in drinking water), and an HFD/BCAA + Rap intervention group. Periodic acid-Schiff (PAS) staining, Oil Red O staining, and detection of renal triglyceride content were performed to assess renal pathological morphology and lipid deposition. Biochemical assays were applied to detect the urinary microalbumin and creatinine levels, as well as to calculate the urinary albumin-to-creatinine ratio. Glomerular podocyte functional markers (Nephrin and Synaptopodin) and fibrosis-related molecules (Collagen IV) were detected by immunofluorescence assay and RT-PCR. The expression levels of renal lipid metabolism-related molecules (FABP4, CD36, PGC1α, and PPARα), as well as the mTOR signaling pathway and apoptotic pathway molecules were detected by immunohistochemistry and Western blotting.

(1) Cellular Experiments: ① High-glucose treatment decreased PPM1K expression and increased BCKD pSer293 expression in the podocytes (P<0.000 1). BCAAs downregulated the expression of Nephrin (P<0.000 1) and Synaptopodin (P<0.01) and upregulated Cleaved Caspase-3 expression (P<0.000 1) in the podocytes under high glucose condition. BCAAs significantly upregulated the protein levels of p70s6K pThr389, p70s6K, ATF4 pSer166, ATF4, Chop, and Trib3 in the podocytes (P<0.000 1). ② Knockout of ATF4 significantly blocked BCAA-induced Chop and Trib3 expression activated by mTOR (P<0.000 1). ③ The mTOR inhibitor Rap significantly suppressed the expression of ATF4 pSer166, ATF4, Chop, and Trib3 (P<0.000 1). (2) Animal Experiments: ① Exogenous BCAA supplementation increased the urinary albumin-to-creatinine ratio (P<0.000 1), aggravated the damage to glomerular filtration barrier, downregulated the expression of WT1, Nephrin, and Synaptopodin (P<0.000 1), and upregulated glomerular p70s6K pThr389 (P<0.01) and Chop (P<0.000 1) expression. Additionally, BCAA supplementation promoted renal tubular cast formation and renal lipid accumulation (P<0.000 1), and upregulated the expression of FABP4 and CD36 in renal tubules of HFD-fed mice. ② The mTOR inhibitor Rap blocked the mTOR-ATF4-Chop/Trib3 pathway, downregulated the expression of ATF4 pSer166, ATF4, Chop, and Trib3 (P<0.000 1), and ameliorated renal lipid deposition (P<0.000 1), renal tubular cast formation, and proteinuria (P<0.000 1).

BCAA metabolism disorder induces glomerular podocyte dysfunction and apoptosis by activating the mTOR-ATF4-Chop/Trib3 signaling pathway, leading to renal lipid deposition, renal tubular cast formation, and progression of renal fibrosis, thereby promoting the development and progression of DN.

The immuno-inflammatory mechanisms underlying acute and chronic Brucella osteoarthritis (BOA) remain unclear, and the dynamic changes in T follicular helper (Tfh) cells and follicular regulatory T (Tfr) cells in this disease, as well as their associations with immune-inflammatory responses, have not been systematically reported. This study aimed to characterize the stage-specific changes in Tfh and Tfr cells in peripheral blood and synovial tissue of BOA patients, and to analyze their relationships with related cytokines, transcription factors, and immunoglobulins, thereby providing the immunological evidence for pathogenesis and clinical management of the disease.

A cross-sectional study design was adopted in this research. A total of 13 patients with acute BOA and 21 patients with chronic BOA, who were diagnosed in the Department of Orthopedics at the First Affiliated Hospital of Shihezi University and its medical consortium hospitals from January 2024 to August 2025, were enrolled, and another 20 healthy individuals were subjected and served as the control group. Peripheral blood samples were collected from all participants, while synovial tissue specimens were obtained from 3 chronic BOA patients and 3 patients with non-infectious joint injury undergoing surgery for local tissue-level validation, which were not included in the overall clinical statistical analysis. Flow cytometry was performed to determine the proportions of Tfh cells (CD4⁺CXCR5⁺CD25⁻CD127⁺) and Tfr cells (CD4⁺CXCR5⁺CD25⁺CD127⁻) in peripheral blood, as well as the Tfh/Tfr ratio. Serum levels of IL-4, IL-21, IL-10, TGF-β, and immunoglobulins (IgA, IgG, IgE and IgM) were measured by ELISA. The mRNA expression of Tfh-related transcription factor BCL-6 and cytokine IL-21, as well as Tfr-related transcription factor FOXP3 and cytokine IL-10, was assessed in peripheral blood mononuclear cells (PBMCs) using qRT-PCR. Western blotting was used to detect the expression of IL-21, FOXP3, and joint matrix metabolism-related proteins MMP-13, type Ⅱ collagen (COLⅡ), and ADAMTS5) in synovial tissues.

① In the synovial tissues, the chronic BOA group showed significantly higher protein levels of FOXP3 (P=0.020 1), MMP-13 (P=0.004 8), and ADAMTS5 (P=0.002 3), while lower levels of IL-21 (P<0.000 1) and COLⅡ (P=0.009 2) compared with the control group. ② Flow cytometric analysis of peripheral blood revealed that the proportion of Tfh cells in acute-phase patients was significantly higher than that in the control group (P=0.001 4) and the chronic-phase group (P<0.000 1); so was the Tfh/Tfr ratio when compared with that in the control group (P=0.020 4) and the chronic-phase group (P<0.000 1); whereas the proportion of Tfr cells was lower than that in the control group (P=0.015 5) and the chronic-phase group (P<0.000 1). ③ qRT-PCR in PBMCs showed that the mRNA levels of the Tfh-related cytokine IL-21 and transcription factor BCL-6 were upregulated in acute-phase patients than the control group (P=0.000 8, P<0.000 1); those of the cytokine IL-10 and transcription factor FOXP3 were also enhanced in chronic-phase patients compared with the control group (both P<0.000 1). ④ ELISA results showed that serum levels of IL-21, IL-4, and IgG were significantly elevated in acute-phase patients, all higher than those in the control group (all P<0.000 1); these 3 indicators showed a decreasing trend in the chronic phase compared with the acute group (P<0.05). In contrast, serum IL-10 level was significantly increased in the chronic phase, higher than that in the control group (P<0.000 1) and the acute-phase patients (P=0.034 3). Serum IgA and IgM levels in patients in both acute and chronic phases were significantly higher than those in the control group (P<0.05), but no significant difference was observed between the 2 phase groups. ⑤ Spearman correlation analysis indicated that, in the acute phase, the proportion of Tfh cells was positively correlated with IL-21, IgA, and IgM (r=0.26, 0.34, and 0.37, respectively), and negatively with Tfr cells (r=-0.54). IL-21 showed a strong positive correlation with IgG and IgM (r=0.75 and 0.58). In the chronic phase, the above correlations overall weakened, while correlations with Tfr-related indexes exhibited stronger associations compared with the other indicators.

This study preliminarily revealed the changes in Tfh/Tfr cell imbalance in BOA, with the acute phase characterized by Tfh cells and high expression of related factors, and the chronic phase by larger proportion of Tfr cells and high expression of related factors, accompanied by pathological joint damage.

Endotoxemia is a common high-risk subtype of sepsis, primarily caused by lipopolysaccharide (LPS) released from Gram-negative bacteria. Macrophages, essential components of the innate immune system, represent one of the most critical defense cells within the immune system once LPS breaches physical barriers; LPS can activate macrophages and induce a severe inflammatory response. Mitochondria, vital organelles regulating cellular metabolism and inflammatory responses, undergo structural and functional damage that further exacerbates the inflammatory activation of macrophages. This study aims to investigate the inhibitory effects of a novel artemisinin derivative, disuccinate artemisinin (DA), on macrophage mitochondrial damage and inflammatory responses induced by low-concentration LPS, as well as the interrelationships between these effects and the preliminary mechanisms of action.

Low-concentration LPS (20 ng/mL) was used to induce mitochondrial damage and inflammatory cytokine expression in the mouse monocyte/macrophage cell line RAW264.7. Cell toxicity of DA at concentrations of 0, 1, 2, 4, 8, 16, 32, and 64 μg/mL was assessed using CCK-8 assay (n=6); qPCR was employed to monitor the dynamic changes in mRNA levels of TNF-α, IL-6 and IL-1β in RAW264.7 cells at 0, 1/12, 1/6, 1/3, 0.5, 1, 2, 4, 8, 24, and 48 h after stimulation with 20 ng/mL LPS (n=3 or 4). qPCR was further performed to assess the effects of 5, 10, and 20 μg/mL DA on the expression of the aforementioned genes in RAW264.7 cells stimulated with 20 ng/mL LPS (n=3 or 4). RAW264.7 cells were divided into the control group (medium), 20 μg/mL DA group, 20 ng/mL LPS group, LPS+DA (5 μg/mL) group, LPS+DA (10 μg/mL) group, and LPS+DA (20 μg/mL) group. Western blotting was applied to detect the expression of nuclear factor kappa B p65 (NF-κB p65), NF-κB p50, and NF-κB inhibitor alpha (IκB-α) in cytoplasmic and nuclear proteins (n=3). RAW264.7 cells were divided into a control group (medium), a 10 μg/mL DA group, a 20 ng/mL LPS group, and an LPS+DA (10 μg/mL) group. Western blotting was applied to detect the expression of Toll-like receptor 4 (TLR4) pathway proteins in total cell lysates (n=3). RAW264.7 cells were divided into a control group (medium), a 20 ng/mL LPS group, and an LPS+DA (10 μg/mL) group. Western blotting, fluorescence imaging, and qPCR were utilized to detect the expression of p-NF-κB p65（Ser536）, inhibitor of κB kinase α (IKKα), inhibitor of κB kinase β (IKKβ), p-IKKα/β (Ser176/180) and cGAS-STING pathway proteins in total cell lysates (n=3). The mitochondrial morphology, membrane potential (n=5), and reactive oxygen species (ROS) (n=4) were observed. Free mitochondrial DNA and chromosomal DNA in the cytoplasm were also detected (n=4).

The IC₁₀ value of DA was 13.2 μg/mL for the proliferation of RAW264.7 cells. Peak TNF-α expression occurred at 1 h after LPS stimulation (P<0.05), that of IL-6 at 24 h (P<0.05), and that of IL-1β at 4 h (P<0.05). DA sustainably downregulated the expression of these LPS-induced genes. Compared with 20 ng/mL LPS, DA also downregulated the expression of TNF-α, IL-6, and IL-1β genes in a concentration-dependent manner (P<0.05), with an optimal concentration of 10 μg/mL (<IC₁₀). Western blotting showed that, compared with 20 ng/mL LPS, DA concentration-dependently inhibited LPS-induced IκB-α degradation, reduced the nuclear translocation of NF-κB p50 and NF-κB p65, and decreased p-NF-κB p65（Ser536） levels, thereby inhibiting the activation of NF-κB (P<0.05). DA exerted no significant effect on the TLR4 pathway (P>0.05), but it did inhibit the activation of p-IKKα/β (Ser176/180) (P<0.05). Mitochondrial damage assays demonstrated that, compared to 20 ng/mL LPS, DA inhibited LPS-induced mitochondrial fragmentation, membrane potential decline, ROS production, and mitochondrial DNA release (P<0.05), thereby downregulating cGAS, p-STING (Ser366), p-TBK1 (Ser172), and p-IRF3 (Ser396) (P<0.05), thereby inhibiting the activation of the cGAS-STING pathway.

DA mitigates mitochondrial damage induced by low-concentration LPS in macrophages, thereby inhibiting the activation of cGAS-STING pathway to alleviate mitochondria-related inflammatory responses. DA is considered an anti-inflammatory candidate drug with mitochondrial protective properties.

Based on the neuroprotective and anti-inflammatory properties of semaglutide, this study aims to investigate whether semaglutide improves core symptoms in BTBR T(+) Itpr3(tf)/J(BTBR) mice, a model of autism spectrum disorder (ASD), through modulation of inflammation-related targets and signaling pathways.

A total of 32 male C57BL/6J (C57) and BTBR mice (7 weeks old) were randomly divided into 4 groups (n=8): The treatment group received intraperitoneal injection of 25 nmol/kg semaglutide, while the control group received normal saline, with continuous intervention for 7 d, and body weight was monitored continuously throughout the intervention period. Mouse behavioral indicators were evaluated using various behavioral tests, including the three-chamber sociability test, grooming test, marble-burying test, novel object recognition test, Y-maze test and open field test. After behavioral assessments, the brain tissues were collected, and network pharmacology, GO/KEGG enrichment analysis, protein-protein interaction analysis, molecular docking technology, and qRT-PCR were employed to explore the potential mechanisms of semaglutide.

Semaglutide intervention for 7 d significantly reduced the body weight of BTBR mice (P<0.05), increased the preference index from chamber time (P<0.01) and preference index from sniffing time (P<0.05), elevated the novel object recognition discrimination index (P<0.01), and reduced repetitive stereotyped behaviors such as self-grooming (P<0.001) and marble burying (P<0.01). However, no significant effects on the above mentioned behaviors were observed in C57 mice, and no obvious impact on locomotor activity was demonstrated in the open field test. Network pharmacology analysis identified 78 common targets which enriched in inflammation-related pathways. Semaglutide exhibited favorable binding affinity with potential targets in inflammation-related pathways including Serpine1, Mmp9, Pparg, Stat3, Ppara, and Nr1h3, with binding energies all ≤-4 kcal/mol. qRT-PCR further confirmed that semaglutide intervention significantly downregulated mRNA expression levels of Serpine1, Mmp9, Stat3, Il6, Tnfa, Il17a, and Il1b (P<0.05), and upregulated Pparg expression (P<0.05) in the hippocampus of BTBR mice.

Semaglutide alleviates ASD-like symptoms in BTBR mice by regulating inflammation-related pathways, thus offering a promising potential treatment and foundational research for the clinical management of ASD.

Traditional hemorrhagic shock (HS) assessment methods focus solely on macrocirculatory indicators, failing to detect microcirculatory disturbances at an early stage, which may lead to misjudgment of disease severity or delayed intervention. This randomized controlled animal experimental study aims to construct a novel three-level quantitative assessment integrating basic vital signs, blood gas indicators, and microcirculatory parameters, to determine its accuracy and reliability in distinguishing mild, moderate, and severe HS, thereby providing a scientific tool for early precise staging and targeted resuscitation in clinical practice.

Following the quality control principles of experimental research (randomization, blinded assessment), 20 experts with associate senior professional titles or above in the fields of anesthesiology, critical care medicine, field surgery and other relevant disciplines were selected to conduct 3 rounds of anonymous Delphi consultations. Shock evaluation indicators were screened and their weights were determined by calculating the expert positive coefficient, opinion concentration degree and opinion coordination degree. A three-level assessment system consisting of basic vital signs, blood gas indicators and microcirculatory parameters was constructed, and quantitative scoring standards were formulated. A total of 64 SPF-grade SD rats (12 weeks old) were randomly divided into 4 groups (n=16): a sham operation group and mild, moderate, and severe HS groups (with blood loss accounting for 20%, 35% and 50% of total blood volume, respectively). Side stream dark-field (SDF) microcirculation imaging was employed to detect microcirculatory indicators, and mean arterial pressure (MAP) and oxygen saturation were recorded simultaneously to validate the accuracy of the assessment method.

The positive coefficients (100.0%, 100.0%, 88.9%) and coordination coefficients (Kendall's W increased from 0.144 to 0.444, P<0.05) of the 3 rounds of expert consultations were relatively high, with a coefficient of variation ranging from 0.07 to 0.27, indicating a significant improvement in the consistency of expert opinions. Finally, 5 core secondary indicators were identified, with their weights as follows: perfused vessel density (0.138 8), MAP (0.131 8), oxygen saturation (0.129 9), microvascular flow index (0.128 1) and perfused vessel proportion (0.126 3). The quantitative scoring standard showed that 5 to 10 points indicated mild HS, 11 to 15 points moderate, and 16-20 points severe. In animal experimental validation, the accuracy of this method in distinguishing mild, moderate and severe HS was 93.75% (95%CI: 71.7% to 98.9%), 93.75% (95%CI: 71.7% to 98.9%) and 100% (95%CI: 83.8% to 100%), respectively.

Our novel quantitative HS assessment tool based on SDF technology and Delphi method, can accurately distinguish HS of different severity levels (accuracy rate >90%), effectively integrate the monitoring dimensions of macrocirculation, oxygenation, and microcirculation. Our tool addresses the limitation of traditional assessment tools in neglecting microcirculation, providing reliable assessment for early precise identification, dynamic monitoring of disease progression, and targeted resuscitation of HS, with significant potential for clinical translation.

Cervical cancer, as the fourth most common malignancy among women worldwide, poses a serious threat to global women’s health. Early identification and intervention of high-grade squamous intraepithelial lesions (HSIL) are of great significance for the prevention and control of cervical cancer and precancerous lesions. Current screening methods are relatively singular, leading to a coexistence of missed diagnosis risk and overtreatment. How to achieve individualized precision diagnosis and treatment for lesions staged ≥HSIL has become a vital clinical issue. This study aims to integrate multimodal information, including demographics, social behavior, molecular biology, and radiology, identify independent risk factors for high-grade lesions, and construct an individualized risk prediction nomogram model based on modified Poisson regression (MPR) to achieve precision diagnosis and treatment and individual stratification of cervical cancer and precancerous lesions.

A retrospective observational study was conducted on 741 patients who underwent biopsies at Cervical Disease Diagnosis and Treatment Center of Women and Children’s Hospital of Chongqing Medical University between July 2022 and July 2024. Based on the histopathological gold standards, they were divided into a low-grade squamous intraepithelial lesion group (≤LSIL group, n=484, including 206 cases of chronic cervicitis and 278 cases of LSIL) and a high-grade squamous intraepithelial lesion group (≥HSIL group, n=257, including 243 cases of HSIL, 8 cases of cervical adenocarcinoma in situ, and 6 cases of cervical cancer). Multimodal data were systematically collected, including age, parity, human papillomavirus (HPV) vaccination history, thin-prep cytologic test (TCT) results, HPV genotypes, duration of persistent HPV infection, and colposcopic impression (such as acetowhite epithelial thickness and vascular patterns). Independent samples t-test (for continuous variables with normal distribution and homogeneity of variance) and Pearson Chi-square test (Fisher’s exact test when theoretical frequency <5) were used for univariate analysis. After incorporating variables with P<0.1 from univariate analysis into the candidate set and after forcibly controlling confounders such as age, gravidity and parity, a backward elimination method was used within the MPR framework to identify independent risk factors and calculate risk ratios (RR) with 95%CI. A nomogram was constructed using R software, and its discrimination and consistency were evaluated via the AUC value of ROC curve analysis and calibration curve analysis (Bootstrap method, B=500).

Univariate analysis showed statistically significant differences between the 2 groups in terms of (t=-2.264, P=0.024), gravidity (t=-3.527, P<0.001), parity (t=-3.222, P<0.001), contraceptive methods (χ²=10.712，P=0.013), TCT results (χ²=44.883, P<0.001), HPV genotypes (χ²=15.692, P=0.001), cumulative duration of HPV infection (χ²=11.670, P=0.009), HPV vaccination status (χ²=15.685, P<0.001), colposcopic impression (χ²=87.284, P<0.001), acetowhite findings (χ²=72.771, P<0.001), vascular patterns (punctation/mosaicism) (χ²=67.099, P<0.001), and type of cervical transformation zone (χ²=20.316, P<0.001). Multivariate MPR identified 5 independent predictors: ① age (RR=1.015, 95%CI: 1.000 to 1.030, P=0.048); ② gravidity (RR=1.066, 95%CI: 1.002 to 1.134, P=0.043); ③ duration of persistent HPV infection (RR=1.405, 95%CI: 1.010 to 1.956, P=0.044); ④ colposcopic impression (RR=2.108, 95%CI: 1.545 to 2.878, P<0.001); and ⑤ HPV vaccination (protective factor, RR=0.631, 95%CI: 0.510 to 0.781, P<0.001). The nomogram model constructed based on these factors achieved an AUC value of 0.74 (95%CI: 0.702 to 0.778) in predicting ≥HSIL risk. The calibration curve showed good consistency between predicted probabilities and actual observed values, with a calibration slope of 0.958 0 and a Brier score of 0.191 4.

Our nomogram model constructed by integrating multimodal information demonstrates good discrimination and clinical reliability. It enables intuitive and visualized quantification of individualized risk, facilitating optimized efficiency in cervical cancer prevention and control.

Staphylococcus aureus (SA)-induced osteomyelitis (OM) is a common refractory orthopedic infection, presenting substantial challenges in early diagnosis and immune microenvironment characterization. Expression profiles of pyroptosis-related genes (PRGs) are closely associated with SA-OM; these genes may influence the immune microenvironment through mitochondrial-related pathways, thereby participating in disease progression, and specific gene combinations can be utilized to construct high-precision diagnostic models. This study aims to integrate multi-omics and machine learning to screen key pyroptosis-related diagnostic biomarkers in SA-OM, construct a high-precision diagnostic model, and elucidate its molecular mechanism influencing the immune microenvironment through “mitochondria-inflammation” crosstalk.

Based on 3 SA-OM datasets (GSE6269/GSE16129/GSE30119) retrieved from the GEO database, a total of 143 SA-OM patients and 79 healthy control samples were enrolled. Data preprocessing (batch effect correction using the sva package), differential expression analysis (DE-PRGs screened via the limma package, adj.P<0.05 & |log₂FC|>0.263), co-expression network construction (key module genes identified through WGCNA algorithm, softThreshold=5), multi-omics cross-validation (Pearson correlation analysis for MR-PRGs screening), machine learning modeling (feature genes selected via SVM-RFE/LASSO/random forest cross-validation, n=9), and diagnostic model construction (logistic regression nomogram model, efficacy evaluated through AUC, calibration curve slope, and DCA) were performed, combined with immune microenvironment analysis (CIBERSORT/ssGSEA quantitative analysis of 22 immune cell infiltration levels).

Among 23 DE-PRGs, a diagnostic model comprising 8 key genes demonstrated excellent performance in both the training set (AUC=0.89, 95%CI: 0.83 to 0.95) and validation set (AUC=0.83, 95%CI: 0.76 to 0.90). RT-qPCR experiments further validated that the mRNA expression levels of the key pyroptosis pathway genes Caspase-1 and IL-18 in the SA-OM group were significantly upregulated compared with the control group (P<0.05), corroborating the bioinformatics findings.The METTL3-MRPL39 axis was significantly enriched in “metabolic pathways” and “mitochondrial gene expression” biological processes. Furthermore, Th1/Th17 cell infiltration levels in the disease group were 3.2-fold higher than those in the control group (P<0.001), and METTL3 expression exhibited positive correlation with effector T cell infiltration (r=0.65, P=0.008).

This study systematically elucidates the regulatory network of pyroptosis-related genes in SA-OM. The constructed diagnostic model provides a novel tool for early screening, while the identified mitochondrial-inflammation interplay mechanisms and specific immune microenvironment characteristics establish a theoretical foundation for the development of targeted therapeutic strategies.

Childhood trauma is closely associated with decreased cognitive flexibility in college students. To explore a safer and more effective cognitive intervention approach for this population, this study aims to determine the effects of flash technique (FT) on improving subjective and objective cognitive flexibility among college students with childhood trauma.

A randomized controlled study design was adopted. From April to October 2025, Childhood Trauma Questionnaire (CTQ) and semi-structured interviews were used to assess the levels of childhood trauma among college students in some universities in Changqing and Kunming. A total of 54 eligible participants were randomly assigned into an intervention group (n=27) and a waitlist group (n=27). The intervention group received 70-minute FT intervention, once per week for 6 weeks, while the waitlist group received no intervention during the same period. At baseline (T1) and post-intervention (T2), subjective cognitive flexibility was assessed using the Cognitive Flexibility Inventory (CFI). In the letter-number switching task, objective switching efficiency was measured by switching time cost, and switching accuracy was determined by switching error rate cost.

All 54 participants completed the study (27 in each group). ① No significant differences were observed between the 2 groups in demographic characteristics, CTQ, CFI, switching time cost, or switching error rate cost at baseline (P>0.05). ② Repeated measures analysis of variance revealed significant group-by-time interactions for CFI (F=24.654, P<0.001, partial η²=0.322) and switching time cost (F=6.603, P=0.013, partial η²=0.113), whereas the group-by-time interaction for switching error rate cost was not significant (F=1.397, P=0.243, Partial η²=0.02).③ Simple effect analysis demonstrated that post-intervention CFI was significantly higher in the intervention group than in the waitlist group (t=3.054, P=0.004, 95%CI: 3.022 to 14.608), with switching time cost significantly lower (t=-3.117, P=0.003, 95%CI: -93.438 to -20.251). At T2, the intervention group showed significantly higher CFI (t=7.424, P<0.001, 95%CI: 9.999 to 17.408) and significantly lower switching time cost (t=-2.875, P=0.006, 95%CI: -60.582 to -10.780) compared with T1. No significant differences were observed CFI or switching time cost between T1 and T2 in the waitlist group (P>0.05).

FT can effectively improve subjective cognitive flexibility and objective cognitive switching efficiency in college students with childhood trauma, serving as an effective auxiliary psychological intervention for this population.

The mental health problems among senior high school students require urgent attention in recent years. Ideal level, as an essential psychological quality, its long-term impact on depressive emotions remains unclear, and the mediating role of frustration tolerance between these 2 factors still lacks prospective evidence. This study aims to determine the predictive effect of ideal level on depressive symptoms and the mediating mechanism of frustration tolerance among high school students in Chongqing.

This study adopted a prospective cohort design. A total of 308 high school students from 3 high schools in Chongqing were surveyed at 3 time points: T1 (November 2024), T2 (May 2025), and T3 (November 2025). Revised Contemporary Adolescent Ideal Questionnaire, Frustration Tolerance Scale for Students, and Patient Health Questionnaire-9 were used to assess the levels of ideal, frustration tolerance, and depressive symptoms, respectively. Descriptive analysis, correlation analysis, cross-lagged analysis, and structural equation modeling were performed on the questionnaire data.

① High school students demonstrated relatively high ideal levels, with a total score of 154.28±13.68, which remained stable over 1 year. The frustration tolerance scores were 61.77±14.39 at baseline and increased progressively to 65.83±15.68 after 1 year (P<0.001). The depressive symptom scores were 1.23±2.45 at baseline and elevated significantly to 4.79±4.33 after 1 year (P<0.001). The career ideal scores were higher in 16-year-old adolescents than in 15-year-old counterparts (P<0.05), and the male students had higher total frustration tolerance scores than the female (P<0.01). ② The ideal level was positively correlated with frustration tolerance (r=0.17 to 0.30, P<0.01), and both were negatively correlated with depressive symptoms (r=-0.23 to -0.15, P<0.01). ③ The results from the cross-lagged model indicated that ideal level positively predicted frustration tolerance levels at 6 months later (β=0.10, P<0.01). ④ Frustration tolerance played a fully mediating role between ideal level and depressive symptom scores (β=-0.07, 95%CI: -0.19 to -0.02, P<0.01), with the total indirect effect of the chain mediation accounting for 8.24% of the total effect.

Ideal level in high school students positively predicts frustration tolerance, and frustration tolerance plays a fully mediating role between ideal level and depressive symptoms. It is recommended that families, schools, and communities seize the critical period of ideal formation to strengthen frustration tolerance training, thereby reducing depressive symptoms and laying a foundation for achieving national strategic goals.

Under the guidance of enhanced recovery after surgery(ERAS), this study aims to investigate the safety and feasibility of an immediate postoperative diet regimen for patients undergoing painless abortion surgery, analyze early postoperative discomfort symptoms(including nausea and vomiting, hunger, thirst, pain, etc.) and recovery outcomes(including time to resume normal diet, length of hospital stay, and vaginal bleeding), and clarify the clinical application value of this study in clinical practice.

A retrospective cohort study was conducted on 210 patients who underwent intravenous anesthesia for painless abortion in our department from October 2024 to March 2025. According to postoperative dietary regimens, they were divided into a control group(n=109, a conventional 2-hour postoperative diet regimen from October to December 2024), and an observation group(n=101, an immediate postoperative diet regimen from January to March 2025). Primary outcome indicators included the incidence and severity of nausea and vomiting at 1, 6, and 24 h postoperatively(WHO nausea and vomiting grading), thirst and hunger discomfort scores(a graded scoring), pain scores [Numerical Rating Scale(NRS)], as well as duration of surgery, time to return to regular diet, length of hospital stay, and duration of postoperative vaginal bleeding. All data were extracted from the electronic medical record(EMR) systems and follow-up records using a standardized data extraction protocol. Data extraction was performed independently by 2 research nurses who received uniform training and were blinded to group allocation, using double independent data extraction and entry; discrepancies were evaluated by a third party to ensure the authenticity and reliability of the data.

There were no statistical differences between the 2 groups in baseline characteristics such as age, gravidity and parity, BMI, and duration of amenorrhea(P>0.05). The incidence and severity of nausea and vomiting at 1 and 6 h postoperatively were significantly lower in the observation group than in the control group(Cliff’s delta=0.201, 95%CI: 0.048 to 0.354; Cliff’s delta=0.393, 95%CI: 0.249 to 0.537, P<0.05). The scores for postoperative thirst and hunger discomfort were significantly lower in the observation group than in the control group(Cramer’s V=0.411, 95%CI: 0.295 to 0.527, P<0.001). Compared with the control group, the observation group exhibited significantly lower pain scores at 6 h postoperatively(1.12±1.13 vs 2.26±0.91, mean difference: -1.14, 95%CI: -1.41 to -0.87, P<0.001), shorter time to return to regular diet(143.70±56.39 vs 361.07±144.45 min, mean difference: -217.37, 95%CI: -249.39 to 185.35, P<0.001), reduced length of hospital stay(61.46±19.13 vs 69.43±14.11 min, mean difference: -7.97, 95%CI: -12.54 to -3.40, P<0.001), and fewer days of postoperative vaginal bleeding(5.58±1.96 vs 6.71±2.08 d, mean difference: -1.13, 95%CI: -1.68 to -0.58, P<0.001).

Under the guidance of ERAS, the immediate postoperative feeding regimen for patients undergoing painless abortion is safe and feasible, effectively alleviating postoperative nausea, vomiting, and abdominal pain, reducing discomfort such as thirst and hunger, shortening postoperative hospital observation time and duration of vaginal bleeding, and further improving nursing quality and patient experience.

The promotion of enhanced recovery after surgery has shortened hospital stay of patients after radical prostatectomy, with most being discharged during the critical recovery period. These patients are prone to inadequate discharge preparation due to issues such as urinary dysfunction and indwelling catheterization. Although readiness for hospital discharge has been regarded as an important factor influencing patient prognosis, the mechanism by which it affects quality of life remains unclear. Based on the stress and coping theories, this study aims to explore the mediating role of coping styles in the relationship between readiness for hospital discharge and quality of life among patients after radical prostatectomy, providing evidence for developing targeted transitional care interventions.

A prospective longitudinal study design was adopted. From August 2024 to September 2025, 161 patients undergoing radical prostatectomy in the urology departments of 3 tertiary grade A hospitals in Chongqing were conveniently selected as the survey subjects. Within 24 h before discharge, the general information questionnaire, Readiness for Hospital Discharge Scale (RHDS), and Medical Coping Modes Questionnaire (MCMQ) were used for the investigation. Quality of Life (QOL) score was assessed through on-site or telephone evaluation at 1 month after surgery. The Process macro program Model 4 was utilized to construct a mediating effect model to test the mediating effect of coping styles.

The mean RHDS score of the 161 patients after radical prostatectomy was 84.72±17.96. The 3 dimensions of coping styles scored as follows: confrontation 19.02±4.02, avoidance 14.57±2.69, and resignation 8.19±2.57. The QOL score was 46.50±7.11. Pearson correlation analysis showed that the total score of quality of life was positively correlated with the total score of discharge readiness and the scores of each dimension (r=0.485 to 0.618, P<0.01), positively correlated with the confrontation dimension of medical coping modes (r=0.361, P<0.01), not significantly correlated with the avoidance dimension, and negatively with the resignation dimension (r=-0.383, P<0.01). Process mediating effect analysis indicated that the mediating effect value of coping styles between readiness for hospital discharge and quality of life was 0.038, with a 95%CI of 0.014 to 0.068, and the total mediating effect was significant (P<0.01). The mediation effect accounted for 15.89% of the total effect, with confrontation coping and resignation coping accounting for 6.74% and 9.15%, respectively.

Coping styles play a partial mediating role between readiness for hospital discharge and quality of life, with the mediating effect of reducing resignation coping being stronger. This suggests that clinicians should focus on identifying and intervening in patients with resignation coping tendencies to improve quality of life.

Malignant neoplasms represent a major public health threat to women of child-bearing age (WCBA) worldwide, with incidence rates significantly higher than those in men of comparable age. However, systematic research remains lacking regarding the long-term evolution patterns of WCBA-specific cancer disease burden and their socioeconomic determinants across extended timeframes. This study aims to comprehensively evaluate the disease burden and spatiotemporal trends of 30 cancer types among global WCBA from 1990 to 2021, providing scientific evidence for developing targeted precision prevention and control strategies for female malignancies.

A cross-sectional design was adopted in this study, and the data from the Global Burden of Disease Study (GBD) 2021 on the incidence, prevalence, and disability- adjusted life-years (DALYs) of 30 cancers among WCBA from 1990 to 2021 were extracted. Stratification was performed by age groups (15 to 29 and 30 to 49 years old) and socio-demographic index (SDI). Incidence rates, DALYs rates, and their estimated annual percentage change (EAPC) with 95%CI were calculated. Spearman correlation analysis and restricted cubic spline (RCS) models were applied to fit the non-linear relationship between disease burden and SDI (significance level P<0.05).

In 2021, the 3 leading cancers by incidence among global WCBA were breast cancer (28.81/100 000, 95%UI: 26.84 to 30.94), cervical cancer (15.77/100 000, 95%UI: 14.40 to 17.23), and ovarian cancer (4.40/100 000, 95%UI: 3.86 to 4.88). From 1990 to 2021, the incidence of colorectal cancer demonstrated a significant upward trend (EAPC=0.48, 95%CI: 0.42 to 0.55, P<0.05), whereas the burden of stomach cancer (EAPC=-2.01, 95%CI: -2.07 to -1.95, P<0.05) and leukemia (EAPC=-0.90, 95%CI: -0.97 to -0.83, P<0.05) declined significantly. RCS fitting revealed significant non-linear correlations between disease burden of tracheal, bronchial, and lung cancer and SDI (P for non-linearity <0.05), with the incidence peaking at an SDI of approximately 0.8. Age-stratified analysis indicated that the 15 to 29 years age group was predominantly affected by leukemia and central nervous system tumors, while the burden in the 30 to 49 years age group concentrated on breast cancer, cervical cancer, and colorectal cancer.

Between 1990 and 2021, the overall cancer burden among global WCBA remained substantial, with significant evolutionary shifts in the disease spectrum. Cancer incidences demonstrate close associations with socio-economic development levels, characterized by high incidence in high-SDI regions coupled with low DALYs. This study provides macro-level data support for developing intervention strategies that integrate cancer prevention and control with reproductive health management. Countermeasures　Health policymakers are recommended to implement stratified precision prevention and control policies based on age and regional SDI levels: for the 15- to 29- years-old population, priority should be given to promoting HPV vaccination and implementing fertility preservation measures during antineoplastic therapy; for those aged 30 to 49 years, coverage of combined breast and cervical cancer screening should be expanded, and early intervention for metabolic-related tumors such as colorectal cancer should be incorporated into workplace and community health management systems.