Anhui Provincial Children's Hospital

BackgroundOsteoglycin (OGN), an extracellular matrix protein, has emerging but poorly characterized roles in cancer. This study presents the first pan-cancer investigation of OGN’s expression patterns, clinical significance, immune interactions, and functional mechanisms.MethodsMulti-omics data from Genotype Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), The Cancer Genome Atlas (TCGA), and Human Protein Atlas (HPA) databases were integrated. Differential expression was analyzed in normal tissues and tumor samples. Diagnostic utility was evaluated using area under the curve (AUC) of receiver operating characteristic (ROC) curve. Prognostic value was assessed via Kaplan-Meier [overall survival (OS); disease-specific survival (DSS); disease free interval (DFI); progression-free interval (PFI)] and Cox regression analyses. Immune microenvironment correlations were quantified using ESTIMATE, CIBERSORT, and gene set enrichment. Functional pathways were explored through gene set enrichment analysis (GSEA) and correlation with hallmark cancer signatures.ResultsOGN was broadly expressed in normal tissues (brain, liver, kidney) but significantly downregulated in most tumor types (P<0.05, TCGA; validated at protein level, HPA). OGN demonstrated high diagnostic accuracy in pan-cancer (AUC: 0.703–0.990), achieving near-perfect performance in colon adenocarcinoma (COAD) (AUC: 0.966) and thyroid cancer (THCA) (AUC: 0.920). High OGN expression correlated with improved survival outcomes in thymoma (THYM) (OS/DSS) and cholangiocarcinoma (CHOL) (PFI/DFI), but worse prognosis in lung adenocarcinoma​/liver hepatocellular carcinoma​ (LUAD/LIHC), indicating cancer-type specificity. OGN expression strongly associated with immune cell infiltration (macrophages, natural killer cells, T cells), chemokine signaling, programmed death-ligand 1 (PD-L1) levels, microsatellite instability (MSI), and tumor mutation burden (TMB). GSEA revealed enrichment of OGN-linked genes in epithelial-mesenchymal transition (EMT), angiogenesis, JAK-STAT, and PI3K pathways across cancers.ConclusionsOur pan-cancer analysis highlights OGN as a context-dependent regulator linking extracellular matrix (ECM) remodeling with immune and angiogenic signaling. Its pan-cancer dysregulation, diagnostic/prognostic value, and crosstalk with immune evasion mechanisms nominate OGN as a promising multi-functional biomarker and therapeutic target.

Aberrant right subclavian artery is a common anatomical variant of the embryonic aortic arch, with a prevalence ranging from 0.4 to 2.0%. Although frequently associated with vascular rings or congenital cardiac defects, prenatal assessment primarily relies on the three-vessel and trachea view in ultrasonography. Currently, there is no consensus regarding whether isolated ARSA necessitates invasive diagnostic procedures. This study aimed to evaluate the necessity of routine invasive prenatal diagnosis for fetuses with sonographically isolated ARSA. By conducting a long-term postnatal follow-up of a large cohort and utilizing Bayesian analysis for risk assessment, we sought to provide empirical data to support clinical decision-making. The fetuses diagnosed with ARSA via prenatal ultrasound at Hefei Maternal and Child Health Care Hospital from January 2019 to December 2022 were retrospectively analyzed. They were divided into isolated ARSA and non-isolated ARSA groups based on the presence or absence of other ultrasound abnormalities. Within each of these two groups, the fetuses were further categorized into diagnostic and undiagnosed subgroups based on whether they underwent invasive prenatal diagnosis. The study explored the baseline characteristics, genetic testing results, pregnancy outcomes, infant feeding and developmental status, and the results of neonatal color Doppler ultrasound re-examinations in these two groups. A total of 540 cases of ARSA fetuses were identified, including 449 cases (83.1%) of isolated ARSA and 91 cases (16.9%) of non-isolated ARSA. There were no statistically significant differences in baseline characteristics such as age, pre-pregnancy BMI, and history of diabetes between the two groups (P > 0.05). However, the proportion of non-invasive prenatal testing (NIPT) applications and the pregnancy termination rate were significantly higher in the non-isolated group compared to the isolated group (P < 0.05). Pregnancy outcomes revealed that there were 496 live births (91.6%), while 44 cases (8.1%) chose to terminate their pregnancies due to chromosomal abnormalities and/or severe structural abnormalities. Among the 90 fetuses that underwent invasive prenatal diagnosis, the overall detection rate of chromosomal abnormalities was 11.1%. The detection rates for isolated and non-isolated ARSA were 9.1% (6/66) and 16.7% (4/24), respectively, with no statistically significant difference between the two groups (P > 0.05).The follow-up results of live births showed that 25 (5.0%) of 496 cases had abnormal phenotypes. Among 446 live births with isolated ARSA, 10 cases (2.2%) were found to have abnormal manifestations, with 1.6% (1/66 cases, diagnosed as 21-trisomy mosaicism) in the invasive diagnosis group and 2.4% (9/380 cases) in the undiagnosed group. The difference between the two groups was not statistically significant (P > 0.05). In contrast, the abnormal phenotype rate of live births with non-isolated ARSA was nearly 30.0%. Bayesian risk assessment indicated that the overall posterior risk of abnormal phenotype for isolated ARSA was 2.46% (95% HDI: 1.195%-4.080%), and whether or not invasive diagnosis was performed did not alter this risk. Among the 407 live births that did not undergo invasive diagnosis, 17 cases (4.2%) exhibited abnormalities during follow-up, among whom, genetic testing identified pathogenic variants in two neonates. The positive predictive value for postnatal aberrant clinical symptoms in fetuses with sonographically isolated ARSA is low (2.24%). In the absence of additional ultrasound markers or significant risk factors, routine invasive prenatal diagnosis is not recommended. Comprehensive genetic counseling should be prioritized to facilitate informed and autonomous decision-making by pregnant women and their families.

Wilms tumor is a highly heterogeneous tumor, and patients with high-risk Wilms tumor still do not have a good prognosis. DNA instability caused by abnormal genes in the base excision repair (BER) pathway is closely related to cancer. However, the important role of BER pathway gene variants in Wilms tumor remains largely unknown. We enrolled 621 patients with Wilms tumor and 1737 controls from eight hospitals. We calculated odds ratios and 95% confidence intervals to evaluate the association strength. Stratification analysis was performed to further evaluate the associations of significant polymorphisms with the risk of Wilms tumor in different subgroups. False-positive report probability analysis was adopted to evaluate the robustness of the positive results. The associations of polymorphisms with gene expression were analyzed via eQTLs from the GTEx database. We found that the FEN1 rs174538 GG, FEN1 rs4246215 GG, APEX1 rs3136817 CC, and XRCC1 rs25487 TT genotypes were associated with an increased risk of Wilms tumor, whereas the FEN1 rs4246215 TG/GG genotype was associated with a decreased risk. Stratification analysis revealed that significant polymorphisms remained associated with the risk of Wilms tumor in some subgroups. False-positive report probability analysis also revealed that some positive results were more robust. The eQTL results revealed that all four polymorphisms were associated with alterations in the expression of host or nearby genes. FEN1 rs174538 A>G, FEN1 rs4246215 T>G, APEX1 rs3136817 T>C, and XRCC1 rs25487 C>T are associated with Wilms tumor susceptibility, which provides potential molecular markers for the early diagnosis of Wilms tumor.

IntroductionTo explore how MP and RTX impact TRPC6's expression and localization, and assess MP's and RTX's effects on podocyte injury and recovery.MethodsMPC5 cells were simultaneously grown alongside a control group and under various conditions: exposure to puromycin aminonucleoside (PAN) stimulation, treatment with methylprednisolone (MP), and treatment with rituximab (RTX), and a combined treatment with both MP and RTX.ResultsAt 8, 24, and 48 h, CCK-8 assay showed that PAN (50 μg/mL) had a decrease in cell viability and an increase in cell death, and it could be used as the optimum concentration to induce podocyte injury; MP (100 ng/mL) and RTX (100 μg/mL) maintained cell viability and had minimal impact on cell morphology, and they were the best concentrations. Following 24 and 48-h exposure to MP or RTX, there was a decrease of 30%–50% in apoptosis rates by flow cytometry in comparison to the group stimulated with PAN, accompanied by a substantial reduction in nearly 10%–60% of TRPC6 mRNA and 5%–20% of protein levels which were measured using qRT-PCR and western blot analyses, akin to the observed decrease in levels of IL-1β and IL-18. Additionally, calcium entry showed considerable reductions after 8, 24, and 48 h of MP treatment relative to the PAN-stimulation group, paralleling the effect seen with 24-h RTX treatment.DiscussionTherefore, MP and RTX safeguarded podocytes, and averted proteinuria by decreasing podocyte apoptosis, diminishing TRPC6 mRNA and protein levels, and suppressing inflammatory markers and calcium entry.

BackgroundCervical cancer, as the leading malignant tumor among women globally, underscores the critical need for early screening; however, effective models for predicting cervical lesions remain lacking.ObjectiveTo construct a predictive model for cervical intraepithelial neoplasia II+(CINII+), and to compare the predictive performance of machine learning models integrating thinprep cytologic test (TCT) + human papillomavirus (HPV) testing with clinical data versus TCT combined with traditional clinical data for CIN II+.MethodsClinical data from women undergoing cervical cancer screening at Linquan Maternity and Child Healthcare Hospital (2020–2024) were collected, including TCT results, HPV status, cervical pathology, age, sexual history and other clinical data. Ten machine learning algorithms were applied to develop two predictive models: Model 1(TCT+HPV+clinical data) and Model 2(TCT+traditional clinical data). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analysis (DCA).ResultsMultivariate logistic regression analysis showed that HPV positivity, TCT indicates High-Grade Squamous Intraepithelial Lesion(HSIL), colposcopy result indicates a high-grade lesion and the first age of pregnancy as predictors of CINII+. Model 1 (TCT+HPV+clinical data) demonstrated significantly higher predictive efficacy than Model 2(TCT+clinical data), the difference in AUC is statistically significant. (P=0.006 in training set; P=0.035 in testing set).ConclusionThe TCT+HPV-integrated model outperformed the TCT-only model in predicting CIN II+, supporting the incorporation of HPV testing into routine screening to enhance early diagnostic accuracy.

Mycoplasma pneumoniae pneumonia (MPP) is a common pediatric infection frequently accompanied by systemic inflammation and psychological stress; however, its potential bidirectional relationship remains poorly defined. We retrospectively analyzed 120 hospitalized children aged 5-12 years using the Child Stress Questionnaire (CSQ), inflammatory mediators (CRP, IL-6), and three clinical biomarkers (LDH, D-dimer, MP-DNA load). Elevated LDH and D-dimer were significantly associated with higher CSQ scores (r = 0.67, p < 0.01) and more severe inflammatory responses. Children with prolonged illness (>7 days) and high MP-DNA load had markedly higher stress scores (mean 38 vs. 25, p < 0.01). LDH ≥ 450 U/L independently predicted extended hospitalization (OR = 2.1, 95% CI: 1.2-3.7), and ROC analysis demonstrated strong discriminative power for severe complications (AUC = 0.89, 95% CI: 0.83-0.95; sensitivity = 82%, specificity = 81%). These findings support a bidirectional link between psychological stress and immune dysregulation in pediatric MPP and highlight LDH and D-dimer as practical biomarkers for early identification of high-risk children.

Background and ObjectiveSepsis-associated encephalopathy (SAE) is a severe multifactorial brain dysfunction triggered by severe infections, characterized by neuroinflammation, blood-brain barrier (BBB) breakdown, and persistent neurocognitive deficits. Accumulating evidence indicates that phenotypic polarization of microglia—resident immune cells in the central nervous system (CNS)—plays a central role in SAE pathogenesis. In SAE, microglia exhibit an imbalance in polarization, with sustained pro-inflammatory states and impaired reparative functions, accompanied by activation of the NLRP3 inflammasome, forming a deleterious cycle of neuroinflammation and neuronal damage. This review focuses on three underexplored domains in SAE: neuronal/glial dysfunction, circadian disruption, and gut-brain axis dysregulation.MethodsA systematic literature search was performed in PubMed (1985–2025) using fuzzy-matching mode, with search terms including “microglia”, “sepsis-associated encephalopathy”, “blood-brain barrier (BBB)”, “microglia polarization”, “M1/M2 polarization”, “NLRP3 inflammasome”, “inflammation” “quercetin”, and related Medical Subject Headings (MeSH) terms.Key Content and FindingsThis review elaborates on the mechanisms underlying neuronal/glial dysfunction, circadian rhythm disruption, and gut-brain axis imbalance in SAE, emphasizing their interactions with microglial polarization and neuroinflammation. Experimental interventions targeting microglial activity (e.g., CSF1R inhibitors) show promise, but complete suppression of microglia is inadvisable due to their essential role in maintaining neural network homeostasis.ConclusionsFuture therapeutic strategies for SAE should aim to balance the inhibition of harmful inflammatory responses with the preservation of microglia-mediated reparative processes, while targeting the underexplored domains identified herein to improve neuroprotective efficacy and ultimately translate into tangible clinical benefits for patients.