Nanjing Traditional Chinese Medicine Hospital

Severe burns are characterized by high mortality and morbidity rates. Immune dysfunction during the acute phase of severe burns exacerbates tissue damage. Complement C3a receptor 1 (C3AR1) is a key receptor associated with severe burn shock. This study aimed to investigate the effects of C3AR1 on T-cell immunity in the intestine following burns. We established a mouse model of severe burns and performed in vitro stimulation of CD3+ Tcells with C3AR1 agonist. Quantitative real-time PCR, Western blot, ELISA, and flow cytometry were used to analyze the expression of C3AR1, IL-2, IL-10 and factors related to the NF-κB signaling pathway, changes in the proportions of Th1 and Th2 subsets, and the apoptosis rate of CD3+ Tcells after C3AR1 stimulation. The results showed that C3AR1 expression in the intestinal mucosa of severely burned mice was significantly elevated, while IL-2 expression was decreased, exhibiting a negative correlation. After C3AR1 overexpression, the proportion of Th1 cells decreased, the apoptosis rates of Th2 cells and CD3+ Tcells increased, IL-2 expression was reduced, and the NF-κB signaling pathway was activated. In conclusion, C3AR1 participates in intestinal T-cell immune responses after burns through activation of the NF-κB signaling pathway, indicating that C3AR1 is a crucial regulator in the recovery of intestinal mucosal injury and immune function balance, and may serve as a potential molecular target for burn treatment.

Introduction: This study aimed to assess the association of Geriatric Nutritional Risk Index (GNRI) with cognitive function level and cognitive impairment risk among older adults with cardiometabolic disease using data from the National Health and Nutrition Examination Survey (NHANES). Methods: Using cross-sectional data from the NHANES, this research included 1,937 participants aged 60 years or older with at least one cardiometabolic disease (diabetes, hypertension, stroke, or congestive heart failure). Cognitive function was assessed using the CERAD tests, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Multivariable linear and logistic regression analyses were used to estimate the β coefficients and odds ratios (ORs) with 95% confidence intervals (CIs) for the associations of GNRI with cognitive function level and risk of cognitive impairment. Results: A total of 1937 participants aged≥60 years with cardiometabolic disease were included. The results showed that per 1-SD increase in GNRI was associated with increased cognitive function levels, including CERAD: Trial 1 (β=0.11, 95% CI: 0.03-0.19), CERAD: Trial 3 (β=0.12, 95% CI: 0.04-0.21), CERAD: Delayed Recall (β=0.21, 95% CI: 0.11-0.32), CERAD test (β=0.53, 95% CI: 0.23-0.82), and AFT (β=0.34, 95% CI: 0.11-0.57) scores. Restricted cubic splines showed significantly positive linear dose-response associations between GNRI and cognitive function. Compared to participants with the lowest quartile (Q1) of GNRI, those with the highest quartile (Q4) had a lower cognitive impairment risk (OR=0.59, 95% CI: 0.41-0.85). Discussion: Potential mechanisms underlying GNRI’s protective effect against cognitive impairment may involve the pleiotropic neuroprotection of albumin and body mass index-mediated brain structural changes. Conclusion: Higher GNRI is independently associated with better cognitive function and reduced risk of cognitive impairment in older adults with cardiometabolic diseases. To mitigate cognitive risk, implementing GNRI screening may identify high-risk older adults with cognitive impairment, prompting timely nutritional support that improves cognitive health and disease management.

BackgroundWe analyzed the prevalence and clinical characteristics of children with plastic bronchitis (PB) caused by severe Mycoplasma pneumoniae (SMPP) and explored its risk factors.MethodsThis retrospective study included pediatric patients with SMPP who were admitted to the Respiratory Department of Children’s Hospital of Soochow University and underwent fiberoptic bronchoscopy (FB) treatment between January 1 and December 31, 2024. The SMPP patients were divided into a PB group and a non-PB group according to whether there was a plastic shape under FB. Epidemiological characteristics, general information, clinical manifestations, laboratory findings, imaging features, and treatment regimens were collected and compared between the two groups. Risk factors for PB were identified using logistic regression analysis, and their predictive value was assessed with receiver operating characteristic (ROC) curves.ResultsThis study incorporated a total of 510 children diagnosed with SMPP, with 60 and 450 assigned to the PB and non-PB groups, respectively. The epidemic peak of SMPP occurred in summer and autumn; the highest detection rate of PB was recorded in winter (19.30%), with the PB positivity rate peaking in December (32.26%). In the PB group, fever days, runny nose, diminished breath sounds, abnormal liver function, abnormal coagulation function, number of bronchoscopic interventions, neutrophil percentage, C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), D-dimer, atelectasis, and pleural effusion were all significantly higher compared to the non-PB group (P < 0.05). In the PB group, lymphocyte percentage and platelet count were significantly lower compared to the non-PB group (P < 0.05). Multivariate logistic regression analysis identified LDH, pleural effusion, and length of hospital stay as independent predictors of PB in children. The combination of these three indicators yielded a notably higher predictive value, with an area under the receiver operating characteristics curve (AUC) of 0.911 (95% CI: 0.868∼0.953).ConclusionLDH, pleural effusion, and length of hospital stay were independent risk factors for PB in SMPP children. For children suspected of PB, pediatricians should pay close attention to the above indicators, strive for early diagnosis and treatment, and improve prognosis.

Rituximab (RIT) resistance significantly hampers the treatment efficacy in diffuse large B-cell lymphoma (DLBCL), leading to poor prognosis. We aim to investigate the potential of stigmasterol, a natural compound, to reverse RIT resistance in DLBCL through modulation of the mitogen-activated protein kinase 1 (MAPK1) signaling pathway. The RIT-resistant DLBCL model, Raji-4RH cells, was established by prolonged exposure to increasing concentrations of RIT. The effects of stigmasterol on cell viability, proliferation, migration, and invasion were assessed using Cell Counting Kit-8 (CCK-8) assays, 5-ethynyl-2'-deoxyuridine (EdU) staining, and Transwell assays. Additionally, the role of MAPK1 signaling in stigmasterol's mechanism of action was evaluated by overexpressing MAPK1 in Raji-4RH cells, and the expression of key multidrug resistance (MDR) proteins was analyzed. Stigmasterol effectively reversed RIT resistance by inhibiting cell proliferation, migration, and invasion. It induced G0/G1 cell cycle arrest and apoptosis, significantly downregulated MDR proteins P-gp, MRP5, and BCRP, and inhibited MAPK1 phosphorylation. The anti-resistance effects of stigmasterol were partially reversed by MAPK1 overexpression, confirming that MAPK1 signaling plays a critical role in its mechanism. Stigmasterol significantly reverses RIT resistance in DLBCL by inhibiting MAPK1 phosphorylation and downregulating MDR protein expression. These findings provide new insights into overcoming RIT resistance and support the potential of stigmasterol as a therapeutic strategy for refractory DLBCL.

To investigate the potential role of the environmental pollutant tris(2-butoxyethyl) phosphate (TBOEP) in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) and to elucidate its underlying molecular mechanisms. We employed an integrated multi-omics approach. First, a multidatabase strategy identified overlapping targets between TBOEP and MASLD, which were subjected to functional enrichment and protein-protein interaction (PPI) network analysis. Molecular docking was then used to predict binding affinities. Second, transcriptomic profiling (RNA sequencing (RNA-seq)) was performed on TBOEP-treated AML-12 hepatocytes to identify differentially expressed genes and pathways. Finally, key findings were validated in vitro using Oil Red O staining, triglyceride quantification and western blot analysis. We identified 154 common targets between TBOEP and MASLD, with enrichment analysis pointing to pathways in non-alcoholic fatty liver disease and insulin resistance. PPI analysis highlighted ACTB, IL6, PPARG and PPARA as pivotal hub proteins. RNA-seq revealed 326 differentially expressed genes, with significant alterations in metabolic pathways. Cross-referencing pathways predicted from target genes with RNA-seq data revealed 10 pathways potentially impacted by TBOEP, emphasising its multifaceted effects on hepatocyte function. In vitro studies showed that TBOEP promotes lipid accumulation in hepatocytes by increasing PPARγ expression. Our study provides evidence that TBOEP acts as a potential environmental risk factor for MASLD. We demonstrate that TBOEP promotes hepatocyte steatosis, likely through the dysregulation of metabolic pathways centred on PPARγ signalling. These findings provide new insights into the pathogenesis of MASLD.

The progressive process from normal oral tissue (ONT) to precancerous lesions (oral dysplasia [OD], leukoplakia-oral precancerous lesion [OPL]) and ultimately to oral squamous cell carcinoma (OSCC) involves dynamic molecular and immunological alterations. Four transcriptomic datasets were analyzed using GEO2R and the R package "IOBR" for differentially expressed genes (DEGs) and immune infiltration profiling. Two-sample Mendelian randomization (TSMR) was employed to validate the causal effects of immune cells and genes on 11 oral-related cohorts. WDR66 was the only consistently upregulated DEG across all stages (ONT, OD, OPL, OSCC; p < 0.001), with expression levels increasing from premalignant to malignant tissues. Immune infiltration indicates that neutrophils and CD4+ effector memory T cells (Tem) show high correlation with OSCC and OD (these 2 cells were intersection cells in OSCC based on 3 cohorts, high correlation cells in OD based on 1 cohort). TSMR indicated that WDR66: OR M (Q1, Q3) = 0.8513 (0.8453, 0.8759), p, M (Q1, Q3) = 0.0057 (0.0029, 0.0104); CD4+ T cells: OR M (Q1, Q3) = 0.5888 (0.4556, 0.7254), p, M (Q1, Q3) = 0.0000 (0.0000, 0.0002). WDR66 emerges with its expression tightly coupled to CD4+ T cell dysfunction in OSCC.