Bozhou People's Hospital

Traumatic brain injury (TBI) triggers complex pathological cascades, including inflammation, oxidative stress, apoptosis, and gliosis, particularly during the acute phase after injury. Trigonelline has been reported to exert neuroprotective effects in experimental models; however, its molecular mechanisms in acute TBI remain insufficiently defined. This study aimed to elucidate the molecular targets and mechanisms by which trigonelline attenuates acute TBI using an integrated network pharmacology and experimental validation approach. A trigonelline-target interaction network was constructed based on network pharmacology, followed by GO/KEGG analyses to predict the biological processes and pathways involved. Molecular docking was conducted to validate the binding affinity of trigonelline with key targets. Animal experiments were carried out to confirm the mechanistic predictions. Network pharmacology identified GAPDH, IL6, ALB, TNF, and IL1B as major hub genes associated with trigonelline. GO/KEGG analyses suggested that the neuroprotective effects of trigonelline against TBI primarily involved the MAPK and PI3K-Akt pathways. Invivo assays demonstrated that trigonelline treatment significantly reduced brain water content, inflammation, and oxidative stress levels within 72 h post-injury, while ameliorating histopathological damage, as confirmed by ELISA, HE, and LFB staining. TUNEL, NeuN, and FJB staining further revealed that trigonelline attenuated TBI-induced neuronal apoptosis. Western blotting demonstrated that trigonelline suppressed MMP-9 and AQP4 expression and attenuated the triggering of the MAPK signaling pathway. By attenuating MAPK signaling and apoptosis, trigonelline mitigates neural damage following TBI. The present findings provide experimental evidence supporting the neuroprotective effects of trigonelline in an acute TBI model.

Inflammasomes canonically trigger pyroptotic cell death through GSDMD-mediated membrane rupture. This study investigates a distinct sublytic pyroptosis in Schwann cells following peripheral nerve injury, where inflammasome activation causes functional impairment without extensive cell death. Using a mouse sciatic nerve transection-repair model combined with in vitro and in vivo analyses, we examined NLRP3 inflammasome activation and cell fate. Primary Schwann cell cultures and RSC96 cells were used for biochemical assays, while ultrastructural analyses were performed on sciatic nerve segments. Despite NLRP3 inflammasome activation, Schwann cells showed minimal GSDMD cleavage and maintained membrane integrity, resulting in low cell death rates (~ 8% in primary mouse Schwann cells and ~ 2–3% in RSC96 rat Schwann cells). However, these surviving cells failed to transition from repair to myelinating phenotype. Activated Caspase-1 directly cleaves Tyro3 receptor at Asp495, detaching the intracellular kinase domain and abolishing receptor function. This proteolytic inactivation disrupts the Gas6-Tyro3-Fyn signaling axis essential for Schwann cell myelination. Combined treatment with Caspase-1 inhibitor VX-765 and Gas6 prevented Tyro3 cleavage, restored downstream signaling, and promoted expression of myelin transcription factors Oct6 and Krox20 as well as myelin basic protein (MBP). In vivo application significantly enhanced myelin thickness, axon regeneration, and functional recovery assessed by sciatic function index and electrophysiology. Sublytic pyroptosis represents a novel inflammasome-mediated proteolytic receptor inactivation as a previously unrecognized mechanism, distinct from classical pyroptosis. Targeting this pathway with VX-765 and Gas6 represents a promising therapeutic strategy for peripheral nerve regeneration.

Indoor carbon dioxide (CO 2 ) accumulation in university classrooms is associated with fluctuations in students’ cognitive performance. This study investigated the preliminary associations between short-term CO 2 exposure, heart rate (HR), and cognitive accuracy (ACC), leveraging a small-N intensive longitudinal design with 54 synchronized observation sets over 6 days. Results indicated that HR responded to CO 2 in two stages under the observed conditions: an initial sensitive response with relatively stable HR when CO 2 was below the 1000 ppm reference level, followed by a gradual adaptive decline as concentrations increased. Standardized mediation analysis confirmed a global indirect effect (β = −0.106, p < 0.05). Notably, segmented analysis revealed that this physiological-cognitive coupling was primarily driven by the intensified impact of HR on cognitive accuracy in Phase II (β = 0.389, p = 0.022), whereas the mechanism remained exploratory in Phase I. These preliminary findings suggest that the relationship between CO 2 and cognition may be mediated by autonomic regulation (reflected by HR). Under the observed classroom conditions, 1000 ppm may serve as a guideline-aligned environmental reference associated with physiological–cognitive shifts. Practical applications This pilot study suggests that heart rate (HR) mediates the association between indoor CO 2 and cognitive performance in university classrooms. Specifically, CO 2 levels exceeding 1000 ppm were associated with distinct physiological changes and reduced cognitive accuracy, highlighting this value as a critical reference for ventilation control. Practically, these results support implementing occupancy-sensitive ventilation strategies to limit CO 2 accumulation. Additionally, the observed CO 2 -HR coupling indicates that aggregate HR trends derived from wearable devices could serve as non-invasive, supplementary indicators of indoor environmental conditions. These exploratory findings inform future human-centric approaches to indoor environmental quality (IEQ) management in educational settings.

Lipoprotein(a) [Lp(a)] promotes atherosclerotic plaque vulnerability through pro-inflammatory and thrombogenic pathways, while the CatLet© angiographic score quantifies coronary lesion complexity. We hypothesized that their integration would improve prognostication in acute myocardial infarction (AMI) after emergency percutaneous coronary intervention (ePCI). In this retrospective cohort, 307 AMI patients undergoing successful ePCI (2020-2022) were stratified by 1-year major adverse cardiovascular/cerebrovascular events (MACCE). Serum Lp(a) and troponin I were measured post-admission. CatLet© and Gensini scores were assessed by blinded analysts. Multivariable logistic regression and ROC analyses evaluated predictive performance. MACCE patients (n = 78) exhibited higher Lp(a) (135.99 ± 33.07vs. 123.35 ± 42.70nmol/L, P = 0.0178) and CatLet© scores (33.58 ± 9.04vs. 30.80 ± 8.24, P = 0.0012) versus controls. Lp(a) (OR=2.339,95%CI:1.519-3.603, P < 0.001) and CatLet© score (OR=1.092, 95%CI:1.027-1.161, P = 0.005) independently predicted MACCE. The combined model Lp(a)≥70.70 nmol/L + CatLet© ≥ 18.6) significantly outperformed individual markers (AUC 0.862 [95%CI:0.83-0.96] vs. 0.780/0.833; DeLong's test confirmed the superiority of the combined model over individual predictors (P = 0.0089, Z = 2.64 vs. Lp(a); P = 0.034, Z = 2.12 vs. CatLet© score), with 88% sensitivity and 83% specificity. The Lp(a)-CatLet© synergy enhances MACCE risk stratification in ePCI-treated AMI, reflecting complementary pathobiological (Lp(a)-driven plaque vulnerability) and anatomical (CatLet©-quantified complexity) pathways. This dual-parameter approach could support post-PCI risk stratification and follow-up planning.

Approximately 85-90% patients with small for gestational age (SGA) experience catch-up growth (CUG) by the age of 2, with their height reaching - 2 standard deviation scores (SDS) or 3% of the height of children of the same age and sex. However, SGA patients with CUG (CUG-SGA) tend to be at a higher risk of developing insulin resistance, obesity, metabolic syndrome, and cardiovascular diseases. This study explored the metabolic conditions of CUG-SGA patients in East China and analyzes the risk factors that may contribute to metabolic issues. This multi-center study in East China involved 151 SGA patients aged 2-8 years. Patients were categorized into two groups: CUG-SGA (height not below - 2 SDS among the children of the same age and gender) and NCUG-SGA (SGA patients without CUG, height below - 2 SDS among the children of the same age and gender). Tests for insulin-like growth factor 1 (IGF-1), blood glucose (BG), insulin (INS), triglycerides (TG), total cholesterol (TC), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and leptin (LEP) were conducted after a 12-hour fast. Body mass index (BMI) and homeostatic model assessment for insulin resistance (HOMA-IR) were calculated. (1) Out of 151 SGA patients, 82 were girls and 69 were boys. There were 85 patients in CUG-SGA group, including 38 girls and 47 boys. There were 66 patients in NCUG-SGA group, including 44 girls and 22 boys. The height SDS (H-SDS) and weight SDS (W-SDS) of CUG-SGA group were significantly higher than those of NCUG-SGA group (P < 0.05). (2) The level of IGF-1 SDS, ALT, and GGT in the CUG-SGA group were significantly higher than those in the NCUG-SGA group (P < 0.01). The level of W-SDS, LEP, INS, and HOMA-IR in the CUG-SGA group are significantly higher than those of the NCUG-SGA group (P < 0.05). (3) Correlation analysis in SGA patients indicated positive correlations between BG and W-SDS, LEP, and GGT (P < 0.05). INS was positively correlated with IGF-1 SDS, GGT (P < 0.01), and W-SDS (P < 0.05). HOMA-IR was positively correlated with IGF-1 SDS (P < 0.01). TC was positively correlated with LEP (P < 0.05), and TG was negatively correlated with IGF-1 SDS (P < 0.01). (4) After further controlling for confounding factors and performing multiple regression analyses, the results showed that BMI-SDS had a significant positive effect on INS and a significant negative effect on HOMA-IR. IGF-1 had a significant positive effect on INS and HOMA-IR, and a significant negative effect on TG. LEP had a significant positive effect on BG, INS, HOMA-IR, TC, and TG. ALT had a significant negative effect on INS and HOMA-IR, and a significant positive effect on TC and TG. GGT had a significant positive effect on BG, INS, HOMA-IR, TC, and TG. (1) IGF-1 SDS was significantly positively correlated with fasting INS (FINS) and HOMA-IR, and exerted a significant positive effect on fasting BG. If IGF-1 levels in CUG-SGA infants remain persistently high, careful monitoring of changes in glucose metabolism is warranted. (2) CUG-SGA patients had higher LEP resistance compared to NCUG-SGA patients, potentially contributing to future metabolic issues. (3) Elevated ALT and GGT levels in SGA patients may warrant close monitoring of glucose metabolism, particularly in CUG-SGA patients.