沧州医学高等专科学校

Ulcerative colitis (UC) is a chronic, relapsing disease, imposing a heavy disease burden and severely reducing the quality life of patients. This study verified the influence of the PVT1/miR-216a-5p/TLR4 signaling axis on UC. LPS-stimulated RAW264.7 cells were co-cultured with Caco-2 cells to establish an in vitro model. The C57BL/6 J mice induced by 3% DSS were used as an in vivo model. Cytotoxicity and barrier function were evaluated in Caco-2 cells. The PVT1, miR-216a-5p, and TLR4 levels were detected by RT-qPCR. ELISA was used to detect the level of pro-inflammatory factors in RAW264.7 supernatant and colon tissue, and the level of ZO-1 and occludin in Caco-2 cells and colon tissue. TEER was used to evaluate the integrity of the barrier function of Caco-2 cells. The targeting relationships between PVT1, miR-216a-5p, and TLR4 were verified by dual-luciferase reporter gene assay. The PVT1 and TLR4 levels were increased, but miR-216a-5p was decreased in the LPS-treated RAW264.7, co-cultured Caco-2, and colon tissue of DSS mice. The pro-inflammatory factor levels in RAW264.7 and colon tissue of DSS mice were increased, while in Caco-2, the cytotoxicity was aggravated, and the integrity of the barrier function was disrupted. The levels of ZO-1 and occludin were decreased in Caco-2 cells and tissue. If the PVT1 expression was inhibited, the results showed an opposite trend. In contrast, inhibition of miR‑216a‑5p reversed the protective effects induced by PVT1 knockdown. The PVT1/miR-216a-5p signaling axis affects the inflammation and intestinal epithelial cell barrier function in UC, which may be a possible therapeutic target for UC.

Diabetic nephropathy (DN) is a major microvascular complication of diabetes and a leading cause of end-stage renal disease, with current treatments failing to halt progression, creating demand for better interventions. Astragalus membranaceus shows promise for DN, and microbial fermentation enhances herbal bioavailability and efficacy. This study compared fermented A. membranaceus broth (FA) and its aqueous extract (EA) in streptozotocin-induced DN rats, with 8-week low/medium/high-dose treatment. FA outperformed EA in improving metabolic parameters and renal function: superior body weight recovery, greater reductions in fasting blood glucose, serum BUN, ALT, and TG, enhanced renal antioxidant capacity (elevated SOD/GSH-Px and reduced MDA), and alleviated glomerular/tubular injury and interstitial inflammation. Chemical profiling identified 14 FA bioactive components; network pharmacology revealed core targets (STAT3, IL6, and TGFB1) and key pathways (AGE-RAGE, HIF-1, and FoxO). Fermentation boosts A. membranaceus efficacy in DN via better active constituent bioavailability, conferring stronger antioxidant, metabolic, and renoprotective effects, making FA a promising therapeutic and bioprocessing a strategy to upgrade traditional herbs.

Objective:To compare the efficacy and safety of adjuvant almonertinib versus icotinib in patients with resected stage II-IIIA epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Methods:This retrospective study included 80 patients treated with adjuvant almonertinib or icotinib after complete resection. Disease-free survival (DFS) was the primary endpoint; secondary endpoints included overall survival (OS) and safety. Multivariate Cox regression was used to identify factors associated with DFS and OS. Results:Baseline characteristics were well balanced. After a median follow-up of 40.0 months, almonertinib demonstrated a significant DFS advantage (HR = 0.36, 95% CI: 0.16-0.82), with the median DFS not reached versus 29.0 months for icotinib (p = 0.0142). The 24-month DFS rates were 85.1 and 61.2%, respectively. Subgroup analyses showed consistent benefits in male patients, patients younger than 65 years, patients with stage IIIA disease and those with smoking history. OS also favored almonertinib (HR = 0.43, 95% CI: 0.19-0.94), with the median OS not reached versus 41.2 months (p = 0.0355). Recurrence occurred in 17.5% of the almonertinib group and 45.0% of the icotinib group (p = 0.0150). The 24-month central nervous system (CNS) metastasis-free survival rate reached 100% in the almonertinib group versus 96.6% in the icotinib group; however, the total number of CNS metastatic events was very small (n = 3), so this numerical difference should only be interpreted as an exploratory trend rather than definitive evidence of CNS protection. Safety profiles were comparable, although grade ≥3 TEAEs were less frequent with almonertinib (7.5% vs. 25.6%, p = 0.0367). No TEAEs or TRAEs leading to death were observed. Conclusion:In this retrospective cohort, adjuvant almonertinib was associated with significantly improved DFS and OS, recurrence prevention, and a more favorable safety profile compared with icotinib. A numerical trend of reduced CNS metastasis was observed, but limited CNS events preclude firm conclusions regarding CNS protective activity. A tentative early OS survival trend favoring almonertinib was observed, but OS data remain immature with limited death events; long-term follow-up is needed to verify this potential survival benefit.

Junctional adhesion molecule 3 (JAM3) has been increasingly recognized as a critical regulator of cell migration and adhesion, and JAM3 mutation in humans results in severe skeletal dysplasia and death. However, the underlying mechanism by which JAM3 regulates bone formation is unclear. Here, we identified increased JAM3 levels in both osteoblast and adipocyte differentiation. Functional experiments revealed that JAM3 in bone marrow mesenchymal stromal cells (BMSCs) promoted osteoblast differentiation while inhibiting adipogenesis. In vivo, both the bone marrow cavity-delivered Jam3 siRNA mouse model and the osteoblast progenitor-specific Jam3 conditional knockout mouse model (Osx-Cre; Jam3fl/fl) consistently exhibited a marked reduction in osteoblasts, an increase in adipocytes and osteoclasts, and a significant decrease in tibial bone mass and bone density. It has been demonstrated that JAM3 can activate LRP5 protein. Structural modeling using AlphaFold3, combined with molecular dynamics simulations, confirmed that JAM3 could form a stable complex with LRP5. Consistently, cellular assays demonstrated that JAM3 suppressed the degradation of LRP5, supporting its role in stabilizing the receptor. Mechanistic studies confirmed that inhibiting β-catenin activation significantly reversed the effect of JAM3 on regulating osteogenesis/adipogenesis differentiation in BMSCs. Regarding osteoclast differentiation, overexpression of JAM3 in BMSCs led to an increased Rankl/Opg ratio, indicating that JAM3 promotes osteoclastogenesis and bone resorption via a RANKL-dependent pathway. This study provides evidence that JAM3 in BMSCs reciprocally regulates bone homeostasis by modulating LRP5/β-catenin and down-regulating the expression of RANKL.

Human Anatomy and Histology Embryology are foundational courses in nursing education but are often challenging for students due to their complex spatial structures, dense knowledge points, and high cognitive load. Recent advances in generative artificial intelligence (AI) and knowledge graph technologies provide new opportunities for enhancing medical education. This study aimed to evaluate the effectiveness of a blended teaching model integrating a generative AI-powered digital tutor with a knowledge graph in improving learning outcomes among nursing students. A three-arm parallel randomized controlled trial was conducted among 362 first-year nursing students at Cangzhou Medical College, of whom 301 completed the study. Participants were randomly assigned to an AI-Enhanced Group, a Blended Teaching Group, or a Traditional Teaching Group. All groups followed the same 16-week course structure based on Gagné’s Nine Events of Instruction, differing only in the teaching tools and tutoring strategies used. Learning outcomes were evaluated using module examination scores, final comprehensive scores, knowledge graph comprehension scores, knowledge retention rates, case-based inference accuracy, and multidimensional questionnaires. Statistical analyses were conducted using one-way ANOVA with post-hoc comparisons. Significant differences were observed among the three groups across multiple learning outcomes. The AI-Enhanced Group achieved higher module scores (82.5 ± 7.3) compared with the Blended Group (77.6 ± 8.1) and Traditional Teaching Group (74.1 ± 8.5) (F = 28.64, p < 0.001). Final comprehensive scores were also significantly higher in the AI-Enhanced Group (84.2 ± 6.8) (F = 32.16, p < 0.001). Knowledge graph comprehension scores showed a large effect size (F = 103.72, p < 0.001). Furthermore, the AI-Enhanced Group demonstrated higher knowledge retention rates (82.3