Background: Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder. Cellular drug screening represents a key approach in the preclinical discovery of AD therapeutics. Moreover, selecting an appropriate cellular model is essential for exploring the mechanisms underlying AD pathogenesis. Objective: This study aimed to establish a progressive strategy integrating cell model construction, monomer evaluation, and effective component group-based drug discovery for the development of novel therapeutics targeting AD. Methods: A novel AD12 cell line stably expressing the double-transgenic genes amyloid precursor protein (APP)695/presenilin 1(PS1)-ΔE9 was first constructed and subjected to lipopolysaccharide (LPS) stimulation. The resulting LPS-induced neuroinflammatory response was characterized using metabolomic analysis. Subsequently, 16 alkaloids derived from traditional Chinese medicine(TCM) were screened with the LPS-AD12 cell model. Molecular docking was then performed to assess the binding affinity of benzoylaconitine (BAC) with APP and PS1 proteins. A targeted metabolomics approach focusing on amino acids and the tricarboxylic acid (TCA) cycle was applied to BAC-treated LPS-AD12 cells. Finally, aconite extract was administered to five-familial-AD-mutations(5xFAD) transgenic mice, and therapeutic efficacy was evaluated through phenotypic and metabolomic analyses. Results: LPS stimulation induced neuroinflammation in AD12 cells, characterized by elevated levels of interleukin-6, amyloid-β (Aβ ), and PS1. The primary metabolic pathways affected in AD12 cells included alanine, aspartate, and glutamate metabolism, as well as arginine biosynthesis. Notably, BAC significantly reduced the levels of Aβ and interleukin-6 in LPS-AD12 cells. Furthermore, molecular docking analyses revealed a strong binding affinity of BAC with APP and PS1 proteins. Targeted metabolomics analysis indicated that the pharmacological activity of BAC was primarily associated with its anti-inflammatory effects, modulation of the cholinergic signaling pathway, and regulation of energy metabolism. Behavioral experiments in 5xFAD mice, together with immunofluorescence assessments of brain tissues (amyloid-β, glial fibrillary acidic protein, and ionized calcium-binding adapter molecule 1), demonstrated that aconite extract treatment significantly alleviated AD-related symptoms. In addition, metabolomics-based mechanistic analyses revealed that serine, acetylcholine, ornithine, and gamma-aminobutyric acid exhibited consistent trends in both brain tissue and serum samples from treated mice. Conclusion: This study established a novel AD12 cell model and an effective, reliable LPS-induced cell-based screening system. Additionally, we proposed a new drug discovery strategy integrating cell model construction, monomer evaluation, and effective component group-based drug discovery. This screening system has the potential to accelerate the identification of anti-AD agents and provides a feasible framework for subsequent in-depth investigations into new drug development from TCM, thereby contributing to the modernization of TCM-derived therapeutics.

Objective To investigate the clinical effect of aribulin combined with vinorelbine+cisplatin(NP)regimen in the treatment of advanced breast cancer patients.Methods Eighty patients with advanced breast cancer were selected and divided into the conventional group(treated with chemotherapy using NP regimen)and the combined group(treated with aribulin combined with NP regimen),with 40 cases in each group.The clinical benefit rate(CBR),objective response rate(ORR)and overall efficacy of the two groups were compared.Patients were followed for 12 months.The progression-free survival(PFS)was recorded in the two groups of patients.Serum levels of vascular endothelial growth factor(VEGF)A,VEGFB and VEGFC before treatment and 4 cycles after treatment were detected by enzyme-linked immunosorbent assay(ELISA).Adverse reactions of patients were evaluated and graded according to common adverse event evaluation criteria.Results The ORR and CBR of the combined group were significantly higher than those of the conventional group,and the overall curative effect of the combined group was better than that of the conventional group(P＜0.05).PFS in the combination group was longer than that in the conventional group(P＜0.01).After treatment,the levels of VEGFA,VEGFB and VEGFC in the 2 groups were lower than those before treatment,and the levels in the combined group were significantly lower than those in the conventional group(P＜0.05).The main adverse reactions of 2 groups during treatment were grade Ⅰto Ⅱ,including neutropenia,gastrointestinal reaction,peripheral nerve abnormality,fatigue,liver function injury and alopecia,with no statistical significance.Conclusion Aribulin combined with NP regimen in the treatment of advanced breast cancer can increase CBR and decrease VEGF expression level,with good safety.

Objective To investigate the clinical effect of aribulin combined with vinorelbine+cisplatin(NP)regimen in the treatment of advanced breast cancer patients.Methods Eighty patients with advanced breast cancer were selected and divided into the conventional group(treated with chemotherapy using NP regimen)and the combined group(treated with aribulin combined with NP regimen),with 40 cases in each group.The clinical benefit rate(CBR),objective response rate(ORR)and overall efficacy of the two groups were compared.Patients were followed for 12 months.The progression-free survival(PFS)was recorded in the two groups of patients.Serum levels of vascular endothelial growth factor(VEGF)A,VEGFB and VEGFC before treatment and 4 cycles after treatment were detected by enzyme-linked immunosorbent assay(ELISA).Adverse reactions of patients were evaluated and graded according to common adverse event evaluation criteria.Results The ORR and CBR of the combined group were significantly higher than those of the conventional group,and the overall curative effect of the combined group was better than that of the conventional group(P＜0.05).PFS in the combination group was longer than that in the conventional group(P＜0.01).After treatment,the levels of VEGFA,VEGFB and VEGFC in the 2 groups were lower than those before treatment,and the levels in the combined group were significantly lower than those in the conventional group(P＜0.05).The main adverse reactions of 2 groups during treatment were grade Ⅰto Ⅱ,including neutropenia,gastrointestinal reaction,peripheral nerve abnormality,fatigue,liver function injury and alopecia,with no statistical significance.Conclusion Aribulin combined with NP regimen in the treatment of advanced breast cancer can increase CBR and decrease VEGF expression level,with good safety.

Objective To evaluate the effects of ultrasonic scalpel and traditional electrocautery on postoperative complications in axillary dissection for breast cancer treatment.Methods The clinical data of 92 breast cancer patients with axillary dissection were analyzed retrospectively.The surgical proce-dures were randomly chosen by patients,including 37 cases with ultrasonic scalpel and 55 cases with elec-trocautery.Both groups were compared in operation time,number of harvested lymph nodes,postoperative drainage in 24 h,seroma formation rate,and drain removal time.Results There were no significant differ-ences in operation time[(148.2 ±30.4)min vs(143.5 ±40.8)min],number of harvested lymph nodes (17 nodes vs 16 nodes),and drain removal time[(16.0 ±5.3)d vs(16.7 ±4.4)d]between ultrasonic scalpel group and electrocautery group(P >0.05 ).There were significant differences in postoperative drainage [(118.8 ±65.8)ml vs(159.2 ±71.3)ml]and seroma formation rate(8.1% vs 20%)between ultrasonic scalpel group and electrocautery group(P <0.01).Conclusion For breast cancer,ultrasonic scalpel is similar to electrocautery in axillary dissection,but it can reduce postoperative complications.