OBJECTIVE To explore the key mechanism of Bazi Bushen capsule(BZBS)in delaying the senescence of mesenchymal stem cells(MSCs)through network pharmacology and in vitro experiments.METHODS Network phar-macology was used to predict the mechanism targets of BZBS in delaying MSCs senescence.A MSCs senescence model induced by D-galac-tose(D-gal)was used to investigate the effect and mechanism of BZBS on MSCs senescence in vitro.RESULTS Network pharmacology analy-sis showed that BZSB could delay MSCs senes-cence.The experiment showed that BZBS could significantly improve the survival activity of the aged MSCs.It significantly reduced the positive rate of β-galactosidase staining and p16,p21 expression in aged MSCs,enhanced the ability of adipogenic differentiation and osteogenic differ-entiation,and increased expression of Nanog,OCT4 and SOX2 in senescent MSCs.CONCLU-SIONS Network pharmacology and in vitro cell experiments verified that BZBS could delay MSCs senescence.

Objective:To construct a novel prognostic risk model using basement membrane-related genes (BMRG) to explore the relationship between breast cancer and basement membrane.Methods:Transcriptome and clinical data were collected from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, the TCGA data was used as the training set and the GEO database as the validation set. Then univariate Cox regression, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were applied to build a BMRG prognostic model. The risk model was further validated and evaluated by Kaplan-Meier method and receiver operating characteristic (ROC) curve. The risk model and clinical characteristics were then combined to construct a nomogram to predict the overall survival of breast cancer. The biological pathways that may be involved were investigated by gene set enrichment analysis (GSEA). In addition, the differences in drug sensitivity between high-risk and low-risk groups of patients by the Wilcoxon rank sum test.Results:A total of 193 differentially expressed genes were identified, and risk models based on eight BMRG was constructed, including COL6A2, CTSA, EVA1B, ITGAX, MMP-1, ROBO3, SDC1, and UNC5A. Kaplan-Meier and ROC analyses showed that the model could well predict the prognosis of breast cancer, with an area under the curve of 0.779, indicating a high degree of accuracy as well. In addition, the nomogram showed good predictive consistency and net clinical benefit. Univariate and multivariate Cox regression analyses validated the BMRG model as an independent risk factor for breast cancer. GSEA analysis showed that the high-risk group was predominantly enriched in the extracellular matrix receptor interaction pathway. In addition, high-risk patients were more sensitive to taxanes chemotherapeutic agents and targeted therapeutic agents, while low-risk patients were more sensitive to gemcitabine and rapamycin. Conclusion:The risk model constructed based on eight BMRG can be used as a valid prognostic indicator for breast cancer and can improve the prediction of patient response to treatment.

Objective:To investigate the predictive value of fluid-attenuated inversion recovery (FLAIR) signal strength ratio (SIR) in onset time≤4.5 h in patients with acute ischemic stroke.Methods:A retrospective analysis was performed; 180 acute ischemic stroke patients admitted to Department of Neurology, Nanjing Hospital Affiliated to Nanjing Medical University from January 2020 to June 2023 were chosen. Hypoperfusion intensity ratio (HIR) was used to evaluate the collateral circulation (poor collateral circulation: HIR≤0.4; good collateral circulation: HIR>0.4); clinical data and imaging indexes between poor collateral circulation and good collateral circulation groups were compared. Univariate and multivariate Logistic regressions were used to analyze the influencing factors for onset time≤4.5 h in patients with acute ischemic stroke. Correlation between SIR and onset time was analyzed in patients with acute ischemic stroke. Role of HIR as agency between SIR and onset time was explored. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of SIR and diffusion weighted imaging (DWI)-FLAIR mismatch in onset time≤4.5 h in acute ischemic stroke patients.Results:Of the 180 patients, 100 were into the good collateral circulation group and 80 were into the poor collateral circulation group; compared with the good collateral circulation group, the poor collateral circulation group had significantly higher percentage of patients with hyperlipidemia, larger DWI infarction volume before treatment, larger perfusion weighted imaging (PWI)-DWI mismatch volume and higher SIR ( P<0.05). In these 180 patients, 76 had onset time≤4.5 h and 104 had onset time>4.5 h. Univariate Logistic regression analysis showed that hyperlipidemia, DWI infarct volume before treatment, DWI-FLAIR mismatch, HIR and SIR were influencing factors for onset time≤4.5 h in acute ischemic stroke patients ( P<0.05). Multivariate Logistic regression analysis showed that hyperlipidemia ( OR=6.654, 95% CI: 5.751-8.824, P<0.001), HIR ( OR=0.724, 95% CI: 0.521-1.321, P=0.041) and SIR ( OR=739.881, 95% CI: 383.296-14 258.065, P<0.001) were independent influencing factors for onset time≤4.5 h in acute ischemic stroke patients. Pearson correlation analysis showed that SIR was positively correlated to onset time in patients with acute ischemic stroke ( r=0.420, P<0.05), and SIR was positively correlated to onset time in patients from poor collateral circulation group ( r=0.781, P<0.05). ROC curve showed that AUC of SIR in predicting onset time≤4.5 h was 0.917 (95% CI: 0.814-1.000, P<0.001) and that of DWI-FLAIR mismatch in predicting onset time≤4.5 h was 0.530 (95% CI: 0.509-0.757, P=0.075) in poor collateral circulation group, enjoying significant difference in predictive efficacy. Conclusion:Acute ischemic stroke patients with low HIR and SIR have higher odds of onset time≤4.5 h; SIR can more accurately predict the onset time in these patients with poor collateral circulation.

OBJECTIVE To explore the new indications and key mechanism of Bazi Bushen capsule(BZBS)by network pharmacology and in vitro experiment.METHODS The potential tar-get profiles of the components of BZBS were pre-dicted.Subsequently,new indications for BZBS were predicted by disease ontology(DO)enrich-ment analysis and initially validated by GO and KEGG pathway enrichment analysis.Further-more,the therapeutic target of BZBS acting on AD signaling pathway were identified by intersec-tion analysis.Two Alzheimer's disease(AD)cell models,BV-2 and SH-SY5Y,were used to pre-liminarily verify the anti-AD efficacy and mecha-nism of BZBS in vitro.RESULTS In total,1499 non-repeated ingredients were obtained from 16 herbs in BZBS formula,and 1320 BZBS targets with high confidence were predicted.Disease enrichment results strongly suggested that BZBS formula has the potential to be used in the treat-ment of AD.In vitro experiments showed that BZ-BS could significantly reduce the release of TNF-α and IL-6 and the expression of COX-2 and PSEN1 in A β 25-35-induced BV-2 cells.BZBS reduced the apoptosis rate of A β 25-35 induced SH-SY5Y cells,significantly increased mitochon-drial membrane potential,reduced the expres-sion of Caspase3 active fragment and PSEN1,and increased the expression of IDE.CONCLU-SIONS BZBS formula has a potential use in the treatment of AD,which is achieved through regu-lation of ERK1/2,NF-κB signaling pathways,and GSK-3β/β-catenin signaling pathway.Further-more,the network pharmacology technology is a feasible drug repurposing strategy to reposition new clinical use of approved TCM and explore the mechanism of action.The study lays a foun-dation for the subsequent in-depth study of BZBS in the treatment of AD and provides a basis for its application in the clinical treatment of AD.