Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

The study was carried out to understand the changes in the ethical cognition status of laboratory animals and the effectiveness of laboratory animal ethics education among medical students in Xiangya School of Medicine of Central South University (CSU), and provide new enlightenment for further strengthening the ethical education of laboratory animals. In the study, the same self-compiled questionnaire was used to investigate the ethical cognition of experimental animals among medical students in Xiangya School of Medicine of CSU in 2011 and 2021, and 359 and 363 questionnaires were collected respectively. Through comparative analysis of the questionnaire results before and after ten years, it was found that medical students’ animal experiment operation and attitudes towards laboratory animals, cognition of experimental animal ethics knowledge and their attitude to animal experiment ethics education were significantly improved. It showed that the state of experimental animal ethics cognition among medical students in Xiangya School of Medicine of CSU had improved significantly in recent 10 years, but the cognition of experimental animal ethics knowledge was higher than the actual behavior of caring for experimental animals, and there was the phenomenon of "separation of knowledge and action". The ethics education of experimental animals needs to pay more attention to the development of students’ behavior of caring for experimental animals.

Objective To investigate the effect of Yigong San(YGS)on learning and memory abilities of rats with lipopolysaccharide(LPS)-induced cognitive decline and explore its possible mechanism in light of intestinal microbiota.Methods Forty SD rats were randomly divided into control group,model group,donepezil(1.3 mg/kg)group,and high-dose(5.25 g/kg)and low-dose(2.63 g/kg)YGS treatment groups.After 24 days of treatment with the corresponding drugs or water by gavage,the rats in the latter 4 groups received an intraperitoneal injection of LPS(0.5 mg/kg)to establish models of Alzheimer's disease(AD).Water maze test and HE staining were used to evaluate the changes in learning and memory abilities and pathomorphology of the hippocampus.The changes in gut microbial species of the rats were analyzed with 16S rRNA sequencing,and the levels of IL-6,TNF-α,and IL-1β in the brain tissue and serum were detected using ELISA.Results Compared with the AD model group,the YGS-treated rats showed significantly shortened escape latency on day 5 after modeling,reduced neuronal degeneration and necrosis in the hippocampus,lowered pathological score of cell damage,and decreased levels IL-6,TNF-α and IL-1β in the brain tissue and serum.The YGS-treated rats showed also obvious reduction of Alpha diversity indicators(ACE and Chao1)of intestinal microbiota with significantly increased abundance of Prevotellaceae species at the family level and decreased abundance of Desulfovibrionaceae,which were involved in such metabolic signaling pathways as cell community prokaryotes,membrane transport,and energy metabolism.Conclusion YGS improves learning and memory abilities and hippocampal pathomorphology in AD rat models possibly by regulating the abundance of intestinal microbial species such as Prevotellaceae to affect the metabolic pathways for signal transduction,cofactors,and vitamin metabolism.

Objective To explore the effect of training mode based on action learning on improving the practicing ability of hospital pharmacists.Methods Thirty pharmacists who received training from September 2022 to December 2023 at Panzhihua Central Hospital were randomly divided into an education reform group(16 cases)and a routine group(14 cases).The education reform group adopted a routine teaching method based on action learning,while the routine group adopted a routine teaching method.The differences between the two groups of pharmacists in theoretical knowledge,practical operation,pharmaceutical services,emergency response,and comprehensive quality were compared.Results The pharmacists in the education reform group were better than the routine group in prescription review,clinical medication analysis,pharmaceutical services,emergency response,andcomprehensive quality.The difference was statistically significant(P＜0.05).Conclusion The teaching model based on action learning can effectively enhance the higher order thinking ability of pharmacists and help them better apply medical knowledge and skills to serve patients and physicians.

OBJECTIVE To investigate the mechanism of Yifei xuanfei jiangzhuo formula （YFXF） against vascular dementia （VD）. METHODS The differentially expressed genes of YFXF （YDEGs） were obtained by network pharmacology. High-risk genes were screened from YDEGs by using the nomogram model. The optimal machine learning models in generalized linear， support vector machine， extreme gradient boosting and random forest models were screened based on high-risk genes. VD model rats were established by bilateral common carotid artery occlusion， and were randomly divided into model group and YFXF group （12.18 g/kg， by the total amount of crude drugs）， and sham operation group was established additionally， with 6 rats in each group. The effects of YFXF on behavior （using escape latency and times of crossing platform as indexes）， histopathologic changes of cerebral cortex， and the expression of proteins related to the secreted phosphoprotein 1 （SPP1）/phosphoinositide 3-kinase （PI3K）/protein kinase B （aka Akt） signaling pathway and the mRNA expression of SPP1 in cerebral cortex of VD rats were evaluated. RESULTS A total of 6 YDEGs were obtained， among which SPP1， CCL2， HMOX1 and HSPB1 may be high-risk genes of VD. The generalized linear model based on high-risk genes had the highest prediction accuracy （area under the curve of 0.954）. Compared with the model group， YFXF could significantly shorten the escape latency of VD rats， significantly increase the times of crossing platform （P＜0.05）； improve the pathological damage of cerebral cortex， such as neuronal shrinkage and neuronal necrosis； significantly reduce the expressions of SPP1 protein and mRNA （P＜0.05）， while significantly increase the phosphorylation levels of PI3K and Akt （P＜0.05）. CONCLUSIONS VD high-risk genes SPP1， CCL2， HMOX1 and HSPB1 may be the important targets of YFXF. YFXF may play an anti-VD role by down-regulating the protein and mRNA expressions of SPP1 and activating PI3K/Akt signaling pathway.

Objective To investigate the effect of Yigong San(YGS)on learning and memory abilities of rats with lipopolysaccharide(LPS)-induced cognitive decline and explore its possible mechanism in light of intestinal microbiota.Methods Forty SD rats were randomly divided into control group,model group,donepezil(1.3 mg/kg)group,and high-dose(5.25 g/kg)and low-dose(2.63 g/kg)YGS treatment groups.After 24 days of treatment with the corresponding drugs or water by gavage,the rats in the latter 4 groups received an intraperitoneal injection of LPS(0.5 mg/kg)to establish models of Alzheimer's disease(AD).Water maze test and HE staining were used to evaluate the changes in learning and memory abilities and pathomorphology of the hippocampus.The changes in gut microbial species of the rats were analyzed with 16S rRNA sequencing,and the levels of IL-6,TNF-α,and IL-1β in the brain tissue and serum were detected using ELISA.Results Compared with the AD model group,the YGS-treated rats showed significantly shortened escape latency on day 5 after modeling,reduced neuronal degeneration and necrosis in the hippocampus,lowered pathological score of cell damage,and decreased levels IL-6,TNF-α and IL-1β in the brain tissue and serum.The YGS-treated rats showed also obvious reduction of Alpha diversity indicators(ACE and Chao1)of intestinal microbiota with significantly increased abundance of Prevotellaceae species at the family level and decreased abundance of Desulfovibrionaceae,which were involved in such metabolic signaling pathways as cell community prokaryotes,membrane transport,and energy metabolism.Conclusion YGS improves learning and memory abilities and hippocampal pathomorphology in AD rat models possibly by regulating the abundance of intestinal microbial species such as Prevotellaceae to affect the metabolic pathways for signal transduction,cofactors,and vitamin metabolism.

Objective:To investigate the relationship between KRAS gene mutation, programmed death receptor ligand 1 (PD-L1) expression and prognosis of first-line concurrent chemoradiotherapy in patients with locally advanced non-small cell lung cancer.Methods:The clinical data of 50 patients with locally advanced non-small cell lung cancer who were admitted to Nanping First Hospital from January 2018 to December 2021 were retrospectively analyzed. All patients were treated with first-line concurrent chemoradiotherapy. Tissue samples of patients were obtained and paraffin embedded before treatment. Real-time fluorescence quantitative polymerase chain reaction was used to detect the type of KRAS gene mutation in tissues before treatment, and the expression of PD-L1 was determined by immunohistochemistry (the percentage of positive cells in tumor cells ≥1% was positive), and the relationship between KRAS gene status, PD-L1 expression and clinical characteristics and short-term efficacy of patients was analyzed. Patients were followed up for 1 year, and progression-free survival (PFS) curves were plotted by Kaplan-Meier method, and log-rank test was used for comparison. Univariate and multivariate Cox proportional hazards models were used to analyze the influencing factors of PFS.Results:Among the 50 patients, 11 (22.00%) were KRAS mutant, and 36 (72.00%) were PD-L1 positive. Among the 11 patients with KRAS mutation, there were 2 cases of codon 13 mutation and 9 cases of codon 12 mutation in exon 2. The objective response rate (ORR) and clinical control rate (DCR) were 76.00% (38/50) and 86.00% (43/50). There were no significant differences in patients' age, pathological type, TNM stage, ORR and DCR between KRAS mutant group and KRAS wild type group (all P > 0.05). The proportions of male patients [72.73% (8/11) vs. 38.46% (15/39)], patients with smoking history [90.91% (10/11) vs. 20.51% (8/39)] and patients with PD-L1 positive expression [100.00% (11/11) vs. 64.10% (25/39)] in KRAS mutant group were higher than those in KRAS wild type group (all P < 0.05). There were no significant differences in patients' age, pathological type, gender, smoking history, TNM stage, ORR and DCR between PD-L1 positive group and PD-L1 negative group (all P > 0.05). The median PFS time of patients in KRAS mutant group and wild type group was 8.75 and 11.32 months, and the difference in PFS between the two groups was statistically significant ( P = 0.039). The median PFS time of patients with PD-L1 positive and negative was 10.19 and 11.16 months, and there was no statistical significance in PFS between the two ( P = 0.116). Multivariate Cox regression analysis showed that KRAS gene mutation was an independent risk factor for PFS in patients with locally advanced NSCLC after first-line concurrent chemoradiotherapy ( HR = 1.449, 95% CI 1.071-1.196, P = 0.017). PD-L1 expression, smoking history and gender were not independent influencing factors for PFS (all P > 0.05). Conclusions:KRAS gene status is closely related to the prognosis of patients with locally advanced non-small cell lung cancer treated with first-line concurrent chemoradiotherapy, while PD-L1 expression is not.

Objective To explore the value of MRI in assessing regional invasion and neural spread of sinonasal and nasopharyngeal adenoid cystic carcinoma(ACC).Methods A retrospective collection of MRI and clinical data was analyzed in 22 patients with sinonasal and nasopharyngeal ACC confirmed by pathology.Results A total of 22 patients were included in the study.Invasion of the pterygopalatine fossa was observed in 15 cases,involvement of the masticatory muscles in 13 cases,skull base involvement in 13 cases,infiltration of the cavernous sinus in 9 cases,involvement of the infraorbital fissure in 9 cases,orbital involvement in 5 cases,and intracranial involvement in 6 cases.Only 3 patients presented with cranial nerve symptoms.MRI revealed thickening and enhancement of cranial nerves in 10 cases,with involvement of the maxillary and mandibular(V2,V3)branches of the trigeminal nerve(V)in 9 cases,and muscle denervation caused by nerve damage in 6 cases.Among the 12 patients who underwent surgery,9 cases were confirmed to have neural invasion by pathology,with MRI showing cranial nerve alterations in 7 cases of them,one case showed tumor involvement from the pterygopalatine fossa and medial pterygoid muscle to the cavernous sinus and Meckel cavity,while the other case showed tumor involvement from the pterygopalatine fossa to the sphenopalatine foramen.During the follow-up after treatment,4 of 11 patients experienced recurrence,all of which were accompanied by lung metastasis and pre-treatment neural invasion.Conclusion Sinonasal and nasopharyngeal ACC is characterized by a tendency for neural spread,extensive local invasion,and a high risk of recurrence.MRI is helpful in determining the extent of invasion and neural spread.