Objective To explore the targets and molecular mechanisms of salidroside in improving cognitive function at high altitudes using network pharmacology,molecular docking,and experimental validation.Methods The SwissTargetPrediction platform was used to screen for salidroside-related targets,and the GeneCards database was used to search for targets associated with high-altitude cognitive function.The VENNY 2.1 platform was used to create a Venn diagram showing the intersection of salidroside and the targets of high-altitude cognitive function.The STRING11.5 database was used to construct a protein-protein interaction network diagram to screen for the key targets.The DAVID database was used to perform the Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,and a component-target-pathway network was constructed using the Cytoscape 3.7.2 software platform.Furthermore,molecular docking and experimental studies were conducted for preliminary validation.Male C57BL/6J mice were randomly assigned to three groups,a low-altitude control group(Con group)receiving sterile water via intragastric gavage,a high-altitude hypoxia group(Hyp group)receiving sterile water via intragastric gavage,and a salidroside group administered with 10 mg/kg salidroside via intragastric gavage.The Hyp group and the salidroside group were pre-treated for 3 days(once daily)before rapid ascension to an altitude of 4010 m.Then,the 2 groups were exposed to a hypoxic environment for 1 day and received an additional treatment.Hippocampal tissues were collected from all three groups,and the relevant proteins were measured by Western blot.Results A total of 100 salidroside targets,2212 high-altitude cognition-related gene targets,and 52 common targets were identified.The improvement in high-altitude cognitive function by salidroside could be closely associated with core targets such as VEGFA,GAPDH,MMP-9,HRAS,FGF-2,HSP90AA1,and MAPK1,involving mainly the PI3K-Akt,MAPK,and VEGF signaling pathways.According to the molecular docking results,GAPDH,MMP-9,and VEGFA showed the best binding ability with salidroside.Experimental findings showed that salidroside improved high-altitude cognitive function by regulating the levels of Bcl-2/Bax,SRC-1,NF-κB,Beclin-1,and LC3B Ⅱ/Ⅰ.Conclusion Salidroside exerts its therapeutic effects in improving high-altitude cognitive function by regulating the expression levels of proteins associated with cell apoptosis,cell proliferation,and cell autophagy,inhibiting inflammation and stress response,and reducing apoptosis and excessive autophagy in hippocampal neurons.

Humans ; Hypertension, Pulmonary/surgery* ; Learning Curve ; Angioplasty, Balloon ; Pulmonary Embolism/therapy* ; Chronic Disease ; Pulmonary Artery/surgery*

Objective To investigate the influencing factors for knowledge,attitude and practice(KAP)of the Three-manager mode about hierarchical medical system of Chronic diseases of the community residents in Xiamen,and provide references for the implementation of hierarchical medical system.Methods Multi-stage random sampling method was adopted,and 400 residents were randomly sampled from 5 communities of Xiamen for questionnaire survey.The survey features the dependent variable of the community residents′ knowing and joining-in the Three-manager mode,the internal factors(social demographic characteristics),and the external factors(medical expenditure and healthcare insurance).On such basis,four logistic regression models were built for analysis of such influencing factors.Results 41.10% of the surveyed were aware of the Three-manager mode,and 39.71% of the hypertension/diabetes patients among them joined in the hypertension network or diabetes network.Age,education,medical expenditure and referral experiences were significant influencing factors for KAP level of the Three-manager mode,while the residents of older age,higher education and referral experiences were high in their KAP;those of lower per capita monthly income,hypertension or diabetes,with coverage of medical insurance and satisfied with medical consultation in community were high in their awareness of Three-manager mode.Conclusions The KAP level of Three-manager mode of the community residents in Xiamen is acceptable,yet expected of further improvement.Room of further improvement includes enhancement of synergy of the Three-manager mode,enhanced motivation of government financial support and medical insurance,better service functions of community institutions,and especially the construction of hierarchical medical system.