Based on serum metabolomics and gut microbiota technology, this study explores the effects and mechanisms of the water extract of Ziziphi Spinosae Semen(SZRW) and the petroleum ether extract of Ziziphi Spinosae Semen(SZRO) in improving depressive-like behaviors induced by sleep deprivation. A modified multi-platform water environment method was employed to establish a rat model of sleep deprivation. Depressive-like behaviors in rats were assessed through the sucrose preference test and forced swim test. The expression of barrier proteins, such as Occludin, in the colon was determined by immunofluorescence. UPLC-Q-Orbitrap MS was utilized to analyze the serum metabolic profiles of sleep-deprived rats, screen for differential metabolites, and analyze metabolic pathways. The diversity of the gut microbiota was detected using 16S rRNA gene sequencing. Spearman correlation coefficient analysis was conducted to assess the correlation between differential metabolites and gut microbiota. The results indicated that SZRO significantly increased the sucrose preference index and decreased the immobility time in the forced swim test in rats. A total of 34 differential metabolites were identified through serum metabolomics. SZRW and SZRO shared five metabolic pathways, including phenylalanine metabolism. SZRW uniquely featured taurine and hypotaurine metabolism, while SZRO uniquely featured linoleic acid metabolism and tyrosine metabolism. Correlation analysis revealed that SZRW could upregulate the abundance of Bilophila, promoting the production of indole-3-propionic acid and subsequently upregulating the expression levels of intestinal tight junction proteins such as ZO-1, Occludin, and Claudin-1. SZRO could indirectly influence metabolic pathways such as arginine metabolism and linoleic acid metabolism by upregulating the abundance of gut microbiota such as Coprococcus and Eubacterium species. Both SZRW and SZRO can regulate endogenous metabolism, including amino acids, energy, and lipids, alter the gut microbiota microecology, and improve depressive-like behaviors. SZRO demonstrated superior effects in regulating metabolic pathways and gut microbiota structure compared to SZRW. The findings of this study provide a scientific basis for elucidating the pharmacodynamic material basis of Ziziphi Spinosae Semen.
Animals ; Rats ; Gastrointestinal Microbiome/drug effects* ; Male ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Depression/blood* ; Rats, Sprague-Dawley ; Sleep Deprivation/complications* ; Ziziphus/chemistry* ; Antidepressive Agents/administration & dosage* ; Behavior, Animal/drug effects* ; Humans

Objective:To explore and stimulate the pathway mechanism for doctors from core hospitals,which are the high-quality medical resources in loose medical alliances,to sink to the grassroots level on their own initiative and continue to participate in the co-operation,so as to provide useful references for improving the effectiveness of cooperation within medical alliances.Methods:The fuzzy set Qualitative Comparative Analysis(fsQCA)method was used to investigate 205 doctors in the core hospitals of a loose medical alliance in District X of City B.This investigation was grounded in relationship commitment theory,motivation theory,social exchange theory,and cooperation reinforcement theory.Results:The level of relationship commitment of doctors in the core hospitals to proactively participate in cooperation was influenced by multiple factors,including doctors'perception of job significance,opportunity cost perception,organizational support,and teamwork experience.This resulted in the formation of three concurrent driving mechanism pathways:merger-driven effect,experience-enhancing effect,and altruistic trigger effect.Among these factors,the perception of work significance was a necessary condition,and cooperative experience played an important role in doctors'continuous participation.Conclusion:The level of relational commitment of doctors to participate in cooperative efforts is driven by a combination of various factors,with different incentive mechanisms exhibiting heterogeneity within loose medical alliances.Designing appropriate incentive and support strategies tailored to specific contexts can effectively drive the proactive downward flow of high-quality medical resources from core hospitals within loose medical alliances.