OBJECTIVE: This study investigated the antidepression mechanisms of Xiaoyaosan (XYS), a classic Chinese prescription, from the perspective of energy metabolism in the brain and intestinal tissues. METHODS: Chronic unpredictable mild stress model-a classic depression rat model-was established. Effects of XYS on behaviors and gastrointestinal motility of depressed rats were investigated. Effects of XYS on energetic charge (EC), adenosine triphosphate-related enzymes, and key enzymes of energy metabolism in both hippocampus and jejunum tissues of depressed rats were investigated using high-performance liquid chromatography, biochemical analysis, and real-time quantitative polymerase chain reaction, respectively. Spearman correlation analysis was conducted to construct a correlation network of "behavior-brain energy metabolism-intestinal energy metabolism" of depression. RESULTS: XYS significantly reduced the abnormal behaviors that observed in depressed rats and increased the EC and the activity of Na⁺-K⁺-adenosine triphosphatase (ATPase) and Ca²⁺-Mg²⁺-ATPase in hippocampus and jejunum tissues of depressed rats. XYS restored the key energetic pathways that had been interrupted by depression, including glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, XYS exhibited antidepressive effects in terms of regulating energy metabolism in tissues of both brain and intestine. CONCLUSION XYS significantly corrected the disturbances in EC and energy metabolism-related enzymes of both brain and intestinal tissues, alleviating both core and concomitant symptoms of depression. The current findings underscore the role of energy metabolism in the antidepressive activity of XYS, providing a fresh perspective on depression, and novel research strategies for revealing the mechanism of actions of traditional Chinese medicines on multi-site and multi-symptom diseases. Please cite this article as: Xiao MT, Wang SY, Wu XL, Zhao ZY, Wang HM, Liu HM, Qin XM, Liu XJ. Antidepressant mechanism of Xiaoyaosan: A perspective from energy metabolism of the brain and intestine. J Integr Med. 2025; 23(6):706-720.
Animals ; Energy Metabolism/drug effects* ; Antidepressive Agents/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Brain/drug effects* ; Male ; Depression/metabolism* ; Rats ; Rats, Sprague-Dawley ; Intestines/drug effects* ; Hippocampus/drug effects*

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

Listeria brainstem encephalitis with myelitis is extremely rare in clinical practice.Since the clinical manifestations are non-specific,MRI is helpful for diagnosis.Positive cerebrospinal fluid culture is considered the gold standard for diagnosis.This article reports a case of an immunocompetent individual with listeria brainstem encephalitis with myelitis,aiming to enhance the awareness of this condition.
Humans ; Brain Stem/pathology* ; Diagnostic Errors ; Encephalitis/complications* ; Encephalomyelitis, Acute Disseminated/diagnosis* ; Listeriosis/complications* ; Myelitis/complications*

This study aimed to investigate the effect of Flos Farfarae (FF) fumigation on cigarette smoke-induced lung injury mice, and analyze the metabolic profile of lung tissue by metabolomics. All animal experiments were conducted under the guidance and approval of the Animal Ethics Review Committee of Shanxi University (Approval number: SXULL2019014). By using HS-GC-MS to analyze volatile components of Flos Farfarae, 23 compounds were identified. The results showed that FF fumigation improved the lung tissue morphology of cigarette smoke-induced lung injury mice, lowered the levels of interleukin 6 (IL-6) and interleukin-1β (IL-1β). The lung tissue samples were applied for metabolomic analysis based on UHPLC-QTOF MS, the results showed that 70 metabolites were changed in the lung tissue of mice after cigarette exposure, and 35 of them could be regulated, including lysophosphatidylcholine (LPC), 12-HETE, adenosine, and xanthine. These metabolites, such as LPC, 12-HETE, adenosine, and xanthine were mainly associated with the body's inflammatory response. It was observed that these metabolites are primarily involved in purine metabolism, arachidonic acid metabolism, phospholipid metabolism, and pyruvate metabolism pathways. These findings suggest that the volatile terpenoids in the FF may regulate the metabolites associated with the inflammatory response in the lung tissue, such as lysophosphatidylcholine, 12-HETE, and adenosine, which could further alleviate lung inflammation induced by cigarette smoke through the metabolic pathways of purine metabolism and others. This study proved the scientific basis of the traditional application of FF fumigation, and provided a theoretical basis for the further product development.

ObjectiveHuman Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. MethodsRNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. ResultsWe revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. ConclusionOur study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective To assess the risk factors for carbapenem-resistant Acinetobacter baumannii(CRAB)bloodstream infection(BSI)and 28-day short-term mortality in elderly patients,and provide reference for the pre-vention and treatment of CRAB BSI.Methods Clinical data of patients aged ≥60 years and diagnosed with AB BSI in a hospital in Yulin City from January 2013 to December 2022 were retrospectively analyzed,including demogra-phic and microbiological characteristics,as well as clinical outcomes of the patients.Variables which were significant in univariate analysis were selected for multivariate analysis using binary logistic regression model and Cox propor-tional hazards model.Independent risk factors for infection were further determined,and survival analysis was per-formed using Kaplan-Meier curve.Results A total of 150 patients were included in the study,out of which 16 pa-tients(10.7％)had CRAB BSI and 134 had carbapenem-sensitive AB(CSAB)BSI.The 28-day short-term mortali-ty of AB BSI in elderly patients was 15.3％(23/150,95％CI:9.6％-21.1％),and the short-term mortality of CRAB BSI was higher than that of CSAB([56.3％,9/16]vs[10.4％,14/134]).Deep venous catheterization(OR:15.598,95％CI:1.831-132.910)and combined infections of other sites(OR:15.449,95％CI:1.497-159.489)were related to CRAB BSI in elderly patients.The independent risk factors for 28-day mortality in elderly patients with AB BSI were hemodialysis(OR:11.856,95％CI:2.924-48.076),intensive care unit admission(OR:9.387,95％CI:1.941-45.385),and pulmonary infection being suspected source of bacteremia(OR:7.019,95％CI:1.345-36.635).Conclusion The occurrence of CRAB BSI in elderly patients is related to the combined infection of other sites and deep vein catheterization.Hemodialysis,admission to ICU,and pulmonary infection being suspected source of bacteremia are independent risk factors for the prognosis of AB BSI in elderly patients.

This study used kidney metabolomics to investigate the underlying mechanisms of Guilingji (GLJ) on mild cognitive impairment (MCI) rats. The rats were randomly divided into 6 groups (n = 8), i.e., control group, model group, positive drug (Ginkgo biloba tablet, donepezil) group, GLJ group (low and high dose group). The MCI rat model was replicated using subcutaneous injection of D-galactose into the back of the neck along with a semi-high-fat diet for a total of 8 weeks, and drug was administered from the 5th week for 4 weeks. The kidney function and renal pathological changes of each group of rats were tested. And LC-MS based kidney metabolomics coupled with multivariate data analysis were conducted to explore the potential biomarkers, and corresponding metabolic pathways were then determined. After administration of GLJ, the level of urea nitrogen was decreased compared with those of the model group, and the abnormalities of morphology in kidney tissues were improved. The positive drugs (ginkgo biloba tablet and donepezil) had no significant modulating effect on renal function indexes. Ginkgo biloba tablet can lessen the pathological injury of kidney tissue, and donepezil had no improvement on renal histopathology. A total of 23 MCI related differential metabolites were identified in kidney, and 17 metabolites were signifcantly restored by GLJ compared with those of the model group. Additionally, we found that the cysteine and methionine metabolism, nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism were significantly involved in the regulatory effect of GLJ. The results illuminate the "cong shen zhi nao" mechanism of GLJ, and also provide a research basis for the clinical use of GLJ for the treatment of MCI. The animal experiment of this study was approved by the Ethics Committee of Shanxi University (approval number: 2020DW121).

The human gut is inhabited by a large number and variety of microorganisms, which constitute the intestinal microecosystem with the intestinal environment where they reside. After oral administration, Chinese medicine undergoes metabolism by these intestinal microorganisms within the gastrointestinal tract. The resulting metabolites are absorbed into the bloodstream to produce pharmacological effects. This paper provides a comprehensive review of the characteristics and influencing factors related to the mediation of Traditional Chinese Medicine (TCM) metabolism by intestinal flora. Additionally, recent progress in the microbial-mediated metabolism of TCM components such as flavonoids, saponins, iridoids, and lignans is summarized. This serves as a foundation for understanding the connection between intestinal bacteria and the chemical structural alterations of TCM components. It also offers insight into the regulations and mechanisms governing the intestinal bacterial metabolism of TCM constituents.

To explore the absorption mechanism of APS-Ⅱ in vivo by establishing M cell model. First, Astragalus polysaccharides (APS) was divided into two different molecular weight polysaccharides APS-I ( > 2 000 kDa) and APS-II (10 kDa) by ultrafiltration, and APS-II (10 kDa) was prepared and fluorescently labeled. Meanwhile, M cell model was constructed by Caco-2 cells and Raji cells. The M cell model was treated with transport inhibitors to explore the transport of APS-Ⅱ on M cells. The results show that FITC has been successfully labeled to the end of APS-Ⅱ, and the M cell model was successfully constructed, which found that APS-Ⅱ could be transported by M cells, and four transport inhibitors of 5-(N-ethyl-N-isopropyl) amiloride (EIPA), genistein, dynasore and nocodazole indicated that APS-II may enter cells through clathrin and caveolin-mediated endocytosis.