Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory condition with chronic and relapsing manifestations and is characterized by a disturbance in the interplay between the intestinal microbiota, the gut, and the brain. The microbiota-gut-brain axis involves interactions among the nervous system, the neuroendocrine system, the gut microbiota, and the host immune system. Increasing published data indicate that psychological stress exacerbates the severity of IBD due to its negative effects on the microbiota-gut-brain axis, including alterations in the stress response of the hypothalamic-pituitary-adrenal (HPA) axis, the balance between the sympathetic nervous system and vagus nerves, the homeostasis of the intestinal flora and metabolites, and normal intestinal immunity and permeability. Although the current evidence is insufficient, psychotropic agents, psychotherapies, and interventions targeting the microbiota-gut-brain axis show the potential to improve symptoms and quality of life in IBD patients. Therefore, further studies that translate recent findings into therapeutic approaches that improve both physical and psychological well-being are needed.
Humans ; Inflammatory Bowel Diseases/metabolism* ; Stress, Psychological/microbiology* ; Gastrointestinal Microbiome/physiology* ; Brain/metabolism* ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Animals

This paper aims to study the effect of Ziziphi Spinosae Semen extracts on chronic unpredictable mild stress(CUMS)-induced depression-like and insomnia behavior models of mice. The CUMS-induced depression-like and insomnia behavior model of mice was established by CUMS treatment for three weeks. The mice were randomly divided into control group, model group, positive drug diazepam group(2 mg·kg~(-1)), as well as low-dose group(1.95 g·kg~(-1)), medium-dose group(3.9 g·kg~(-1)), and high-dose group(7.8 g·kg~(-1)) of Ziziphi Spinosae Semen extracts, with 18 mice in each group. On the 15th day of modeling, the drug was administered intragastrically once a day for one week. Then, the pentobarbital sodium cooperative righting experiment, open field experiment, and elevated plus maze experiment were carried out, respectively. The contents of neurotransmitters 5-hydroxytryptamine(5-HT) and 5-hydroxyindoleacetic acid(5-HIAA) in serum and thalamus of mice, as well as the levels of corticotropin releasing hormone(CRH), adrenocorticotropic hormone(ACTH), and corticosterone(CORT) in serum, were determined by enzyme-linked immunosorbent assay(ELISA). The neuron damage in the hippocampus of mice was observed by hematoxylin-eosin(HE) staining and Nissl staining. Western blot was used to detect the expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), monoamine oxidase A(MAOA), five prime repressors under dual repression binding protein 1(Freud1), synaptic plasticity-related proteins [cellular gene FOS(C-FOS), postsynaptic density protein 95(PSD95), synapsin 1(SYN1), and activity-regulated cytoskeleton-associated gene(ARC)], blood-brain barrier(BBB) permeability-related proteins [zonula occludens 1(ZO-1), occludin, and claudin 1], inflammatory factors [NOD-, LRR-and pyrin domain-containing protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), gasdermin D(GSDMD), caspase-3, and caspase-8], and antioxidant factors [nuclear factor erythroid 2-related factor 2(NRF2) and heme oxygenase 1(HO1)] in thalamic tissue of mice. The results indicated that compared with that in the model group, the sleep latency was significantly shortened, and the sleep duration was significantly prolonged in each dose group of Ziziphi Spinosae Semen extracts. The number of visits to the central area of the open field and the distance and time of visits were significantly increased in each dose group of Ziziphi Spinosae Semen extracts. In addition, the proportion of distance and time of entering the open arm area of the elevated plus maze was significantly increased in each dose group of Ziziphi Spinosae Semen extracts. The contents of 5-HT and 5-HIAA in serum and thalamus of mice increased to varying degrees in each dose group of Ziziphi Spinosae Semen extracts; the contents of CRH, ACTH, and CORT in serum of mice were significantly decreased. The protein expression of TPH2 was significantly increased. The protein expression of MAOA, SERT, and Freud1 was significantly decreased. Ziziphi Spinosae Semen extracts could also significantly reduce the protein expression of C-FOS but significantly increase the protein expression of PSD95, ARC, and SYN1. They could reduce the pathological damage of the hippocampus in mice and significantly increase the protein expression of ZO-1, occluding, and claudin 1. The protein expression of NLRP3, GSDMD, ASC, caspase-3, and caspase-8 in the thalamic tissue of mice was significantly decreased, and the protein expression of HO1 and NRF2 was significantly increased. In conclusion, Ziziphi Spinosae Semen extracts could effectively improve sleep disorders and depression-like behaviors in CUMS-induced model mice, which may be related to regulating the 5-HT anabolism process and hypothalamic-pituitary-adrenal(HPA) axis-related hormone levels, reducing pathological damage in the hippocampus, improving synaptic plasticity, repairing BBB integrity, and alleviating inflammatory response and oxidative stress damage.
Animals ; Ziziphus/chemistry* ; Mice ; Male ; Depression/psychology* ; Drugs, Chinese Herbal/administration & dosage* ; Sleep Initiation and Maintenance Disorders/psychology* ; Stress, Psychological/complications* ; Behavior, Animal/drug effects* ; Humans ; Disease Models, Animal

Stress is a critical inducer in the onset and progression of many chronic diseases. Prolonged or intense stress can disrupt the overall balance between the nervous, immune, and endocrine systems. The resulting biological signals may act on corresponding receptors in the cervical spine region, leading to adverse pathological changes. The vertebral artery and the surrounding muscular and connective tissues are influenced by biomechanical abnormalities and inflammatory cascades associated with cervical spondylosis of vertebral artery type (CSA), which promotes the release of various hormones. These hormones, through the neuroendocrine-immune system, affect the central nervous system, inducing or exacerbating negative emotional feedback and thereby establishing a "central-local-central" vicious cycle. This article explores the mechanisms underlying the impact of stress on the key CSA symptoms through the neuroendocrine-immune network (NEI) theory, providing a more comprehensive framework for targeted therapeutic interventions in CSA.
Humans ; Neurosecretory Systems/immunology* ; Spondylosis/etiology* ; Vertebral Artery/immunology* ; Stress, Psychological/complications* ; Chronic Disease

OBJECTIVE: To evaluate the application effect of mindfulness-based stress reduction (MBSR) therapy on the patients treated with image fusion-guided transperineal prostate biopsy. METHODS: A total of 160 patients who underwent image fusion-guided transperineal prostate biopsy in the Urology Department from April 2023 to April 2024 were included. Patients were randomly assigned to a control group and an observation group, with 80 cases in each group. The control group received routine care, while the observation group received combined MBSR on the basis of routine care. The surgical indicators, pain levels, psychological states, nursing satisfaction, and postoperative complication rates of both groups were compared. RESULTS: There was no statistically significant difference in general personal information and clinical data between the two groups（P>0.05）. The surgery duration, secondary fusion rate, and postoperative complication rate in the observation group were all lower than those in the control group (［23.54±2.07］min vs ［26.25±1.69］min, P<0.05； 8.75% vs 22.50%, P=0.017； 17% vs 29%, P=0.036), and nursing satisfaction was higher in the observation group than in the control group ( 77% vs 69%, P=0.025). The VAS scores biopsy (5.11±0.93 vs 6.27±1.32, P=0.041), discharge (0.74±0.67 vs 1.85±0.95, P=0.004), and scores of SDS (47.76±2.06 vs 50.46±2.07, P=0.009) and SAS (46.89±2.68 vs 49.75±2.83, P=0.031) in the observation group were all lower than those in the control group. CONCLUSION The application of MBSR in image fusion-guided prostate biopsy can synergistically utilize the advantages of minimally invasive technology, significantly optimize surgical indicators, and improve patients' psychological experiences, which is worthy of clinical application and promotion.
Humans ; Male ; Mindfulness ; Prostate/pathology* ; Image-Guided Biopsy ; Stress, Psychological/therapy* ; Middle Aged ; Prostatic Neoplasms/pathology* ; Aged

BACKGROUND: Although the influence of maternal distress during pregnancy on newborn Apgar scores has been studied in various populations, there is limited research specifically addressing this issue among Asian women. This study of Japanese women aims to investigate the association between maternal distress during pregnancy and the risk of a low 5-min-Apgar score among newborns. METHODS: We analyzed data from 87,765 mother-newborn pairs in the Japan Environment and Children's Study. Using multivariable logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for low Apgar scores (<7) at 5 minutes about maternal distress during early and mid-late pregnancy, as measured by the Kessler Psychological Distress Scale (K6). Apgar scores were obtained from newborns' medical records. RESULTS: A higher risk of low Apgar score in newborns at 5 minutes was found in mothers with moderate to severe distress than in those with low distress during mid-late pregnancy. The adjusted OR (95% CI) was 1.22 (1.05-1.42) for moderate distress (K6 = 5-12) and 1.42 (1.00-2.01) for severe distress compared to low distress (p for trend = 0.002). The positive association between maternal distress and the risk of low Apgar score was observed in preterm birth (<37 weeks) and low birth weight (<2,500 g) but not in term birth and normal birth weight. CONCLUSION Maternal distress during mid-late pregnancy was positively associated with the risk of low Apgar score of newborns, specifically in preterm birth and low birth weight.
Humans ; Female ; Pregnancy ; Japan/epidemiology* ; Apgar Score ; Infant, Newborn ; Adult ; Stress, Psychological/epidemiology* ; Male ; Young Adult ; Pregnancy Complications/epidemiology* ; Mothers/psychology* ; Risk Factors

BACKGROUND: Technological innovations in the public transport sector are increasingly leveraged to support the goals of environmental sustainability and public health. Eco-driving assistance (EDA) systems represent one such intervention, aimed at reducing fuel consumption, emissions, and operating costs while improving passenger comfort. However, the potential unintended impacts of EDA technologies on driver health and well-being remain understudied. The EDA Trial, part of the EU-funded INTERCAMBIO project, seeks to evaluate whether the use of EDA systems may introduce new psychosocial stressors for professional drivers, with implications for occupational and public health. METHODS: The EDA tested in this trial is called "NAVIG". Buses will be assigned randomly. Operating EDA-equipped vehicle will be considered as intervention condition, operating vehicle without EDA as control. Each participant will be monitored for 10 working days maximum to accumulate at least 5 intervention shifts during the trial. Heart rate variability (HRV) will be continuously recorded during working hours to assess autonomous stress responses. The root mean square of successive differences (RMSSD) will be averaged over intervention and control shifts to enable within-subject comparisons between intervention and control conditions. Subjective stress levels will be evaluated using the self-report instruments: Cohen's perceived stress scale at baseline and visual analogous scale at baseline and daily. Moreover, neuroendocrine stress biomarkers (salivary cortisol and cortisone) will be collected repeatedly across shifts, as additional outcomes. Mixed-effects models with participant's ID as a random effect variable will be used to compare stress outcomes between EDA and non-EDA driving conditions. Models will be adjusted for potential confounders. RESULTS: A sample size of 26-40 participants was estimated to provide 80% power (α = 0.05) to detect differences of 12-15% between conditions. Ethical approval was obtained from the Swissethics (CER-VD 2024-01573), and participant recruitment is ongoing, with 27 drivers enrolled as of June 2025. CONCLUSIONS: This study will provide empirical evidence on the potential health trade-offs associated with implementing eco-driving technologies in real-world settings. By assessing physiological and psychological stress responses to EDA, the trial supports a more integrated approach to environmental technology evaluation-one that considers not only energy efficiency but also the health and sustainability of the workforce. TRIAL REGISTRATION The trial was registered in the ClinicalTrials.gov database (NCT06688721).
Humans ; Automobile Driving/psychology* ; Stress, Psychological ; Motor Vehicles ; Adult ; Male ; Randomized Controlled Trials as Topic ; Female

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

OBJECTIVE: To investigate the antidepressant effects of Xiaoyao Pill (XYP) by exploring its interactions with gut microbiota and tryptophan metabolism. METHODS: Utilizing network pharmacology, the functional substance groups, key targets, and pathways of XYP in the treatment of depression were identified. The chronic unpredictable mild stress (CUMS) protocol was implemented in male Sprague-Dawley rats to establish depression model. Thirty rats were randomly divided into 3 groups according to their body weight (10 for each): control, CUMS and XYP groups (1.8 g/kg). After 28-day interventions, behavioral phenotyping including sucrose preference test (SPT) and open field test (OFT) were performed. Biochemical validation encompassed enzyme-linked immunosorbent assay for serum cortisol, hematoxylin-eosin histopathology, and immunohistochemistry. Liquid chromatography-mass spectrometry was utilized to profile serum metabolites, while fecal samples underwent metagenomic sequencing for gut microbiota characterization. RESULTS: Network pharmacology studies predicted that key components can protect the nervous system by regulating inflammatory pathways through the blood-brain barrier. SPT and OFT showed that XYP treatment significantly ameliorated depressive-like behaviors (all P<0.05). XYP treatment also restored hippocampal neuronal density, increased serum neurotransmitter levels of neurotransmitters such as 5-hydroxytryptamine and vasoactive intestinal peptide, and while suppressing inflammatory markers such as tumor necrosis factor-alpha, interleukin-1 beta (IL-1 β), and IL-6 (all P<0.05). Metagenomics revealed significant restructuring of gut microbiota, notably the regulation of Parabacteroides distasonis (P<0.05). Non-targeted metabolomics analysis showed that the level of metabolites in the tryptophan and kynurenine pathway significantly changed (variable importance in the projection >1, P<0.05), and the change of metabolic flux was significantly correlated with behavioral improvement (P<0.05). CONCLUSIONS XYP exerts antidepressant effects by increasing neurotransmitter levels, reducing inflammatory makers and modulating Parabacteroides distasonis. Through further exploration of metabolomics, we found that XYP may play a protective role in depression by regulating tryptophan metabolism.
Animals ; Tryptophan/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/blood* ; Male ; Stress, Psychological/drug therapy* ; Behavior, Animal/drug effects* ; Rats ; Chronic Disease ; Hippocampus/drug effects*

OBJECTIVE: To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits. METHODS: The male C57BL/6J mice were assigned to 4 groups using the complete randomization method, including control (CON, n=19), CRS (n=19), SZRD (n=21), and fluoxetine (Flu, n=22) groups. Mice were restrained for 6 h per day, over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily, respectively, 30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test, elevated plus maze test, and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence, while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings. RESULTS: SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (P<0.05 or P<0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (P<0.01). Additionally, SZRD selectively attenuated excitatory (P<0.01), but not inhibitory, synaptic transmission onto BLA pyramidal neurons. CONCLUSION SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Depression/complications* ; Pyramidal Cells/pathology* ; Male ; Mice, Inbred C57BL ; Basolateral Nuclear Complex/pathology* ; Restraint, Physical ; Anxiety/complications* ; Behavior, Animal/drug effects* ; Stress, Psychological/physiopathology* ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Action Potentials/drug effects* ; Synaptic Transmission/drug effects*

OBJECTIVES: Depression is a common negative emotion that can significantly impact physical and mental health. Due to their occupational characteristics, medical staff are more susceptible to depression compared to the general population. This study aims to explore the influence of future-oriented coping on depression among medical staff and the mediating roles of psychological resilience and perceived stress, providing theoretical guidance for depression intervention strategies in this group. METHODS: A cross-sectional survey was conducted among medical staff at a tertiary hospital using convenience sampling. Data were collected via the "Wenjuanxing" platform. A total of 754 questionnaires were distributed; after excluding invalid responses (e.g., duplicate IPs or insufficient completion time), 655 valid questionnaires were retained (valid response rate: 86.87%). Instruments included a demographic questionnaire, the Future-Oriented Coping Scale, the Connor-Davidson Resilience Scale, the Perceived Stress Scale, and the Self-Rating Depression Scale. All scales demonstrated high internal consistency (Cronbach's α>0.88) and validity. SPSS 27.0 was used for descriptive analysis, and PROCESS macro (Model 6) was used to test the chain mediation model. Harman's one-factor test was applied to control for common method bias. RESULTS: Descriptive analyses showed that future-oriented coping was positively correlated with psychological resilience and negatively correlated with perceived stress and depression. Mediation analysis revealed that future-oriented coping significantly predicted lower depression levels among medical staff (β=-0.283, P<0.001). Psychological resilience partially mediated the relationship (effect size=-0.329, accounting for 34.13% of the total effect), as did perceived stress (effect size=-0.099, 10.27%). A significant chain mediation path was identified: "future-oriented coping → psychological resilience → perceived stress → depression" (effect size=-0.253, 26.24%). The total indirect effect accounted for 70.64% of the overall effect, highlighting the substantial role of the mediating pathways. CONCLUSIONS Future-oriented coping can reduce depressive symptoms in medical staff, with psychological resilience and perceived stress serving as key mediators in a chain structure. These findings suggest that enhancing future-oriented coping strategies and psychological resilience may improve stress adaptation and reduce depression levels in this population.
Humans ; Adaptation, Psychological ; Resilience, Psychological ; Cross-Sectional Studies ; Depression/psychology* ; Surveys and Questionnaires ; Stress, Psychological/psychology* ; Male ; Female ; Adult ; Middle Aged ; Medical Staff/psychology* ; Occupational Stress/psychology*