OBJECTIVES: To explore the bioactive components in Jiawei Xiaoyao Pills (JWXYP) and their mechanisms for alleviating depression-like behaviors. METHODS: The active compounds, key targets, and pathways of JWXYP were identified using TCMSP and TCMIP databases. Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress (CUMS)-induced depression groups. After modeling, the 5 model groups were treated with daily gavage of normal saline, 1.8 mg/kg fluoxetine hydrochloride (positive control drug), or JWXYP at 1.44, 2.88, and 4.32 g/kg. The depression-like behaviors of the rats were evaluated using behavioral tests, and pathological changes in the liver and hippocampus were examined with HE staining. The biochemical indicators in the serum and brain tissues were detected using ELISA. Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA, and gut microbiota changes were analyzed using 16S rDNA sequencing. RESULTS: Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system. In the rat models subjected to CUMS, treatment with JWXYP significantly improved body weight loss, sucrose preference and open field activities, reduced liver inflammation, alleviated structural changes in the hippocampal neurons, decreased serum levels of TNF‑α, IL-1β, IL-6 and LBP, and increased 5-HT and VIP concentrations in the serum and brain tissue, and these effects were the most pronounced in the high-dose group. Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats, involving the pathways for bile acid biosynthesis and amino acid metabolism. 16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats. CONCLUSIONS JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters, inhibiting inflammation and oxidation, and modulating gut microbiota.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Neurotransmitter Agents/metabolism* ; Rats ; Inflammation ; Male ; Hippocampus ; Behavior, Animal/drug effects*

OBJECTIVES: To explore the therapeutic mechanism of Chaihu Shugan (CHSG) Decoction for improving cognitive impairment in rats with epilepsy induced by lithium chloride and pilocarpine. METHODS: Male SD rat models of cognitive impairment model after epilepsy induced by intraperitoneal injection with lithium chloride and pilocarpine were randomly divided into 5 groups (n=12) for treatment with daily gavage of saline, donepezil (90 mg/kg), or CHSG Decoction at 2.5, 5.0, 10, 20 and 40 g/kg for 4 consecutive weeks, with 10 rats with intraperitoneal injection with saline as the blank control group. Morris water maze test was used to evaluate cognitive and behavioral changes of the rats after treatment. The mRNA and protein expressions of ASIC1, NR1, NR2A and NR2B in the hippocampus of rats were detected using RT-qPCR and Western blotting. RESULTS: Compared with those with saline treatment, the rat models treated with CHSG Decoction at 5 and 10 g/kg showed significantly shortened escape latency and prolonged stay in the target quadrant with increased number of platform crossings in Morris water maze test. CHSG Decoction treatment at the two doses significantly increased ASIC1, NR1, NR2A and NR2B protein expressions in the hippocampus of the rat models, and their mRNA expression levels were all increased significantly after the treatment at the doses above 2.5 g/kg. CONCLUSIONS CHSG Decoction can improve cognitive impairment in rats after epilepsy possibly by regulating the expression and channel activity of NMDAR protein and its subunit protein via upregulating ASIC1 to modulate neuronal excitability and synaptic plasticity in the hippocampus.
Animals ; Hippocampus/drug effects* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Acid Sensing Ion Channels/metabolism* ; Rats, Sprague-Dawley ; Male ; Rats ; Epilepsy/complications* ; Cognitive Dysfunction/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Up-Regulation ; Maze Learning

OBJECTIVES: To explore the mechanisms of Qingre Lidan Jiedu Recipe (QLJR) for improving cognitive dysfunction in rats with high copper load. METHODS: Seventy-five male SD rats were randomized into normal control group, model group, QLJR group, penicillamine (PCA) group, and QLJR+ PCA group. Except for those in the control group, all the rats were fed a high-copper diet for 12 weeks. The effects of the treatments on cognitive function of the rats were assessed using the Barnes maze and passive avoidance tests. Hippocampal expressions of NIX, FUNDC1 and LC3 of the rats were detected using Western blotting and immunofluorescence staining, and changes in mitochondrial morphology were observed with transmission electron microscopy. RESULTS: Behavioral tests showed prolonged target hole latency, shortened latency to enter the dark chamber, and increased error counts of the rats in the model group, which were significantly improved in QLJR+PCA group; the error counts were significantly lower in QLJR+PCA group than in either QLJR or PCA group. Among all the groups, the hippocampal expressions of NIX and FUNDC1 were the lowest and LC3 I/II expression the highest in the model group; NIX and FUNDC1 expressions were significantly higher and LC3 I expression was lower in QLJR+PCA group than in QLJR group and PCA group. Immunofluorescence staining revealed weakened NIX and FUNDC1 expressions and enhanced LC3 expression in the hippocampus of the rats in the model group as compared with those in the normal control and QLJR+PCA groups, but their expressions did not differ significantly between QLJR and PCA groups. The rats in the model group showed obvious structural disarray of the mitochondria, which were improved in all the treatment groups. CONCLUSIONS QLJR improves cognitive dysfunction in rats with high copper load possibly by regulating mitophagy.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Drugs, Chinese Herbal/therapeutic use* ; Copper/toxicity* ; Mitophagy/drug effects* ; Hippocampus/drug effects* ; Cognition Disorders/drug therapy* ; Cognitive Dysfunction/chemically induced*

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*

In order to explore effective ways to reduce non-suicidal self-injury (NSSI) among female adolescents, a total of 45 female adolescent patients with NSSI in West China Hospital of Sichuan University and Guizhou Second Provincial People's Hospital from June 2021 to June 2024 were selected randomly that divided into groups A, B and C, with 15 cases in each group. Group A was treated with repeated transcranial magnetic stimulation (rTMS) and bipolar depression triple therapy, and group B was treated with bipolar depression triple therapy to compare the effectiveness and safety. Group C received bipolar depression triple therapy combined with sham stimulation which only produced stimulating sounds but no stimulating magnetic field as a control in the study. After treatment, the Hamilton Anxiety Score (HAMA), Hamilton Depression Score (HAMD) and Nurses' Global Assessment of Suicide Risk (NGASR) in group A were significantly lower than those in group B and C ( P < 0.01). rTMS combined with bipolar depression triple therapy has a definite effect on reducing NSSI in female adolescents, which can reduce the incidence rate of short-term NSSI behavior in patients.
Humans ; Female ; Adolescent ; Self-Injurious Behavior/prevention & control* ; Transcranial Magnetic Stimulation/methods* ; Bipolar Disorder/therapy* ; Combined Modality Therapy ; Treatment Outcome

In order to meet the need of autonomous control of patients with severe limb disorders, this paper designs a nursing bed control system based on motor imagery-brain computer interface (MI-BCI). In view of the low decoding performance of cross-subjects and the dynamic fluctuation of cognitive state in the existing MI-BCI technology, the neural network structure optimization and user interaction feedback enhancement are improved. Firstly, the optimized dual-branch graph convolution multi-scale neural network integrates dynamic graph convolution and multi-scale convolution. The average classification accuracy is higher than that of multi-scale attention temporal convolution network, Gram angle field combined with convolution long short term memory hybrid network, Transformer-based graph convolution network and other existing methods. Secondly, a dual visual feedback mechanism is constructed, in which electroencephalogram (EEG) topographic map feedback can improve the discrimination of spatial patterns, and attention state feedback can enhance the temporal stability of signals. Compared with the single EEG topographic map feedback and non-feedback system, the average classification accuracy of the proposed method is also greatly improved. Finally, in the four classification control task of nursing bed, the average control accuracy of the system is 90.84%, and the information transmission rate is 84.78 bits/min. In summary, this paper provides a reliable technical solution for improving the autonomous interaction ability of patients with severe limb disorders, which has important theoretical significance and application value.
Humans ; Brain-Computer Interfaces ; Deep Learning ; Electroencephalography ; Feedback, Sensory ; Neural Networks, Computer ; Beds

BACKGROUND AND OBJECTIVE

Mindfulness-based interventions (MBI), a novel treatment, and cognitive behavioral therapy (CBT), the standard treatment, are both effective in treating anxiety in adolescents. This study determined the effectiveness of mindfulness-based interventions versus cognitive behavioral therapy in reducing symptoms of anxiety among adolescents experiencing social anxiety through a systematic review and meta-analysis.

A systematic approach was used to identify eligible studies. Electronic databases, reference lists of relevant articles, and gray literature were searched. Data was analyzed using RevMan to calculate standard mean differences with 95% confidence intervals and subgroups. Heterogeneity was measured using visual assessment, the I2 statistic, and chi-square test.

Randomized controlled trials comparing MBI to CBT for adolescents diagnosed with social anxiety or social phobia disorder were analyzed, with non-randomized studies being excluded. Structured searches in electronic databases, reference lists, and gray literature were conducted by four independent reviewers who initially identified potential articles through title and abstract screening. After a comprehensive review of full-text articles and a consensus-building process, the selection of included articles was finalized. Data was analyzed using RevMan to calculate standard mean differences with 95% confidence intervals and to examine subgroups, with heterogeneity being assessed through visual evaluation, the I² statistic, and chi-square tests. Total number of participants was 255; 101 were male and 158 were women. Mean age was 27.5 years old, and diagnosed with Social Anxiety Disorder, Social Phobia, or DSM-IV-Defined-Anxiety-Disorder. They were divided into two groups: 125 participated in 8- to 12-week MBI sessions lasting 2 hours each, while 130 underwent 2-hour CBT sessions spanning 8, 12, or 14 weeks. There is moderate quality of evidence reporting non-significant difference on MBI vs CBT's effectiveness in alleviating symptoms of social anxiety [mean (95% CI) = -0.04 (-0.58, 0.51)].

Study found that there were no significant differences between Mindfulness-Based Interventions and Cognitive Behavioral Therapy in reducing social anxiety in adolescents. Mindfulness interventions have advantages in terms of cost-effectiveness for reducing symptoms of anxiety. Future research should include larger sample sizes and longer follow-up periods to further assess long-term effects of these interventions.

OBJECTIVE: To approach the evaluation of relative α variant score monitored by bedside continuous electroencephalography and optic nerve sheath diameter (ONSD) evaluated by ultrasound in patients with ischemic hypoxic encephalopathy, and to observe the effect of neurofeedback training on brain function. METHODS: A prospective observational study was conducted. The patients admitted to the emergency and intensive care department of Shanghai Pudong New Area People's Hospital from January 2021 to December 2023, who meet the diagnostic criteria of ischemic hypoxic encephalopathy with the Glasgow coma score (GCS) ≤ 8 at admission receiving neurofeedback training were enrolled as the study object (observation group), and the patients without neurofeedback training and GCS score ≤ 8 at admission were enrolled as the controls (control group). Both groups received intravenous neurotrophic therapy combining ganglioside and cerebrolysin for 10 days as one course of treatment. On this basis, the observation group additionally received continuous neurofeedback training including visual feedback, auditory feedback, meditation and relaxation for 14 days. Bedside continuous electroencephalography was used for monitoring relative α variation score, and ultrasound was used to determine ONSD. The average power and slow wave power [expressed as delta-theta ratio (DTR)] of five channels in electroencephalography before and 14 days after neurofeedback training were examined. The differences in peripheral blood neutrophil/lymphocyte ratio (NLR), Hamilton depression scale (HAMD) score, National Institutes of Health stroke scale (NIHSS) score, plasma levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF). RESULTS: A total of 60 patients were enrolled in the observation group and 50 patients in the control group finally. There was no significant difference in gender, age or course of disease between the two groups. The ONSD and relative α variant score in the observation group were significantly higher than those in the control group [ONDS (mm): 5.59±0.42 vs. 3.23±0.34, relative α variant score: 2.28±0.39 vs. 0.83±0.28, both P < 0.01]. After neurofeedback training for 14 days, the mean power and DTR in five channels of electroencephalography in the observation group were significantly lower than those before treatment [mean power (μV²/Hz): 95.35±3.61 vs. 102.58±4.23 in frontal pole 1 (Fp1), 38.56±4.73 vs. 46.13±2.36 in frontal 3 (F3), 34.33±5.87 vs. 51.71±4.65 in central 3 (C3), 58.37±4.45 vs. 62.95±3.22 in F7, 45.23±2.41 vs. 54.14±2.45 in temporal 3 (T3); DTR (μV²/Hz): 75.21±11.34 vs. 84.12±11.35 in ground electrode (GND), 72.31±21.67 vs. 88.23±10.25 in reference electrode (REF), 81.34±8.57 vs. 92.41±8.56 in F4, 71.25±5.42 vs. 87.23±5.64 in parietal 3 (P3), 70.12±5.88 vs. 85.67±6.12 in P4; all P < 0.05]. However, there was no significant difference in the mean power of five channels before and after treatment in the control group. There was no significant difference in the HAMD score or NIHSS score before treatment between the two groups. The above scores at 14 days after treatment were significantly lower than before, and the decrease was more significant in the observation group (HAMD score: 4.59±1.06 vs. 10.69±0.97, NIHSS score: 6.81±0.66 vs. 8.45±0.87, both P < 0.01). There was no significant difference in the plasma 5-HT, BDNF or peripheral blood NLR before treatment between the two groups. The above parameters at 14 days after treatment were improved as compared with before, and the levels in the observation group were superior to control group [5-HT (mg/L): 150.25±17.37 vs. 123.34±16.18, BDNF (mg/L): 19.37±2.35 vs. 12.48±2.18, NLR: 4.78±0.83 vs. 5.81±1.17, all P < 0.01]. CONCLUSIONS Both ONDS determined by ultrasound and relative α variation score monitored by electroencephalography changed significantly in the patients with ischemic hypoxic encephalopathy. Neurofeedback training can effectively improve brain function in patients with ischemic hypoxic encephalopathy.
Humans ; Electroencephalography ; Prospective Studies ; Neurofeedback ; Optic Nerve/diagnostic imaging* ; Ultrasonography ; Hypoxia-Ischemia, Brain/physiopathology* ; Male ; Female ; Middle Aged

OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points

Triggering receptor expressed on myeloid cells 2 (TREM2)-mediated microglial phagocytosis is an energy-intensive process that plays a crucial role in amyloid beta (Aβ) clearance in Alzheimer's disease (AD). Energy metabolic reprogramming (EMR) in microglia induced by TREM2 presents therapeutic targets for cognitive impairment in AD. Jiawei Xionggui Decoction (JWXG) has demonstrated effectiveness in enhancing energy supply, protecting microglia, and mitigating cognitive impairment in APP/PS1 mice. However, the mechanism by which JWXG enhances Aβ phagocytosis through TREM2-mediated EMR in microglia remains unclear. This study investigates how JWXG facilitates microglial phagocytosis and alleviates cognitive deficits in AD through TREM2-mediated EMR. Microglial phagocytosis was evaluated through immunofluorescence staining in vitro and in vivo. The EMR level of microglia was assessed using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kits. The TREM2/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway was analyzed using Western blotting in BV₂ cells. TREM2^-/- BV₂ cells were utilized for reverse validation experiments. The Aβ burden, neuropathological features, and cognitive ability in APP/PS1 mice were evaluated using ELISA kits, immunohistochemistry (IHC), and the Morris water maze (MWM) test. JWXG enhanced both the phagocytosis of EMR disorder-BV₂ cells (EMRD-BV₂) and increased EMR levels. Notably, these effects were significantly reversed in TREM2^-/- BV₂ cells. JWXG elevated TREM2 expression, adenosine triphosphate (ATP) levels, and microglial phagocytosis in APP/PS1 mice. Additionally, JWXG reduced Aβ-burden, neuropathological lesions, and cognitive deficits in APP/PS1 mice. In conclusion, JWXG promoted TREM2-induced EMR and enhanced microglial phagocytosis, thereby reducing Aβ deposition, improving neuropathological lesions, and alleviating cognitive deficits.
Drugs, Chinese Herbal/pharmacology* ; Microglia/drug effects* ; Phagocytosis ; Cognitive Dysfunction/drug therapy* ; Metabolic Reprogramming ; Animals ; Mice ; Cell Line ; Receptors, Immunologic/metabolism* ; Membrane Glycoproteins/metabolism* ; Signal Transduction ; Amyloid beta-Peptides/metabolism* ; Energy Metabolism