This study aims to investigate the mechanism through which Xiangshao Granules treat anxiety and depression using metabolomics and gut microbiota techniques, combined with animal experiments. Sixty female ICR mice were selected for the experiment and randomly divided into six groups: a control group, a model group, a low-dose Xiangshao Granules group, a medium-dose Xiangshao Granules group, a high-dose Xiangshao Granules group, and an estradiol(positive drug) group. Except for the control group, rats in other groups were induced for anxiety and depression model by ovariectomy(OVX) combined with chronic unpredictable mild stress(CUMS). After successful modeling, the mice received oral administration of Xiangshao Granules or estradiol for three weeks. Anxiety and depression behaviors in mice were evaluated using light-dark box tests, open field tests, and elevated plus-maze tests. The levels of substances closely related to anxiety and depression, such as serotonin(5-HT) and estrogen(E_2), were quantified in plasma and hippocampal tissue using enzyme-linked immunosorbent assay(ELISA). Metabolomics and 16S rDNA amplicon sequencing techniques were employed to analyze the regulatory effects of Xiangshao Granules on plasma metabolites and metabolic pathways in anxiety and depression mice, as well as their impact on the distribution of gut microbiota. Finally, the correlation between plasma metabolites and differential gut microbiota was constructed using the Spearman correlation coefficient method. Behavioral experimental results indicated that, compared to the control group, the model group exhibited significantly decreased dwell time in the light box, reduced total distance in the open field, and diminished dwell time in the open arm. In contrast, high dose of Xiangshao Granules were found to increase the dwell time in the light box and total distance in the open field. ELISA results indicated that the levels of 5-HT, gamma-aminobutyric acid(GABA), E_2 were significantly decreased, luteinizing hormone(LH), adrenocorticotropic hormone(ACTH), and corticosterone(CORT) were significantly elevated in the anxiety and depression mice, and treatment with middle, high dose of Xiangshao Granules reversed the levels of these substances. Additionally, in the anxiety and depression mouse model, the levels of follicle-stimulating hormone(FSH) were significantly increased, whereas middle, high dose of Xiangshao Granules decreased FSH levels. Metabolomics analysis revealed that Xiangshao Granules significantly changed the metabolic profile of the anxiety and depression mice, affecting central carbon metabolism, amino acid biosynthesis, and ABC transporter pathways. The results from 16S rDNA amplicon sequencing showed that Xiangshao Granules improved the relative abundance of genera such as Bacteroidia, Bacilli, Lactobacillales, and Lactobacillus. Spearman correlation analysis indicated a close association between specific differential gut microbiota and plasma differential metabolites. This study suggests that Xiangshao Granules significantly ameliorate anxiety and depression symptoms in mice by altering the levels of substances associated with these conditions, including 5-HT, GABA, E_2, LH, and ACTH. The metabolomics and gut microbiota data suggest that the therapeutic mechanism may be closely related to the regulation of amino acid biosynthesis, central carbon metabolism, and the alteration of key microbial community compositions.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Anxiety/microbiology* ; Depression/microbiology* ; Gastrointestinal Microbiome/drug effects* ; Mice ; Female ; Mice, Inbred ICR ; Metabolomics ; Serotonin/metabolism* ; Humans ; Disease Models, Animal ; Rats ; Behavior, Animal/drug effects*

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Aim To explore the therapeutic effect and mechanism of Qingjie Huagong decoction in modulating PI3K/AKT/NF-κB signaling pathway in inflammatory response of acute pancreatitis(AP)mice.Methods Twenty-four mice were randomly divided into Blank group,Model group,Ustekin group,and Qingjie Hua-gong decoction group,with six mice in each group.The AP model was prepared by using rain frogin.Serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α lev-els were detected by ELISA;the pancreatic pathology was detected by HE staining;the expressions of PI3K,AKT,and NF-κB-related proteins and mRNAs were de-tected by immunohistochemistry,Western blot,and RT-qPCR.Results Compared with the blank group,the model group showed obvious pathological damage to the pancreas,with significantly higher serum α-AMS,PN-LP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels(P＜0.01),and significantly higher levels of PI3K,AKT,and NF-κB-related proteins and mRNA expression(P＜0.01).Compared with the model group,both the Qingjie Huagong decoction group and the ustekin group improved the histopathological changes in the pancreas of AP mice,decreased the serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels,and down-reg-ulated the expression levels of pancreatic PI3K,AKT,NF-κB-related proteins and mRNA(P＜0.05 or P＜0.01).Conclusion Qingjie Huagong decoction may inhibit the inflammatory response and protect pancreat-ic tissues by regulating the expression of PI3K/AKT/NF-κB signaling pathway.

Objective:To explore the clinical efficacy of Shexiang Baoxin pill in patients with unstable angina pectoris(UAP)and type 2 diabetes mellitus(T2DM)using meta-analysis.Methods:We searched the databases including Pubmed,Web of Science,EMbase,EBSCO,Cochrane,CBM,CNKI and Wanfang for randomized controlled trials(RCTs)about the therapeutic effect of Shexiang Baoxin pill on patients with UAP and T2DM from the establish-ment to January 20th,2023.RevMan 5.3 software was used to perform meta-analysis to investigate the effect of Shexiang Baoxin pill on angina improvement and blood glucose fluctuation in patients with UAP and T2DM.Results:Six eligible literatures were included,including 346 patients in Shexiang Baoxin pill group and control group respec-tively.The results of meta-analysis showed that compared to participants in control group,those in Shexiang Baox-in pill group had significantly higher clinical overall efficiency(OR=3.13,95％CI 2.01～4.89,P＜0.001),and significantly lower angina attack frequency(MD=-0.66,95％CI-0.79～-0.52,P＜0.001),duration of angi-na(MD=-3.10,95％CI-4.11～-2.09,P＜0.001),and 2-hour postprandial blood glucose(MD=-1.79,95％CI-2.00～-1.57,P＜0.001).Conclusion:Shexiang Baoxin pill could improve clinical overall efficiency,an-gina attack frequency and duration,and reduce 2-hour postprandial blood glucose in patients with unstable angina pectoris and type 2 diabetes mellitus.

Aim To explore the therapeutic effect and mechanism of Qingjie Huagong decoction in modulating PI3K/AKT/NF-κB signaling pathway in inflammatory response of acute pancreatitis(AP)mice.Methods Twenty-four mice were randomly divided into Blank group,Model group,Ustekin group,and Qingjie Hua-gong decoction group,with six mice in each group.The AP model was prepared by using rain frogin.Serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α lev-els were detected by ELISA;the pancreatic pathology was detected by HE staining;the expressions of PI3K,AKT,and NF-κB-related proteins and mRNAs were de-tected by immunohistochemistry,Western blot,and RT-qPCR.Results Compared with the blank group,the model group showed obvious pathological damage to the pancreas,with significantly higher serum α-AMS,PN-LP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels(P＜0.01),and significantly higher levels of PI3K,AKT,and NF-κB-related proteins and mRNA expression(P＜0.01).Compared with the model group,both the Qingjie Huagong decoction group and the ustekin group improved the histopathological changes in the pancreas of AP mice,decreased the serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels,and down-reg-ulated the expression levels of pancreatic PI3K,AKT,NF-κB-related proteins and mRNA(P＜0.05 or P＜0.01).Conclusion Qingjie Huagong decoction may inhibit the inflammatory response and protect pancreat-ic tissues by regulating the expression of PI3K/AKT/NF-κB signaling pathway.

Objective:To explore the clinical efficacy of Shexiang Baoxin pill in patients with unstable angina pectoris(UAP)and type 2 diabetes mellitus(T2DM)using meta-analysis.Methods:We searched the databases including Pubmed,Web of Science,EMbase,EBSCO,Cochrane,CBM,CNKI and Wanfang for randomized controlled trials(RCTs)about the therapeutic effect of Shexiang Baoxin pill on patients with UAP and T2DM from the establish-ment to January 20th,2023.RevMan 5.3 software was used to perform meta-analysis to investigate the effect of Shexiang Baoxin pill on angina improvement and blood glucose fluctuation in patients with UAP and T2DM.Results:Six eligible literatures were included,including 346 patients in Shexiang Baoxin pill group and control group respec-tively.The results of meta-analysis showed that compared to participants in control group,those in Shexiang Baox-in pill group had significantly higher clinical overall efficiency(OR=3.13,95％CI 2.01～4.89,P＜0.001),and significantly lower angina attack frequency(MD=-0.66,95％CI-0.79～-0.52,P＜0.001),duration of angi-na(MD=-3.10,95％CI-4.11～-2.09,P＜0.001),and 2-hour postprandial blood glucose(MD=-1.79,95％CI-2.00～-1.57,P＜0.001).Conclusion:Shexiang Baoxin pill could improve clinical overall efficiency,an-gina attack frequency and duration,and reduce 2-hour postprandial blood glucose in patients with unstable angina pectoris and type 2 diabetes mellitus.

Objective: To explore the balance of peripheral blood T helper 17 cells/regulatory T cell (Th17/Treg) ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans (ASO). Methods: A rat model of lower extremity ASO was established, and blood samples from patients with lower extremity ASO before and after surgery were obtained. ELISA was used to detect interleukin 6 (IL-6), IL-10, and IL-17. Real-time RCR and Western blot analyses were used to detect Foxp3, IL-6, IL-10, and IL-17 expression. Moreover, flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio. Results: Compared with the control group, the iliac artery wall of ASO rats showed significant hyperplasia, and the concentrations of cholesterol and triglyceride were significantly increased (P<0.01), indicating the successful establishment of ASO. Moreover, the levels of IL-6 and IL-17 in ASO rats were pronouncedly increased (P<0.05), while the IL-10 level was significantly decreased (P<0.05). In addition to increased IL-6 and IL-17 levels, the mRNA and protein levels of Foxp3 and IL-10 in ASO rats were significantly decreased compared with the control group. The Th17/Treg and M1/M2 ratios in the ASO group were markedly increased (P<0.05). These alternations were also observed in ASO patients. After endovascular surgery (such as percutaneous transluminal angioplasty and arterial stenting), all these changes were significantly improved (P<0.05). Conclusions: The Th17/Treg and M1/M2 ratios were significantly increased in ASO, and surgery can effectively improve the balance of Th17/Treg, and reduce the ratio of M1/M2, and the expression of inflammatory factors.

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy holds promise in mitigating several shortcomings, including the indiscriminate suppression of the immune system by traditional immunosuppressants, and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints. By persisting and proliferating in vivo, CAR-T cells can offer a tailored and precise therapeutics. This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases, incorporating innovations well-studied in the field of hematological tumors, aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.