Irritable bowel syndrome with diarrhea （IBS-D）， as a prototypical disorder involving the microbiota-gut-brain axis， remains poorly understood in terms of its pathogenesis， posing ongoing challenges for clinical diagnosis. Omics technologies， leveraging their high-throughput detection and systematic analysis advantages， has emerged as a critical tool for deciphering the complex mechanisms underlying traditional Chinese medicine （TCM） treatment of IBS-D. This systematic review summarizes the research progress of transcriptomics， proteomics， metabolomics， microbiomics， and multi-omics integration techniques in TCM interventions for IBS-D. In single-omics studies， transcriptomics using techniques like RNA-seq， reveals the regulatory mechanisms of TCM on IBS-related signaling pathways. Proteomics， leveraging quantitative technologies such as 2D-difference gel electrophoresis and tandem mass tag， identifies differentially expressed proteins and elucidates the action targets of TCM in treating IBS-D. Metabolomics， employing methods like UPLC-Q-TOF-MS and LC-MS/MS， discovers metabolic pathways regulated by TCM to improve metabolic disturbances in IBS-D. Microbiomics， based on 16S rRNA sequencing， confirms that TCM can reshape the gut microbiota structure and restore the intestinal microecological balance， thereby improving IBS-D. Multi-omics integration further overcomes the limitations of single-omics approaches by synthesizing information from transcriptomics， proteomics， metabolomics， and microbiomics， enabling a more comprehensive and systematic elucidation of the complex mechanisms underlying TCM treatment for IBS-D. In the future， research related to IBS-D should be advanced from three aspects： stratified clinical research based on TCM syndrome types， multi-omics integration verification mechanisms， and emerging omics to explore new mechanisms， providing more innovative ideas for the precise diagnosis and treatment of this disease.

OBJECTIVES: Depressive and anxiety disorders are among the most common mental disorders worldwide and are associated with unhealthy lifestyle behaviors. The Life's Simple 7 (LS7) guideline proposed by the American Heart Association aims to reduce cardiovascular risk by improving behaviors such as diet and physical activity, but its impact on mental health is not yet fully clear. This study examined the association between LS7 scores and symptoms of anxiety and depression in adults undergoing routine health examinations. METHODS: Data were collected from individuals who underwent health examinations from May 2015 to December 2024 at the Health Management Center of the Third Xiangya Hospital. All participants completed the LS7 assessments, the Self-Rating Depression Scale (SDS), and the Self-Rating Anxiety Scale (SAS). Participants were categorized into 4 LS7 score groups: Low (≤7), average (8-9), good (10), and excellent (11-14). Those with SDS or SAS≥50 were classified as having mental disorder symptoms; with this group, SAS≥50 indicated anxiety, SDS≥50 indicated depression, and SDS and SAS≥50 indicated comorbid anxiety-depression. Binary logistic regression was used to assess associations between LS7 score and mental symptoms, calculating odds ratio (OR) and 95% confidence interval (CI). A restricted cubic spline (RCS) regression model was used to analyze the dose-response relationship between LS7 score (continuous variable) and the risk of mental symptoms. Nodes were set at the 5th, 35th, 65th, and 95th percentiles of the LS7 score, with the 5th percentile as the reference point. All models were adjusted for covariates such as gender, age, living alone, drinking status, education level, and sleep quality. Logistic regression framework was used to fit and calculate the adjusted OR (aOR) and 95% CI. Nonlinear relationship tests were also conducted. Subgroup analysis was performed to explore the interaction between gender, age, drinking habits, education level, and other factors and the LS7 score in influencing the risk of mental symptoms. RESULTS: A total of 5 449 participants were included; 1 363 (25.01%) had depressive symptoms, 398 (7.30%) had anxiety symptoms, and 259 (4.75%) had comorbid anxiety-depression. The prevalence of mental symptoms decreased significantly as LS7 scores increased. Univariate and multivariate Logistic regression indicated that LS7 score≥8 was protective against mental symptoms. Multivariate Logistic regression demonstrated moderate discriminative ability (AUC=0.672). Among individuals with anxiety, depression, or comorbid symptoms, LS7 score distributions showed a graded decrease from poor to excellent groups. After adjustment, an excellent LS7 score was associated with a 39% lower risk of depression (aOR=0.61, 95% CI 0.47 to 0.78, P<0.001), a 63% lower risk of anxiety (aOR=0.37, 95% CI 0.22 to 0.59, P<0.001), and a 66% lower risk of comorbid anxiety-depression (aOR=0.34, 95% CI 0.17 to 0.62, P=0.001). The AUC values of the anxiety model, depression model, and comorbid anxiety and depression model were 0.632, 0.672, and 0.619, respectively. All models demonstrated moderate discriminatory ability, which was statistically significant, but their capacity to distinguish cases from non-cases was limited. RCS analysis confirmed a linear inverse relationship between LS7 score and mental symptom risk. Not smoking and regular physical activity were the strongest protective behaviors. Subgroup analysis suggested stronger protective effects in men, younger adults (≤60), non-drinkers, and those with higher education levels, and revealed a significant interaction between alcohol use and LS7 score (P for interaction=0.021), indicating that alcohol consumption may weaken the protective effect of LS7. CONCLUSIONS Ideal healthy lifestyle behaviors, as reflected by higher LS7 scores, are associated with lower risks of anxiety and depression in adults. Promoting LS7-based lifestyle practices may serve as a practical and effective strategy for the prevention and management of anxiety and depression in both clinical and daily life settings.
Humans ; Cross-Sectional Studies ; Depression/epidemiology* ; Anxiety/epidemiology* ; Adult ; Male ; Female ; Middle Aged ; Healthy Lifestyle ; Risk Factors ; Anxiety Disorders/epidemiology* ; Exercise ; Physical Examination ; Aged

Objective To explore the effect and preliminary mechanism of the plant-derived immunostimulatory molecule,ophiopogonin,on enhancing the immune response of a subunit vaccine with the receptor-binding domain(RBD)of coronavirus spike protein as the antigen.Methods CCK-8 assay was used to determine the cytotoxicity of ophiopogonin D'(OPD')on bone marrow-derived dendritic cells(BMDCs).Female Balb/c mice were randomly divided into RBD,RBD/OPD',RBD/Alum,and control groups.The immunization dose was 5 μg of antigen per mouse and 100 μg of adjuvant per mouse,and immunization was carried out according to the intramuscular injection immunization procedure on days 0,21,and 42.The titers of specific IgG and its subtype antibodies were detected by ELISA.The cytokine levels in the supernatant of splenocytes were detected using ELISA.The number of splenocytes secreting IFN-γ was detected by ELISpot.Laser confocal microscopy was employed to observe the uptake of antigen by BMDCs.The phagocytic ability of BMDCs for antigen was quantitatively analyzed by flow cytometry.The mechanism of its enhanced immune effect was preliminarily explored using transcriptomics technology combined with bioinformatics research.Results When the concentration of OPD'was less than 5 μg/mL,the survival rate of BMDCs was 100%.After a single intramuscular injection in mice,except for a slight decrease in body weight,the other biochemical indicators were within corresponding normal ranges.After intramuscular injection immunization of the vaccine,the titers of serum-specific IgG,IgG1,and IgG2a in the RBD/OPD'group were significantly higher than those in the RBD group(P<0.05).Compared with the RBD group,the RBD/OPD'group induced a high-level Th1 cell immune response of IL-1β,TNF-α,and IFN-γ(P<0.01)and had more lymphocytes secreting IFN-γ(P<0.001).Laser confocal microscopy displayed that BMDCs took up more antigens after OPD'treatment,which was further confirmed with flow cytometry in quantitative analysis on antigen uptake rate(P<0.01).Transcriptomics results indicated that there was more significant enrichment of the PPAR signaling pathway in the RBD/OPD'group than the RBD group,suggesting that OPD'may activate the PPAR signaling pathway to exert its adjuvant effect.Conclusion OPD'effectively enhances the immune response of the RBD subunit vaccine,and its action mechanism may be related to the activation of the PPAR signaling pathway.

Objective To establish a mouse model of infection with the minimum lethal dose of Vibrio vulnificus(V.vulnificus)and to evaluate the protective efficacy of inactivated whole-cell(IWC)vaccine using this model.Methods A mouse model of lethal-dose infection was established by intraperitoneal injection of different doses of V.vulnificus.Bacterial colonization in the organs was detected with tissue homogenate plating,and pathological changes in the organs were observed after tissue section staining.Flow cytometry was used to detect immune cell responses after liver tissues were digested into single-cell suspension.IWC vaccine of V.vulnificus was prepared,and the mice were immunized through different routes to observe the protective efficacy of the vaccine.Results A mouse model of infection with the minimum lethal dose at 1×106 CFU of V.vulnificus was successfully established.After infection,the bacteria were mainly colonized in the liver of mice and caused severe pathological damages.Compared with the uninfected mice,the proportion of neutrophils in the liver was significantly increased in the infected mice,whereas the proportions of B cells and T cells were correspondingly decreased(P<0.05).A single intramuscular or intraperitoneal injection of the IWC vaccine could protect the mice effectively against lethal infection of V.vulnificus in 7 d later(P<0.01),although the level of serum IgG having no significant increase.Conclusion A mouse model of lethal-dose infection with V.vulnificus is successfully established,with histopathological characteristics.The IWC vaccine of V.vulnificus rapidly mediates immune protection in this model probably independent of IgG.

OBJECTIVE To study the effects of Tongxie yaofang reducing colon hypermotility in irritable bowel syndrome with diarrhea （IBS-D） rats by regulating gut microbiota-enteric nervous system （ENS）-muscularis macrophages （MM） crosstalk. METHODS Forty newborn male SD rats were randomly divided into control group， model group， TCM group [Tongxie yaofang 2.68 g/（kg·d）， calculated by raw material]， and positive control group [Live combined bifidobacterium and lactobacillus tablets 0.27 g/（kg·d）]， with 10 rats in each group. Except for the control group， the IBS-D model of liver stagnation and spleen deficiency syndrome was induced in the other 3 groups with the method of mother-child separation+chronic restraint+Folium Sennae- induced diarrhea. After modeling， the administration groups were given relevant drug liquid intragastrically， once a day， for consecutive 2 weeks. At the end of modeling and after administration， the fecal properties （the incidence and the rate of loose stools）， colonic motility （colon emptying time）， and visceral sensitivity [abdominal withdrawal reflex （AWR） scores under different pressures] of rats were observed in each group. The concentration of lipopolysaccharide （LPS） in serum was detected after medication， and the expressions and distribution of bone morphogenetic protein 2 （BMP2）， colony stimulating factor 1 （CSF1） and Toll-like receptor 4 （TLR4） in colon tissue were detected； the diversity， species composition and differences of gut microbiota were also determined. RESULTS At the end of modeling， compared with the control group， all rats of the other three groups suffered from loose stools （100%）， the rate of loose stools and AWR scores at different pressures increased significantly， and colon emptying time was shortened significantly （P＜0.01 or P＜0.05）. The incidences of loose stools were 20% in TCM group and 80% in the positive control group； the rate of loose stools and AWR scores at different pressures， serum concentration of LPS and protein expressions of CSF1 and TLR4 in muscle layer of colon tissue in TCM group significantly decreased， compared with the model group； colon emptying time， the average optical density of BMP2 protein in muscle layer of colon tissue， and the indexes of Chao 1， Shannon and Faith’s PD and Simpson E-mail：772699670@qq.com index of rats in TCM group were all prolonged or increased significantly， compared with the model group （P＜0.01 or P＜ E-mail：aiwangzi312@163.com 0.05）. The relative abundance ratio of Firmicutes/Bacteroidetes， from low to high， was in the order of TCM group， control group， positive control group and model group； the species composition of gut microbiota in TCM group was closer to control group， with dominant bacterial genera including Prevotella and Blautia. CONCLUSIONS Tongxie yaofang can regulate the expressions of BMP2 and CSF1， the key proteins of gut microbiota-ENS-MM crosstalk， by changing the gut microbiota， thus alleviating the abnormal hyperfunction of colon motility in IBS-D rats.

Objective To explore the mechanism underlying the protective effect of α2-macroglobulin (A2M) against glucocorticoid-induced femoral head necrosis. Methods In a human umbilical vein endothelial cell (HUVEC) model with injuries induced by gradient concentrations of dexamethasone (DEX;10-8-10-5 mol/L), the protective effects of A2M at 0.05 and 0.1 mg/mL were assessed by examining the changes in cell viability, migration, and capacity of angiogenesis using CCK-8 assay, Transwell and scratch healing assays and angiogenesis assay. The expressions of CD31 and VEGF-A proteins in the treated cells were detected using Western blotting. In BALB/c mouse models of avascular necrosis of the femoral head induced by intramuscular injections of methylprednisolone, the effects of intervention with A2M on femoral trabecular structure, histopathological characteristics, and CD31 expression were examined with Micro-CT, HE staining and immunohistochemical staining. Results In cultured HUVECs, DEX treatment significantly reduced cell viability, migration and angiogenic ability in a concentration- and time-dependent manner (P<0.05), and these changes were obviously reversed by treatment with A2M in positive correlation with A2M concentration (P<0.05). DEX significantly reduced the expression of CD31 and VEGF-A proteins in HUVECs, while treatment with A2M restored CD31 and VEGF-A expressions in the cells (P<0.05). The mouse models of femoral head necrosis showed obvious trabecular damages in the femoral head, where a large number of empty lacunae and hypertrophic fat cells could be seen and CD31 expression was significantly decreased (P<0.05). A2M treatment of the mouse models significantly improved trabecular damages, maintained normal bone tissue structures, and increased CD31 expression in the femoral head (P<0.05). Conclusion A2M promotes proliferation, migration, and angiogenesis of DEX-treated HUVECs and alleviates methylprednisolone-induced femoral head necrosis by improving microcirculation damages and maintaining microcirculation stability in the femoral head.

Objective To explore the mechanism underlying the protective effect of α2-macroglobulin (A2M) against glucocorticoid-induced femoral head necrosis. Methods In a human umbilical vein endothelial cell (HUVEC) model with injuries induced by gradient concentrations of dexamethasone (DEX;10-8-10-5 mol/L), the protective effects of A2M at 0.05 and 0.1 mg/mL were assessed by examining the changes in cell viability, migration, and capacity of angiogenesis using CCK-8 assay, Transwell and scratch healing assays and angiogenesis assay. The expressions of CD31 and VEGF-A proteins in the treated cells were detected using Western blotting. In BALB/c mouse models of avascular necrosis of the femoral head induced by intramuscular injections of methylprednisolone, the effects of intervention with A2M on femoral trabecular structure, histopathological characteristics, and CD31 expression were examined with Micro-CT, HE staining and immunohistochemical staining. Results In cultured HUVECs, DEX treatment significantly reduced cell viability, migration and angiogenic ability in a concentration- and time-dependent manner (P<0.05), and these changes were obviously reversed by treatment with A2M in positive correlation with A2M concentration (P<0.05). DEX significantly reduced the expression of CD31 and VEGF-A proteins in HUVECs, while treatment with A2M restored CD31 and VEGF-A expressions in the cells (P<0.05). The mouse models of femoral head necrosis showed obvious trabecular damages in the femoral head, where a large number of empty lacunae and hypertrophic fat cells could be seen and CD31 expression was significantly decreased (P<0.05). A2M treatment of the mouse models significantly improved trabecular damages, maintained normal bone tissue structures, and increased CD31 expression in the femoral head (P<0.05). Conclusion A2M promotes proliferation, migration, and angiogenesis of DEX-treated HUVECs and alleviates methylprednisolone-induced femoral head necrosis by improving microcirculation damages and maintaining microcirculation stability in the femoral head.

Objective: To conduct a scoping review on prognostic prediction models for patients with comorbidity of chronic diseases, and understand modeling methods, predictive factors and predictive effect of the models, so as to provide the reference for prognostic evaluation on patients with comorbidity of chronic diseases. Methods: Literature on prognostic prediction models for patients with comorbidity of chronic diseases was collected through SinoMed, CNKI, Wanfang Data, VIP, PubMed, Embase, Cochrane Library and Web of Science published from the time of their establishment to November 1, 2023. The quality of literature was assessed using prediction model risk of bias assessment tool (PROBAST), then modeling methods, predictive factors and predictive effects were reviewed. Results: Totally 2 130 publications were retrieved, and nine publications were finally enrolled, with an overall high risk of bias. Thirteen models were involved, with three established using machine learning methods and ten established using logistic regression. The prediction results of four models were death, with main predictive factors being age, gender, body mass index (BMI), Barthel index and pressure ulcers; the prediction results of nine models were rehospitalization, with main predictive factors being age, BMI, hospitalization frequency, duration of hospital stay and hospitalization costs. Eleven models reported the area under the receiver operating characteristic curve (AUC), ranging from 0.663 to 0.991 6; two models reported the C-index, ranging from 0.64 to 0.70. Eight models performed internal validation, one model performed external validation, and four models did not reported verification methods. Conclusions The prognostic prediction models for patients with comorbidity of chronic diseases are established by logistic regression and machine learning methods with common nursing evaluation indicators, and perform well. Laboratory indicators should be considered to add in the models to further improve the predictive effects.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

ObjectiveTo explore the brain mechanism of repetitive transcranial magnetic stimulation (rTMS) on dysfunction after stroke using functional magnetic resonance imaging (fMRI). MethodsLiteratures about the functional magnetic resonance imaging study about repetitive transcranial magnetic stimulation for dysfunction after stroke were retrieved in PubMed, Web of Science, CNKI and Wanfang data from establishment to June 1st, 2021. The quality of the literature was evaluated with Physiotherapy Evidence Database (PEDro) scale. Literature screening, and data extraction were performed by two researchers. ResultsA total of 14 randomized controlled trials were finally enrolled. They were of high or very high quality. They mainly involved the therapeutic effect and imaging mechanisms of rTMS on dysfunction after stroke. ConclusionrTMS could change the excitability of the cerebral cortex and the effective connections between brain regions after stroke, promote the reorganization of brain function, and achieve the recovery of post-stroke dysfunction.