ObjectiveTo observe the clinical efficacy of Sanren Runchang formula in treating constipation-predominant irritable bowel syndrome （IBS-C） by regulating the brain-gut axis and the effects of the formula on serum levels of 5-hydroxytryptamine （5-HT）， vasoactive intestinal peptide （VIP）， and substance P （SP）. MethodsA randomized controlled design was adopted， and 72 IBS-C patients meeting Rome Ⅳ criteria were randomized into observation and control groups （36 cases）.The observation group received Sanren Runchang formula granules twice daily， and the control group received lactulose oral solution daily for 4 weeks. IBS Symptom Severity Scale （IBS-SSS）， IBS Quality of Life Scale （IBS-QOL）， and Bristol Stool Form Scale （BSFS） were used to assess clinical symptoms， and bowel movement frequency was recorded. The Self-Rating Anxiety Scale （SAS） and Self-Rating Depression Scale （SDS） were employed to evaluate psychological status. ELISA was employed to measure the serum levels of 5-HT， VIP， and SP. ResultsThe total response rate in the observation group was 91.67% （33/36）， which was higher than that （77.78%， 28/36） in the control group （χ²=4.50， P<0.05）. After treatment， both groups showed increased defecation frequency and BSFS scores， decreased IBS-SSS total score， abdominal pain and bloating scores， IBS-QOL health anxiety， anxiety， food avoidance， and behavioral disorders scores， SAS and SDS scores， serum 5-HT and VIP levels， and increased SP levels （P<0.05， P<0.01）. Moreover， the observation group showed more significant changes in the indicators above than the control group （P<0.05， P<0.01）. The SP level showed no significant difference between the two groups. During the 4-week follow-up， the recurrence rate was 5.88% in the observation group and 31.25% in the control group. No adverse events occurred in observation group， and 2 cases of mild diarrhea occurred in the control group. ConclusionSanren Runchang formula demonstrated definitive efficacy in alleviating gastrointestinal symptoms and improving the psychological status and quality of life in IBS-C patients， with a low recurrence rate. The formula can regulate serum levels of neurotransmitters such as 5-HT and VIP， suggesting its potential regulatory effect on the brain-gut axis through modulating neurotransmitters and neuropeptides. However， its complete mechanism of action requires further investigation through detection of additional brain-gut axis-related biomarkers.

ObjectiveTaking classical herbal pair compatibility research as the entry point， this study aimed to deeply investigate the material basis and compatibility rules underlying the antidepressant effects of the traditional Chinese medicine （TCM） formula Zhizi Houpotang， and to elucidate its antidepressant mechanism， with a particular focus on its regulation of neuroinflammatory responses mediated by the NOD-like receptor protein 3 （NLRP3）/gasdermin D （GSDMD） signaling pathway and the consequent improvement of neuronal synaptic plasticity. MethodsC57BL/6J mice were randomly divided into a blank control group， a chronic unpredictable mild stress （CUMS） depression model group， a Zhizi Houpotang full-formula group （6 g·kg^-1·d^-1）， a Magnoliae Officinalis Cortex （MOC）-Aurantii Fructus Immaturus （AFI） herbal pair group （4.2 g·kg^-1·d^-1）， a Gardeniae Fructus （GF）-MOC herbal pair group （4.2 g·kg^-1·d^-1）， a GF-AFI herbal pair group （3.6 g·kg^-1·d^-1）， and a positive drug group （fluoxetine， 12 mg·kg^-1·d^-1）. Depressive-like behaviors in mice were evaluated using behavioral tests. Immunofluorescence staining was used to label and quantify the expression of the microglial marker ionized calcium-binding adaptor molecule 1 （Ibal） and the purinergic receptor P2X ligand-gated ion channel 7 （P2RX7） in the prefrontal cortex （PFC）. Enzyme-linked immunosorbent assay （ELISA） was applied to detect the levels of inflammatory cytokines interleukin-1β （IL-1β） and interleukin-18 （IL-18） in serum and PFC tissues. Western blot was employed to determine the expression of pannexin 1 （Panx1）， P2RX7， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， Caspase-1， GSDMD， postsynaptic density protein 95 （PSD95）， and the presynaptic protein Synapsin 1 in PFC tissues. Golgi staining was used to assess dendritic spine density of neurons in the PFC. ResultsCompared with the blank control group， the depression model group exhibited significant depressive-like behaviors. In addition， the immunofluorescence areas of Ibal and P2RX7 in the PFC were significantly increased （P<0.01）， the levels of IL-1β and IL-18 in serum and the PFC were significantly elevated （P<0.01）， and the protein expression levels of Panx1， P2RX7， NLRP3， ASC， Caspase-1， and GSDMD in the PFC were significantly upregulated （P<0.01）. In contrast， the protein expression levels of PSD95 and Synapsin 1 were significantly downregulated （P<0.01）， and neuronal dendritic spine density was significantly reduced （P<0.01）. Compared with the model group， the Zhizi Houpotang full-formula group and the GF-MOC herbal pair group showed significant improvement in all the above indicators （P<0.01）. The GF-AFI herbal pair group improved all the above indicators except P2RX7， Caspase-1， GSDMD， and PSD95 （P<0.05， P<0.01）. In contrast， the MOC-AFI herbal pair group showed no statistically significant improvement in any of the above indicators compared with the model group. ConclusionZhizi Houpotang and its key herbal pair， GF-MOC， can effectively ameliorate CUMS-induced depressive-like behaviors in mice. Its core antidepressant mechanism may involve inhibition of P2RX7/Panx1 signaling， thereby blocking the NLRP3/GSDMD-mediated pyroptosis pathway and significantly reducing the release of inflammatory cytokines IL-1β and IL-18. Simultaneously， it upregulates the expression of synapse-related proteins PSD95 and Synapsin 1 and increases dendritic spine density， promoting the recovery of synaptic plasticity. These results suggest that GF plays a key role in the antidepressant effects of this formula， and that the compatibility of GF with MOC may represent the principal herbal pair combination responsible for its core therapeutic action.

Abstract In order to explore the influence of different environmental endocrine disruptors (EEDs) on the onset of youth in children and adolescents, the study introduces the advance trend of the onset of youth in children and adolescents at home and abroad, and the influence of EEDs, such as bisphenol A, organophosphate esters, phthalic acid esters, per and polyfluoroalkyl substances, which children and adolescents often contact on the onset of youth. The related mechanisms are expounded from the aspects of direct interference of EEDs on neuroendocrine axis, hormone simulation and antagonism mediated by receptors, epigenetic programming changes, indirect pathways mediated by obesity and inflammation, etc., in order to provide scientific basis for formulating preventive measures for abnormal puberty onset of children and adolescents in EEDs exposure and promote their health.

ObjectiveTo explore the potential mechanism of Huoxue Xiaoyi Formula （活血消异方， HXF） in treating ovarian endometriosis （OEM） from the perspective of T follicular helper （Tfh） cells and the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway. MethodsForty-five female SD rats with normal estrous cycles were randomly divided into three groups， HXF group， model group， and normal group， with 15 rats in each group. A rat model of OEM was established by autologous endometrial tissue implantation. After successful modeling， the treatment group received HXF at 5.85 g/（kg·d） by gavage for 14 consecutive days. The model group and normal group received 1 mL/d of normal saline by gavage. RNA-sequencing data from human proliferative-phase endometriotic and normal endometrial tissues were downloaded from the GEO database. Transcriptomic sequencing was used to analyze gene expression in rat ovarian ectopic tissues and normal uterine tissues， and comparisons were made with human data to verify JAK/STAT pathway activation in proliferative-phase ectopic tissues. Immunohistochemistry was used to detect the positive expression of CXC chemokine receptor 5 （CXCR5） and interleukin-21 （IL-21） in rat ovarian ectopic and normal uterine tissues. Western Blotting was performed to detect the protein levels of IL-21， IL-21 receptor （IL-21R）， Janus kinase 1 （JAK1）， signal transducer and activator of transcription 6 （STAT6）， and B-cell lymphoma 2 （Bcl-2）. Tfh cell infiltration was analyzed using immune cell infiltration methods. ResultsGene set enrichment analysis showed that the JAK/STAT pathway was significantly activated in human proliferative-phase endometriotic tissues compared to normal endometrial tissues. Similarly， the JAK/STAT pathway was markedly activated in rat ovarian ectopic tissues in the model group compared to the normal group， but suppressed in the HXF group compared to the model group. Compared with normal uterine tissues， ovarian ectopic tissues in the model group showed increased Tfh cell infiltration scores， higher CXCR5 and IL-21 expression， and elevated levels of IL-21， IL-21R， JAK1， STAT6， and Bcl-2 proteins. Compared with the model group， HXF group showed reduced CXCR5 and IL-21 expression and decreased protein levels of IL-21， IL-21R， JAK1， STAT6， and Bcl-2. ConclusionHXF may suppress activation of the JAK/STAT signaling pathway in ovarian endometriotic tissues by inhibiting IL-21 secretion from Tfh cells.

Objective: To explore the causal relationship between gut microbiota and upper urinary tract stones using Mendelian randomization (MR) analysis，and to investigate the potential mediating role of plasma metabolites. Methods: Data on gut microbiota，plasma metabolites，and upper urinary tract stones were obtained from publicly available Genome-wide Association Studies (GWAS).Bidirectional MR analysis was performed to examine the causal relationship between gut microbiota and upper urinary tract stones.Subsequently，a two-step MR approach was employed to determine whether gut microbiota contribute to upper urinary tract stones through plasma metabolites，and the mediating effects and mediator ratio were calculated.The inverse variance weighted (IVW) method was used as the primary analytical tool，supplemented by Bayesian weighted Mendelian randomization (BWMR)，MR-Egger，and weighted median (WM) analyses.Horizontal pleiotropy and heterogeneity tests were conducted to ensure the robustness of the findings. Results: Bidirectional MR analysis identified causal associations between 7 gut microbial taxa and 6 microbial metabolic pathways with upper urinary tract stones，while the development of upper urinary tract stones affected 13 gut microbial taxa and 5 metabolic pathways.Additionally，43 plasma metabolites (including 27 identified metabolites，8 unidentified metabolites，and 8 metabolite ratios) were causally associated with upper urinary tract stones.The two-step MR analysis identified 11 potential causal pathways.After metabolic pathways and unidentified metabolites were excluded，a causal link mediated by Bacteroides faecis between galactarate and upper urinary tract stones was confirmed，with a mediation proportion of 16.99% (95%CI：5.76%-33.95%，P=0.0371). Conclusion: This study establishes a causal relationship between parabacteroides and upper urinary tract stones，and elucidates the mediating role of galactarate，offering new insights into the pathogenesis and prevention strategies for upper urinary tract stones.

Abstract Modern western medicine typically focuses on treating specific symptoms or diseases, and traditional Chinese medicine (TCM) emphasizes the interconnections of the body’s various systems under external environment and takes a holistic approach to preventing and treating diseases. Phenomics was initially introduced to the field of TCM in 2008 as a new discipline that studies the laws of integrated and dynamic changes of human clinical phenomes under the scope of the theories and practices of TCM based on phenomics. While TCM Phenomics 1.0 has initially established a clinical phenomic system centered on Zhenghou (a TCM definition of clinical phenome), bottlenecks remain in data standardization, mechanistic interpretation, and precision intervention. Here, we systematically elaborates on the theoretical foundations, technical pathways, and future challenges of integrating digital medicine with TCM phenomics under the framework of “TCM phenomics 2.0”, which is supported by digital medicine technologies such as artificial intelligence, wearable devices, medical digital twins, and multi-omics integration. This framework aims to construct a closed-loop system of “Zhenghou–Phenome–Mechanism–Intervention” and to enable the digitization, standardization, and precision of disease diagnosis and treatment. The integration of digital medicine and TCM phenomics not only promotes the modernization and scientific transformation of TCM theory and practice but also offers new paradigms for precision medicine. In practice, digital tools facilitate multi-source clinical data acquisition and standardization, while AI and big data algorithms help reveal the correlations between clinical Zhenghou phenomes and molecular mechanisms, thereby improving scientific rigor in diagnosis, efficacy evaluation, and personalized intervention. Nevertheless, challenges persist, including data quality and standardization issues, shortage of interdisciplinary talents, and insufficiency of ethical and legal regulations. Future development requires establishing national data-sharing platforms, strengthening international collaboration, fostering interdisciplinary professionals, and improving ethical and legal frameworks. Ultimately, this approach seeks to build a new disease identification and classification system centered on phenomes and to achieve the inheritance, innovation, and modernization of TCM diagnostic and therapeutic patterns.

Vascular aging (VA) is a common etiology of various chronic diseases and represents a major public health concern. Intermittent hypoxia (IH) associated with obstructive sleep apnea-hypopnea syndrome (OSAHS) is a primary pathological and physiological driver of OSAHS-induced systemic complications. A substantial proportion of OSAHS patients, estimated to be between 40% and 80%, have comorbidities such as hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, aneurysm, and stroke, all of which are closely associated with VA. This review examines the molecular and cellular features common to both OSAHS and VA, highlighting decreased melatonin secretion, impaired autophagy, increased apoptosis, increased inflammation and pyroptosis, increased oxidative stress, accelerated telomere shortening, accelerated stem cell depletion, metabolic disorders, imbalanced protein homeostasis, epigenetic alterations, and dysregulated neurohormonal signaling. The accumulation and combination of these features may underlie the pathophysiological link between OSAHS and VA, but the exact mechanisms by which OSAHS affects VA may require further investigation. Taken together, these findings suggest that OSAHS may serve as a novel risk factor for VA and related vascular disorders, and that targeting these features may offer therapeutic potential to mitigate the vascular risks associated with OSAHS.
Humans ; Sleep Apnea, Obstructive/pathology* ; Aging/physiology* ; Oxidative Stress/physiology* ; Animals

BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*