Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

Objective: To define the mechanism by which swine TRIM25 restricts vesicular stomatitis virus replication. Methods: Porcine 3D4/21 cells with TRIM25 overexpression or knockdown were infected with vesicular stomatitis virus. Viral replication was quantified by immunoblotting, quantitative reverse transcription polymerase chain reaction, and 50% tissue culture infectious dose assays. Type I interferon signaling was assessed by transcript quantification, interferon-beta and interferon-stimulated response element reporter assays, and co-immunoprecipitation.Viral RNA binding was tested by RNA immunoprecipitation. Results: TRIM25 overexpression reduced viral RNA and infectious titers, whereas TRIM25 knockdown increased replication (p < 0.01). TRIM25 increased interferon-beta and interferon-stimulated gene expression and enhanced interferon-beta and interferonstimulated response element promoter activity (p < 0.01). Mechanistically, TRIM25 promoted Lys63-linked ubiquitination of RIG-I and increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3. TRIM25 also bound vesicular stomatitis virus genomic RNA, and binding required the C-terminal region. Conclusions and Relevance: Porcine TRIM25 restricts vesicular stomatitis virus replication by amplifying type I interferon signaling and directly binding viral RNA.

Objective To systematically evaluate the efficacy and safety of traditional Chinese medicine (TCM) compound in treating pulmonary nodules, providing evidence-based medical evidence for TCM intervention in pulmonary nodules. Methods Computer search of PubMed, CNKI, Wanfang, VIP, and SinoMed was conducted to select randomized controlled trials (RCTs) of TCM compound intervention in pulmonary nodules, with the retrieval time from the inception to November 29, 2023. The Cochrane bias risk assessment tool was used to evaluate the quality of the included studies, and Review Manager 5.4 was used for Meta-analysis. Results A total of 18 RCTs were included, covering 8 provinces across the country, with a total sample size of 1301 patients. The TCM compounds used in the included studies all incorporated the method of dissolving phlegm and dissipating nodules. There was a high risk of bias uncertainty in the included studies. Meta-analysis results suggested that TCM compound could significantly reduce the diameter of pulmonary nodules [MD=−1.41, 95%CI (−1.70, −1.13), P<0.001], decrease the number of nodules [MD=−0.37, 95%CI (−0.73, −0.01), P=0.05], alleviate clinical symptoms [MD=−4.84, 95%CI (−6.04, −3.64), P<0.001], and improve lung function [forced expiratory volume in one second (FEV1), MD=0.55, 95%CI (0.09, 1.01), P=0.02; FEV1/forced vital capacity, MD=6.12, 95%CI (4.47, 7.78), P<0.001]. However, there was no statistically significant difference in the probability of malignancy between the experimental group and the control group [MD=−0.01, 95%CI (−0.01, 0.00), P=0.09]. Conclusion TCM compound can significantly reduce the diameter of pulmonary nodules, decrease the number of nodules, alleviate clinical symptoms, and improve lung function, but future multicenter, large-sample, high-quality RCTs are still needed to further explore and verify this conclusion.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

Objective To explore the short-term efficacy of endoscopic submucosal dissection (ESD) in the treatment of early carcinoma in the remnant stomach. Methods A retrospective study was conducted on 45 patients with early residual gastric cancer underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2014 to April 2024, with a total of 45 lesions. The patients were divided into an anastomotic group (n=15) and a non-anastomotic group (n=30) based on the location of tumor occurrence, and their clinical data, endoscopic diagnosis and treatment, and histopathological conditions were compared between the two groups. Results All 45 patients had lesions with redness and erosion. There were 9 cases of poor lifting of submucosal injection in the anastomotic group and 2 cases in the non-anastomotic group, respectively, and the difference was statistically significant (P<0.05). ESD surgery was performed on 13 lesions in the anastomotic group and 28 lesions in the non-anastomotic group, with surgery times of 80.00 (50.00, 100.00) min and 55.00 (43.75, 80.00) min, respectively. The difference in surgery time between the two groups was statistically significant (P=0.03). Among the 45 patients, ESD surgery achieved curative resection in 35 cases, including 11 cases in the anastomotic group and 24 cases in the non-anastomotic group, with no statistically significant difference. Conclusions Careful preoperative evaluation of early carcinoma in the remnant stomach is essential to prevent oversight. Lesions at anastomotic sites and suture lines present higher technical challenges for complete resection. ESD is safe and effective, with auxiliary traction technique available when necessary.

Objective To explore the effectiveness of drawing-based method in medical courses and their impact on students' learning habits,academic performance,and comprehensive competencies,in order to meet the demand for high-quality,interdisciplinary,and innovative talent,and provide theoretical support for integrating aesthetic education into medical training.Methods A questionnaire survey was conducted among medical students(n=310)at Dalian Medical University,covering the frequency of using drawing method and their effects on learning outcomes,innovation ability,and humanistic qualities.Data were analyzed using the Chi-square test and Fisher's exact test(P＜0.05).Results Totally 93.6％of students approved of using drawing method for learning medical courses,with 70.8％having developed a habit of drawing-based learning.Students with stronger drawing skills were more inclined to use drawing method and supported their application in teaching.The frequency of drawing-based learning was positively correlated with anatomy scores(P＜0.05).Students generally agreed that drawing method enhanced knowledge comprehension,learning interest,long-term memory,innovation ability,critical thinking,and humanistic qualities.However,students with weaker drawing skills perceived drawing method as potentially increasing learning burdens and being less efficient,but this perception significantly decreased with increased drawing frequency(P＜0.05).Conclusion Drawing methods are widely used in medical courses and effectively improve learning outcomes and comprehensive competencies.Drawing proficiency and frequency are key factors influencing students' acceptance and learning effectiveness.Future efforts should focus on promoting drawing method,strengthening students' drawing skills,and optimizing learning processes to deepen the integration of aesthetic education in medical training.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

BACKGROUND: Spinal cord injury (SCI) survivors often experience constipation, which contributes to a reduced sense of well-being and a lower quality of life. Acupressure offers a non-pharmacological and non-invasive alternative therapy for treating constipation. OBJECTIVE: This study examined the effects of home-based acupressure on constipation and subjective well-being among SCI survivors. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This randomized controlled trial randomly assigned 80 adults from Hong Kong with SCI to two study groups. Using a video demonstration filmed by a registered traditional Chinese medicine practitioner, the intervention group performed home-based acupressure (self-administered or caregiver-assisted) twice daily, 15 min/session, for 10 consecutive days. The control group performed manual light touching of the abdomen with the same frequency and duration as the intervention group. Both groups received defecation education through a structured booklet. MAIN OUTCOMES MEASURES: The primary outcome was constipation severity. Secondary outcomes included bowel habits, psychological well-being, and quality of life. Focus group interviews were conducted after the intervention to collect subjective feedback from participants. RESULTS: Significant group-by-time interaction effects on constipation severity (P = 0.005) and quality of life (P = 0.001) revealed that home-based acupressure produced better results than the control. These treatment effects persisted at the one-month follow-up and continued to have a large effect size (Cohen's d > 0.8). Compared to the control group, the acupressure group also had improvements in anxiety (Cohen's d = 0.69) and depression (Cohen's d = 0.72) at the end of the intervention period. Three qualitative categories were identified from the focus group interviews: improvements in bowel function and management; reduced psychological distress following relief from constipation; and acceptability of home-based acupressure. CONCLUSION: Acupressure effectively relieves constipation, enhances psychological well-being, and improves quality of life in people with SCI. These data provide novel evidence supporting the use of home-based acupressure as an acceptable and effective therapy for treating constipation after SCI. TRIAL REGISTRATION ClinicalTrials.gov (NCT05558657). Please cite this article as: Li MQ, Li Y, Lam W, Yeung WF, Ho YS, Li JY, Sun TC, Yuen S, Hu YL, Yorke J. Home-based acupressure for managing constipation and subjective well-being in spinal cord injury survivors: A randomized controlled trial. J Integr Med. 2025; 23(6):660-669.
Humans ; Acupressure/methods* ; Constipation/psychology* ; Male ; Female ; Spinal Cord Injuries/complications* ; Middle Aged ; Adult ; Quality of Life ; Aged