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 investigate the role and mechanism of inflammatory marker C5a in regulating the polarization of M2 macro-phages as well as its clinical application value in the prognosis evaluation of lung cancer.Methods The phorbol 12-myristate 13-ace-tate(PMA)-pulsed human monocytic leukemia cell line THP-1 was stimulated with C5a for 0,6,12,24,and 48 h or 0,1,2,3,6,and 12 h,and then the expression levels of M2 markers CD163 and CD206 mRNA were determined by real-time fluorescence quantita-tive PCR(qRT-PCR).The expression level of general control non-repressed protein 5(GCN5)with histone acetyltransferase(HAT)activity was detected by Western blot.Co-immunoprecipitation(co-IP)was used to determine the acetylation of GATA binding protein 3(GATA3),a key transcription factor for macrophages,and its binding ability to GCN5 and E1A binding protein p300(Ep300/p300).After the macrophages pre-treated with GCN5 inhibitor butyrolactone 3(MB-3)were stimulated with C5a,the expression levels of CD163 and CD206,acetylation of GATA3,and its binding ability to GCN5 were determined by Western blot and co-IP.The clinical significance of the expression of C5a receptor 1(C5aR1)and GCN5 in lung cancer tissues in the prognosis of lung cancer patients was analyzed using the KM plotter database.Results C5a could significantly increase the expression levels of CD163 and CD206 mRNA,expression of GCN5,acetylation of GATA3,and its binding ability to GCN5 in PMA-induced adherent macrophages,but did not affect the binding of GATA3 to p300.Inhibiting the activity of GCN5 not only significantly reduced the acetylation of GATA3 and its binding ability to GCN5,but also down-regulated the expressions of CD163 and CD206.The overall survival rate of lung cancer patients with high expression of C5aR1 or GCN5 was significantly reduced.Conclusion C5a promotes the polarization of M2 macrophages by indu-cing GCN5 to acetylate GATA3.The expressions of C5aR1 and GCN5 in lung cancer tissues may have certain clinical application value for the prognosis of the patients.

AIM To investigate the protective effects of Shuangyi Qushi Tongluo Capsules(Shuangyi Capsules)on Dexamethasone(Dex)induced osteoporosis in mice.METHODS The C57BL/6J mice were randomly divided into the control group,the model group,the Xianling Gubao Capsules group(1.5 g/kg),and the low-dose,moderate-dose,and high-dose Shuangyi Capsules groups(0.6,1.2,and 2.4 g/kg).The mouse model of osteoporosis was induced by 8-week intraperitoneal injection of Dex sodium phosphate injection(5 mg/kg).The mice had their femur osteogenesis observed with hematoxylin and eosin(HE)staining and tartrate-resistant acid phosphatase(TRAP)staining;their serum alkaline phosphatase(ALP)and osteocalcin(BGP)activities detected by ELISA;their femoral mRNA expressions of Col-Ⅰ,OCN,and OPN detected by RT-qPCR;and their femoral protein expressions of OPG and RANKL detected by Western blot.Upon the MC3T3-E1 cells exposed to Dex and Shuangyi Capsules,their viability was evaluated by CCK-8 assay;their mineralization determined by alkaline phosphatase staining and alizarin red staining(ARS);and their intracellular ROS level detected using DCFH-DA probe.RESULTS Compared with the model group,Shuangyi Capsules groups demonstrated improved fracture of femoral trabeculae and reduced number of osteoclasts;increased serum ALP and BGP activities(P＜0.05,P＜0.01);increased femoral expressions of Col-Ⅰ mRNA and OPG protein(P＜0.05,P＜0.01);and decreased RANKL protein expression(P＜0.05).Compared with the MC3T3-E1 cells stimulated by Dex,those underwent further treatment of Shuangyi Capsules demonstrated increased cell viability and ALP activity(P＜0.05,P＜0.01);increased mineralization and calcium nodule formation;increased expressions of Col-Ⅰ,OCN,OPN mRNA and OPG protein(P＜0.05,P＜0.01);decreased RANKL protein expression(P＜0.05,P＜0.01);and reduced ROS levels.CONCLUSION Shuangyi Capsules ameliorate Dex-induced osteoporosis in mice by suppressing osteoclast overactivation,enhancing osteoblast activity,and stimulating bone formation through modulation of Col-Ⅰ,OCN,OPN mRNA and OPG/RANKL protein levels.

Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P＜0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P＜0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P＜0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P＜0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.

Objective:To evaluate the clinical predictive value of SPECT myocardial perfusion imaging (MPI) in the occurrence of cardiac death in patients with chronic kidney disease (CKD).Methods:A retrospective follow-up was performed for 160 patients (109 males, 51 females; age: 68.5(61.0, 74.0) years) who underwent MPI in Beijing Anzhen Hospital, Capital Medical University between June 2017 and March 2024. The 17-segment 5-point method was used for image analysis to obtain the left ventricular myocardial perfusion and functional parameters. The patients were followed up for cardiac death, and divided into death group and survival group. Clinical data of those 2 groups were compare by χ2 test, the independent-sample t test or Mann-Whitney U test. Cox proportional hazards regression analysis was used to analyze the predictors related to cardiac death. The ROC curve was used to analyze the performance of predictors. Survival curves were obtained by the Kaplan-Meier method, and log-rank test was performed to compare the difference between 2 groups. Results:The follow-up time of 160 patients with CKD was 26.0(10.0, 46.5) months. Of 160 patients, 17 died and 143 survived. There were statistically significant differences in body mass index (BMI), previous myocardial infarction, previous revascularization, hypersensitive C-reactive protein (hs-CRP), positive MPI, left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS) between the death group and the survival group ( χ2 values: 4.58-16.13, t values: -2.34, -3.97, Z values: from -2.81 to 5.02, all P<0.05). Multivariate Cox regression analysis showed that SSS (hazard ratio ( HR)=1.153, 95% CI: 1.062-1.252, P=0.001) and hs-CRP ( HR=1.031, 95% CI: 1.004-1.058, P=0.023) were independent risk factors for cardiac death in patients with CKD. The optimal cut-off value of SSS for predicting cardiac death in those patients was determined to be 8 with the AUC of 0.815, and the incidence of cardiac death in the SSS ≥8 group was significantly higher than that in the SSS<8 group (33.3%(12/36) vs 4.0%(5/124); χ2 = 25.44, P<0.001). Conclusion:MPI is an important imaging method for the evaluation of cardiac death in patients with CKD, SSS and hs-CRP are important risk factors in predicting cardiac death in those patients.

Prostate cancer is one of the most common male urological malignancies,in which bone metastasis of desmo-plasia-resistant prostate cancer is an important stage in the progression of the disease,which seriously affects the quality of life and survival of patients.With the development of nuclide therapy technology in recent years,223-Ra,as a new type of alpha-targeted therapy,has shown good efficacy in the treatment of desmoplasia-resistant prostate cancer bone metastasis.The purpose of this pa-per is to review the characteristics,mechanism of action,treatment,and the main research results of its treatment of desmoplasia-resistant prostate cancer bone metastasis,and provide a comprehensive review of the clinical application of 223-Ra in the treatment of desmoplasia-resistant prostate cancer bone metastasis for the clinical application of 223-Ra in prostate cancer bone metastasis.

Objective This study aims to investigate the epidemiological characteristics of mental disorders in a rural town of Huazhou City,Guangdong Province,and explore their association with the rural revitalization strategy,so as to provide evidence for policy formulation.Methods A combination of questionnaire surveys and in-depth interviews was used to collect in-formation on the demographic characteristics,disease status,economic conditions,and policy awareness of registered mental dis-order patients in the town.Semi-structured interviews were also conducted with local doctors and village committee members.Da-ta were analyzed using descriptive statistics and logistic regression models to assess the impact of awareness of rural revitalization policies on patients'income.Results The average age of the study subjects was 47.71 years,with an average disease duration of 18.38 years.A total of 86.36％of patients had a family history of mental disorders.After onset,42.11％of patients had an annual income≥￥ 10 000,which was an increase compared to pre-illness levels,but 60.75％had completely lost their ability to work.Awareness of rural revitalization policies was low(only 18.29％were fully aware),but policy awareness was significant-ly associated with increased patient income(OR=18.03,P＜0.001).Additionally,medical expenditures were significantly higher among female patients than male patients(P＜0.001).Conclusion In a town in Huazhou City,Guangdong Province,60.75％of mental disorder patients have completely lost their ability to work,while 42.11％have an annual income exceeding ￥ 10,000.Income is positively correlated with policy awareness(OR=18.03).It is recommended to strengthen policy promo-tion,optimize the allocation of medical resources,and develop specialized assistance programs to promote the coordinated devel-opment of mental health and rural revitalization.

Toxin-antitoxin(TA)systems serve as central hubs of bacterial adaptive regulation and play critical roles in the pathogenesis of Mycobacterium tuberculosis(M.tb)and Bordetella pertussis(B.per-tussis).This review summarizes the functional evolution and therapeutic potential of TA systems in M.tb and B.pertussis.It systematically outlines the molecular mechanisms and pathogenic functions of TA sys-tems in these two pathogens.M.tb relies on type Ⅱ TA systems(e.g.,VapBC,MazEF)to drive persis-ter formation and antibiotic tolerance through toxin-mediated ribonuclease activity that cleaves host nucle-ic acids or DarT/DarG-mediated DNA modification.In contrast,B.pertussis utilizes a unique tempera-ture-sensing PhtA/PhtB system to release adenylate cyclase toxin,which targets the host cAMP signaling pathway to achieve immune evasion.Both pathogens employ TA toxins to suppress host defenses-such as VapC cleaving tRNA and RelE degrading NF-κB components.Their high-frequency mutation sites(e.g.,the VapC47-Ser46Leu mutation frequency＞50 000 in M.tuberculosis)reveal strong positive selec-tion pressure,closely associated with persister phenotypes and virulence evolution.This review further discusses therapeutic strategies,including small-molecule inhibitors targeting toxin-antitoxin interactions,TA-deletion attenuated vaccines,and antitoxin-based immunization approaches.Finally,it highlights the need for future research to elucidate TA-host interaction networks and develop nanocarrier delivery tech-nologies to advance breakthroughs in precision therapy for tuberculosis and pertussis.

Objective:To evaluate the anti-reflux effect of digestive tract reconstruction using esophageal-tubular gastric asymmetric anastomosis after radical resection of esophageal and esophagogastric junction cancer.Methods:The main steps were as follows:(1)oblique incision of the lower esophagus;(2)curved incision of the tubular anterior gastric wall;(3)the lower end of the esophagus was anastomosed to the tubular gastric incision with a 90-degree torsion; (4)The anterior wall of the anastomosis was reinforced with a transverse-inverted suture,the posterior wall with a folded suture,and the corners of the gastric stump were buried with sutures.The anastomosis operation time,postoperative complications and postoperative hospital stay were recorded;the reconstructed structure and anti-reflux effect of the anastomosis were observed by digestive tract radiography,gastroscopy and follow-up investigation.Results:The Department of Gastrointestinal and Thoracic Surgery of Huaian First People's Hospital, affiliated to Nanjing Medical University, treated 5 patients of esophagogastric junction cancer and 20 esophageal cancer cases between August 2022 and November 2024, including 19 men and 6 women, with a mean age of (66.7±7.4) years. The mean anastomosis time was (35.4±5.9) minutes, the intraoperative blood loss was (117.6±33.4) ml and the mean postoperative hospital stay was(16.6±5.2) days, with no complications such as anastomotic leakage and bleeding. Postoperative digestive tract radiography (Trendelenburg position)showed that all the patients had no contrast reflux,gastroscopy showed no signs of reflux esophagitis and bile reflux gastritis, the anastomosis showed an inverted whiskers valve-like structure. The median follow-up time was (16.8±6.3) months, and all patients had no reflux symptoms such as acid reflux and belching,and no acid suppressive medication was needed.Conclusion:The esophageal-tubular gastric asymmetric anastomosis is a safe and effective antireflux reconstruction technique.

Objective By simulating the etiology of abnormal uterine bleeding-ovulatory dysfunction(AUB-O)and establishing a rat model of abnormal uterine bleeding(AUB),this study aims to provide an experimental platform for investigating pathological mechanisms and developing therapeutic drugs for AUB.Methods After acclimation,24 adult(10-week-old)female SD rats were randomly divided into a normal control group(6 rats)and a model group(18 rats).The normal control group was housed in a barrier environment,while the model group underwent bilateral ovariectomy via dorsal approach in the same environment and rested for one week before starting to receive modeling drugs.In the model group,from Days 1 to 3 of modeling,each rat received a daily subcutaneous injection of 0.5 mg estradiol into the dorsal region.From Days 4 to 7,a daily subcutaneous injection of 5.0 mg progesterone was administered.On Day 6,rats received bilateral injections of 0.5 mL soybean oil per uterine cavity(total 1.0 mL)via the same dorsal surgical incision.On Day 8,mifepristone(10 mg/kg)was administered via oral gavage.The estrous cycle stage and its dynamic changes were continuously monitored during modeling.Uterine bleeding was recorded during the 48-hour observation period post-modeling.Serum and uterine tissue samples were collected from the model group at 0,12,24,36,and 48 h after mifepristone administration,while the normal control group was sampled at 36 h.The samples were subjected to HE staining,serum sex hormone ELISA,immunohistochemistry,TUNEL apoptosis staining,Western blotting,transcriptome sequencing,and bioinformatics analysis for comprehensive evaluation of the AUB rat model.Results The AUB rats exhibited uterine bleeding,endometrial detachment and injury,incomplete uterine restoration,inflammatory cell infiltration in the endometrium,enhanced tissue apoptosis,and structural damage of the stroma,glands,and vasculature.Compared with the normal control group,the levels of serum follicle-stimulating hormone(FSH),estradiol,and luteinizing hormone(LH)were significantly increased in the AUB rats(P＜0.05).The vascular density of the endometrium was significantly reduced(P＜0.05).The expression of vascular endothelial growth factor(VEGF)was qualitatively observed to be markedly enhanced at the site of endometrial detachment but significantly decreased around the stromal blood vessels(P＜0.01).Matrix metalloproteinase-9(MMP-9)expression was qualitatively observed to be strongly upregulated at the site of endometrial injury but significantly reduced in the non-detached stroma and glands(P＜0.01).Endometrial stromal cell apoptosis was significantly enhanced(P＜0.01).The expression levels of fibroblast growth factor 2(FGF2)and endothelin-1(ET-1)in uterine tissues were significantly decreased(P＜0.05).After comparing the transcriptome sequencing results of uterine tissues between AUB and normal rats,a total of 4 723 differentially expressed genes were identified,including 2 191 up-regulated genes and 2 532 down-regulated genes.KEGG enrichment analysis revealed that these differentially expressed genes were significantly enriched in pathways related to inflammation,immune apoptosis,cell signal transduction,proliferation and differentiation,and muscle contraction,among others.Conclusion An AUB rat model can be successfully established using a sequential administration protocol of estrogen,progesterone,and mifepristone to simulate the etiology of AUB-O.In this model,endometrial injury is associated with inflammation and apoptosis,with pathological manifestations influenced by abnormal vasoconstriction and impaired endometrial regeneration.This rat model closely recapitulates pathological characteristics of non-structural AUB observed in clinical practice,making it a validated experimental platform for exploring the pathological mechanisms and therapeutic interventions of non-structural AUB.