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.

AIM To investigate the clinical effects of Modified Banxia Xiexin Decoction combined with Lizhong Decoction on patients with type 2 diabetes mellitus due to Cold-heat Complex in the Middle Energizer.METHODS One hundred and sixty-eight patients were randomly assigned into control group(84 cases)for 12-week intervention of conventional treatment,and observation group(84 cases)for 12-week intervention of Modified Banxia Xiexin Decoction,Lizhong Decoction and conventional treatment.The changes in clinical effects,compliance rate of blood glucoses,discontinuation and reduction rate of hypoglycemic drugs,continuous glucose parameters(TIR,GVP,FPG-ARV,MAGE),FPG,2 hPG,HbA1c,FINS,HOMA-β,HOMA-IR,lnISI,intestinal flora metabolites(SCFAs,CA,DC A,CDCA,CA/CDCA),score for Cold-heat Complex in the Middle Energizer and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher marked improvement rate,total effective rate,compliance rate of blood glucoses and discontinuation and reduction rate of hypoglycemic drugs,than the control group(P＜0.05).After the treatment,the two groups displayed increased TIR,FINS,HOMA-β,lnISI,SCFAs,CDCA(P＜0.05),and decreased GVP,FPG-ARV,MAGE,FPG,2 hPG,HbA1c,HOMA-IR,CA,DC A,CA/CDCA,score for Cold-heat Complex in the Middle Energizer(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with type 2 diabetes mellitus due to Cold-heat Complex in the Middle Energizer,Modified Banxia Xiexin Decoction combined with Lizhong Decoction can improve islet β cell function and insulin resistance,enhance insulin sensitivity index and compliance rate of blood glucoses,reduce blood glucose fluctuation and dosages of hypoglycemic drugs,regulate intestinal flora metabolites,and affect glucose metabolism.

Central nervous system(CNS)degenerative disorders refer to a spectrum of pathological alterations triggered by struc-tural damage to cerebral neural tissues,clinically manifested as diverse neurological dysfunction syndromes,including multiple sclerosis(MS),neurodegenerative diseases(NDs),and ische-mic stroke.The hallmark pathological features of these disorders involve irreversible neuronal damage and decompensation of functional neural networks,ultimately leading to progressive neurological deficits.Notably,with the accelerating global popu-lation aging,the incidence of these diseases has surged signifi-cantly.According to WHO statistics,they now rank among the top three global causes of disability and mortality.Current re-search has confirmed that the pathogenesis of CNS degenerative disorders exhibits high heterogeneity,encompassing multifaceted pathophysiological processes such as genetic predisposition,oxi-dative stress,protein misfolding,and metabolic dysregulation.This intricate pathogenic network not only complicates clinical differential diagnosis but also poses substantial challenges to the development of precision therapeutic strategies.Importantly,re-cent studies have revealed that mitochondrial homeostasis disrup-tion-induced inflammatory cascades(termed mitochondrial in-flammation)play a pivotal regulatory role in neurodegenerative progression.Key molecular mechanisms include impaired mito-phagy,aberrant mitochondrial DNA(mtDNA)release and NL-RP3 inflammasome activation.This review systematically deci-phers the molecular regulatory network of mitochondrial inflam-mation,with a focus on its biological effects in critical pathologi-cal events such as blood-brain barrier disruption,microglial hy-peractivation and neuronal apoptosis.The overarching aim is to provide a theoretical foundation for developing innovative thera-peutic strategies targeting mitochondrial homeostasis restoration.

Objective:To explore the application value of coronary CT angiography(CCTA)combined with serum levels of Krueppel like factor 4(KLF4)and histone deacetylase 4(HDAC4)in assessment of coronary artery steno-sis severity in patients with coronary heart disease(CHD).Methods:A total of 152 CHD patients admitted to Suzhou High tech District People's Hospital between December 2021 and December 2023 were prospectively selected.According to coronary angiography(CAG)quantitative analysis method,patients with CHD were divided into mild stenosis group(n=57),moderate stenosis group(n=49)and severe stenosis group(n=46).Kappa consistency a-nalysis was used to determine the consistency between CCTA detection and CAG in determining the degree of coro-nary stenosis.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of CCTA combined with serum KLF4 and HDAC4 levels for the degree of coronary artery stenosis.Results:Compared to pa-tients in mild stenosis group,those in moderate stenosis group and severe stenosis group had significantly lower levels of KLF4 and HDAC4(P＜0.01 all),and those in severe stenosis group had significantly lower levels of KLF4 and HDAC4 compared to those in moderate stenosis group(P＜0.01 all).According to CCTA diagnosis,there were 53 cases with mild stenosis,53 cases with moderate stenosis and 46 cases with severe stenosis.The consistency rate with CAG diagnosis was 80.92％(123/152),which was relatively high(Kappa=0.713,P＜0.001).The accuracy of CCTA in diagnosing mild,moderate and severe stenosis was 88.16％(134/152),85.53％(130/152)and 88.16％(134/152)respectively.ROC curve analysis indicated the area under the curve(AUC)of CCTA combined with ser-um KLF4 and HDAC4 in the diagnosis of moderate and severe coronary artery stenosis was 0.949(95％CI 0.901～0.978),which was significantly higher than those of CCTA(AUC=0.867,95％CI 0.802～0.916),serum KLF4(AUC=0.895,95％CI 0.825～0.939)and HDAC4(AUC=0.809,95％CI 0.738～0.869)alone(Z=2.806,P＜0.001;Z=2.065,P=0.039;Z=3.552,P＜0.001,respectively).Conclusion:In patients with coronary heart dis-ease,serum levels of KLF4 and HDAC4 are closely related to the degree of coronary artery stenosis.The combina-tion of CCTA,serum KLF4 and HDAC4 levels has good performance in predicting the degree of coronary artery stenosis.

Colorectal cancer(CRC)is a malignant tumor formed in the colon or rectum,usually caused by uncontrolled growth and division of normal cells in the body.Cell apoptosis,pyroptosis,and necroptosis are key pathways of cell death in colorectal cancer.The comprehensive treatment strategy includes the synergistic effect of cell death inducers with chemotherapy,immunotherapy,and targeted therapy.Traditional Chinese medicine plays an important role as an adjuvant therapy in regulating cell death.The combination of traditional Chinese and western medicine has shown significant effects in precancerous lesions,improving efficacy,reducing adverse reactions,and reducing drug resistance.Although the research on the mechanism of cell death is not yet sufficient,emphasizing the unique characteristics of traditional Chinese medicine,clarifying the anti-tumor mechanism of traditional Chinese medicine,and achieving modern scientific internationalization of integrated traditional Chinese and western medicine treatment for colorectal cancer have become future research directions.This article will comprehensively review the molecular mechanisms of cell apoptosis,pyroptosis,and necroptosis from the perspective of combining traditional Chinese and Western medicine,as well as their regulatory role in the treatment of colorectal cancer.

Colorectal cancer(CRC)is a malignant tumor formed in the colon or rectum,usually caused by uncontrolled growth and division of normal cells in the body.Cell apoptosis,pyroptosis,and necroptosis are key pathways of cell death in colorectal cancer.The comprehensive treatment strategy includes the synergistic effect of cell death inducers with chemotherapy,immunotherapy,and targeted therapy.Traditional Chinese medicine plays an important role as an adjuvant therapy in regulating cell death.The combination of traditional Chinese and western medicine has shown significant effects in precancerous lesions,improving efficacy,reducing adverse reactions,and reducing drug resistance.Although the research on the mechanism of cell death is not yet sufficient,emphasizing the unique characteristics of traditional Chinese medicine,clarifying the anti-tumor mechanism of traditional Chinese medicine,and achieving modern scientific internationalization of integrated traditional Chinese and western medicine treatment for colorectal cancer have become future research directions.This article will comprehensively review the molecular mechanisms of cell apoptosis,pyroptosis,and necroptosis from the perspective of combining traditional Chinese and Western medicine,as well as their regulatory role in the treatment of colorectal cancer.

Objective:To explore the application value of coronary CT angiography(CCTA)combined with serum levels of Krueppel like factor 4(KLF4)and histone deacetylase 4(HDAC4)in assessment of coronary artery steno-sis severity in patients with coronary heart disease(CHD).Methods:A total of 152 CHD patients admitted to Suzhou High tech District People's Hospital between December 2021 and December 2023 were prospectively selected.According to coronary angiography(CAG)quantitative analysis method,patients with CHD were divided into mild stenosis group(n=57),moderate stenosis group(n=49)and severe stenosis group(n=46).Kappa consistency a-nalysis was used to determine the consistency between CCTA detection and CAG in determining the degree of coro-nary stenosis.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of CCTA combined with serum KLF4 and HDAC4 levels for the degree of coronary artery stenosis.Results:Compared to pa-tients in mild stenosis group,those in moderate stenosis group and severe stenosis group had significantly lower levels of KLF4 and HDAC4(P＜0.01 all),and those in severe stenosis group had significantly lower levels of KLF4 and HDAC4 compared to those in moderate stenosis group(P＜0.01 all).According to CCTA diagnosis,there were 53 cases with mild stenosis,53 cases with moderate stenosis and 46 cases with severe stenosis.The consistency rate with CAG diagnosis was 80.92％(123/152),which was relatively high(Kappa=0.713,P＜0.001).The accuracy of CCTA in diagnosing mild,moderate and severe stenosis was 88.16％(134/152),85.53％(130/152)and 88.16％(134/152)respectively.ROC curve analysis indicated the area under the curve(AUC)of CCTA combined with ser-um KLF4 and HDAC4 in the diagnosis of moderate and severe coronary artery stenosis was 0.949(95％CI 0.901～0.978),which was significantly higher than those of CCTA(AUC=0.867,95％CI 0.802～0.916),serum KLF4(AUC=0.895,95％CI 0.825～0.939)and HDAC4(AUC=0.809,95％CI 0.738～0.869)alone(Z=2.806,P＜0.001;Z=2.065,P=0.039;Z=3.552,P＜0.001,respectively).Conclusion:In patients with coronary heart dis-ease,serum levels of KLF4 and HDAC4 are closely related to the degree of coronary artery stenosis.The combina-tion of CCTA,serum KLF4 and HDAC4 levels has good performance in predicting the degree of coronary artery stenosis.

Icaritin(ICT)is an 8-isopentenylflavonoid,which is the main effective component of the tra-ditional Chinese medicine Epimedium.Previously,we found that Icaritin inhibits the growth of glioblasto-ma(GBM)cells.Herein we aim to study the in vivo anti-GBM effectiveness of Icaritin and explore its mechanism.The results of MTT assay,flow cytometry,comet assay and cellular immunofluorescence as-say in vitro showed that ICT inhibited the proliferation of four kinds of GBM cells,U87,U251,U118 and A172,induced early apoptosis(P＜0.001)and late apoptosis(P＜0.05)in U87 cells,induced DNA damage in U87 cells,and blocked the growth of U87 cells at the G0/G1 phase(P＜0.0001)in a concen-tration-time-dependent manner.In vivo subcutaneous tumor transplantation tumor experiments showed that feeding 200 mg/kg(P＜0.01)and 400 mg/kg(P＜0.001)ICT had a significant inhibitory effect on the growth of GBM subcutaneous tumors,and had no significant toxic effects on heart,liver,spleen,lung and kidney tissues.The results of network pharmacological analysis,molecular docking and cellular thermodynamic experiments showed that there were 26 possible target proteins between ICT and GBM,a-mong which the expression of p53 in GBM tissues was significantly(P＜0.001)higher than in normal tis-sues,and the binding energy of ICT and p53 was lower;cellular thermodynamic experiments verified that ICT significantly enriched the level of p53 in the living cells of GBM,which indicated that ICT could tar-get p53.The expression of key proteins in the DNA damage repair and apoptosis-associated FOXO signa-ling pathway was detected by ICT.The results showed that the expression of ATR(P＜0.01),P53(P＜0.001),P21(P＜0.05)and γ-H2AX(P＜0.05)was up-regulated,whereas the expression of Cyc-lin E1(P＜0.01),E2F1(P＜0.05),CDK2(P＜0.01),Rb(P＜0.001),p-Rb(P＜0.0001)and WRN(P＜0.0001)expression were down-regulated.There was no significant change in the expres-sion of FOXO 1 in the FOXO pathway or a significant down-regulation of its phosphorylation level.This study demonstrated that ICT could effectively inhibit the growth of GBM cells in vivo.It targets p53 to regulate the DNA damage repair pathway and FOXO signaling pathway to induce GBM cell cycle arrest and apoptosis.

Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

Objective:To construct a medical education metaverse based on cloudytization virtual reality (VR) technique,so as to resolve various issues encountered with conventional VR devices in use process,and enhance the user's experience and teaching effect of virtual space education. Methods:The technical architecture of the medical education metaverse was conducted from the perspectives included the underlying technique layer,learning interface layer,teaching activity space and knowledge layer. The medical education mateverse,which based on cloudytization VR technique,was constructed,and the system performance and user's experience were optimized from a supporting environment included the content layer,platform layer,cloud computing layer,network layer and terminal layer. Results:The medical students could conduct practical operation in virtual environment at any time and any place by the deployment approach on cloudy terminal and lightweight devices. The efficient and convenient cross-disciplinary collaborative learning was convenient for students to acquire knowledge from multiple perspectives,to better response complex medical environments. The real-time interactive remote medical approach expanded the boundaries of medical education,and ensured equity and inclusivity in medical education. Conclusion:The application of medical education metaverse based on cloudytization VR technique in medical teaching can effectively reduce the application threshold of medical education metaverse,and expand the coverage of educational resources of high quality,and enhance the use experience of teaching of the virtual space of medical education based on VR,and meet the demands of medical teaching for diverse application scenarios.