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.

Syringa pinnatifolia, belonging to the family Oleaceae, is a species endemic to China. It is predominantly distributed in the Helan Mountains region of Inner Mongolia and Ningxia of China. The peeled roots, stems, and thick branches have been used as a distinctive Mongolian medicinal material known as "Shan-chen-xiang", which has effects such as suppressing "khii", clearing heat, and relieving pain and is employed for the treatment of cardiovascular and pulmonary diseases and joint pain. Over the past five years, significant increase was achieved in research on chemical constituents and pharmacological effects. There were a total of 130 new constituents reported, covering sesquiterpenoids, lignans, and alkaloids. Its effects of anti-myocardial ischemia, anti-cerebral ischemia/reperfusion, sedation, and analgesia were revealed, and the mechanisms of agarwood formation were also investigated. To better understand its medical value and potential of clinical application, this review updates the research progress in recent five years focusing on the chemical constituents and pharmacological effects of S. pinnatifolia, providing reference for subsequent research on active ingredient and support for its innovative application in modern medicine system.
Medicine, Mongolian Traditional ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Syringa/chemistry*

Objective:To explore the clinicopathological features of rectal neuroendocrine tumor (R-NET) G2, identify prognostic factors, and summarize treatment experience.Methods:The clinical data of patients diagnosed with R-NET G2 by pathological diagnosis admitted to Cancer Hospital of the Chinese Academy of Medical Sciences from January 2003 to September 2023 were retrospectively analyzed. The Fisher's exact test and Kaplan-Meier curves were performed to analyze the association between pathological features and prognosis.Results:A total of 22 patients were enrolled in this study and 21 patients were followed up for a period of 6-98 months with a median follow-up time of 42 months. 5 patients died due to tumor progression during the follow-up period. The 1-, 3-, and 5-year cancer-specific survival (CSS) of the whole group were 100.0%, 92.9%, and 69.6%, respectively. Of the 22 patients, 20 underwent surgical treatment, of which 15 underwent postoperative adjuvant therapy; 2 underwent medical treatment for liver and bone multiple metastases. The 5-year survival rates of patients with tumours ≥2 cm in length, T2-3 stage, lymph node metastasis, and distant metastasis (57.1%, 68.8%, 66.7%, and 63.6%, respectively) were shorter than those of patients with tumours <2 cm in length, T1 stage, no lymph node metastasis, and no distant metastasis (all 100.0%, P＜0.001). In addition, patients with liver metastases had larger primary tumor diameters and higher T-stages compared with those without distant metastasis ( P＜0.05). Conclusions:R-NET G2 has a high degree of malignancy compared with G1 and a high propensity for metastasis. Clinicians should formulate appropriate diagnostic and treatment strategies based on factors such as tumor size, depth of invasion, lymph node status, presence of distant metastasis, and the location and extent of distant metastasis.

Objective To explore the application value of serum cystatin C(CysC)and cluster of differentiation 147(CD147)in predicting restenosis after intracranial artery stenosis stenting(ICASS)in patients with acute ischemic stroke(AIS).Methods A total of 151 AIS patients who received ICASS were selected as the study group,and 112 healthy individuals who underwent physical examinations during the same period were chosen as the control group.The study group was further divided into the restenosis group(30 cases)and the non-stenosis group(121 cases)based on the restenosis status within 6 months after ICASS.The serum CysC levels of the subjects were detected by immunoturbidimetry,and the serum CD147 levels were measured by enzyme-linked immunosorbent assay.Multivariate Logistic regression analysis was conducted to identify factors influencing restenosis after ICASS in AIS patients.The receiver operating characteristic(ROC)curve was used to evaluate the application efficacy of serum CysC and CD147 levels in predicting restenosis after ICASS in AIS patients.Results Serum levels of CysC and CD147 were higher in the study group than those in the control group(P＜0.01).The proportion of patients with stenosis degree>75%and serum levels of CysC and CD147 were higher in the restenosis group than those in the non-stenosis group(P＜0.01).The degree of stenosis>75%and the increased serum levels of CysC and CD147 were risk factors for restenosis after ICASS in AIS patients(P＜0.01).ROC curve analysis showed that serum CysC and CD147 levels independently predicted the AUC of AIS patients with restenosis after ICASS were 0.845 and 0.850,respectively,and the combined predicted AUC was 0.942.The combined prediction efficiency was significantly better than that of single indicator prediction(P＜0.05).Conclusion The increased levels of serum CysC and CD147 in AIS patients are risk factors for restenosis after ICASS,and the combination of the two is more effective in predicting intracranial artery restenosis after ICASS in AIS patients.

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

Objectives:To describe the use of antihypertensive, antidiabetic and lipid-lowering drugs, and evaluate the effects on blood pressure, blood glucose and blood lipids controls required by Chinese Guideline on the Primary Prevention of Cardiovascular Diseases (the guideline) in a community-based cohort of individuals at high risk for cardiovascular disease. To analyze the association of the uses of antihypertensive, antidiabetic and lipid-lowering drugs, and the comprehensive control of blood pressure, blood glucose and blood lipids with cardiovascular disease. Methods:From the CHinese Electronic health Records Research in Yinzhou (CHERRY), those who were at high risk for cardiovascular disease and aged 40-75 years as of January 1, 2013 in in Yinzhou District of Ningbo, Zhejiang Province were selected as study subjects. The information about their antihypertensive, antidiabetic, and lipid-lowering drug uses between 2013 and 2015 was collected, and blood pressure, blood glucose, and blood lipid measurements were conducted during the follow-up. The study constructed two kinds of comprehensive scores: the comprehensive medication score based on the guideline requirement for the treatment of hypertension, diabetes and hyperlipidemia, dividing the study participants into the compliancy group and non-compliancy group; and the comprehensive control score based on the guideline requirement for blood pressure, blood glucose, and blood lipids control, dividing the study participants into better control group, moderate control group, and poor control group. Cox proportional hazards regression model was used to analyze the association of the comprehensive medication score and comprehensive control score with cardiovascular disease. The incidence data of cardiovascular disease were collected from January 1, 2015 (baseline time) to August 31, 2020 (follow up end time).Results:A total of 79 734 participants at high risk for cardiovascular disease were included in the study, in whom 68.4%, 27.4%, and 4.2% had 1, 2, or 3 cardiometabolic conditions (hypertension, diabetes, or hyperlipidemia), respectively. In the participants with hypertension, diabetes, and hyperlipidemia from 2013 to 2015, the proportions of those who had two years of medication compliancy records were 66.0%, 67.4%, and 13.9%, respectively. In the hypertension patients, 59.2% had better blood pressure control, in the diabetes patients, 28.7% had better blood glucose control, and in the patients with hyperlipidemia, 27.4% had better blood lipid control. After a median follow-up of 5.66 years, 4 088 cardiovascular disease cases or deaths occurred. After multivariate adjustment, compared with the non-compliancy group, the compliancy group had lower risk for cardiovascular disease ( HR=0.91, 95% CI: 0.85-0.96). Compared with the better control group, the poor control group had an increased risk for cardiovascular disease ( HR=1.67, 95% CI: 1.53-1.81). In the moderate control group, the risk increased significantly in the diabetes patients ( HR=1.29, 95% CI: 1.07-1.56), while no additional risk for cardiovascular disease was observed in non-diabetes patients ( HR=1.06, 95% CI: 0.97-1.16). Conclusions:Compliancy to the medication required by the guideline is associated with lower risk for cardiovascular disease. However, it is still necessary to improve the medication compliancy in people at high risk in primary prevention, especially in the patients with hyperlipidemia, due to their low taking rate of lipid-lowering drugs. Additionally, as the requirement of the guideline becomes more stringent, the management of disease has met more challenges. Notably, diabetes patients who have not met the guideline requirement are at high risk for cardiovascular disease, to whom the disease management should be strengthened.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of alisol A,23-acetyl alisol B,alisol A-24-acetate,alisol B,alisol C,23-acetyl alisol C,alisol F,alisol G,atractylenolideⅠ,atractylenolide Ⅱ,atractylenolide Ⅲ,atractylon and ferulic acid in Zexie Decoction.METHODS The analysis was performed on a 30 ℃ thermostatic Waters ACQUITY UPLC HSS C18 column(100 mm×2.1 mm,1.8μm),with the mobile phase comprising of water(containing 0.1％formic acid)-acetonitrile(containing 0.1％formic acid)flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS Thirteen constituents showed good linear relationships within their own ranges(r＞0.999 1),whose average recoveries were 95.05％-103.8％with the RSDs of 1.4％-6.7％.CONCLUSION This simple,rapid and accurate method can provide experimental basis for the quality control of Zexie Decoction.

Aberrant expression of Colgalt1 is closely associated with tumorigenesis and tumor progres-sion;however,the mechanism by which it regulates macrophages to influence tumor development remains poorly understood.This study aimed to establish a macrophage-specific Colgalt1 gene knockout mouse model to delve into the mechanisms through which Colgalt1 modulates macrophage function and subse-quently affects the occurrence and progression of tumor-related diseases.Initially,Colgalt1flox+mice were generated using gene editing techniques,followed by crossing with Lyz2-Cre+mice,which exhibit tissue-specific expression in the myeloid lineage(including monocytes and mature macrophages).Through this strategy,mice with the genotype Colgalt1-/-Lyz2-Cre+were successfully obtained,achieving conditional knockout of the Colgalt1 gene in macrophages.Colgalt1flox/flox Lyz2-Cre-mice were used as control.PCR and agarose gel electrophoresis were employed to identify the Flox and Cre genotypes of the knockout mice.RT-qPCR and Western Blot techniques were utilized to detect the expression levels of Colgalt1 in BMDMs from knockout mice at both the mRNA and protein levels,respectively.Western Blot results re-vealed a significant downregulation of Colgaltl expression in BMDMs from knockout mice compared to controls(P＜0.01).RT-qPCR results demonstrated a significant reduction in Colgalt1 mRNA levels in BMDMs from knockout mice compared to contro1s(P＜0.001),while no significant differences in Col-galt1 mRNA expression were observed in liver,lung,or spleen tissues between the two groups.Addition-ally,immunohistochemistry was employed to detect Colgalt1 expression in liver-specific macrophages,re-vealing an absence of Colgalt l-positive staining in liver macrophages from knockout mice.HE staining was used to observe cellular morphology in liver tissues from both groups of mice,showing no significant differences in cellular morphology or obvious pathological changes in tissues and organs.Moreover,the o-verall survival of the mice was not affected.Finally,RT-qPCR was used to assess the expression of mac-rophage-related inflammatory factors in BMDMs from both groups of mice.The results indicated that com-pared to controls,knockout mice exhibited downregulated expression of TNF-α(P＜0.05)and signifi-cantly upregulated expression of IL-10(P＜0.01),Arginase1(P＜0.001),and CD206(P＜0.001)in BMDMs,suggesting an anti-inflammatory trend and M2 polarization of macrophages following Colgalt 1 knockout.In summary,this study successfully established a macrophage-specific Colgalt1 gene knockout mouse model,providing a more reliable experimental animal model for in-depth exploration of the specific roles of Colgalt1 in macrophage functional regulation and the pathogenesis of tumor-related diseases.This model holds promise for identifying novel therapeutic targets and strategies for tumors and other diseases.

This study aims to investigate the anti-inflammatory and anti-apoptotic effects of total flavonoids of hawthorn leaves(TFHL)on lipopolysaccharide(LPS)-induced inflammatory injury in rat intestinal epithelial(IEC-6)cells,as well as the underlying mechanisms.An in vitro inflam-mation model was first established by treating IEC-6 cells with lipopolysaccharide(LPS).IEC-6 cells were then incubated with three concentrations of TFHL for 24 h prior to a further 24 h LPS treatment.RT-qPCR was used to quantify mRNA levels of the inflammatory genes COX-2 and iN-OS,while Western blotting was used to assess protein levels of the apoptotic markers Bax,cleaved Caspase-3,Bcl-2,and the JNK/p-JNK signaling pathway.Finally,cells were pretreated with TFHL and/or the JNK inhibitor SP600125 for 24 h before LPS exposure for 24 h,in order to evaluate the combined effects of TFHL and SP600125 on LPS-induced inflammatory cytokine expression and apoptotic protein levels in IEC-6 cells.The results showed that,compared with the LPS group,the mRNA level of COX-2 and iNOS in the 2.5,5.0,10.0 mg/L TFHL group and the Bax and Caspase-3 protein levels decreased significantly(P＜0.01),and the Bcl-2 protein level was significantly higher(P＜0.01),p-JNK protein level and p-JNK/JNK ratio decreased significantly(P＜0.01);compared with the LPS group,the COX-2 and iNOS mRNA levels of the TFHL+LPS group de-creased significantly(P＜0.01),Bax,and Caspase-3 protein levels decreased significantly(P＜0.01),and the level of Bcl-2 protein increased significantly(P＜0.05);compared with the LPS group,the COX-2 and iNOS mRNA levels of the TFHL+SP600125 group decreased significantly(P＜0.01),Bax and Caspase-3 protein levels decreased significantly(P＜0.01),and Bcl-2 protein level increased significantly(P＜0.01).These findings indicate that TFHL exerts anti-inflammato-ry and anti-apoptotic effects in LPS-challenged IEC-6 cells by inhibiting the JNK signaling path-way.

Objectives:To describe the use of antihypertensive, antidiabetic and lipid-lowering drugs, and evaluate the effects on blood pressure, blood glucose and blood lipids controls required by Chinese Guideline on the Primary Prevention of Cardiovascular Diseases (the guideline) in a community-based cohort of individuals at high risk for cardiovascular disease. To analyze the association of the uses of antihypertensive, antidiabetic and lipid-lowering drugs, and the comprehensive control of blood pressure, blood glucose and blood lipids with cardiovascular disease. Methods:From the CHinese Electronic health Records Research in Yinzhou (CHERRY), those who were at high risk for cardiovascular disease and aged 40-75 years as of January 1, 2013 in in Yinzhou District of Ningbo, Zhejiang Province were selected as study subjects. The information about their antihypertensive, antidiabetic, and lipid-lowering drug uses between 2013 and 2015 was collected, and blood pressure, blood glucose, and blood lipid measurements were conducted during the follow-up. The study constructed two kinds of comprehensive scores: the comprehensive medication score based on the guideline requirement for the treatment of hypertension, diabetes and hyperlipidemia, dividing the study participants into the compliancy group and non-compliancy group; and the comprehensive control score based on the guideline requirement for blood pressure, blood glucose, and blood lipids control, dividing the study participants into better control group, moderate control group, and poor control group. Cox proportional hazards regression model was used to analyze the association of the comprehensive medication score and comprehensive control score with cardiovascular disease. The incidence data of cardiovascular disease were collected from January 1, 2015 (baseline time) to August 31, 2020 (follow up end time).Results:A total of 79 734 participants at high risk for cardiovascular disease were included in the study, in whom 68.4%, 27.4%, and 4.2% had 1, 2, or 3 cardiometabolic conditions (hypertension, diabetes, or hyperlipidemia), respectively. In the participants with hypertension, diabetes, and hyperlipidemia from 2013 to 2015, the proportions of those who had two years of medication compliancy records were 66.0%, 67.4%, and 13.9%, respectively. In the hypertension patients, 59.2% had better blood pressure control, in the diabetes patients, 28.7% had better blood glucose control, and in the patients with hyperlipidemia, 27.4% had better blood lipid control. After a median follow-up of 5.66 years, 4 088 cardiovascular disease cases or deaths occurred. After multivariate adjustment, compared with the non-compliancy group, the compliancy group had lower risk for cardiovascular disease ( HR=0.91, 95% CI: 0.85-0.96). Compared with the better control group, the poor control group had an increased risk for cardiovascular disease ( HR=1.67, 95% CI: 1.53-1.81). In the moderate control group, the risk increased significantly in the diabetes patients ( HR=1.29, 95% CI: 1.07-1.56), while no additional risk for cardiovascular disease was observed in non-diabetes patients ( HR=1.06, 95% CI: 0.97-1.16). Conclusions:Compliancy to the medication required by the guideline is associated with lower risk for cardiovascular disease. However, it is still necessary to improve the medication compliancy in people at high risk in primary prevention, especially in the patients with hyperlipidemia, due to their low taking rate of lipid-lowering drugs. Additionally, as the requirement of the guideline becomes more stringent, the management of disease has met more challenges. Notably, diabetes patients who have not met the guideline requirement are at high risk for cardiovascular disease, to whom the disease management should be strengthened.