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.

ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

Objective:To explore the efficacy of percutaneous vertebroplasty (PVP) using the partition injection technique in the treatment of Kümmell’s disease of stages Ⅰ and Ⅱ.Methods:A retrospective study was conducted of the 30 patients with stage Ⅰ or Ⅱ Kümmell’s disease (the partition group) who had been treated by PVP using the partition injection technique at Department of Spinal Surgery, Zhengzhou Orthopedic Hospital from January 2020 to January 2022. The data of another 30 patients who had been treated at the same department and the same period using conventional PVP for stage Ⅰ or Ⅱ Kümmell's disease were selected as the conventional group. In the partition group, there were 13 males and 17 females, with an age of (72.3±10.1) years and disease duration of (3.1±1.5) months. Seventeen thoracic and 13 lumbar vertebrae were affected. In the conventional group, there were 11 males and 19 females, with an age of (75.5±12.7) years and disease duration of (3.5±1.8) months. Eighteen thoracic and 12 lumbar vertebrae were affected. Surgical time, volume of bone cement injected, bone cement leakage, and bone cement distribution were compared between the 2 groups. The heights of the anterior and middle vertebral bodies, kyphotic Cobb angle, visual analog scale (VAS) pain score, and Oswestry disability index (ODI) were assessed postoperatively at 1 day, 6 months, and the last follow-up and compared between the 2 groups.Results:No significant differences were found in the baseline data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (17.3±3.1) months. There were no significant differences in the surgical time or bone cement leakage between the 2 groups ( P>0.05). The volume of bone cement injected in the partition group was significantly higher [(6.3±1.5) mL] than that in the conventional group [(4.9±1.0) mL] ( P<0.05). Bone cement distribution was significantly better in the partition group than that in the conventional group ( P<0.05). At postoperative 1 day, 6 months, and the last follow-up, the partition group was significantly better than the conventional group in anterior vertebral body height, middle vertebral body height, and kyphotic Cobb angle ( P<0.05). At the 6-month and the last follow-ups, the partition group was also significantly better than the conventional group in VAS pain score and ODI ( P<0.05). Conclusion:In the treatment of Kümmell’s disease of stages Ⅰ and Ⅱ, compared with conventional PVP, PVP using the partition injection technique may lead to better long-term outcomes due to its better bone cement distribution, more adequate cement injection, and better restoration of vertebral body heights and correction of local deformity.

Objective:To investigate the effects and mechanism of metformin on the proliferation and expression of fibrotic proteins of human hypertrophic scar (HS) fibroblasts (Fbs).Methods:The study was an experimental study. From June 2021 to June 2022, 5 patients with HS were admitted to the Department of Burns and Cutaneous Surgery of the First Affiliated Hospital of Air Force Medical University, including 3 males and 2 females, aged from 21 to 36 years. HS tissue was collected, Fbs were isolated and cultured, and Fbs of passage 5 to 7 were used for experiment. Fbs were taken and cultured in their respective media supplemented with phosphate buffered solution (PBS) or metformin at final molarities of 5, 10, 20, and 40 mmol/L for 48 hours. The cell proliferation activity was detected using the cell counting kit-8 (CCK-8), and the proliferation inhibition rate of cells was calculated. The content of hydroxyproline in the cell culture supernatant was measured using a hydroxyproline assay kit. The phosphorylation levels of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) in the cells were detected by Western blotting, and the ratios of phosphorylated Akt (p-Akt) to Akt and phosphorylated mTOR (p-mTOR) to mTOR were calculated. After 24 hours of culture, the mRNA expressions of type Ⅰ collagen, type Ⅲ collagen, and α-smooth muscle actin (α-SMA) in the cells were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Another batch of Fbs were divided into control group (with conventional culture), LY294002 group, metformin group, and LY294002+metformin group. LY294002, metformin, and LY294002+metformin were added to the culture media of the last three groups, respectively, with the final molarities of LY294002 and metformin being 20 μmol/L and 10 mmol/L, respectively. CCK-8 was used to detect the cell proliferation activity at 0 (immediately), 24, and 48 hours of culture. After 48 hours of culture, Western blotting was used to detect the phosphorylation levels of Akt and mTOR in the cells, and the ratios of p-Akt to Akt and p-mTOR to mTOR were calculated. The sample size for the cell proliferation inhibition rate experiment was 4, and the sample size for the other experiments was 3.Results:After 48 hours of culture, compared with the cells treated with PBS, the proliferation inhibition rates of the cells treated with 5, 10, 20, and 40 mmol/L metformin were significantly increased (with t values of 10.69, 14.20, 19.73, and 52.54, respectively, P<0.05), the content of hydroxyproline in the culture supernatants of the cells treated with 10, 20, and 40 mmol/L metformin was significantly decreased (with t values of 8.06, 7.86, and 10.25, respectively, P<0.05), and the ratios of p-Akt to Akt in the cells treated with 10, 20, and 40 mmol/L metformin and the ratios of p-mTOR to mTOR in the cells treated with 20 and 40 mmol/L metformin were significantly decreased (with t values of 2.82, 4.28, 9.88, 5.66, and 9.08, respectively, P<0.05). After 24 hours of culture, compared with those treated with PBS, the mRNA expressions of type Ⅰ collagen and α-SMA in the cells treated with 5, 10, 20, and 40 mmol/L metformin and the mRNA expressions of type Ⅲ collagen in the cells treated with 10, 20, and 40 mmol/L metformin were significantly decreased (with t values of 4.35, 8.53, 9.57, 14.77, 4.14, 5.58, 7.89, 9.37, 5.18, 6.85, and 9.15, respectively, P<0.05). At 24 and 48 hours of culture, the proliferation activities of the cells in LY294002 group (with t values of 6.30 and 13.60, respectively) and metformin group (with t values of 6.47 and 10.69, respectively) were significantly lower than those in control group ( P<0.05). After 48 hours of culture, the ratios of p-Akt to Akt in the cells of LY294002 group and metformin group were 0.554±0.027 and 0.681±0.029, respectively, which were significantly lower than 1.053±0.193 in control group (with t values of 4.45 and 3.31, respectively, P<0.05). The ratio of p-Akt to Akt in the cells of LY294002+metformin group was 0.387±0.023, which was significantly lower than that in metformin group ( t=5.95, P<0.05). After 48 hours of culture, the ratio of p-mTOR to mTOR in the cells of LY294002 group was significantly lower than that in control group ( t=4.01, P<0.05), and the ratio of p-mTOR to mTOR in the cells of LY294002+metformin group was significantly lower than that in metformin group ( t=6.05, P<0.05). Conclusions:Metformin can inhibit the proliferation and expression of fibrotic proteins type Ⅰ collagen, type Ⅲ collagen, and α-SMA of human HS Fbs through phosphatidylinositol 3-kinase/Akt/mTOR signaling pathway.

Objective:To investigate the feasibility of the bortezomib, lenalidomide, and dexamethasone (VRD) regimen combined with autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma (MM) and renal impairment, analyze treatment efficacy and renal responses stratified based on renal dysfunction severity, and explore the prognostic significance of early renal response and its affecting factors.Methods:This retrospective study, conducted at the First Affiliated Hospital of Soochow University, categorized 316 patients with newly diagnosed MM (NDMM) from August 2018 to October 2022 based on renal function for analysis of clinical characteristics, treatment response, and prognosis. Continuous variables were compared using t-tests or Mann-Whitney U tests, categorical variables utilizing Chi-square tests, survival outcomes employing Kaplan-Meier and Log-rank tests, and renal response predictors with logistic regression.Results:Patients were stratified based on baseline estimated glomerular filtration rate (eGFR) : normal [≥90 ml·min -1· (1.73 m 2) -1, n=160], mild [≥60 ml·min -1· (1.73 m 2) -1 to <90 ml·min -1· (1.73 m 2) -1, n=55], moderate [≥30 ml·min -1· (1.73 m 2) -1 to <60 ml·min -1· (1.73 m 2) -1, n=39], and severe impairment [<30 ml·min -1· (1.73 m 2) -1, n=62]. Moderate and severe renal impairment correlated with advanced International Staging System/Revised International Staging System classification, lower hemoglobin levels, frailty, and higher light-chain/IgD subtype prevalence ( P<0.05). Despite younger age ( P=0.001) and higher transplant rates ( P=0.041) in severe cases, overall response rates ( ORR: 93.7% ; ≥VGPR: 82.9% ) were comparable across groups ( P>0.05). Among 24 dialysis-dependent patients at diagnosis, 11 (45.8% ) achieved dialysis independence after induction [median: 3.0 (0.5–4.0) months], including 10 undergoing auto-HSCT. In 89 evaluable patients [baseline eGFR <50 ml·min -1· (1.73 m 2) -1], renal ORR (RORR) was 70.8% [rapid complete response: 31.5% ; rapid partial response: 11.2% ; rapid minimal response (RMR) : 28.1% ]. Renal response predicted better survival (overall survival: HR=0.36, 95% CI: 0.13–0.99, P=0.049). Moderate-to-severe renal impairment was associated with increased transplant-related adverse events and delayed engraftment ( P<0.05) ; however, auto-HSCT significantly improved outcomes after 33.5-month median follow-up (range: 2–65 months). Multivariate analysis identified 1q21+ ( OR=3.58, 95% CI: 1.17–11.02, P=0.026) and light-chain subtype ( OR=2.86, 95% CI: 1.08–7.69, P=0.036) as independent predictors of poor renal response. Conclusion:VRD regimen plus auto-HSCT demonstrates robust efficacy in NDMM, including patients with renal impairment, with a 70.8% RORR and manageable toxicity. Achieving ≥RMR correlates with superior prognosis, whereas 1q21+ and light-chain subtype independently predict inferior renal response.

Objective:To investigate the effect of changes in metabolic syndrome status and persistence on carotid plaque risk.Methods:This retrospective cohort study analyzed individuals who underwent routine health check-ups at the health management center of the Second Affiliated Hospital of Dalian Medical University from 2014 to 2023. Participants with at least three carotid ultrasound records meeting the inclusion criteria were classified into 4 groups based on changes in metabolic status: persistently metabolic health, transitioning from metabolic health to unhealth, transitioning from metabolic unhealth to health, and persistently metabolic unhealth. The cumulative incidence of carotid plaque in these groups was compared. A Cox proportional risk model was used to evaluate the relationship between changes in metabolic syndrome status, the number of metabolic syndrome components, and the risk of carotid plaque development. Restricted cubic spline analysis was applied to explore the association between changes in individual metabolic syndrome components and carotid plaque risk.Results:Compared to the persistently metabolic health group, the persistent unhealth group had the highest risk of developing carotid plaque( HR=1.35, 95% CI 1.05-1.74, P=0.021), followed by those who transitioned from metabolic health to unhealth and those who improved from metabolic unhealth to health. Furthermore, the risk of carotid plaque increased progressively with the number of metabolic syndrome components. Restricted cubic spline analysis revealed a nonlinear relationship between fasting blood glucose change and carotid plaque risk, while systolic blood pressure, diastolic blood pressure, waist circumference, triglycerides, and high-density lipoprotein-cholesterol showed a linear dose-response relationship with carotid plaque. Conclusions:The change of metabolic syndrome is associated with the risk of developing carotid plaque, and maintaining metabolic health, recovering from metabolic syndrome, or minimizing the number of metabolic syndrome components may be effective strategies to prevent carotid plaque formation.

Objective:To explore the relationship between thyroid hormone sensitivity and metabolic dysfunction-associated steatotic liver disease(MASLD) in a population with normal thyroid function, with a particular focus on sex-specific differences.Methods:This retrospective study included 41 355 euthyroid cases who underwent routine health examinations at the Health Management Centre of the Second Affiliated Hospital of Dalian Medical University from January 2014 to December 2023 were included. The free triiodothyronine(FT 3) to free thyroxine(FT 4) ratio(FT 3/FT 4) was calculated in order to reflect the peripheral sensitivity of the thyroid gland. Similarly, thyroid feedback quantile-based index(TFQI), thyrotrophic thyroxine resistance index(TT 4RI), and the FT 3-based TFQI-derived index(TFQI-FT 3) were calculated in order to reflect the central sensitivity of the thyroid gland. A Logistic regression was employed to analyse the effect of sex-specific thyroid hormone sensitivity indices on the prevalence of MASLD. The restricted cubic spline was used to analyse the non-linear relationship between the thyroid sensitivity hormone indices and MASLD. Furthermore, the correlation between the thyroid hormone sensitivity indices and MASLD in different subgroups was also analysed. Results:The prevalence of MASLD in the study population was 28.8%. After adjusting the model for confounders, the risk of MASLD increased by 7%, 3%, 10%, and 5% for each standard deviation increase in FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI in the total population, respectively. The risk of MASLD increased by 6% and 5% for each standard deviation increase in FT 3/FT 4 and TFQI-FT 3 in men, respectively. For each standard deviation increase in FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI in women, the risk of MASLD increased by 6%, 5%, 11%, and 5%, respectively. Higher FT 3/FT 4 and TFQI-FT 3 were positively associated with the risk of developing MASLD in men, and higher FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI were positively associated with the risk of developing MASLD in women. There was a non-linear, inverted U-shaped relationship between TFQI and risk of MASLD in women. Subgroup analyses showed positive associations between FT 3/FT 4, TFQI, TFQI-FT 3, and MASLD. Conclusions:The thyroid hormone sensitivity indices may provide a basis for clinical prevention and management of MASLD in individuals with normal thyroid function. Additionally, FT 3/FT 4 and TFQI-FT 3 may indicate the risk of MASLD in the general population, while TFQI and TT 4RI are more suitable for assessing the risk of MASLD in women.

As one of the chronic diseases with high incidence in contemporary society, cervical spondylosis has increasing patient groups who gradually present a low age, and it seriously affects social and public health. Although modern medicine has made great progress in the pathological research and clinical treatment of cervical spondylosis, patients still face gastrointestinal side effects of nonsteroidal anti-inflammatory drugs(NSAIDs), neck pain, limited mobility, upper limb numbness, and other symptoms after conservative or surgical treatment. In the theory of traditional Chinese medicine(TCM), cervical spondylosis belongs to the categories of "Bi syndrome" "stiff neck" "stiff Bi", etc. With the change of the times, the change of lifestyle, and the application of western medicine treatment, the etiology and pathogenesis of TCM in cervical spondylosis also show new characteristics. In terms of etiology and pathogenesis, it involves the invasion of wind, cold, and dampness, long-term strain, liver and kidney deficiency, Qi and blood stasis, which are associated with factors such as cervical degeneration, muscle tension and spasm, intervertebral disc herniation, and nerve root compression in modern medicine. In terms of the evolution of pathogenesis, in the early stage, wind, cold, and dampness, were more common in Xuanfu, resulting in unfavorable muscles and bones, poor flow of Qi and blood, and cervical spondylosis and radiculopathy. Medium-term phlegm stasis and internal knots, sluggish muscles and veins, and long-term weathering and fire are more likely to occur in the vertebral artery and sympathetic radiculopathy. In the later stage, the positive Qi is depleted; the true Yin is damaged, and the viscera Qi and blood are deficient, which is most common in cervical myelopathy. The strategy of treating cervical spondylosis with TCM classic formulas applies Gegen Decoction, Wutou Decoction, Qianghuo Shengshi Decoction, Mahuang Jiazhu Decoction to patients with wind, cold, and dampness. Patients with phlegm dampness and blood stasis are treated with Huoxue Xiaoling Dan, Jinlingzi Powder, Siwu Decoction, Banxia Baizhu Tianma Decoction, Shuanghe Decoction, etc. For those patients with liver, spleen, and kidney deficiency, Huangqi Guizhi Wuwu Decoction, Tianma Gouteng Decoction, Guishao Dihuang Pills, Shenling Baizhu Powder, and Lizhong Decoction are used to invigorate the spleen, nourish Qi and blood, and tonify liver and kidney. In clinical practice, the authors advocate a safe and effective treatment plan of classic formulas based on deficiency and excess, the integration of formulas and syndromes, and the combination of modern research results, so as to relieve symptoms, reduce recurrence, and reduce medical burden.
Humans ; Spondylosis/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Cervical Vertebrae/pathology*

OBJECTIVE: To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells. METHODS: A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1_126-134 ( RMFPNAPYL) complex (hereafter referred to as HLA-A2:WT1) was synthesized to evaluate the function of antigen processing and presentation machinery (APM) in AML cells. AML cell line THP1 was incubated with increasing concentrations of IFN-γ, hypomethylating agents (HMA), immunomodulatory drugs (IMiD), proteasome inhibitors (PI) and γ-secretase inhibitors (GSI), followed by measuring of HLA-ABC, HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points. RESULTS: The TCR-like antibody we generated only binds to HLA-A*0201⁺WT1⁺ cells, indicating the specificity of the antibody. HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ, showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM. Among the anti-tumor agents screened in this study, GSI (LY-411575) and HMA (decitabine and azacitidine) could significantly increase the HLA-A2:WT1 level. The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time. As proteasome inhibitors, carfilzomib could significantly decreased the expression of HLA-A2:WT1, while bortezomib had no significant effect on HLA-A2:WT1 expression. CONCLUSION HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function. Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Antineoplastic Agents/pharmacology* ; Antigen Presentation/drug effects* ; HLA-A2 Antigen/immunology* ; Receptors, Antigen, T-Cell/immunology* ; Cell Line, Tumor ; Interferon-gamma