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.

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

Sympathectomy, as an emerging treatment method for cardiovascular diseases, has received extensive attention in recent years. Stereotactic radiotherapy (SRT), a precise and noninvasive therapeutic technique, has gradually been introduced into interventions targeting the sympathetic nervous system and has shown promising prospects in the management of cardiovascular conditions. Using three-dimensional imaging, SRT can accurately localize sympathetic ganglia and deliver high-energy radiation to disrupt nerve fibers, thereby achieving effects similar to conventional sympathectomy while reducing surgery-related complications and shortening recovery time. It also offers the advantages of being noninvasive and causing fewer adverse effects, and thus holds potential as an alternative to traditional approaches in the future. The integration of SRT with sympathectomy opens new avenues for the treatment of cardiovascular diseases and presents broad clinical application prospects.
Radiosurgery/methods* ; Cardiovascular Diseases/radiotherapy* ; Humans ; Imaging, Three-Dimensional ; Ganglionectomy/methods* ; Ganglia, Sympathetic/radiation effects* ; Blood Vessels/physiopathology* ; Heart/physiopathology*

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Objective:To explore the correlation between serum ferritin (SF) and risk of lean non-alcoholic fatty liver disease (NAFLD), so as to provide the basis for the prevention and treatment of lean NAFLD.Methods:A total of 7 187 people without NAFLD at baseline who took at least 2 physical examinations in the Health Management Center of the Second Hospital of Dalian Medical University from January 2014 to December 2023 and met the selection criteria were selected as the research subjects, and all the subjects had no NAFLD at baseline. Subjects were divided into four groups according to baseline SF quartiles: 1 797 cases in the first quartile ( Q1) group, 1 797 cases in the second quartile ( Q2) group, 1 797 cases in the third quartile ( Q3) group, and 1 796 cases in the fourth quartile ( Q4) group. The incidence of lean NAFLD in each group were observed. Kaplan-Meier curve was plotted to calculate the cumulative incidence of lean NAFLD which compared by log-rank test. Cox proportional hazard regression model was used to analyze the correlation between SF and new-onset lean NAFLD, Q1, Q2, Q3 and Q4 of SF were taken as continuous variables into the model for trend test.The stability of the results was verified by two item sensitivity analyses. Time-dependent receiver operating characteristic curve (ROC) was plotted to evaluate the predictive value of SF for the onset of lean NAFLD. Results:The cumulative follow-up were 25 076 person-years. There were 230 new cases of lean NAFLD, and the incidence density was 9.172/1 000 person-years. The incidence densities of lean NAFLD in Q1, Q2, Q3 and Q4 groups were 6.915/1 000 person-years, 8.552/1 000 person-years, 9.641/1 000 person-years, 12.003/1 000 person-years, respectively. Kaplan-Meier curve indicated that the incidence of lean NAFLD was increased with the increment of SF, and the difference was statistically significant (log-rank test, χ2=9.92, P=0.019). Cox proportional hazard regression model results showed that the risk of developing lean NAFLD in Q4 group increased by 72.8% ( HR=1.728, 95% confidence interval (95% CI): 1.059 to 2.820) compared with Q1 group. Trend analysis revealed that the risk of lean NAFLD increased by 18.9% for each one-quartile increase of SF( HR=1.189, 95% CI: 1.012 to 1.396). Two sensitivity analyses indicated that the risk of NAFLD in Q4 group was 1.795 times ( HR=1.795, 95% CI: 1.083 to 2.975) or 1.654 times ( HR=1.654, 95% CI: 1.022 to 2.678) higher than that in Q1 group. The area under the curve (95% CI) of SF for predicting the incidence of lean NAFLD at 2-, 3-, 7- and 8-year follow-up based on time-dependent ROC were 0.645 (0.593 to 0.698), 0.652 (0.603 to 0.700), 0.605 (0.539 to 0.672) and 0.716 (0.597 to 0.836), respectively. Conclusion:SF is an independent risk factor for lean NAFLD and has predictive value for the new-onset of lean NAFLD.

Objective:To analyze the effects of different doses of butorphanol on prolactin, serotonin and lipid hydrogen peroxide after cesarean section.Methods:A total of 124 women who underwent cesarean section in the Affiliated Hospital of Jining Medical University from January 2023 to January 2024 were prospectatively selected as study subjects, and divided into the study group 1 (41 cases), study group 2 (41 cases) and study group 3 (42 cases) according to random number table method. All three groups underwent patient-controlled analgesia after surgery, and 0.2 mg fentanyl was used as analgesic drug. However, the doses of butorphanol were 100 mg/L in the study group 1, 120 mg/L in the study group 2, and 140 mg/L in the study group 3. The level of PRL and first lactation time before and after surgery were compared among the three groups at different time points, serotonin and LHP levels were compared among the three groups at different time points after surgery, Ramsay and visual analog scale (VAS) scores were compared among the three groups at different time points after surgery, and the occurrence of adverse reactions and satisfaction with analgesic effect were compared among the three groups.Results:At 24, 48 and 72 h after operation, the level of PRL in the study group 3 was higher than that in the study group 2 and study group 1: (383.02 ± 47.57) μg/L vs. (376.39 ± 46.83), (302.88 ± 41.38) μg/L; (412.38 ± 40.22) μg/L vs. (394.82 ± 38.30), (315.09 ± 37.93) μg/L; (434.39 ± 39.39) μg/L vs. (427.48 ± 40.27), (344.39 ± 42.78) μg/L, there were statistical differences ( P<0.05). The first lactation time in the study group 2 and study group 3 was lower than that in the study group 1: (50.31 ± 6.52), (49.54 ± 6.27) h vs. (53.91 ± 8.42) h, there was statistical difference ( P<0.05). At 2 h (T 1), 12 h (T 2), 24 h (T 3) and 48 h (T 4) after surgery, the levels of serotonin in the study group 3, study group 2 and study group 1 were increased successively, and the levels of LHP were decreased successively, there were statistical differences ( P<0.05). At 30 min after surgery (T 0), T 1, T 2, T 3 and T 4, the Ramsay score in the study group 3, study group 2 and study group 1 were increased successively, and the VAS score were decreased successively, there were statistical differences ( P<0.05). There was no significant difference in the incidence of adverse reactions among the three groups ( P>0.05). The total satisfaction of study group 3 was higher than that of study group 2 and study group 1: 92.86%(39/42) vs. 73.17%(30/41), 68.29%(28/41), there was statistical difference ( Z = 2.52, P = 0.008). Conclusions:Butorphanol 140 mg/L has a more significant analgesic effect after cesarean section, and can improve the levels of serum PRL, serotonin and LHP, reduce the occurrence of adverse reactions, and improve the satisfaction of analgesia