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 explore the laboratory testing methods and clinical management strategies for immune hemolytic anemia induced by Ceftizoxime sodium drug-dependent antibodies. Methods: Patient blood samples were subjected to blood typing, direct antiglobulin test, and unexpected antibody identification. Ceftizoxime sodium drug-dependent antibodies were detected using the immune complex method and drug-sensitized red cell method. The properties and titers of the drug antibodies were further assessed. Flow cytometry was used to assess the complement activation capacity of the drug antibodies in vitro. Results: Direct antiglobulin tests (IgG and C3d) were positive. Ceftizoxime sodium drug-dependent antibodies were identified using both the immune complex method and the sensitized red cell method, their titers significantly increased following the addition of the drug. Flow cytometry confirmed the complement activation capability of these antibodies and identified 30 minutes as the optimal time for activation in vitro. The patient's condition improved rapidly after drug withdrawal and supportive transfusion, resulting in a favorable outcome. Conclusion: Ceftizoxime sodium can cause drug-induced immune hemolytic anemia via complement activation mediated by drug-dependent antibodies. Serological testing is essential for diagnosing drug-induced hemolytic anemia. Clinicians should be vigilant for this adverse reaction. The offending drug must be promptly discontinued, and supportive care should be initiated upon the onset of symptoms.

ObjectiveTo investigate the mechanism of action of Huangqi Guizhi Wuwutang （HGWT） against cerebral ischemia-reperfusion injury （CIRI） based on bioinformatics and experimental validation. MethodsBiological informatics methods were used to screen for active components of HGWT and their targets. The GEO database was utilized to obtain CIRI-related differentially expressed genes （DEGs）， and platforms such as GeneCards were used to identify disease targets. Venn diagram analysis was conducted to identify overlapping targets， followed by protein-protein interaction （PPI）， gene ontology （GO）， and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis， as well as immune infiltration and immune cell differential analysis. Core genes （Hub genes） were screened using LASSO regression and ROC curves， and molecular docking was used to validate the binding efficiency between the active components of the drug and the core targets. A rat CIRI model was established， with rats randomly divided into five groups （n=10）： Sham surgery group （Sham）， model group （MG）， and low-dose （LD，5.3 g·kg^-1）， medium-dose （MD，10.6 g·kg^-1）， and high-dose （HD，21.2 g·kg^-1） HGWT groups. From 3 days before modeling to 7 days after surgery， oral administration was performed daily： Sham and MG groups received physiological saline， while each drug group received the corresponding dose of HGWT. Hematoxylin-eosin （HE） staining， Nissl staining， and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL staining） were used to assess the repair effects of HGWT on neural damage. Western blot analysis was used to detect B-cell lymphoma-2 protein （Bcl-2）， Bcl-2-associated X protein （Bax）， signal transducer and activator of transcription 3 （STAT3）， phosphorylated STAT3 ［p-STAT3 （Tyr705）］， protein kinase B1 （Akt1）， and phosphorylated Akt1 ［p-Akt1 （Ser473）］， among other target proteins. ResultsAfter screening， 56 common target points of DEGs-disease-drug were obtained. GO and KEGG analyses indicated that HGWT primarily functions in pathways such as apoptosis， oxidative stress， and inflammatory responses. Immune infiltration analysis revealed a significant association between HGWT's anti-CIRI activity and immune cells such as Th17 cells and myeloid-derived suppressor cells （MDSCs） （P0.01）. LASSO-ROC analysis identified Akt1， Caspase-3， glycogen synthase kinase-3β （GSK-3β）， and STAT3 as core genes. Molecular docking confirmed that Hub genes exhibit significant binding affinity with the active components of HGWT （binding energy ≤ -5 kJ·mol^-1）（1 cal≈4.186 J）. Animal experiment results showed that compared with the sham group， the MG group exhibited significant neuronal necrosis， nuclear condensation， and vacuolar degeneration in rat brains， with a significant decrease in Nissl body density （P0.01） and increased neuronal apoptosis in rat brains as indicated by TUNEL staining （P0.01）. Compared with the MG， the LD， MD， and HD groups showed reduced neuronal necrosis， nuclear condensation， and vacuolar degeneration in rat brain neurons， increased Nissl body density， and reduced apoptosis （P0.01）， with significant differences among the drug groups （P0.01）. Western blot results showed that compared with the sham group， the MG group had reduced Bcl-2 and p-Akt1 （P0.01） and increased Bax and p-STAT3 （P0.01）. Compared with the MG group， the drug groups showed increased Bcl-2 and p-Akt1 （P0.01） and decreased Bax and p-STAT3 （P0.01）. There were no significant changes in total Akt1 and STAT3 protein levels among the groups. ConclusionBased on network pharmacology and experimental verification， HGWT may exert its neuroprotective effects by regulating the phosphorylation levels of Akt1 and STAT3， thereby alleviating cell apoptosis， inflammatory responses， and oxidative stress in rat brain tissue following CIRI. This provides theoretical support for the clinical treatment of CIRI.

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

The prelimbic cortex (PL) plays a critical role in processing both the sensory and affective components of pain. However, the underlying molecular mechanisms remain poorly understood. In this study, we observed a reduction in hyperpolarization-activated cation current (I_h) in layer V pyramidal neurons of the contralateral PL in a mouse model of spared nerve injury (SNI). The expression of hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channels was also decreased in the contralateral PL. Conversely, microinjection of fisetin, a partial agonist of HCN2, produced both analgesic and anxiolytic effects. Additionally, we found that cyclin-dependent kinase 5 (CDK5) was activated in the contralateral PL, where it formed a complex with HCN2 and phosphorylated its C-terminus. Knockdown of CDK5 restored HCN2 expression and alleviated both pain hypersensitivity and anxiety-like behaviors. Collectively, these results indicate that CDK5-mediated dysfunction of HCN2 in the PL underlies nerve injury-induced mechanical hypersensitivity and anxiety.
Animals ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism* ; Hyperalgesia/metabolism* ; Cyclin-Dependent Kinase 5/metabolism* ; Neuralgia/metabolism* ; Male ; Anxiety/metabolism* ; Mice ; Potassium Channels/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Pyramidal Cells/metabolism*

Objective To construct the respiratory rehabilitation calisthenics for school-age children with asthma,and evaluate its effects,in order to provide a guidance for the scientific and effective implementation of respiratory rehabilitation in clinical work.Methods By convenience sampling method,the school-age children with asthma treated in the respiratory outpatient department of a tertiary specialized children's hospital in Chongqing from De-cember 2023 to February 2024 were selected.The children were randomly divided into an experimental group and the control group(25 of each group)by a random number table.Both groups were given routine asthma drug in-halation treatment and health education.Additionally,the experimental group received respiratory rehabilitation calis-thenics training and the control group received conventional aerobic exercise training.After 3-month intervention,the effects of adherence to respiratory rehabilitation training,lung functions,exercise capacity,inspiratory muscle strength and occurrence of adverse events were evaluated between 2 groups.Results 24 children of each group completed the study.After 3-month intervention,the adherence to respiratory rehabilitation training,exercise capacity and in-spiratory muscle strength were improved in the experimental group compared with those in the control group,and all differences were statistically significant(P＜0.05).There were no adverse events in both groups.Conclusion The respiratory rehabilitation calisthenics for school-age children with asthma constructed in this study was scientif-ic,feasible and safe,and could improve exercise capacity and inspiratory muscle strength for children with asthma.

[Abtract]Nursing safety management is crucial to patient health outcomes,and real-time monitoring and early warning systems play a vital role in enhancing nursing safety and reducing medical incidents.Wearable flexible devices enable non-invasive,continuous monitoring of various physiological parameters and provide timely alerts.These devices not only improve the efficiency and quality of nursing safety management but also offer patients more convenient,accurate,and personalized care services.This article provides a comprehensive review of the application of wearable flexible devices in nursing safety management,examining their application scenarios,advantages,and challenges,and offering insights to facilitate the further integration of this technology into nursing safety practices.

As a physical treatment technique, modified electro-convulsive therapy (MECT) is used to treat mental and certain neurological disorders by causing seizures with short, suitable electrical currents applied to the brain while the patient is under general anesthesia and muscle relaxants. MECT is recognized for its therapeutic efficacy and clinical safety, rendering it one of the most prevalent interventions in psychiatric care. To enhance clinical outcomes and minimize adverse effects, this consensus document delineates the indications, therapeutic parameters, therapeutic procedures, potential adverse effects, and associated management strategies for MECT. These guidelines are informed by the latest clinical research and expert consensus, integrating evidence-based medicine methodologies. The objective is to furnish clinicians with precise operational guidelines and to advance the standardization of MECT practices in clinical settings.

Objective:To establish an HPLC method to simultaneously determine the contents of 7 components, including Cardol triene, Cardol diene, (8'Z,11'Z,14'Z)-5-(Heptadeca-8',11',14'-trienyl)benzene-1,3-diol, Alkylresorcinol B, 5-(8'Z,11'Z-heptadecadienyl)-1,3-benzenediol, Adipostatin A, and 5-(11'Z-heptadecenyl)-resorcinol in Embelia laeta (L.) Mez. Methods:Chromatographic column was Arcus EP-C18(4.6 mm×250 mm, 5 μm); mobile phase was methanol-water (90∶10); column temperature was 25 ℃; flow rate was 1 ml/min; detection wavelength was 220 nm; the injection volume was 10 μl.Results:The 7 compounds in Embelia laeta (L.) Mez showed good linear relationships, which sample recovery rate ranges from 97.69%- 100.62%. The average contents of the 7 components from 9 origins were 3.099 9, 6.246 3, 9.942 8, 4.093 7, 2.180 3, 0.960 2, 1.855 9 mg/g. Conclusion:The established HPLC method for simultaneous determination of the contents of 7 components in Embelia laeta (L.) Mez is feasible, which can provide references for further development and utilization of Embelia laeta (L.) Mez.