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:This study aimed to explore the molecular mechanisms of the maladaptation of H3N2 influenza virus in chicken embryos, provide a theoretical basis for the restoration of H3N2 influenza vaccine production in chicken embryos.Methods:Samples of respiratory secretions from patients with influenza-like symptoms (Influenza-like Illness, ILI) caused by H3N2 influenza virus were inoculated into chicken embryos and Madin-Darby Canine Kidney cells (MDCK), respectively. After isolating the virus, hemagglutination experiments were conducted to detect hemagglutination titers and hemagglutination inhibition experiments were used to compare antigenic differences; further, whole-genome sequencing of H3N2 influenza virus was performed using second-generation high-throughput gene sequencing (Next Generation High-Throughput Gene Sequencing, NGS), and key amino acid sites of mutations were identified through sequence alignment; combined with sialic acid receptor binding experiments, the differences in the binding of wild-type and mutant receptor binding sites (RBS) to sialic acid receptors were compared; finally, molecular docking and molecular dynamics simulation method were used to explore the specific molecular mechanisms of how mutation sites affect the differences in the affinity of the RBS pocket for sialic acid receptors.Results:The hemagglutination assay result indicated that both chicken embryos and MDCK cells could isolate the influenza virus, and the hemagglutination inhibition test showed that no antigenic differences were produced in the isolated strains. NGS analysis revealed that the H3N2 virus underwent an F195Y mutation in the (RBS) region of the hemagglutinin (HA) protein after adaptation through chicken embryo passages. Receptor-binding experiments demonstrated that the F195Y mutation enhanced the virus′s binding ability to α2, 3-linked sialic acid glycan (Neu5Acα2-3Galβ1-4GlcNAcβ-PAA, 3′SLN), while the mutation did not affect the affinity of the RBS pocket for α2, 6-linked sialic acid glycan (Neu5Acα2-6Galβ1-4GlcNAcβ-PAA, 6′SLN). Molecular docking and molecular dynamics simulation result indicate that the F195Y mutation, by replacing a hydrophobic amino acid with a hydrophilic one, leads to a significant decrease in the structure of the RBS pocket, enhancing the binding stability of the H3N2 influenza virus with α2, 3-sln. This is specifically manifested by an increase in binding time and an increase in the number of hydrogen bonds at the RBS site with the receptor. Furthermore, the F195Y mutation does not alter the binding of the virus to other receptors.Conclusions:The F195Y mutation in the RBS pocket of H3N2 influenza virus is a key site affecting the viral chicken embryo inadaptability.

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*

Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male patients whose semen was analyzed from March 2023 to July 2023. Their clinical data, including semen parameters and age, were also collected. Genetic analysis was used to determine whether the sex chromosome involved in male infertility was abnormal (including the increase, deletion, and translocation of the X and Y chromosomes), and subsequent semen analysis was conducted for clinical grouping purposes. The participants were categorized into five groups: normozoospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, and azoospermia. Patients were randomly selected for further study; 41 patients with normozoospermia were included in the control group and 117 patients with non-normozoospermia were included in the study group according to the proportions of all enrolled patients. Cytokinesis-block micronucleus (CBMN) screening was conducted through peripheral blood. Statistical analysis was used to determine the differences in micronuclei (MNi) among the groups and the relationships between MNi and clinical data. There was a significant increase in MNi in infertile men, including those with azoospermia, compared with normozoospermic patients, but there was no significant difference between the genetic and nongenetic groups in azoospermic men. The presence of MNi was associated with sperm concentration, progressive sperm motility, immotile spermatozoa, malformed spermatozoa, total sperm count, and total sperm motility. This study underscores the potential utility of MNi as a diagnostic tool and highlights the need for further research to elucidate the underlying mechanisms of male infertility.
Humans ; Male ; Infertility, Male/genetics* ; Adult ; Micronucleus Tests ; Semen Analysis ; Oligospermia/genetics* ; Azoospermia/genetics* ; Chromosome Aberrations ; Sperm Count ; Micronuclei, Chromosome-Defective ; Middle Aged

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*

OBJECTIVES: This study aimed to observe the effects of initial periodontal therapy on the level of neutrophil extracellular traps (NETs) in gingival crevicular fluid (GCF) of patients with severe periodontitis and to analyze the factors related to the formation of NETs. METHODS: Thirty-one patients with stage Ⅲ-Ⅳ periodontitis were recruited. Clinical periodontal parameters, including plaque index (PLI), gingival index (GI), probing depth (PD), and clinical atta-chment loss (CAL), were recorded before and 6-8 weeks after initial periodontal therapy. Levels of NETs in GCF were detected by immunofluorescence staining. Quantities of total bacteria, Porphyromonas gingivalis (P. gingivalis), Aggregatibacter actinomycetemcomitans (A. actionomycetemcomitans) and Prevotella intermedia (P. intermedia)in unattached subgingival plaque were determined by real-time quantitative PCR, and levels of tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in GCF were explored by enzyme-linked immunosorbent assay. In addition, the correlations between the level of NETs and the above indicators were analyzed. RESULTS: After initial periodontal therapy, the level of NETs in GCF, PLI, GI, PD, and CAL; quantities of total bacteria, P. gingivalis, A. actinomycetemcomitans, and P. itermedia; and levels of IL-8 and TNF-α significantly decreased (P<0.05). We observed strong positive correlations between the level of NETs and PLI, GI, PD, CAL, the amount of total bacteria, P. gingivalis, TNF-α, and IL-8 (P<0.05). CONCLUSIONS Initial periodontal therapy might decrease the level of NETs in GCF from patients with severe periodontitis, which might be positively correlated with the quantities of P. gingivalis andthe levels of TNF-α and IL-8 in GCF.
Humans ; Gingival Crevicular Fluid ; Extracellular Traps/metabolism* ; Porphyromonas gingivalis/isolation & purification* ; Aggregatibacter actinomycetemcomitans/isolation & purification* ; Periodontitis/metabolism* ; Tumor Necrosis Factor-alpha/analysis* ; Prevotella intermedia/isolation & purification* ; Interleukin-8/analysis* ; Male ; Female ; Middle Aged ; Periodontal Index ; Adult

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective:To evaluate the effect of fiberoptic endoscopic evaluation of swallowing (FEES) on clinical functional outcomes of patients with intensive care unit-acquired swallowing disorders (ICU-ASD).Methods:This retrospective cohort study analyzed clinical data of patients diagnosed with post-extubation dysphagia (PED) in the intensive care unit (ICU) and respiratory intensive care unit (RICU) of the Affiliated Hospital of Inner Mongolia Medical University from February 2020 to February 2025. Patients were categorized into a FEES group of 60 cases [34 males, 26 females, aged 37-80 years (median age 62 years)] and a control group without FEES of 58 cases [32 males, 26 females, aged 39-77 years (median age 61 years)].The patients in two groups received swallowing function and feeding training based on the results of the FEES assessment and the Volume-Viscosity Swallow Test-Clinical Version (VVST-CV), respectively. Clinical functional outcome measures included pneumonia incidence, clinical pulmonary infection score (CPIS), pneumonia severity index (PSI), Functional Oral Intake Scale (FOIS), and dietary method at discharge. χ2 test, Mann-Whitney U test, and Wilcoxon signed-rank test, were employed for statistical analysis of the outcome measures. Results:Compared with the control group, the FEES group had significantly lower aspiration pneumonia incidence at discharge [3.3% (2/60) vs 15.5% (9/58), χ2=5.179, P=0.023]. Regarding dietary methods,a significantly higher proportion of patients in the FEES group achieved complete oral feeding compared with the control group [75.0% (45/60) vs 67.3% (39/58), χ2=8.065, P<0.05]. After training, the FEES group had higher median FOIS scores than the control group (7.00 vs 6.00, Z=-2.370, P=0.018), and lower CPIS scores (2.50 vs 5.00, Z=-2.216, P=0.027) and PSI scores (59.00 vs 73.00, Z=-2.251, P=0.024). Within-group comparisons revealed that FOIS scores significantly improved post-training in both groups (both P<0.001). Conclusion:Early FEES examination for ICU patients with acquired swallowing disorders is associated with a lower incidence of pneumonia, improved swallowing function, and superior clinical functional outcomes.

The aim of this study was to investigate the trend in testicular volume changes after orchiopexy in children with cryptorchidism. The clinical data of 854 children with cryptorchidism who underwent orchiopexy between January 2013 and December 2016 in Shenzhen Children's Hospital (Shenzhen, China) were retrospectively analyzed. The mean (standard deviation) age of the patients was 2.8 (2.5) years, and the duration of follow-up ranged from 1 year to 5 years. Ultrasonography was conducted preoperatively and postoperatively. The variables analyzed included age at the time of surgery, type of surgical procedure, laterality, preoperative testicular position, preoperative and postoperative testicular volumes, and the testicular volume ratio of them. The average testicular volumes preoperatively and at 1 year, 2 years, 3 years, and 5 years postoperatively were 0.27 ml, 0.38 ml, 0.53 ml, 0.87 ml, and 1.00 ml, respectively ( P < 0.001). The corresponding testicular volume ratios were 0.67, 0.76, 0.80, 0.83, and 0.84 ( P < 0.001). The mean volume of the undescended testes was significantly smaller than the mean normative value ( P < 0.001, lower than the 10 th percentile). The postoperative testicular volumes in children with cryptorchidism were generally lower than those in healthy boys but were still greater than the 10 th percentile and exhibited an increasing trend. The older the child is at the time of surgery, the larger the gap in volume between the affected and normal testes. Although testicular volume tends to gradually increase after orchiopexy for cryptorchidism, it could not normalizes. Earlier surgery results in affected testicular volumes closer to those of healthy boys.
Humans ; Male ; Cryptorchidism/diagnostic imaging* ; Orchiopexy ; Child, Preschool ; Testis/surgery* ; Retrospective Studies ; Organ Size ; Ultrasonography ; Infant ; Child ; Postoperative Period ; Follow-Up Studies

Neutrophil extracellular traps (NETs), intricate reticular structures released by activated neutrophils, play a pivotal regulatory role in the pathogenesis of malignant tumors. Lung cancer is one of the most prevalent malignancies globally, with persistently high incidence and mortality rates. Recent studies have revealed that NETs dynamically modulate the tumor microenvironment through unique pathological mechanisms, exhibiting complex immunoregulatory characteristics during the progression of lung cancer, and this discovery has increasingly become a focal point in tumor immunology research. This paper provides a comprehensive review of the latest advancements in NETs research related to lung cancer, offering an in-depth analysis of their impact on lung cancer progression, their potential diagnostic value, and the current state of research on targeting NETs for lung cancer prevention and treatment. The aim is to propose novel strategies to enhance therapeutic outcomes and improve the prognosis for lung cancer patients.
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Extracellular Traps/immunology* ; Humans ; Lung Neoplasms/metabolism* ; Neutrophils/metabolism* ; Animals ; Tumor Microenvironment