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 investigate the effects of individual versus connected microdroplet culture modes in time-lapse (TL) incubators on embryo development parameters and pregnancy outcomes in patients undergoing whole embryo culture to blastocyst stage.Methods:Using a retrospective cohort study, clinical data from 3 507 fresh blastocyst transfer cycles were analyzed. These cycles involved patients who underwent assisted reproductive technology treatment with whole embryo culture to blastocyst stage at the Reproductive Medical Center of Northwest Women's and Children's Hospital between January 2019 and December 2023. Based on different culture modes, patients were divided into two groups, connected group ( n=2 446, using connected microdroplet culture) and individual group ( n=1 061, using individual microdroplet culture). Baseline characteristics, embryo development parameters, pregnancy outcomes, and neonatal outcomes were compared between the two groups. Generalized linear models (GLM) were used to adjust for confounding factors and analyze the effect of culture mode. Results:Embryo development assessment showed the day 3 (D3) high-quality embryo rate in the connected group [60.12% (12 136/20 187)] was significantly lower than that in the individual group [63.62% (4 705/7 395), P<0.001], whereas the high-quality blastocyst formation rate [34.93% (7 052/20 187)] and the available blastocyst formation rate [56.07% (11 319/20 187)] were both significantly higher than those in the individual group [33.08% (2 446/7 395), P=0.004; 51.45% (3 805/7 395), P<0.001], with statistically significant differences. The implantation rate [67.40% (1 774/2 632)], the clinical pregnancy rate [70.20% (1 717/2 446)], and the live birth rate [60.66% (1 469/2 446)] in the connected group were all significantly higher than those in the individual group [63.40% (724/1 142), P=0.017; 66.73% (708/1 061), P=0.041; 55.89% (593/1 061), P=0.021], with statistically significant differences. Neonatal outcomes showed no statistically significant difference between the two groups (all P>0.05). After adjusting for confounding factors using GLM, connected culture was an independent influencing factor for D3 high-quality embryo rate (a MD=-0.017, 95% CI: -0.034-0.000, P=0.046), high-quality blastocyst formation rate (a MD=-0.020, 95% CI: 0.002-0.037, P=0.026), available blastocyst formation rate (a MD=0.032, 95% CI: 0.015-0.048, P<0.001), live birth rate (a OR=1.182, 95% CI: 1.006-1.388, P=0.042). However, it had no effect on D3 available embryo rate, clinical pregnancy rate, or early miscarriage rate (all P>0.05). Conclusion:In TL incubator systems, individual and connected microdroplet culture modes exert different effects at various stages of embryo development. Individual microdroplet culture can significantly enhance cleavage-stage embryo quality, whereas the connected microdroplet culture was more beneficial for enhancing the blastocyst formation rate and quality, ultimately improving the live birth rate without increasing neonatal risks.

Objective To explore the effects of gasless endoscopic thyroidectomy via axillary approach on neck function and aesthetic effect in patients with early thyroid tumor.Methods A prospective study was conducted on 116 patients with early thyroid tumor admitted to our hospital from December 2020 to December 2023.They were divided into the observation group and the control group according to block random method,with 58 cases in each group.Patients in the control group underwent open thyroidectomy,while patients in the observation group underwent gasless endoscopic thyroidectomy via axillary approach.The surgical indicators,neck function,cosmetic effect,and complications of patients in the two groups were compared.Results Compared with the control group,the observation group had a longer surgical time(P<0.05),less intraoperative bleeding and postoperative drainage volume(P<0.05).There were statistically significant differences in terms of the time point,inter-group and interaction effects of the neck injury index and the time point and inter-group effects of swallowing disorder index of patients between the two groups(P<0.05).Compared with 3 days after surgery,the neck injury index and swallowing disorder index at 6 months and 12 months after surgery of patients in both groups decreased(P<0.05),and the neck injury index and swallowing disorder index at 6 months and 12 months after surgery of patients in the observation group were lower than those in the control group(P<0.05).Compared with the control group,the observation group had better cosmetic effects(P<0.05).The total incidence of complications of patients in the observation group was lower than that in the control group(P<0.05).Conclusion Gasless endoscopic thyroidectomy via axillary approach has better efficacy for early thyroid tumor,which can effectively improve neck function and aesthetic effect,promote the recovery of patients,and has high safety and patient satisfaction.

OBJECTIVE: To evaluate the safety and effectiveness of robot-assisted percutaneous coronary intervention (R-PCI) compared to traditional manual percutaneous coronary intervention (M-PCI). METHODS: This prospective, multicenter, randomized controlled, non-inferior clinical trial enrolled patients with coronary heart disease who met the inclusion criteria and had indications for elective percutaneous coronary intervention. Participants were randomly assigned to either the R-PCI group or the M-PCI group. Primary endpoints were clinical and technical success rates. Clinical success was defined as visually estimated residual post-percutaneous coronary intervention stenosis < 30% with no 30-day major adverse cardiac events. Technical success in the R-PCI group was defined as successful completion of percutaneous coronary intervention using the ETcath200 robot-assisted system, without conversion to M-PCI in the event of a guidewire or balloon/stent catheter that was unable to cross the vessel or was poorly supported by the catheter. Secondary endpoints included total procedure time, percutaneous coronary intervention procedure time, fluoroscopy time, contrast volume, operator radiation exposure, air kerma, and dose-area product. RESULTS: The trial enrolled 152 patients (R-PCI: 73 patients, M-PCI: 79 patients). Lesions were predominantly B2/C type (73.6%). Both groups achieved 100% clinical success rate. No major adverse cardiac events occurred during the 30-day follow-up. The R-PCI group had a technical success rate of 100%. The R-PCI group had longer total procedure and fluoroscopy times, but lower operator radiation exposure. The percutaneous coronary intervention procedure time, contrast volume, air kerma, and dose-area product were similar between the two groups. CONCLUSIONS For certain complex lesions, performing percutaneous coronary intervention using the ETcath200 robot-assisted system is safe and effective and does not result in conversion to M-PCI.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

OBJECTIVE: This study aimed to evaluate the relationships of white blood cell (WBC) count, platelet (PLT) count, and PLT-to-WBC ratio (PWR) with muscle mass in Chinese older adults. METHODS: This cross-sectional analysis involved 4,033 Chinese older adults aged ≥ 65 years from the Healthy Ageing and Biomarkers Cohort Study. Muscle mass and total skeletal muscle mass index (TSMI) were measured by bioelectric impedance analysis. WBC, PLT, and PWR were measured using standard methods. Multivariate linear regression was used to examine the associations of WBC count, PLT count, and PWR with TSMI. RESULTS: High WBC count, PLT count, and PWR were associated with low TSMI, with coefficients of -0.0091 (95% confidence interval [ CI]: -0.0142 to -0.0041), -0.0119 (95% CI: -0.0170 to -0.0068), and -0.0051 (95% CI: -0.0102 to -0.0001). The associations between the three inflammatory indices and TSMI were linear. Stratified analyses indicated that the relationship between inflammatory markers and TSMI was more evident in male participants and in individuals aged < 80 years than in their counterparts. CONCLUSION Elevated WBC count, PLT count, and PWR correlated with muscle mass loss. This study highlights the importance of regular monitoring of inflammatory markers as a potential strategy for the screening and management of sarcopenia in older adults.
Humans ; Aged ; Male ; Female ; China ; Leukocyte Count ; Cross-Sectional Studies ; Platelet Count ; Aged, 80 and over ; Muscle, Skeletal/anatomy & histology* ; Independent Living ; Blood Platelets ; Leukocytes ; Sarcopenia

Objective To explore the predictive efficacy of several multimodal MRI-based machine learning models for the promoter methylation states of O6-methylguanine-DNA methyltransferase(MGMT)of glioblastoma muliforme(GBM)patients in terms of the GBM heterogeneity and the complexity of the tumor microenvironment.Methods Firstly,the multimodal MRI images of 317 GBM patients from The University of Pennsylvania Glioblastoma(UPENN-GBM)dataset were pre-processed,with four sequences involved in including T1-weighted imaging(T1WI)sequence,T1-weighted contrast-enhanced imaging(T1CE)sequence,T2-weighted imaging(T2WI)sequence and fluid-attenuated inversion recovery(FLAIR)sequence,and the radiomics features were extracted for two regions of interest(ROIs)such as the tumor core region and the tumor edema region.Secondly,the data of the 317 GBM patients were randomly divided into a training set(254 cases)and a test set(63 cases),which underwent normalization with Z-scores and feature selection and dimensionality reduction with Lasso regression.Finally,three models were established respectively with particle swarm optimization-support vector machine(PSO-SVM),C-support vector classification(C-SVC)and adaptive boosting(adaptive boosting(Adaboost)algorithms,and the predictive efficacy of the three models for glioblastoma multiforme MGMT promoter methylation states were evaluated in terms of accuracy and AUC.Results The Adaboost model based on T2WI sequence and radiomics features of the tumor core region had the highest predictive efficacy with accuracy and AUC values of 67％and 0.74,respectively,higher than those of other combinations of sequences,models and regions of interest.Conclusion The multimodal MRI-based machine learning models can be used for the prediction of glioblastoma multiforme MGMT promoter methylation states,which provides powerful support for personalized treatment and prognostic assessment of GBM.[Chinese Medical Equipment Journal,2025,46(6):7-13]

Objective:To investigate the effects of individual versus connected microdroplet culture modes in time-lapse (TL) incubators on embryo development parameters and pregnancy outcomes in patients undergoing whole embryo culture to blastocyst stage.Methods:Using a retrospective cohort study, clinical data from 3 507 fresh blastocyst transfer cycles were analyzed. These cycles involved patients who underwent assisted reproductive technology treatment with whole embryo culture to blastocyst stage at the Reproductive Medical Center of Northwest Women's and Children's Hospital between January 2019 and December 2023. Based on different culture modes, patients were divided into two groups, connected group ( n=2 446, using connected microdroplet culture) and individual group ( n=1 061, using individual microdroplet culture). Baseline characteristics, embryo development parameters, pregnancy outcomes, and neonatal outcomes were compared between the two groups. Generalized linear models (GLM) were used to adjust for confounding factors and analyze the effect of culture mode. Results:Embryo development assessment showed the day 3 (D3) high-quality embryo rate in the connected group [60.12% (12 136/20 187)] was significantly lower than that in the individual group [63.62% (4 705/7 395), P<0.001], whereas the high-quality blastocyst formation rate [34.93% (7 052/20 187)] and the available blastocyst formation rate [56.07% (11 319/20 187)] were both significantly higher than those in the individual group [33.08% (2 446/7 395), P=0.004; 51.45% (3 805/7 395), P<0.001], with statistically significant differences. The implantation rate [67.40% (1 774/2 632)], the clinical pregnancy rate [70.20% (1 717/2 446)], and the live birth rate [60.66% (1 469/2 446)] in the connected group were all significantly higher than those in the individual group [63.40% (724/1 142), P=0.017; 66.73% (708/1 061), P=0.041; 55.89% (593/1 061), P=0.021], with statistically significant differences. Neonatal outcomes showed no statistically significant difference between the two groups (all P>0.05). After adjusting for confounding factors using GLM, connected culture was an independent influencing factor for D3 high-quality embryo rate (a MD=-0.017, 95% CI: -0.034-0.000, P=0.046), high-quality blastocyst formation rate (a MD=-0.020, 95% CI: 0.002-0.037, P=0.026), available blastocyst formation rate (a MD=0.032, 95% CI: 0.015-0.048, P<0.001), live birth rate (a OR=1.182, 95% CI: 1.006-1.388, P=0.042). However, it had no effect on D3 available embryo rate, clinical pregnancy rate, or early miscarriage rate (all P>0.05). Conclusion:In TL incubator systems, individual and connected microdroplet culture modes exert different effects at various stages of embryo development. Individual microdroplet culture can significantly enhance cleavage-stage embryo quality, whereas the connected microdroplet culture was more beneficial for enhancing the blastocyst formation rate and quality, ultimately improving the live birth rate without increasing neonatal risks.