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 analyze the structural changes in whole blood and apheresis platelet donations in Chinese Society of Blood Transfusion (CSBT) sentinel units from 2021 to 2025, and to provide evidence for donor recruitment and blood service management. Methods: Aggregated data reported by sentinel sites were collected and stratified according to six indicators: age, sex, donation history, donation volume, donation site, and organization mode. Pearson χ test, Cramer′V coefficient, Cochran-Armitage trend test and simple linear regression were adopted for analysis. Results: A total of 16 256 973 whole blood donations and 1 576 546 apheresis platelet donations were included. Among whole-blood donations, the proportion of donors aged 18-22 years decreased from 27.30% to 10.60%. The proportion of male donors increased from 58.81% to 63.13%; the proportion of people aged 30 and above increased from 58.40% to 75.30%; the proportion of fixed locations rose from 28.37% to 36.57%; the proportion of social groups increased from 21.69% to 39.69%. The 400-mL donations decreased from 62.12% to 53.46%, while individually initiated voluntary donations remained above 50%. Apheresis platelet donations were predominantly from males, individuals aged 30-39 years, and repeat donors; 2-treatment-unit apheresis platelet donations increased from 67.19% to 74.93%, and individually initiated donations accounted for 92.97%-96.02%. Statistically significant overall annual compositional differences were observed for all six indicators (all P<0.001), whereas linear trends for some sub-categories were not statistically significant. Conclusion: In the participating CSBT sentinel units, among whole blood donations, the proportions of donors aged 18-22 years, university-organized group donations, and donations at blood mobiles decreased, whereas the proportions of organizational group donations and donations at fixed venues increased. The apheresis platelet donation cohort is relatively mature and is evolving toward a high-efficiency donation model. Individual voluntary donation remains the primary organization mode for both donation types. Strategies such as youth donor recruitment, optimized layout of fixed donation sites, and retention of repeat donors should be strengthened to improve the resilience of blood supply.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

OBJECTIVE: To analyze a Chinese pedigree with Hereditary coagulation factor Ⅻ (FⅫ) deficiency duo to variants of F12 gene and explore its molecular pathogenesis. METHODS: A patient who underwent laparoscopic cystectomy at the Department of Gynecology of the First Affiliated Hospital of Wenzhou Medical University in June 2012 was selected as the study subject. Coagulation factor indexes of the proband and her family members (5 individuals from three generations) were determined. All exons, flanking sequences, 5' and 3' untranslated regions of the F12 gene of the proband and her family members were analyzed by direct sequencing. Three bioinformatics software was used to analyze the conservation, pathogenicity and protein model of the variant. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No. 2012-17). RESULTS: The activated partial thromboplastin time (APTT), FⅫ activity (FⅫ:C) and FⅫ antigen (FⅫ:Ag) of the proband was 180.0 s, 1.0% and 2.1%, respectively. DNA sequencing revealed that she has harbored compound heterozygous variants of the F12 gene, namely c.712_713insT (p.Cys238Leufs *73) in exon 8 and c.1561G>A (p.Glu521Lys) in exon 13. Her mother and younger son were heterozygous for the p.Cys238Leufs*73 variant, while her older son was heterozygous for the p.Glu521Lys variant. Bioinformatic analysis suggested that Cys238 is highly conserved and p.Cys238Leufs*73 is a pathogenic variant, which eventually resulted in a truncated protein. CONCLUSION The c.712_713insT and c.1561G>A compound heterozygous variants of the F12 gene probably underlay the decreased FⅫ level in this pedigree, among which c.712_713insT (NM_000505) was unreported previously.
Adult ; Female ; Humans ; Male ; Middle Aged ; Base Sequence ; China ; Factor XII/genetics* ; Heterozygote ; Mutation ; Pedigree ; Factor XII Deficiency/genetics* ; East Asian People

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To analyze a Chinese pedigree with Hereditary coagulation factor Ⅻ (FⅫ) deficiency duo to variants of F12 gene and explore its molecular pathogenesis. Methods:A patient who underwent laparoscopic cystectomy at the Department of Gynecology of the First Affiliated Hospital of Wenzhou Medical University in June 2012 was selected as the study subject. Coagulation factor indexes of the proband and her family members (5 individuals from three generations) were determined. All exons, flanking sequences, 5′ and 3′ untranslated regions of the F12 gene of the proband and her family members were analyzed by direct sequencing. Three bioinformatics software was used to analyze the conservation, pathogenicity and protein model of the variant. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No. 2012-17). Results:The activated partial thromboplastin time (APTT), FⅫ activity (FⅫ: C) and FⅫ antigen (FⅫ: Ag) of the proband was 180.0 s, 1.0% and 2.1%, respectively. DNA sequencing revealed that she has harbored compound heterozygous variants of the F12 gene, namely c. 712_713insT (p.Cys238Leufs *73) in exon 8 and c. 1561G>A (p.Glu521Lys) in exon 13. Her mother and younger son were heterozygous for the p. Cys238Leufs*73 variant, while her older son was heterozygous for the p. Glu521Lys variant. Bioinformatic analysis suggested that Cys238 is highly conserved and p. Cys238Leufs*73 is a pathogenic variant, which eventually resulted in a truncated protein. Conclusion:The c. 712_713insT and c. 1561G>A compound heterozygous variants of the F12 gene probably underlay the decreased FⅫ level in this pedigree, among which c. 712_713insT (NM_000505) was unreported previously.

Objective:To summarize the medication law and academic experience of Professor Yuan Jinsheng in the treatment of angina pectoris (AP) of coronary heart disease (CHD) through R language data mining technique.Methods:The effective outpatient medical records of Professor Yuan Jinsheng in the treatment of AP of CHD from January 1, 2016 to September 30, 2023 were selected, and the R 4.2.3 was used for frequency statistics, association rule analysis, systematic clustering analysis and correlation analysis of prescription drugs.Results:A total of 292 prescriptions were included, including 268 patients, involving 204 kinds of Chinese materia medica, and the total frequency of Chinese materia medica was 4 253 times. The main properties were warm and neutral, the main tastes were bitter, pungent and sweet, and the main meridians were spleen, lung and liver meridians. The analysis of association rules obtained 125 core TCM combinations, and the commonly used drug pair was Trichosanthis Fructus-Aurantii Fructus Immaturus. The core prescription composed of Aurantii Fructus Immaturus, Chuanxiong Rhizoma, Trichosanthis Fructus, Citri Reticulatae Pericarpium and Salviea Miltiorrhizae Radix et Rhizoma. Seven TCM groups of were obtained by systematic clustering analysis. Correlation analysis showed that the drug pairs with phi coefficient greater than 0.6 were in 8 groups.Conclusions:Studies suggest that AP of CHD is located in the heart, which is related to lung, spleen, liver and kidney, deficiency in root and excess in superficiality, phlegm, blood stasis and qi stagnation are important pathological factors. The treatment is based on the basic principles of tonifying qi, promoting yang, relieving rheumatism, resolving phlegm, activating blood circulation, and promoting qi circulation. It embodies Professor Yuan's academic thoughts and principles of differentiation and treatments of "taking fluency as the main point, regulating the five internal organs and weighing the root and superficiality".

Exercise-induced metabolic remodeling is a fundamental adaptive process whereby the body reorganizes systemic and cellular metabolism to meet the dynamic energy demands posed by physical activity. Emerging evidence reveals that such remodeling not only enhances energy homeostasis but also profoundly influences immune function through complex molecular interactions involving glucose, lipid, and protein metabolism. This review presents an in-depth synthesis of recent advances, elucidating how exercise modulates immune regulation via metabolic reprogramming, highlighting key molecular mechanisms, immune-metabolic signaling axes, and the authors’ academic perspective on the integrated “exercise-metabolism-immunity” network. In the domain of glucose metabolism, regular exercise improves insulin sensitivity and reduces hyperglycemia, thereby attenuating glucose toxicity-induced immune dysfunction. It suppresses the formation of advanced glycation end-products (AGEs) and interrupts the AGEs-RAGE-inflammation positive feedback loop in innate and adaptive immune cells. Importantly, exercise-induced lactate, traditionally viewed as a metabolic byproduct, is now recognized as an active immunomodulatory molecule. At high concentrations, lactate can suppress immune function through pH-mediated effects and GPR81 receptor activation. At physiological levels, it supports regulatory T cell survival, promotes macrophage M2 polarization, and modulates gene expression via histone lactylation. Additionally, key metabolic regulators such as AMPK and mTOR coordinate immune cell energy balance and phenotype; exercise activates the AMPK-mTOR axis to favor anti-inflammatory immune cell profiles. Simultaneously, hypoxia-inducible factor-1α (HIF-1α) is transiently activated during exercise, driving glycolytic reprogramming in T cells and macrophages, and shaping the immune landscape. In lipid metabolism, exercise alleviates adipose tissue inflammation by reducing fat mass and reshaping the immune microenvironment. It promotes the polarization of adipose tissue macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. Moreover, exercise alters the secretion profile of adipokines—raising adiponectin levels while reducing leptin and resistin—thereby influencing systemic immune balance. At the circulatory level, exercise improves lipid profiles by lowering pro-inflammatory free fatty acids (particularly saturated fatty acids) and triglycerides, while enhancing high-density lipoprotein (HDL) function, which has immunoregulatory properties such as endotoxin neutralization and macrophage cholesterol efflux. Regarding protein metabolism, exercise triggers the expression of heat shock proteins (HSPs) that act as intracellular chaperones and extracellular immune signals. Exercise also promotes the secretion of myokines (e.g., IL-6, IL-15, irisin, FGF21) from skeletal muscle, which modulate immune responses, facilitate T cell and macrophage function, and support immunological memory. Furthermore, exercise reshapes amino acid metabolism, particularly of glutamine, arginine, and branched-chain amino acids (BCAAs), thereby influencing immune cell proliferation, biosynthesis, and signaling. Leucine-mTORC1 signaling plays a key role in T cell fate, while arginine metabolism governs macrophage polarization and T cell activation. In summary, this review underscores the complex, bidirectional relationship between exercise and immune function, orchestrated through metabolic remodeling. Future research should focus on causative links among specific metabolites, signaling pathways, and immune phenotypes, as well as explore the epigenetic consequences of exercise-induced metabolic shifts. This integrated perspective advances understanding of exercise as a non-pharmacological intervention for immune regulation and offers theoretical foundations for individualized exercise prescriptions in health and disease contexts.

OBJECTIVE: To evaluate the clinical effect and safety of acupuncture manipulation on treatment of intractable facial paralysis (IFP), and verify the practicality and precision of the Anzhong Facial Paralysis Precision Scale (Eyelid Closure Grading Scale, AFPPS-ECGS). METHODS: A multicentre, single-blind, randomized controlled trial was conducted from October 2022 to June 2024. Eighty-nine IFP participants were randomly assigned to an ordinary acupuncture group (OAG, 45 cases) and a characteristic acupuncture group (CAG, 44 cases) using a random number table method. The main acupoints selected included Yangbai (GB 14), Quanliao (SI 18), Yingxiang (LI 20), Shuigou (GV 26), Dicang (ST 4), Chengjiang (CV 24), Taiyang (EX-HN 5), Jiache (ST 6), Fengchi (GB 20), and Hegu (LI 4). The OAG patients received ordinary acupuncture manipulation, while the CAG received characteristic acupuncture manipulation. Both groups received acupuncture treatment 3 times a week, with 10 times per course, lasting for 10 weeks. Facial recovery was assessed at baseline and after the 1st, 2nd and 3rd treatment course by AFPPS-ECGS and the House-Brackmann (H-B) Grading Scale. Infrared thermography technology was used to observe the temperature difference between healthy and affected sides in various facial regions. Adverse events and laboratory test abnormalities were recorded. The correlation between the scores of the two scales was analyzed using Pearson correlation coefficient. RESULTS: After the 2nd treatment course, the two groups showed statistically significant differences in AFPPS-ECGS scores (P<0.05), with even greater significance after the 3rd course (P<0.01). Similarly, H-B Grading Scale scores demonstrated significant differences between groups following the 3rd treatment course (P<0.05). Regarding temperature measurements, significant differences in temperatures of frontal and ocular areas were observed after the 2nd course (P<0.05), becoming more pronounced after the 3rd course (P<0.01). Additionally, mouth corner temperature differences reached statistical significance by the 3rd course (P<0.05). No safety-related incidents were observed during the study. Correlation analysis revealed that the AFPPS-ECGS and the H-B Grading Scale were strongly correlated (r=0.86, 0.91, 0.93, and 0.91 at baseline, and after 1st, 2nd, and 3rd treatment course, respectively, all P<0.01). CONCLUSIONS Acupuncture is an effective treatment for IFP, and the characteristic acupuncture manipulation enhances the therapeutic effect. The use of the AFPPS-ECGS can more accurately reflect the recovery status of patients with IFP. (Trial registration No. ChiCTR2200065442).
Humans ; Acupuncture Therapy/methods* ; Facial Paralysis/therapy* ; Female ; Male ; Middle Aged ; Adult ; Treatment Outcome ; Acupuncture Points ; Aged

OBJECTIVES: The Charlson comorbidity index reflects overall comorbidity burden and has been applied in cardiovascular medicine. However, its role in predicting in-hospital mortality in patients with acute myocardial infarction (AMI) complicated by ventricular arrhythmias (VA) remains unclear. This study aims to evaluate the predictive value of the Charlson comorbidity index in this setting and to construct a nomogram model for early risk identification and individualized management to improve outcomes. METHODS: Using the open-access critical care database MIMIC-IV (Medical Information Mart for Intensive Care IV), we identified intensive care unit (ICU) patients diagnosed with AMI complicated by VA. Patients were grouped according to in-hospital survival. The predictive performance of the Charlson comorbidity index and other clinical variables for in-hospital mortality was analyzed. Key predictors were selected using the least absolute shrinkage and selection operator (LASSO) regression, followed by multivariable Logistic regression. A nomogram model was constructed based on the regression results. Model performance was assessed using receiver operating characteristic (ROC) curves and calibration plots. RESULTS: A total of 1 492 patients with AMI and VA were included, of whom 340 died and 1 152 survived during hospitalization. Significant differences were observed between survivors and non-survivors in sex distribution, vital signs, comorbidity burden, organ function, and laboratory parameters (all P<0.05). The area under the curve (AUC) of the Charlson comorbidity index for predicting in-hospital mortality was 0.712 (95% CI 0.681 to 0.742), significantly higher than albumin, international normalized ratio (INR), hemoglobin, body temperature, and platelet count (all P<0.001), but comparable to Sequential Organ Failure Assessment (SOFA) score (P>0.05). LASSO regression identified seven key predictors: the Charlson comorbidity index (quartile groups: T1, <6; T2, ≥6-<7; T3, ≥7-<9; T4, ≥9), ventricular fibrillation, age, systolic blood pressure, respiratory rate, body temperature, and SOFA score. Multivariate Logistic regression showed that compared with T1, mortality risk increased significantly in T2 (OR=1.996, 95% CI 1.135 to 3.486, P=0.016), T3 (OR=3.386, 95% CI 2.192 to 5.302, P<0.001), and T4 (OR=5.679, 95% CI 3.711 to 8.842, P<0.001). Age (OR=1.056, P<0.001), respiratory rate (OR=1.069, P<0.001), SOFA score (OR=1.223, P<0.001), and ventricular fibrillation (OR=2.174, P<0.001) were independent risk factors, while systolic blood pressure (OR=0.984, P<0.001) and body temperature (OR=0.648, P<0.001) were protective factors. The nomogram incorporating these predictors achieved an AUC of 0.849 (95% CI 0.826 to 0.871) with high discrimination and good calibration (mean absolute error=0.014). CONCLUSIONS The Charlson comorbidity index is an independent predictor of in-hospital mortality in AMI patients complicated by VA, with performance comparable to the SOFA score. The nomogram model based on the Charlson comorbidity index and additional clinical variables effectively estimates mortality risk and provides a valuable reference for clinical decision-making.
Humans ; Nomograms ; Hospital Mortality ; Myocardial Infarction/complications* ; Male ; Female ; Comorbidity ; Middle Aged ; Aged ; Arrhythmias, Cardiac/complications* ; ROC Curve ; Intensive Care Units