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 dynamic changes and influencing factors of latent tuberculosis infection (LTBI) among junior and senior high school students, so as to provide evidence based references for precise tuberculosis prevention and control on campus. Methods: A retrospective cohort study was conducted among 11 206 junior and senior high school students in Yuhang District, Hangzhou, who underwent tuberculin skin test (TST) at baseline in 2023 (T0). Participants were followed up for two consecutive years (T1 in 2024, T2 in 2025), and TST results were analyzed. Cox proportional hazards regression model was used to identify influencing factors of LTBI, and generalized estimating equations (GEE) were applied to examine the sex-baseline grade-time interaction effects. Results: The cumulative incidence of LTBI among enrolled students was 10.01%, showed a distinct grade related gradient: the grade 7 cohort had the highest cumulative incidence of 12.62%, which decreased significantly with increasing grade level ( χ 2=109.12, P <0.01). Multivariate Cox regression analysis indicated that, compared with the grade 7 cohort, the grade 8 cohort ( aHR =0.60) and the grade 9 cohort ( aHR =0.43) had lower risks of LTBI (both P <0.01). Boarding school students had a 62% lower risk of LTBI than non boarding school students ( aHR =0.38, P <0.01). GEE analysis showed that, with grade 7 girls at T1 as the reference group, LTBI risk significantly increased among grade 7 girls at T2 ( β =0.23), whereas the most prominent risk reduction was observed among grade 9 boys ( β =-1.69) (both P <0.05). Conclusions LTBI risk among junior and senior high school students exhibits significant population heterogeneity and temporal dynamics. The grade 7 academic year represents a critical window for tuberculosis prevention. Girls advancing to the grade 8 should be prioritized as the key population for targeted interventions. The boarding school campus management model exerts a protective effect against LTBI among junior and senior high school students.

OBJECTIVE To systematically analyze the population pharmacokinetics （PPK） studies of lacosamide and expound the influential factors of its pharmacokinetics in different populations. METHODS PPK studies of lacosamide were collected by searching the databases， such as Web of Science， PubMed， Embase， Metasearch， CNKI， Wanfang Data and VIP， both in Chinese and English. Relevant data were extracted， and the Prediction Model Risk of Bias Assessment Tool was used to evaluate the quality of the PPK models in the included studies. RESULTS Among 8 studies ultimately included， 6 were retrospective studies and 2 were prospective studies； 5 studies involved pediatric patients. Seven studies adopted a one-compartment model， while 1 study utilized a two-compartment model. Four studies had a model quality rating of grade A， two of grade B and two of grade C， respectively. Body weight， renal function， and hepatic enzyme inducers were significant covariates influencing PPK of lacosamide. CONCLUSIONS The existing PPK studies of lacosamide are predominantly conducted in pediatric populations. Pharmacokinetic variability is mainly influenced by body weight， renal function， and hepatic enzyme inducers. However， most PPK studies have not conducted external validation， and the generalizability of the models remains to be confirmed.

Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

BACKGROUND:Finite element modeling,as an important engineering analysis technique,has been widely used in various fields of bioengineering research.However,there is little literature on what material properties should be selected for each anatomical structure of the knee joint finite element modeling at different ages for different research purposes.OBJECTIVE:To summarize the material properties of knee joint finite element models at different ages based on previous knee joint finite element studies.METHODS:The search terms were"knee,finite element,material selection,ligament injury,osteoarthritis,elderly,children,young people"in Chinese and English.Articles were searched on CNKI and PubMed,with a timeframe of 1950 to 2024.According to inclusion and exclusion criteria,108 articles were finally included for summary.RESULTS AND CONCLUSION:Children's knee bone density will increase with age,reaching peaks in adulthood.From middle-aged to the age,the elastic modulus of knee joint femur,tibia,fibula,and patella will decrease with age,and then return to the elastic modulus of childhood.The elastic modulus of children and adult cartilage is basically the same,and the elastic modulus of the elderly increases.With the increase of age,the elastic modulus of the knee ligament will decrease to a certain extent,but there is no significant difference in the elastic modulus of the knee ligament of young people and the elderly.With the increase of age,the loss of mechanical integrity of the knee meniscus will damage the biomechanical function of the tissue and disturb the various anisotropic biomechanical responses that are effectively carried and transmitted by the tissue.Knee joint finite element modeling can be used to deeply understand the biomechanical characteristics of the knee joints,develop new implanted materials,predict knee joint diseases,improve surgical technology,and guide patients to rehabilitate exercise.

Objective To explore the relationship between systemic immune-inflammation index(SII),red blood cell distribution width(RDW),25-hydroxy-vitamin-D[25(OH)D]levels and frailty index in elderly pa-tients with type 2 diabetes mellitus(T2DM).Methods A total of 197 elderly patients with T2DM admitted to the hospital from March 2023 to March 2024 were collected as the research subjects.The patients were divided into the frailty group(106 cases)and the non-frailty group(91 cases)according to the scores of the clinical frailty scale.The clinical data and the levels of SII,RDW and 25(OH)D of the two groups were compared.Pearson correlation analysis was used to analyze the correlations between the levels of SII,RDW and 25(OH)D and the frailty index of elderly patients with T2DM.Logistic regression was used to analyze the influencing factors of frailty in elderly patients with T2DM.Results Compared with the non-frailty group,the proportion of women,the history of falls within 1 year,and the age of the frailty group increased,while the body mass in-dex and the proportion of men decreased,and the differences were statistically significant(P＜0.05).The SII and RDW levels in the non-frailty group were lower than those in the frailty group,and the 25(OH)D level was higher than that in the frailty group,and the differences were statistically significant(P＜0.05).Pearson correlation analysis showed that SII and RDW levels were positively correlated with frailty index,and 25(OH)D level was negatively correlated with frailty index in elderly T2DM patients(P＜0.05).Logistic regression analysis showed that female,age ≥ 74.25 years old,SII≥ 938.36,RDW≥ 15.19％,and 25(OH)D≥48.42 nmol/L were independent risk factors for frailty in elderly T2DM patients(P＜0.05).Conclusion The levels of SII,RDW and 25(OH)D in elderly patients with T2DM are related to the frailty index.

Objective To investigate the effect of asperuloside(ASP)on the malignant progression and chemotherapy resistance of hepatocellular carcinoma(HCC)cells by regulating the supersonic hedgehog(SHH)/glioma-associated oncogene homolog 1(GLI1)signaling pathway.Methods The expression of SHH and GLI1 protein in human hepatocellular carcinoma cell line(SMMC-7721)/adriamycin(ADM)and SMMC-7721 cell line were detected by Western blot(WB).The HCC drug-resistant cell line SMMC-7721/ADM were divided into Control group,ADM group,L-ASP group(1 mmol/L ASP),M-ASP group(2 mmol/L ASP),H-ASP group(3 mmol/L ASP),ASP+PM group(1 μmol/L SHH/GLI1 signaling pathway activator PM).Ex-cept for Control group,5 μg/mL ADM was added to each group.The effect of ASP on the proliferation of SMMC-7721/ADM cells was detected by cell counting kit-8(CCK8)assay and plate cloning assay.The effect of ASP on the invasion and migration of SMMC-7721/ADM cells were detected by Transwell assay.The effect of ASP on the apoptosis of SMMC-7721/ADM cells was detected by flow cytometry.The expression of SHH,GLI1,proliferating cell nuclear antigen(PCNA),matrix metalloproteinase-9(MMP-9)and B cell lymphoma-2 associated X protein(Bax)in SMMC-7721/ADM cells were detected by WB.Animal experiments verified the effect of ASP on the growth of HCC xenografts and the expression of SHH/GLI1 signaling pathway proteins.Results The expression of SHH and GLI1 in SMMC-7721/ADM cells were higher than those in SMMC-7721 cells(P＜0.05).L-ASP group,M-ASP group and H-ASP group decreased the proliferation,migration and in-vasion of SMMC-7721/ADM cells in a dose-dependent manner,decreased the expression of SHH,GLI1,PCNA and MMP-9,and promoted cell apoptosis and Bax expression(P＜0.05).SHH/GLI1 signaling pathway acti-vator PM could reverse the inhibitory effect of H-ASP treatment on malignant progression and chemotherapy resistance of SMMC-7721/ADM cells(P＜0.05).ASP could inhibit the growth of HCC transplanted tumor and the expression of SHH and GLI1(P＜0.05).Conclusion ASP can inhibit the malignant progression of HCC cells and enhance the sensitivity of chemotherapy,which may be achieved by inhibiting the SHH/GLI1 signaling pathway.

Objective:To analyze the relationship between neck pain severity and duration and cervical sagittal parameters in non-specific neck pain (NNP) patients from a real world data, and to initially explore the relationship between NNP and cervical sagittal position sequence.Methods:The clinical data of 126 patients with main complaint of neck pain in the outpatient department of Beijing Friendship Hospital, Capital Medical University from January to September 2023 were retrospectively analyzed. This cohort included 84 female and 42 male patients with a mean age of (42.21±14.88) years (aged from 15 to 76 years). According to the duration of neck pain was more than 3 month or not, patients were divided into acute neck pain group ( n=57) and chronic neck pain group ( n=69). Patients were divided into mild neck pain group ( n=72) and moderate and severe neck pain group ( n=54) according to the severity of neck pain. The duration and visual analogue scale (VAS) of neck pain for each patient was recorded. Cervical sagittal related parameters, including cervical lordosis (C 2-C 7 Cobb′ angle, CL), C 2-C 7 sagittal vertical axis (cSVA), T 1 slope (TS) were measured by cervical lateral X-ray, and the value of T 1 slope minus cervical lordosis (TS-CL) was calculated. At the same time, cervical lateral X-ray was used to record whether the patient had cervical kyphosis and whether the patient was associated with ossification of the nuchal ligament (ONL). The VAS score of neck pain was expressed as the median (interquartile) [ M( Q1, Q3)]. Measurement data with normal distribution were represented as mean±standard deviation( ± s), and the comparison between groups was conducted using the t-test; the comparison of count data were represented as cases and percentage, and was conducted by Chi-square test. Spearman correlation analysis was used to investigate the correlation of VAS score and duration of neck pain with age, gender, imaging parameters (CL, cSVA, TS, TS-CL), cervical kyphosis and ONL. Results:The median VAS score of all patients with neck pain was 4(3, 5). For all patients, VAS score of neck pain was significantly correlated with cSVA ( P=0.029) and TS-CL ( P=0.028). There was no correlation between VAS score and CL ( P=0.235), TS ( P=0.355), with cervical kyphosis or not ( P=0.988), or with ONL or not ( P=0.181). The TS-CL values of acute neck pain group and chronic neck pain group were (11.80±8.38)° and (8.77±7.61)°, respectively, with a significant difference ( P=0.035). There was no significant difference in the incidence of cSVA, CL, TS, ONL and cervical kyphosis between the two groups ( P>0.05). The cSVA of mild neck pain group and moderate and severe neck pain group were (1.16±0.94) cm and (1.80±1.04) cm, respectively. CL was (12.25±10.76)° and (8.27±9.08)°, respectively. The TS-CL values were (8.11±7.54)° and (12.84±8.04)°, respectively, and the differences between the two groups were statistically significant ( P<0.05). The incidence of ONL in moderate and severe neck pain group was significantly higher (35.2% vs 19.4%), and the difference was statistically significant ( P<0.05). Conclusions:The severity of NNP was significantly correlated with cSVA, the more severe the neck pain, the more the mismatch between TS and CL was presented. Compared with chronic neck pain, patients with acute neck pain tended to appear TS and CL mismatch. There was a large value of cSVA and TS-CL in moderate and severe neck pain patients. The incidence of ONL was significantly increased in patients with moderate and severe neck pain.

Objective:To evaluate the perioperative application effect of enhanced recovery after surgery (ERAS) clinical pathway in percutaneous vertebro plasty (PVP).Methods:The clinical data of 274 patients who underwent PVP treatment for osteoporotic vertebral compression fracture (OVCF) in Beijing Friendship Hospital, Capital Medical University from May 2023 to August 2024 were retrospectively analyzed. The patients were divided into two groups according to the different numbers of surgical segments: the single-segment group ( n=211) and the multisegment group ( n=63). Patients in the single-segment group underwent single-segment surgery, while patients in the multisegment group underwent surgery on ≥2 segments. The core points of the ERAS clinical pathway adopted in this study include perioperative education, pain management, early mobilization, application of "outfast", and joint guidance from the departments of nutrition and rehabilitation. Comparison was made between the two groups of patients in terms of visual analog scale (VAS) scores for low back pain at preoperative, 2 h, 6 h, 24 h postoperatively, and on the day of discharge; Oswestry disability index (ODI) scores preoperatively and on the day of discharge; time to first ambulation postoperatively, total length of hospital stay, postoperative length of stay, perioperative complications, and perioperative application of Opioid consumption. Measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; count data were expressed as cases and percentage, and the Chi-square test was used for comparison between groups. The VAS pain scores at each stage of the perioperative period were evaluated using repeated measures analysis of variance or generalized estimating equations. Results:Compared with that before the operation [(6.17±0.93) points, (6.29±0.83) points], the VAS scores of low back pain of patients in the single-segment group and the multisegment group at 2 hours after surgery [(3.09±0.82) points, (3.27±0.65) points], 6 hours after surgery [(2.60±0.79) points, (2.62±0.55) points], and 24 hours after surgery [(1.89±0.77) points, (1.97±0.72) points] and on the day of discharge [(1.72±0.71) points, (1.81±0.64) points] were significantly decreased, and the differences were statistically significant ( P<0.05). At the same stage, the VAS scores of low back pain in both groups were not statistically significant ( P>0.05). The ODI scores of patients in the single-segment group and the multisegment group on the day of discharge [(24.21±2.35) points, (24.63±3.31) points] were significantly lower than those before the operation [(64.50±4.81) points, (65.52±4.08) points], and the differences were statistically significant ( P<0.05). There were no statistically significant differences in perioperative complications and the proportion of Opioid drug application between the two groups of patients ( P>0.05). Conclusion:For patients with single-segment or multisegment OVCF, PVP surgical treatment under ERAS clinical pathway management can achieve immediate pain relief, early ambulation exercise, and satisfactory perioperative efficacy.

Brain organoids are three-dimensional (3D) neural cultures that self-organize from pluripotent stem cells (PSCs) cultured in vitro. Compared with traditional two-dimensional (2D) neural cell culture systems, brain organoids demonstrate a significantly enhanced capacity to faithfully replicate key aspects of the human brain, including cellular diversity, 3D tissue architecture, and functional neural network activity. Importantly, they also overcome the inherent limitations of animal models, which often differ from human biology in terms of genetic background and brain structure. Owing to these advantages, brain organoids have emerged as a powerful tool for recapitulating human-specific developmental processes, disease mechanisms, and pharmacological responses, thereby providing an indispensable model for advancing our understanding of human brain development and neurological disorders. Despite their considerable potential, conventional brain organoids face a critical limitation: the absence of a functional vascular system. This deficiency results in inadequate oxygen and nutrient delivery to the core regions of the organoid, ultimately constraining long-term viability and functional maturation. Moreover, the lack of early neurovascular interactions prevents these models from fully recapitulating the human brain microenvironment. In recent years, the introduction of vascularization strategies has significantly enhanced the physiological relevance of brain organoid models. Researchers have successfully developed various vascularized brain organoid models through multiple innovative approaches. Biological methods, for example, involve co-culturing brain organoids with endothelial cells to induce the formation of static vascular networks. Alternatively, co-differentiation strategies direct both mesodermal and ectodermal lineages to generate vascularized tissues, while fusion techniques combine pre-formed vascular organoids with brain organoids. Beyond biological approaches, tissue engineering techniques have played a pivotal role in promoting vascularization. Microfluidic systems enable the creation of dynamic, perfusable vascular networks that mimic blood flow, while 3D printing technologies allow for the precise fabrication of artificial vascular scaffolds tailored to the organoid’s architecture. Additionally, in vivo transplantation strategies facilitate the formation of functional, blood-perfused vascular networks through host-derived vascular infiltration. The incorporation of vascularization has yielded multiple benefits for brain organoid models. It alleviates hypoxia within the organoid core, thereby improving cell survival and supporting long-term culture and maturation. Furthermore, vascularized organoids recapitulate critical features of the neurovascular unit, including the early structural and functional characteristics of the blood-brain barrier. These advancements have established vascularized brain organoids as a highly relevant platform for studying neurovascular disorders, drug screening, and other applications. However, achieving sustained, long-term functional perfusion while preserving vascular structural integrity and promoting vascular maturation remains a major challenge in the field. In this review, we systematically outline the key stages of human neurovascular development and provide a comprehensive analysis of the various strategies employed to construct vascularized brain organoids. We further present a detailed comparative assessment of different vascularization techniques, highlighting their respective strengths and limitations. Additionally, we summarize the principal challenges currently faced in brain organoid vascularization and discuss the specific technical obstacles that persist. Finally, in the outlook section, we elaborate on the promising applications of vascularized brain organoids in disease modeling and drug testing, address the main controversies and unresolved questions in the field, and propose potential directions for future research.