BACKGROUND:Osteoblasts are the main cell types responsible for bone formation and remodeling,and the normal performance of their function is precisely regulated by various signaling pathways.Among them,the bone morphogenetic protein and Wnt signaling pathways play a key role in osteogenesis. OBJECTIVE:To review the role of bone morphogenetic protein/Wnt signaling pathway in the regulation of osteoblast function and analyze its changes in different physiological and pathological conditions in order to further reveal the molecular mechanism of bone formation and remodeling. METHODS:The Chinese and English search terms"BMP signaling pathway,Wnt signaling pathway,and osteogenesis"were searched in CNKI,Wanfang,and PubMed databases for original researches published from the inception to June 2023.Totally 61 articles were finally selected for analysis and summary.Using the method of the literature review,the studies of the bone morphogenetic protein/Wnt signaling pathway in regulating osteogenesis were sorted out and analyzed. RESULTS AND CONCLUSION:(1)Bone morphogenetic protein and Wnt signaling pathways play important roles in the differentiation,proliferation,and maturation of osteoblasts.Bone morphogenetic protein signaling pathway mainly regulates the expression of osteogenesis-related genes through the activation of Smad protein.Smad protein enters the nucleus and regulates the expression of genes related to osteogenesis.Different Wnt signaling pathway from bone morphogenetic protein mainly depends on the activation of β-catenin to exert its biological effects.(2)The regulatory effect of bone morphogenetic protein/Wnt signaling pathway will be affected by many factors in different physiological and pathological states.Growth factors,hormones,and mechanical stress can affect the activity of bone morphogenetic protein/Wnt signaling pathway to some extent.(3)Bone morphogenetic protein/Wnt signaling pathway interacts with other signaling pathways in the regulation of osteogenesis,and they together constitute a complex regulatory network.(4)Chinese medicine and natural compounds can promote bone health by regulating signaling pathways,providing new possibilities for treating bone diseases.(5)Future studies can further explore the interaction of bone morphogenetic protein/Wnt signaling pathway and other signaling pathways and its changes in different physiological and pathological conditions,resolve the key nodes and regulation mechanism in the complex network,to provide more precise targets for the treatment of bone-related diseases,and also provide new ideas to reveal the molecular mechanism of bone formation and remodeling.

Dry eye disease is a multifactorial chronic ocular surface disorder that is challenging to manage because its pathogenesis is not well understood. The gut-eye axis theory provides insights into its pathogenesis to guide prevention and treatment. Intestinal flora dysbiosis induces dry eye disease through complex mechanisms involving inflammation, ocular surface microbiota, nerve damage, and microbial metabolites. This article reviews the immunometabolic regulation of the gut-eye axis and summarizes gut flora-targeted interventions(fecal microbiota transplantation, probiotic supplementation, and dietary modification)to provide a theoretical basis for dry eye disease prevention and treatment.

Objective: To understand current state of physical health levels of first year students in different body mass index (BMI) categories in Ningxia universities, and to explore the correlation between BMI and physical fitness index (PFI), so as to provide a reference for enhancing physical health levels of university students. Methods: In November 2024, physical fitness test data from 16 631 first year students across four universities in Yinchuan City, Ningxia from 2019 to 2023 were collected by adopting convenience and stratified cluster random sampling methods. The PFI was calculated using the Z score of the physical fitness test results, and a nonlinear quadratic model was established via least squares regression to examine the relationship between BMI and PFI among university students. Results: The BMI for males was (21.69±3.53)kg/m 2, while for females was (20.78±2.94)kg/m 2. The composite score for males physical fitness (69.86±9.25) was lower than that for females (72.24± 8.15 ), with a statistically significant difference ( t =-17.54, P <0.01). Moreover, the failure rates of various physical fitness indicators (vital capacity, sit and reach, standing long jump, pull ups/1 minute sit ups, 1 000 m/800 m run) were higher among males than females ( χ 2=103.48, 72.45, 14.38, 5 134.85, 188.89, all P <0.01). Comparisons across BMI categories revealed that among males, the normal weight group outperformed other groups in the 50 m sprint, standing long jump, 1 000 m sprint, composite score, and PFI ( F =89.17, 113.90, 179.02, 573.35, 593.08); among female students, the normal weight group outperformed other groups in the 50 m sprint, sit and reach, 800 m run, composite score, and PFI ( F =10.67, 19.58 , 96.45, 294.05, 183.45) (all P <0.01). The relationship between BMI and PFI among first year students exhibited a parabolic change trend, students with a moderate BMI demonstrated higher PFI, and as BMI increased, PFI decreased (all P <0.01). Conclusions The physical health level of male students in Ningxia universities is lower than that of female students. There is a correlation between BMI classification and PFI. Tailored intervention measures should be implemented according to the physical characteristics of students across different genders and BMI classifications to enhance university students physical health.

5-Hydroxytryptamine(5-HT)type 3 receptor(5-HT3R)is the only type of ligand-gated ion channel in the 5-HT receptor family.Through the high permeability of Na+,K+,and Ca2+ and activation of subsequent voltage-gated calcium channels(VGCCs),5-HT3R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system(CNS).5-HT3Rs are widely expressed in the medial prefrontal cortex(mPFC),amygdala(AMYG),hippocampus(HIP),periaqueductal gray(PAG),and other brain regions closely associated with anxiety reactions.They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions.5-HT3Rs mediate the activation of the cholecystokinin(CCK)system in the AMYG,and the γ-aminobutyric acid(GABA)"disinhibition"mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons(IINs).In contrast,a 5-HT3R-induced GABA"disinhibition"mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects.5-HT2R-mediated regulation of anxiety reactions are also activated by 5-HT3R-activated 5-HT release in the HIP and PAG.This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT3Rs.However,given the circuit specific modulation of 5-HT3Rs on emotion,systemic use of 5-HT3R agonism or antagonism alone seems unlikely to remedy anxiety,which deeply hinders the current clinical application of 5-HT3R drugs.Therefore,the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.

Objective To explore the influencing factors of device-related pressure injuries (DRPI) in critically ill patients, construct a risk prediction model, and validate its effectiveness. Methods A retrospective analysis was conducted on the clinical data of 136 critically ill patients. Based on the occurrence of DRPIs, the patients were divided into occurrence group (32 patients) and non-occurrence group (104 patients). Univariate analysis and binary Logistic regression analysis were used to investigate the influencing factors of DRPIs, and a binary Logistic regression model was constructed. The Hosmer-Lemeshow test was used to assess the goodness of fit of the model, and the area (AUC) under the receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the model.Additionally, the Bootstrap method was employed for internal validation of the model. Results Univariate analysis revealed statistically significant differences between the two groups in terms of age, diabetes, ICU stay duration, duration of non-invasive ventilation mask use, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, Braden scale score, use of vasoactive drugs, prone position ventilation, hemoglobin levels, and lactate levels (P < 0.05). Binary Logistic regression analysis indicated that age, diabetes, ICU stay duration, APACHE Ⅱ score, duration of non-invasive ventilation mask use, use of vasoactive drugs, prone position ventilation, lactate levels, Braden scale score, and hemoglobin levels were independent influencing factors for DRPIs in critically ill patients (P < 0.05). A binary Logistic regression model for predicting the risk of DRPIs in critically ill patients was constructed based on these independent factors. The overall prediction accuracy of the model was 99.26%. The Hosmer-Lemeshow goodness-of-fit test showed that the model had good fitness (χ² < 0.001, P>0.999). Internal validation using the Bootstrap method and ROC curve analysis showed that the AUC of the model for predicting DRPIs in critically ill patientswas 0.952, with a sensitivity of 87.5% and a specificity of 93.3%. Conclusion The risk prediction model for DRPIs in critically ill patients constructed in this study demonstrates good stability and predictive performance. It can assist clinical healthcare professionals in screening high-risk patients and formulating personalized intervention plans.

Objective:To analyze the characteristics of patients with chronic rhinosinusitis (CRS) in the South China region based on pathological tissue biomarkers for regional comparison.Methods:The study population consisted of CRS in-patients in the First Affiliated Hospital of Sun Yat-sen University from October 2019 to June 2022. Among all the 181 cases, 123 of them were male and 58 were female, with an average age of 40. Retrospectively collected clinical data included demographic information, preoperative symptom scores, preoperative endoscopic images, preoperative paranasal sinus computed tomography scanning images, and inflammatory serological features. In addition, 52 variables of pathological tissue biomarkers including cytokines, chemokines and remodeling factors were collected for analysis. Cluster analysis was performed on the integrated data of training set through centroid-based clustering algorithm, and the inflammatory characteristics, post-operation control status, and airway diseases comorbidity of each endotype were analyzed. R project (version 4.2.2) was used in statistical analysis.Results:Cluster analysis divided 181 patients with CRS into 4 endotypes. Cluster 1 ( n=101, 55.80%) showed a locally low inflammatory status. Cluster 2 ( n=23, 12.71%) showed a mixed type of inflammation with predominantly neutrophilic inflammation and tissue remodeling. Cluster 3 ( n=11, 6.08%) was characterized by type Ⅱ inflammation without tissue remodeling. Cluster 4 ( n=46, 25.41%) was mainly characterized by type Ⅱ inflammation with tissue remodeling, showing higher comorbidity rate of asthma and allergic rhinitis. This cluster presented more severe symptoms, significant olfactory dysfunction, extensive overall inflammation based on objective examination results, a notable increase in total eosinophil count and proportion in peripheral blood, and the highest uncontrolled rate observed one year post-surgery. In comparison to other regions, the endotype classification of CRS in Southern China was characterized by a predominant pattern of locally low inflammatory status, a moderate level of type Ⅱ inflammation with tissue remodeling, and a lesser presence of neutrophilic inflammation. Conclusion:CRS distribution in Southern China is mainly characterized by low inflammatory endotype and type Ⅱ inflammation with tissue remodeling. The latter shows more severe clinical manifestations and higher uncontrol rate after surgery.

OBJECTIVE To provide reference for strengthening the standardized management of off-label drug use in cancer hospitals. METHODS The evaluation system for off-label drug use was established to standardize the application， approval， and filing process for off-label drug use in our hospital. The changes in off-label drug application quantity， proportion， disease category and drug category in our hospital were compared before （October 1st， 2021-September 30th， 2022） and after （October 1st， 2022- September 30th， 2023） the establishment of the evaluation system； drug items supported by high-level evidence screened by pharmacy department were analyzed statistically. RESULTS The number of off-label drug use applications in our hospital had gradually increased， from 306 pieces in the fourth quarter of 2021 to 3 828 pieces in the third quarter of 2023. In the year before the construction of the evaluation system， there were a total of 4 482 applications for off-label drug use， and in the year after the construction of the evaluation system， there were 11 840 applications for off-label drug use. After the construction of the evaluation system， the proportion of unregistered off-label drug use significantly decreased， compared to the same period last year （P＜0.05）. Among them， there were no unregistered applications for off-label drug use for digestive system tumors， head and neck tumors， and radioactive drugs； lymphoma， breast tumors，urogenital system tumors， cytotoxic drugs and new anti-tumor drugs all had a decrease of over 70% in unregistered off-label drug applications. Twenty-seven off-label drug use items related to 19 drugs supported by high-level evidence were screened by the pharmacy department of our hospital， among which 25 items were drug use beyond indication. CONCLUSIONS The establishment of off-label drug use evaluation system in cancer hospital is helpful to the rational use and refined management of clinical anti-tumor drugs.

ObjectiveTo demonstrate the long-term effect of Yishi Therapy for primary tinnitus and analyze the factors affecting the effectiveness. MethodsWe conducted long-term follow-ups of primary tinnitus cases treated with Yishi Therapy during 1 January 2017 to 30 June 2023 by face-to-face， online and telephone between 1 July 2023 and 31 January 2024， to understand the final regression of primary tinnitus and lifestyle changes. We retrospectively analysed the basic data of patients before treatment， and statistically analysed the recovery rate and overall effective rate of tinnitus treated by the Yishi Therapy， and the factors affecting the effectiveness such as lifestyle， age， duration of disease， gender， tinnitus location， severity of tinnitus， accompanying symptoms and complications on the overall effective rate. ResultsA total of 496 cases of primary tinnitus completed follow-ups successfully， and the total Tinnitus Evaluation Questionnaire （TEQ） at follow-up was significantly lower than that before treatment （P＜0.001）. Among the 496 cases， 101 （20.36%） cases cured， 189 （38.10%） cases showed significant improvement， 116 （23.39%） cases were effective， 90 （18.15%） cases were ineffective， and the overall effect rate was 81.85% （406/496）. At follow-up， the score of lifestyle was higher than that before treatment （P＜0.001）. Grouped by the score of lifestyle at follow-up， the effective rates of better lifestyle group and poor lifestyle group were 97.53% （237/243） and 66.80% （169/253）， respectively， with statistical significance （P＜0.001）. Grouped by the mean value of the difference in lifestyle scores before and after treatment， the effective rates of the group with greater lifestyle adjustment and the group with smaller adjustment were 97.55% （239/245） and 66.53% （167/251）， respectively， and the differences were statistically significant （P＜0.001）. Binary logistic regression showed that the better lifestyle， the greater lifestyle adjustment and the severity of tinnitus were positively correlated with the total effective rate of tinnitus （P＜0.001）， while older and hearing loss were negatively correlated with the total effective rate of tinnitus （P＜0.05）. ConclusionYishi Therapy on primary tinnitus shows good long-term effect， lifestyle， severity of tinnitus， hearing loss or not， age are the relevant factors affecting the efficacy of tinnitus， lifestyle is the main factor affecting clinical efficacy.

OBJECTIVE To elucidate the possible mechanism, and to explore the main components, core targets, and key signaling pathways of Haimufang Decoction(HMF) in treating non-small cell lung cancer(NSCLC) by the network pharmacology and serum pharmacology methods. METHODS TCMSP and DisGeNET databases were used to search and summarize the components, targets and non-small cell lung cancer-related targets of HMF, respectively. The common targets were obtained by intersection of drug targets and disease targets, and uploaded to the STRING data platform to construct a protein-protein interaction(PPI) network to screen core targets. GO and KEGG enrichment analysis of core targets were performed using DAVID database. Cytoscape 3.9.1 software was used to construct the network of "HMF flavor-components-targets-pathways", predicting the possible mechanisms of action of HMF. Finally, the cell cycle arrest and apoptosis induction experiments of HMF-containing serum on NSCLC NCI-H1975 cells were used to verify the effect of HMF on lung cancer and its potential mechanism. RESULTS A total of 65 compounds were identified from HMF, and 47 main compounds such as 24-keto-cholesterol, quercetin and diisobutyl phthalate were screened out. PPI network analysis shown that tumor protein p53, tumor necrosis factor, cystein-asparate protease-3 and other 55 proteins might be the core target proteins of HMF in the treatment of NSCLC, involving multiple signaling pathways such as pathways in cancer. In subsequent validation experiments, cell cycle arrest and apoptosis induction in the pathways in cancer pathway have been shown to be involved in the inhibition of non-small cell lung cancer. CONCLUSION HMF plays a role in the treatment of NSCLC through multi-component, multi-target and multi-channel signaling pathways, which provides a theoretical basis for the mechanism and clinical application of HMF.

BACKGROUND:The occurrence and development of osteoarthritis is strongly associated with immune abnormalities,and the importance of various immune cells and immune mediators in the pathogenesis of osteoarthritis has been continuously elucidated. OBJECTIVE:To review the role of immune cells and related cytokines in osteoarthritis disease,and provide new ideas for future research and prevention of osteoarthritis. METHODS:Taking"osteoarthritis,knee,macrophages,T cells,B cells,natural killer cells,dendritic cells,cytokines,inflammatory factors,immune cells"as search terms,relevant published literature was searched on CNKI,WanFang,VIP,PubMed and Web of Science databases.After reading the title and abstract for preliminary screening,98 articles were selected for review after reading the full text again. RESULTS AND CONCLUSION:In the past,it was believed that the pathogenesis of osteoarthritis was associated with cartilage wear.In recent years,studies have suggested that osteoarthritis is a chronic inflammatory state in which immune cells are widely involved.With the in-depth study of the pathogenesis of osteoarthritis,scholars believe that the pathogenesis of osteoarthritis is driven by early innate immune response,which will gradually catalyze degenerative changes and eventually lead to changes in the joint microenvironment.Various immune cells and cytokines are the key factors affecting the repair of osteoarthritis.Macrophages and natural killer cells participate in synovial inflammatory reaction,and T cell immune reaction participates in the degradation of osteoarthritis cartilage and aggravates the condition of osteoarthritis.Interleukin-1β secreted by immune cells,interleukin-6,tumor necrosis factor α,interleukin-17 and interleukin-37 play an important role in the pathophysiology of osteoarthritis,among which interleukin-1β is the most important inflammatory factor causing articular cartilage damage.Assessing immunological risk factors at the early stage of osteoarthritis can effectively treat the disease at an early stage,which can significantly reduce disability,morbidity and costs associated with osteoarthritis.At present,the immunomodulatory effect of stem cells and their derived secretions and biomaterials on the treatment of osteoarthritis has been confirmed in different experimental models,but there is still a lot of research to be done before they are used in clinical practice.With the discovery of new therapeutic targets,targeted treatment will bring new hope for the repair of clinical osteoarthritis.