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.

Objective To investigate the feasibility of constructing the risk index of Echinococcus infection based on the classification of echinococcosis lesions, so as to provide insights into the management of echinococcosis. Methods The imaging data of echinococcosis cases were collected from epidemiological surveys of echinococcosis in China from 2012 to 2016, and the detection of incident echinococcosis cases was captured from the annual echinococcosis prevention and control reports across provinces (autonomous regions) and Xinjiang Production and Construction Corps in China from 2017 to 2022. After echinococcosis lesions were classified, a risk index of Echinococcus infection was constructed based on the principle of discrete distribution marginal probability and multi-group classification data tests. The correlation between the risk index of Echinococcus infection and the detection of incident echinococcosis cases was evaluated in the provinces (autonomous regions and corps) from 2017 to 2022, and the correlations between the short and medium-term risk indices and between the medium and long-term risk indices of Echinococcus infection were examined using a univariate linear regression model. Results A total of 4 014 echinococcosis cases in China from 2012 to 2016 were included in this study. The short-, medium- and long-term risk indices of E. granulosus infection varied in echinococcosis-endemic provinces (autonomous regions and corps) of China (χ² = 4.12 to 708.65, all P values < 0.05), with high short- (0.058), medium- (0.137) and long-term risk indices (0.104) in Tibet Autonomous Region, and the short-, medium- and long-term risk indices of E. multilocularis infection varied in echinococcosis-endemic provinces (autonomous regions and corps) of China (χ² = 6.74 to 122.60, all P values < 0.05), with a high short-term risk index in Sichuan Province (0.016) and high medium- (0.009) and long-term risk indices in Qinghai Province (0.018). There were no significant correlations between the risk index of E. granulosus infection and the detection of incident cystic echinococcosis cases during the study period (t = −0.518 to 2.265, all P values > 0.05), and strong correlations were found between the risk indices of E. multilocularis infection and the detection of incident alveolar echinococcosis cases (including mixed type) in 2018, 2020, 2021, 2022, during the period from 2017 through 2020, from 2017 through 2021, from 2017 through 2022 (all r values > 0.7, t = 2.521 to 3.692, all P values < 0.05). Linear regression models were established between the risk index of E. multilocular infection and the detection of alveolar echinococcosis cases (including mixed type), and the models were all statistically significant (b = 0.214 to 2.168, t = 2.458 to 3.692, F = 6.044 to 13.629, all P values < 0.05). The regression coefficients for the correlations between the medium- and short-term, and between the long- and medium-term risk indices of E. granulosus infection were 2.339 and 0.765, and the regression coefficients for the correlations between the medium- and short-term, and between the long- and medium-term risk indices of E. multilocular infection were 0.280 and 1.842, with statistical significance seen in both the regression coefficients and regression models (t = 16.479 to 197.304, F = 271.570 to 38 928.860, all P values < 0.05). Conclusions The risk index of Echinococcus infection has been successfully established based on the classification of echinococcosis lesions, which may provide insights into the prevention and control, prediction, diagnosis and treatment, and classified management of echinococcosis.

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.

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.

Objective:To investigate the influencing of portal vein embolization (PVE) and PVE combined with transcatheter arterial chemoembolization (TACE) on secondary hepatectomy and prognosis of patients with initially unresectable hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 102 patients with initially unresectable HCC who were admitted to the Third Affiliated Hospital of Naval Medical University from October 26,2015 to December 31,2022 were collected. There were 82 males and 20 females, aged 52(range,25?73)years. Of 102 patients, 72 cases undergoing PVE combined with TACE were set as the PVE+TACE group, and 30 cases undergoing PVE were set as the PVE group. Observation indicators: (1) surgical resection rate of secondary hepatectomy and increase of future liver remnant (FLR); (2) situations of secondary hepatectomy; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Results:(1) Surgical resection rate of secondary hepatectomy and increase of FLR. The surgical resection rate of secondary hepatectomy in the PVE+TACE group and the PVE group were 72.2%(52/72) and 53.3%(16/30), respectively, showing no significant difference between the two groups ( χ2=3.400, P>0.05). The surgical waiting time, increasing volume of FLR, growth rate of FLR in the 52 patients of PVE+TACE group receiving secon-dary hepatectomy were 20(range, 14?140)days, 140(range, 62?424)mL, 9.8(range, 1.5?26.5)mL/day, respectively. The above indicators in the 16 patients of PVE group receiving secondary hepatectomy were 16(range, 12?35)days, 160(range, 95?408)mL, 10.5(range, 1.2?28.0)mL/day, respectively. There was no significant difference in the above indicators between the 52 patients of PVE+TACE group and the 16 patients of PVE group ( Z=1.830, 1.498, 1.266, P>0.05). (2) Situations of secondary hepatectomy. The operation time, rate of tumor necrosis (>90%, 60%?90%,<60%), cases with complications ≥ grade Ⅲa in the 52 patients of PVE+TACE group receiving secondary hepatectomy were 200(range, 125?420)minutes, 8, 4, 40, 28, respectively. The above indicators in the 16 patients of PVE group receiving secondary hepatectomy were 170(range, 105?320)minutes, 0, 0, 16, 4, respectively. There were significant differences in the above indicators between the 52 patients of PVE+TACE group and the 16 patients of PVE group ( Z=2.132, ?2.093, χ2=4.087, P<0.05). (3) Follow-up. Sixty-eight patients who completed the surgery were followed up for 40(range, 10?84)months. The 1-, 3-, 5-year recurrence free survival rate in the 52 patients of PVE+TACE group receiving secondary hepatectomy were 73.0%, 53.3%, 35.4%, respectively. The above indicators in the 16 patients of PVE group were 62.5%, 37.5%, 18.8%, respectively. There was a significant difference in the recurrence free survival rate between the 52 patients of PVE+TACE group and the 16 patients of PVE group ( χ2=4.035, P<0.05). The 1-, 3-, 5-year overall survival rate in the 52 patients of PVE+TACE group receiving secondary hepatectomy were 82.5%, 61.2%, 36.6%, respectively. The above indica-tors in the 16 patients of PVE group receiving secondary hepatectomy were 68.8%, 41.7%,20.8%, respectively. There was a significant difference in the overall survival rate between the 52 patients of PVE+TACE group and the 16 patients of PVE group ( χ2=4.767, P<0.05). Conclusion:Compared with PVE, PVE+TACE as stage Ⅰ surgery can increase the surgical resection rate of secondary hepatec-tomy and the recurrence free survival rate of patients with initially unresectable HCC, prolong the long-term survival time, but not influence the growth rate of FLR.

Objective To investigate the effect of acupuncture on the morphology of the dry eye rabbit's cornea and the nuclear factor κB(NF-κB)signaling pathway of the corneal tissue to analyze the mechanism of acupuncture on dry eyes.Methods Twenty-four healthy New Zealand rabbits,without restriction on sex,were randomly divided into four groups,including a blank group,a model group,an acupuncture group,and a sham acupuncture group,with 6 in each group.Rabbits in the blank group were not treated;rabbits in the other three groups were treated with scopolamine hydro-bromide 2.0 mg·kg-1 by subcutaneous injection at 8:00,11:00,14:00 and 18:00 each day for 35 consecutive days un-til the end of the experiment.Rabbits in the sham acupuncture group were treated with sham acupuncture on the 22nd day after successful modeling by quickly pricking acupoints(Jingming BL1,Cuanzhu BL2,Sizhukong SJ23,Taiyang EX-HN5 and Tongziliao GB1)with a blunt acupuncture needle,once a day,for a total of 14 days.Rabbits in the acupuncture group were treated with acupuncture at the same acupoints as the sham acupuncture group after successful modeling.The corneal fluorescence staining was conducted on Days 0,21,28 and 35 after modeling.On Day 35,corneal confocal microscope ex-aminations were conducted.Then,the rabbits were sacrificed,the corneal morphological changes were observed by light microscope and transmission electron microscope,and the expression of corneal NF-κB protein was detected by Western blot.Results Compared with the model group,the score of rabbit corneal fluorescein staining in the acupuncture group and blank group decreased on the 28th and 35th days after modeling,and the differences were statistically significant(all P＜0.05).The results of the confocal microscope examination on Day 35 after modeling showed that,compared with other groups,there were a large number of globular immune cells and activated stromal cells with unclear boundaries and irregu-lar sizes in the stromal layer and inflammation in the area with irregular intercellular space in the model group and the sham acupuncture group.In the acupuncture group,the morphology of stromal layer cells improved,the cells were slightly acti-vated,and there were no obvious abnormalities in the corneal nerve morphology.On the 35th day after modeling,the re-sults of the light microscope showed that,the surface of the corneal tissue in the model group and the sham acupuncture group showed hyperkeratinized flat epithelial cells,lymphocyte infiltration,increased number of focal epithelial cell layers,and epithelial cell detachment.In the acupuncture group,there were 4-6 layers of epithelial cells in the corneal epitheli-um,and epithelial shedding decreased.In addition,the lymphocyte infiltration decreased compared with the model group.On the 35th day after modeling,the results of the transmission electron microscope showed that abnormal microvilli oc-curred and epithelial cells were absent in the corneal epithelial cells of rabbits in the model group and the sham acupuncture group,the cell space was widened,the rough endoplasmic reticulum was severely expanded,and desmosomes were dis-banded with mitochondrial swelling.In the acupuncture group,the microvilli structure of epithelial cells was sparse and short,local deletion was still observed,the rough endoplasmic reticulum was slightly expanded,and no obvious swelling of mitochondria was observed.On the 35th day after modeling,the Western blot examination results showed that,compared with the blank group,the expression of p-NF-κB p65 was up-regulated in both the model group and sham acupuncture group(both P＜0.05);compared with the model group and sham acupuncture group,the expression of p-NF-κB p65 in the acupuncture group was down-regulated(both P＜0.05).Conclusion Acupuncture can inhibit the NF-κB signaling path-way to play an anti-inflammatory role and relieve corneal inflammation and injury of dry eye rabbit models.

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.