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.

This article summarized Professor YAN Xiaoping's clinical experience in treating enthesitis-related juvenile idiopathic arthritis （ERA）. The core pathogenesis of ERA is identified as kidney deficiency with pathogenic invasion， for which the basic treatment principle is tonifying the kidney and eliminating the pathogen. ERA is classified into "two stages and three syndromes" for differentiation and treatment. In the acute stage， the pathogenesis is primarily kidney deficiency with pathogen excess； for heat syndrome， it is suggested to tonify the kidneys and clear heat， using a self-made Bushen Qingre Lijie Decoction （补肾清热利节汤）； for cold syndrome， the treatment is to tonify the kidneys and expel cold， using a self-made Bushen Qyuhan Lijie Decoction （补肾祛寒利节汤）. In the remission stage， the pathogenesis is primarily spleen and kidney deficiency， and the basic treatment principle is to tonify the kidneys and fortify the spleen， and strengthen bones and muscles， for which self-made Bushen Jianpi Lijie Decoction （补肾健脾利节汤） is recommended.

Objective To explore the effective induction scheme for differentiation of adipose-derived mesenchymal stem cell (ADMSC) to insulin producing cell (IPC). Methods Different schemes of small molecule compound were used to induce the differentiation of ADMSC. The purity of cells was analyzed by flow cytometry and the morphological changes of cells were observed under the microscope. The quality, performance and insulin related indicators of cells were detected by hematoxylin-eosin and immunohistochemical staining. The maturity and activity of cells were detected by dithizone (DTZ) and diacetylfluorescein/propidium iodide staining. The induction effect of ADMSC differentiated into IPC was analyzed. Results The purity of ADMSC reached more than 99%, and the sphere forming properties of schemes Ⅰ, Ⅱ and Ⅲ were good. Cell induction mass, the expression effects of pancreatic and duodenal homeobox 1 (PDX1), musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) and insulin and C peptide of schemes Ⅰ were both better than those of other schemes. The DTZ staining depth may be related to IPC maturity, among which the number of apoptotic cells in scheme Ⅰ was significantly less than that of scheme Ⅱ and Ⅲ. Conclusions Induction scheme Ⅰ may improve the differentiation efficiency of ADMSC to IPC and lay a certain foundation for future clinical IPC transplantation applications.

Pulmonary hypertension （PH） is a severe and rare chronic cardiopulmonary disorder for which existing vasodilator therapies can only alleviate symptoms， rather than target or fundamentally reverse the disease. Additionally， the long-term prognosis remains poor. Recent studies have found that some novel anti-tumor drugs （NADs） can relieve PH， such as imatinib， gefitinib， sorafenib， olaparib， piperacillin， everolimus， rituximab， etc. However， some NADs can induce PH or exacerbate its symptoms， including dasatinib， lorlatinib， carfilzomib， bevacizumab， trastuzumab， nivolumab， etc. The effects of lapatinib， ruxolitinib， and bortezomib on PAH are controversial. Individualized medication should be adopted in clinical practice when using NADs for treatment， with close monitoring being essential.

Olfactory disorders are a common symptom in patients with chronic rhinosinusitis, and their diagnosis and treatment have garnered extensive attention from both patients and doctors. Currently, there are various evaluation and treatment methods for olfactory dysfunction; however, choosing a simpler and more accurate assessment, as well as an effective treatment, remains a clinical challenge. In this article, we review the assessment and treatment methods commonly used in clinical practice in recent years to provide better support for the diagnosis and treatment of olfactory disorders.
Humans ; Olfaction Disorders/etiology* ; Sinusitis/complications* ; Chronic Disease ; Rhinitis/complications* ; Rhinosinusitis

Liver fibrosis is a vital cause of morbidity in patients with liver diseases and developing novel anti-fibrotic drugs is imperative. Isovalerylspiramycin I (ISP I) as a major component of carrimycin applied to upper respiratory infections, was first found to possess anti-fibrotic potential. The present study aims to evaluate the functions and mechanisms of ISP I in protecting against liver fibrosis. According to our results, ISP I not only reduced the expressions of fibrogenic markers in LX-2 cells but also appeared great protective effects on liver injury and liver fibrosis in bile duct ligation (BDL) rats and carbon tetrachloride (CCl₄) mice. We proved that nucleotide-binding protein 2 (NUBP2) was the direct target of ISP I. ISP I through targeting NUBP2, increased the amount of vascular non-inflammatory molecule-1 (VNN1) on the cell membrane, which will inhibit oxidative stress and fibrosis. Simultaneously, the original carrimycin's protective effect on liver damage and fibrosis was verified. Therefore, our study provides potential agents for patients with liver fibrosis-related diseases, and the clear mechanism supports wide application in the clinic.

Objective : To investigate the diagnostic value of linear array endoscopic ultrasonography ( EUS) for common bile duct microlithiasis． Methods : Data of patients who attended in the hospital and diagnosed as common bile duct microlithiasis and biliary sludge by EUS were selected．A total of 85 patients with magnetic resonance cholangiopancreatography ( MRCP) examination and ERCP treatment during hospitalization were enrolled．The results of endoscopic retrograde cholangiopancreatography / endoscopic sphincterotomy ( ERCP / EST) were the gold standard for diagnosis．The results of EUS，MRCP，and diagnostic ERCP were compared with the gold standard， and the sensitivity，specificity，positive predictive value，negative predictive value，and diagnostic accuracy of the three methods were calculated，respectively．The chi-square test was used for comparison of the above indices． Results : Of all 85 patients，63 had positive EUS results，among whom 5 had false positive results; 22 had negative EUS results，among whom 1 had false negative results．Of all 85 patients，49 had positive MRCP results，among whom 4 had false positive results; 36 had negative MRCP results，among whom 14 had false negative results．Of all 85 patients，59 had positive diagnostic ERCP results，among whom 10 had false positive results; 26 had negative diagnostic ERCP results，among whom 10 had false negative results．The sensitivity，specificity，positive predictive value( PPV) ，negative predictive value ( NPV) ，and accuracy of EUS in diagnosing common bile duct microlithia- sis were 98. 3% ，80. 8% ，92. 1% ，95. 4% and 92. 9% ，respectively． For MRCP，these values were 76. 3% ， 84. 6% ，91. 8% ，61. 1% and 78. 8% ，respectively．For diagnostic ERCP，these values were 83. 1% ，61. 5% ， 83. 1% ，61. 5% and 76. 5% ，respectively．The EUS group had a significantly higher accuracy than the MRCP group ( χ2 = 6. 986，P ＜0. 05) and diagnostic ERCP group ( χ2 = 8. 900，P ＜0. 05) ．The areas under the ROC curves ( AUC) and 95% CI of EUS group，MRCP group and diagnostic ERCP were 0. 895 ( 95% CI: 0. 802 - 0. 988，P＜0. 001) ，0. 804 ( 95% CI: 0. 702 －0. 907，P ＜0. 001) and 0. 723 ( 95% CI: 0. 598 －0. 848，P = 0. 001) ，respectively． Conclusion EUS has a high diagnostic value in the diagnosis of common bile duct microli- thiasis and thus can be used as the preferred examination before therapeutic ERCP．

Objective To retrospectively analyze multicenter data from domestic sources, aiming to explore the link between intrahepatic cholangiocarcinoma (ICC) tumor size and prognosis, establishing a classification system based on tumor size. Methods Between December 2011 and September 2018, 280 ICC patients from 13 hospitals were included. The tumor size prognosis cutoff was identified by the minimum P-value method, and the classification's overall survival related effectiveness was assessed by Kaplan-Meier analysis. Results All 280 patients were divided into the group of tumor maximum diameter ≤4 cm and >4 cm. Tumor size was confirmed as an independent prognosis factor by multivariate COX regression analysis (HR=2.110, 95% CI: 1.358-3.280). Conclusions The tumor size dichotomy classification system based on the Chinese patient group can expediently predict ICC prognosis and offers an important basis for selecting post-operative individualized adjuvant therapy and follow up plans.

Objective To investigate the clinical efficacy of β-blockers in older patients with hypertension combined with vascular dementia.Methods A total of 152 older patients with hypertension combined with vascular dementia who were admitted to Shanxi Provincial Fenyang Hospital between January 2022 and October 2024 were enrolled.The participants were randomly assigned to either the study group or the control group(76 patients each)using the randomized numerical table method.Both groups received conventional treatment,and the study group received metoprolol for 5 weeks in addition to the conventional treatment.Primary outcome indicators,including changes in systolic blood pressure(SBP)and diastolic blood pressure(DBP)before and after treatment,were examined.Additionally,comparison was made to examine the intergroup difference in serological markers,including high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-8,matrix metalloproteinase 9(MMP-9),homocysteine(Hcy),and superoxide dismutase(SOD)levels,and the scores for intelligence,cognitive,and behavioral assessments.Adverse reactions were recorded.Results After treatment,the study group showed reduced SBP from(146.90±7.35)mmHg(1 mmHg=0.133 kPa)to(120.00±6.03)mmHg and reduced DBP from(90.24±5.97)mmHg to(77.23±6.81)mmHg.The reduction in blood pressure in the study group became more significantly when compared with that of the control group,with intergroup difference in SBP reduction being-8.54 mmHg(P<0.001)and intergroup difference in DBP reduction being-10.80 mmHg(P<0.001).Patients in the 2 groups showed statistically significant differences in the levels of hs-CRP,TNF-α,IL-6,IL-8,MMP-9,and Hcy,and in their cognitive and behavioral scores(P<0.05).No statistically significant differences were found in pulse pressure,von Willebrand factor(vWF)levels,or intelligence scores before and after treatment(P>0.05).The main adverse reactions in the study group were central nervous system reactions(22.37%)and withdrawal syndrome(17.11%).Conclusion The β-blocker metoprolol effectively controlled blood pressure,significantly reduced levels of pro-inflammatory factors and specific vascular injury markers,and improved cognitive function and behavioral symptoms in older patients with hypertension combined with vascular dementia,suggesting its therapeutic efficacy for this condition.However,attention should be paid to its associated adverse reactions.