As the important source of bone cells, osteoblasts are involved in bone formation and repair, and play a key role in maintaining bone balance. If the osteogenic differentiation process in vivo is disrupted, a variety of bone-related diseases may occur. Natural products, which have a wide range of sources, a wide variety of physiological activities, and few toxic side-effects, have been found in recent years to be able to regulate osteoblast differentiation. Based on the sources of natural products, this paper reviews the intervention of natural products from plant, animal and microbial sources on osteogenic differentiation, aiming to provide a theoretical basis for natural products in the treatment of bone diseases.

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Objective: To investigate the prevalence of Dengue virus (DENV) infection among voluntary blood donors in Xishuangbanna Dai Autonomous Prefecture, and to evaluate the necessity of implementing nucleic acid testing (NAT) for blood donors during the rainy season (May-October). Methods: Prior to initiating donor screening, the Xishuangbanna Central Blood Center conducted in-house validation of reagent performance and participated in external quality assessment (EQA) organized by the National Center for Clinical Laboratories (NCCL). During the surveillance period (August-October 2024), a total of 2 919 donor samples were screened using a 6-sample mini-pool NAT strategy. Daily internal quality controls were recorded. Samples that tested positive in pooled screening were deconvoluted and retested in duplicate; only those reactive in both replicate wells were sent to the NCCL for confirmatory testing. At NCCL, samples underwent re-testing using five domestic NAT reagents, as well as serological assays for NS1 antigen and DENV-specific IgG/IgM. Confirmed positive samples were further characterized by serotyping, envelope (E) gene sequencing, and phylogenetic analysis using the maximum likelihood method. Results: The DENV NAT reagent demonstrated consistent detection of 40 copies/mL controls in individual donor (ID)-NAT test (mean CT: 35.61±0.40). During the 63-day quality control monitoring, DENV detection remained stable (mean CT: 22.53±0.72). The center achieved full marks in EQA assessments for 2023 and 2024. Three reactive pools were identified in initial screening, and subsequent individual testing confirmed three DENV RNA-positive donors (sample numbers: 2401, 2402, and 2403). The confirmatory test results from NCCL were: all five NAT platforms consistently detected DENV RNA in the three samples; for serological tests, 2 samples (2402, 2403) were positive for NS1 antigen, while all three samples were negative for both IgG and IgM antibodies. DENV serotyping reagents identified DENV-2 in all cases, which were further confirmed as DENV-2 Genotype Ⅱ-Cosmopolitan by E gene sequencing. Phylogenetic analysis indicated that samples 2401 and 2402 clustered with Southeast Asian strains (Thailand/MZ636802.1, Laos/PQ775621.1), while sample 2403 closely matched a previously reported local Yunnan strain (PV544686.1). Conclusion: DENV-2 infection was detected among blood donors in Xishuangbanna during the rainy season, indicating concurrent risks of imported and local transmission. We recommend implementing pooled NAT screening for blood donors in high-risk areas during dengue epidemic seasons, along with strengthened laboratory quality control, to enhance blood safety.

Objective To investigate the effects of adiponectin(APN)on the proliferation,migration,and invasion of ovarian cancer cells and its potential association with the phosphatidylinositol 3-kinase(PI3K)/pro-tein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.Methods A2780 and SK-OV3 cell lines were selected.AdipoR1 mRNA expression was detected by real-time polymerase chain reaction(RT-PCR).The CCK-8 assay was employed to evaluate APN-induced proliferation,while scratch wound heal-ing and Transwell assays were conducted to assess migration and invasion capabilities.Western blot analysis was performed to measure the expression levels of PI3K,Akt,mTOR,and their phosphorylated forms(p-Akt,p-mTOR)at different time points(0-60 min)after APN treatment and across intervention groups(APN,LY294002,APN+LY294002).Results Both A2780 and SKOV3 cells expressed AdipoR1 mRNA.Compared with the control group,APN significantly enhanced the proliferation,migration,and invasion of o-varian cancer cells(P＜0.05).Under the stimulation of APN,the expression levels of p-Akt and p-mTOR in A2780 and SKOV3 cells showed a significant upward trend.The peak expression of p-Akt and p-mTOR in A2780 cells was observed at 30 minutes,while in SKOV3 cells,it occurred at 60 minutes.The expression lev-els of p-Akt and p-mTOR were significantly reduced in the LY294002 group and APN+LY294002 group(P＜0.001).Conclusion APN enhances the proliferation,migration,and invasion behavior of ovarian cancer cells by activating the PI3K/Akt/mTOR signaling pathway,and its effect can be reversed by PI3K inhibitors,providing a theoretical basis for targeted intervention in ovarian cancer progression.

Chronic urticaria （CU） is a common skin disease worldwide， and its incidence is increasing year by year in various regions. Clinical manifestations such as severe itching can affect normal work， sleep， and daily life and increase the negative psychological burden caused by stress， anxiety， and depression. Mast cell activation and degranulation induced by immunoglobulin（Ig）E hypersensitivity is one of the core pathogenic mechanisms of CU， and there is no cure. Antihistamines such as cetirizine and loratadine are preferred for the clinical treatment of CU. Although they can effectively improve clinical manifestations such as itchiness， long-term application can increase the risk of adverse reactions and drug resistance. The phosphatidylinositol kinase/serine-threonine protein kinase B（PI3K/Akt） signaling pathway， as a classical signaling pathway regulated by phosphatidylinositol and tyrosine kinase receptor （RTK）， is a key target regulating the production and release of cytokines in macrophages and affecting the migration of leukocytes and the activation of mast cells and inflammation， and it can be involved in a variety of metabolic processes， such as mast cell activation and degranulation induced by IgE hypersensitivity and abnormal activation of the complement system so that the PI3K/Akt molecular pathway could be an important target for the future eradication of CU. However， the mechanism and potential role of the PI3K/Akt signaling pathway in the treatment of CU are less reported in China. Now， this paper reviewed the molecular mechanism of PI3K/Akt signaling pathway regulation in the treatment of CU and provided corroborative evidence and therapeutic strategy choices for the treatment of CU with traditional Chinese medicine （TCM） from the perspectives of molecular regulation and network pharmacology analysis.

Objective:This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization's (WHO) hepatitis B prevention and treatment guidelines and the current Chinese hepatitis B prevention and treatment guidelines, so as to explore their impact on the indications for antiviral therapy in Chinese patients with chronic hepatitis B (CHB).Methods:The information of patients with chronic hepatitis B virus infection who did not receive antiviral treatment was collected through the registration database of the China Clinical Research Platform for Hepatitis B Elimination. Descriptive statistics were conducted on the demographic, blood, biochemical, and virological levels of patients according to the treatment recommendations of the two versions of the guidelines. The Mann-Whitney U test and χ2 test were used to compare the differences and proportional distribution of the treatment populations covered by the two guidelines. The χ2 test was used to analyze the coverage rate of different antiviral treatment indications.Results:A total of 21,134 CHB patients without antiviral treatment were enrolled. 69.4% of patients met the 2024 versions of the WHO guidelines' recommendations. 85.0% of patients met the current Chinese hepatitis B prevention and treatment guidelines. The WHO guidelines for antiviral therapy indications were met in younger patients with higher levels of ALT, AST, and APRI scores, as well as greater proportion of patients with higher viral loads (P<0.001). The WHO guidelines recommended a cut-off value of APRI>0.5, which raised the proportion of patients on antiviral therapy from 6.6% to 30.9%. 45.7% of patients met the antiviral indications for HBV DNA >2000 IU/ml with abnormal transaminase (ALT>30 U/L for males and ALT>19 U/L for females). The reduced APRI diagnostic cut-off value and ALT treatment threshold had further increased the treatment coverage rate by 91.6% in patients with chronic HBV infection in line with the 2024 versions of WHO guidelines.Conclusion:The reduction of the APRI diagnostic cut-off value and the ALT treatment threshold, based on the current hepatitis B guidelines of China, will further improve the treatment coverage of CHB patients.

Currently the diagnosis and bed cost accounting methods reflecting the overall level of regional public hospitals have not yet matured.It explores an relatively scientific and practically accounting method based on the financial annual report of public hospitals to gain the per visit costs and per bed-day costs in a certain area,which can help the decisions of the health administra-tive department.The data from a public hospital owned by Shenzhen Health Commission is used for feasibility verification.It aims to promote the innovation and application of cost accounting method of public hospitals,and for give play to the auxiliary deci-sion-making role for the health administrative department,promote the improvement of the fiscal investment mechanism,and help public hospitals with high-quality development.

Currently the diagnosis and bed cost accounting methods reflecting the overall level of regional public hospitals have not yet matured.It explores an relatively scientific and practically accounting method based on the financial annual report of public hospitals to gain the per visit costs and per bed-day costs in a certain area,which can help the decisions of the health administra-tive department.The data from a public hospital owned by Shenzhen Health Commission is used for feasibility verification.It aims to promote the innovation and application of cost accounting method of public hospitals,and for give play to the auxiliary deci-sion-making role for the health administrative department,promote the improvement of the fiscal investment mechanism,and help public hospitals with high-quality development.

Currently the diagnosis and bed cost accounting methods reflecting the overall level of regional public hospitals have not yet matured.It explores an relatively scientific and practically accounting method based on the financial annual report of public hospitals to gain the per visit costs and per bed-day costs in a certain area,which can help the decisions of the health administra-tive department.The data from a public hospital owned by Shenzhen Health Commission is used for feasibility verification.It aims to promote the innovation and application of cost accounting method of public hospitals,and for give play to the auxiliary deci-sion-making role for the health administrative department,promote the improvement of the fiscal investment mechanism,and help public hospitals with high-quality development.