ObjectiveTo determine the optimal combination of the effective monomer components "quercetin-kaempferol-abietic acid-boswellic acid" in Fujin Shengjisan for promoting diabetic ulcer （DU） wound healing through uniform design， thereby achieving the modern application of the ancient formula. MethodsFollowing the principle of "uniform design-pharmacodynamic experiment-mathematical modeling and model verification"， the U₁₄（14⁵） uniform design table was adopted.The four monomer components of Chinese medicine were considered as the independent variables， and the proliferation rate of human umbilical vein endothelial cells （HUVECs） induced by glucose was used as the pharmacodynamic indicator. A mathematical model was constructed using DPS software to correlate the effective monomer components with the pharmacodynamic indicator. The results of uniform design were verified through CCK-8 assay， cell scratch healing， tube formation， Western blot， and Real-time PCR. ResultsAmong the 14 compatibility groups， compared with the high-glucose model group， compound compatibility group 6 showed the strongest proliferation effect and statistical significance （P<0.05）. Four quadratic polynomial regression equations （Y₁-Y₄） were obtained through DPS modeling. Considering the model's fit， stability， and practical application， equations Y₁-Y₃ were selected for the follow-up verification. To ensure experiment reproducibility， group 6 was used for validation. Group 6 and equations Y₁-Y₃ were renamed as compound prescription ① to compound prescription④， respectively， to represent the modern application of the ancient FJSJ Powder through compatibility of monomer components. Verification experiments showed that in the CCK-8， scratch healing， and tube formation assays， the cell viability， wound healing rate， and tube formation number of HUVECs stimulated with 50 mmol·L^-1 glucose were significantly reduced compared with the blank group. Moreover， the expression levels of angiogenesis-related cytokines， vascular endothelial growth factor （VEGF） and fibroblast growth factor 2 （FGF2）， and CD31 secretion were significantly down-regulated. However， after intervention with compound prescriptions ① to ④， compound prescriptions ① and ③ significantly improved the biological functions of HUVECs induced by 50 mmol·L^-1 glucose. Further analysis of the regression coefficients of compound prescriptions ① and ③， and the relative dose ratios of each monomer component， indicated that abietic acid， quercetin， and boswellic acid promoted angiogenesis of HUVECs in the high glucose environment， with a major effect （positive partial correlation coefficients， all > 0.9）. Abietic acid and boswellic acid， as well as kaempferol and boswellic acid， promoted angiogenesis in HUVECs through interaction （positive partial correlation coefficients）. ConclusionCompound prescriptions ① and ③ are the optimal combinations. They can reverse the inhibitory effects of high glucose， stimulate the proliferation， migration， and tube formation abilities of HUVECs in a high glucose environment， and promote the expression of vascular endothelial growth factorA（VEGFA）， FGF2， and CD31， thereby promoting angiogenesis and facilitating DU wound healing. This finding not only confirms the good reproducibility and feasibility of compound prescriptions ① and ③ but also provides new insights and methods for the rational construction of mathematical models to further study the compatibility theory of Chinese medicine.

OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

Osteoporosis （OP） and osteoarthritis （OA） are common bone diseases in clinic. OP is a systemic skeletal disease， and OA is a chronic degenerative joint disease with high prevalence and disability rates. With the advent of the aging population， the incidence rate of OA and OP is increasing year by year， and they have become common diseases of the elderly. The quality of life and physical and mental health of patients are severely affected by the above two bone diseases. Chinese medicine has a long history of treating bone diseases， with a good clinical effect on preventing and treating OP， OA， and other bone diseases with few side effects. It is one of the commonly used methods to treat bone diseases. Polysaccharides， as one of the active substances of Chinese medicine， have various pharmacological activities and a wide range of sources with low toxicity， and their effect cannot be ignored. The role of polysaccharides in the treatment of bone diseases has been deeply studied. It has been found that the mechanism of Chinese medicine polysaccharides in treating OP and OA involves multiple levels， targets， and pathways. Through the analysis and summary of the relevant literature on the mechanism of Chinese medicine polysaccharides in treating OP and OA， it was found that Chinese medicine polysaccharides mainly treated OP by regulating the bone dynamic balance between osteoblasts and osteoclasts and affecting bone marrow mesenchymal stem cells and bone microstructure. The mechanism of Chinese medicine polysaccharides in the treatment of OA is related to the regulation of chondrocyte growth， the increase in the proteoglycan and collagen content in the cartilage matrix， and the reduction of oxygen free radical content and inflammatory mediator level. This study aimed to further explore the internal relationship among mechanisms of Chinese medicine polysaccharides in the treatment of bone diseases， to provide relevant ideas for the study of Chinese medicine polysaccharides in the treatment of bone diseases.

Monoclonal antibodies (mAbs) are widely used in many fields due to their high specificity and ability to recognize a broad range of antigens. IL-17A can induce a rapid inflammatory response both alone and synergistically with other proinflammatory cytokines. Accumulating evidence suggests that therapeutic intervention of IL-17A signaling offers an attractive treatment option for autoimmune diseases and cancer. Here, we present a combinatorial approach for optimizing the affinity and thermostability of a novel anti-hIL-17A antibody. From a large naïve phage-displayed library, we isolated the anti-IL-17A mAb 7H9 that can neutralize the effects of recombinant human IL-17A. However, the modest neutralization potency and poor thermostability limit its therapeutic applications. affinity optimization was then used to generate 8D3 by using yeast-displayed random mutagenesis libraries. This resulted in four key amino acid changes and provided an approximately 15-fold potency increase in a cell-based neutralization assay. Complementarity-determining regions (CDRs) of 8D3 were further grafted onto the stable framework of the huFv 4D5 to improve thermostability. The resulting hybrid antibody 9NT/S has superior stabilization and affinities beyond its original antibody. Human fibrosarcoma cell-based assays and analyses in mice indicated that the anti-IL-17A antibody 9NT/S efficiently inhibited the secretion of IL-17A-induced proinflammatory cytokines. Therefore, this lead anti-IL-17A mAb might be used as a potential best-in-class candidate for treating IL-17A related diseases.

Objective To investigate the prevalence and influencing factors associated with frailty among institutional older adults and to provide evidence for intervention study.Methods A total of 237 older adults living in four welfare homes from Chengdu in Sichuan Province were recruited by convenience sampling.A cross-sectional survey was conducted,and frailty was assessed by the frailty phenotype;general information was collected by selfmade general information questionnaire;functional capacity was assessed by Barthel questionnaire;depressive status was assessed by GDS-15;cognitive function was assessed by clock drawing test and nutritional status was assessed by short form mini nutritional scale questionnaire (MNA-SF).Results The reported rate of frailty was 55.69％ among institutional older adults,and 44.31％ reported no frailty;grip weakness (207,87.3％),slow walking speed (172,72.6％) and low physical activity(131,55.3％) were the main frailty problems.Univariate analysis showed that the elderly'frailty conditions were different in the pre-retirement occupations,smoking,alcohol consumption,physical exercise,chronic diseases,medication,acute events (last year),self-reported health,using assisted walking devices,ability of daily life,depression,cognitive ability and nutritional status,and the differences were statistically significant(P＜0.05).Conclusion The status of frailty is not optimistic among institutional older adults and many factors are associated with frailty.Healthcare providers should pay more attention to the frailty issue and take timely intervention strategies to prevent or delay the frailty.

OBJECTIVETo compare the clinical efficacy differences between acupoint plaster therapy with midnight-noon ebb-flow hour-prescription method and traditional acupoint plaster therapy for senile osteoporosis (SOP).

METHODSWith randomized controlled blind design, 76 SOP patients with deficiency of liver and kidney syndrome were randomly divided into an observation group and a control group, 38 cases in each one. Based on oral administration of caltrate D, the patients in the observation group were treated with acupoint plaster therapy with midnight-noon ebb-flow hour-prescription method at Yingu (KI 10), Taixi (KI 3), Dazhong (KI 4), Fuliu (KI 7) and Zhiyin (BL 67), while the patients in the control group were treated with traditional acupoint plaster therapy. Each plaster therapy lasted for 6 h, once a day; there was an interval of 2 d after consecutive 5-day treatment; 4 weeks were taken as one course, and totally 2 courses were given. Visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to evaluate the pain and dysfunction before intervention, after 4 weeks and 8 weeks intervention. Osteoporosis symptom rating sale and quality of life questionnaire of the European foundation for Osteoporosis (QUALEFFO-41) were adopted to evaluate the TCM syndrome and quality of life before and after 8-week intervention.

RESULTSAll the outcomes were significantly improved after treatment in the two groups (<0.01,<0.05); after 4 weeks and 8 weeks of treatment, the VAS and ODI in the observation group were lower than those in the control group (all<0.05). Repeated ANOVA indicated the VAS and ODI were significant in group effect, time effect and interaction effect (all<0.01). Further comparison showed that VAS and ODI at later time points were lower than those in the early time points (all<0.01). After the treatment, the scores of TCM syndrome and QUALEFFO-41 in the observation group were lower than those in the control group (all<0.05). The effective rate was 85.7% (30/35) in the observation group, which was superior to the effective rate in the control group[74.3%(26/35),<0.05].

CONCLUSIONSThe acupoint plaster therapy with midnight-noon ebb-flow hour-prescription method is superior to traditional acupoint plaster therapy in improving pain, dysfunction, TCM syndrome and quality of life in SOP patients; in addition, its clinical efficacy is significant.