This study aims to systematically characterize the targeted effects of Quanduzhong Capsules on cartilage lesions in knee osteoarthritis by integrating spatial transcriptomics data mining and animal experiments validation, thereby elucidating the related molecular mechanisms. A knee osteoarthritis model was established using Sprague-Dawley(SD) rats, via a modified Hulth method. Hematoxylin and eosin(HE) staining was employed to detect knee osteoarthritis-associated pathological changes in knee cartilage. Candidate targets of Quanduzhong Capsules were collected from the HIT 2.0 database, followed by bioinformatics analysis of spatial transcriptomics datasets(GSE254844) from cartilage tissues in clinical knee osteoarthritis patients to identify spatially specific disease genes. Furthermore, a "formula candidate targets-spatially specific genes in cartilage lesions" interaction network was constructed to explore the effects and major mechanisms of Quanduzhong Capsules in distinct cartilage regions. Experimental validation was conducted through immunohistochemistry using animal-derived biospecimens. The results indicated that Quanduzhong Capsules effectively inhibited the degenerative changes in the cartilage of affected joints in rats, which was associated with the regulation of Quanduzhong Capsules on the thioredoxin-interacting protein(TXNIP)-NOD-like receptor family pyrin domain containing 3(NLRP3)-bone morphogenetic protein receptor type 2(BMPR2)-fibronectin 1(FN1)-matrix metallopeptidase 2(MMP2) signal axis in the articular cartilage surface and superficial zones, subsequently inhibiting cartilage matrix degradation leading to oxidative stress and inflammatory diffusion. In summary, this study clarifies the spatially specific targeted effects and protective mechanisms of Quanduzhong Capsules within pathological cartilage regions in knee osteoarthritis, providing theoretical and experimental support for the clinical application of this drug in the targeted therapy on the inflamed cartilage.
Animals ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Male ; Humans ; Capsules ; Female ; Disease Models, Animal

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Aim To investigate the neuroprotective effect of Takeda G protein-coupled receptor-5(TGR5)activated by INT-777 on hypoxic-ischemic encephalop-athy(HIE)in neonatal rats.Methods Seven-day-old SD rats were randomly divided into the sham opera-tion group(Sham,S),model group(HIE,G),INT-777 low-dose(L),medium-dose(M),and high-dose(H)groups.The modified Rice-Vanucci method was used to construct the HIE model and Intranasal admin-istration 1 h after modeling.Short-term neurobehavioral tests were performed 48 h after modeling to evaluate the neurological function of neonatal rats,TTC staining was used to determine the volume of cerebral infarction,dry and wet specific gravity was used to determine the brain water content,ferrous ion kit was used to deter-mine the brain ferrous ion content,HE staining was used to observe the pathological damage of brain tis-sue,Nissl staining was used to observe the loss of Nissl substance,Transmission electron microscopy(TEM)was used to observe the mitochondrial morphological changes of cortical neurons,and Western blot was em-ployed to detect the expression of ferroptosis-related proteins TFR1 and GPX4.Results Compared with group S,group G had increased short-term neurobehav-ioral test consumption time,higher scores,increased cerebral infarct volume,brain water content,and brain ferrous iron content,significant brain tissue damage on the affected side,severe loss of Nissl substance,smaller neuronal mitochondria,decreased mitochondrial cris-tae,and increased expression of TFR1 and reduced ex-pression of GPX4.Compared with group G,the INT-777 administration group had a shorter consumption time for short-term neurobehavioral tests,lower scores,the cerebral infarction volume,brain water content,and brain ferrous ion content decreased,the brain tissue damage on the affected side was reduced,and there was insignificant loss of Nissl substance,larger neuronal mi-tochondrial volume,increased mitochondrial cristae,re-duced expression of TFR1,and increased expression of GPX4.Conclusions INT-777 agonist TGR5 has a protective effect against hypoxic-ischemic encephalopa-thy in neonatal rats,and its mechanism of action may be related to the inhibition of neuronal ferroptosis.

Encephalomyocarditis virus(EMCV)is a zoonotic pathogen that causes encephalitis and myocarditis as its primary clinical manifestations.To explore effective preventive measures,this study utilized a Bac-to-Bac expression system to insert the EMCV P12A and 3C genes into the pFastBacDual shuttle vector,resulting in the generation of the recombinant baculovirus Ac-P12A-3C.This facilitated the large-scale expression and purification of EMCV virus-like particles(VLPs),which were correctly assembled into particles of approximately 30 nm in diameter,as ob-served by electron microscopy.Immunization and challenge experiments in mice demonstrated that these VLPs could effectively protect against EMCV infection,achieving a protection rate of 100％.Histopathological sections indicated that,compared to the PBS control group,the VLP immuniza-tion group exhibited significantly reduced tissue damage,along with a marked decrease in viral load within the tissues.In piglets,immunization with the VLPs elicited a robust humoral response,with neutralizing antibody titers reaching 1∶320 to 1∶640 after a second immunization,and no signifi-cant adverse reactions were observed throughout the immunization process.This study preliminarily explores the immunogenicity and safety of the VLP vaccine,laying the foundation for the development of a subunit vaccine based on EMCV VLPs and offering a new strategy for the prevention and control of encephalomyocarditis.

Aim To explore the antioxidative effect of the Chinese medicine Baitouweng(BTW)on treating ulcerative colitis(UC).Methods Sixty male mice were randomly divided into six groups:control,dextran sulfate sodium(DSS)(3 g·105 L-1),BTW(20,10,and 5 g·kg-1),and 5-aminosalicylic acid(5-ASA)(800 mg·kg-1).UC model was constructed by 3％DSS for seven days,and the UC model was given by ga-vage once daily from the 5 th day of modeling for seven days.Results BTW effectively reduced the symptoms and histopathological scores of UC mice.Additionally,it downregulated the inflammatory factors,interleukin(IL)-6 and IL-1 β,the immunoglobulins vascular cell adhesion molecule 1 and intercellular adhesion mole-cule 1,and metalloprotease matrix metallopeptidase 9.Moreover,it downregulated high mobility group box 1 protein.Furthermore,it inhibited the nuclear factor er-ythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)pathway.Conclusions BTW improves the general condition,inflammatory indexes and oxidative stress level,and its mechanism may be related to inhib-iting the level of HMGB1 to regulate the Nrf-2/HO-1 signaling pathway and rescue intestinal barrier-related protein expression.

Objective To understand the current situation and influencing factors of salary satisfaction of staff in tertiary public hospitals,and provide suggestions for improving the reform of salary system.Methods A questionnaire survey was conducted on 816 employees from 7 tertiary public hospitals in Hunan Province,and the basic situation,salary level,salary promotion,salary system and salary distribution were studied.Descriptive analysis and binary logistic regression model were used to analyze the status quo and influencing factors of employee salary satisfaction.Results The overall satisfaction score of the 816 survey respondents'salary was 71.56 points,at a relatively high level.There was a large difference in satisfaction levels among different regions.Salary level and salary increase satisfaction were 69.19 and 70.90 points respectively,and satisfaction was low.Region,affiliation with a university,cadre status,and title were the main factors affecting salary satisfaction.Conclusion The salary satisfaction of staff in tertiary public hospitals was generally higher in Hunan Province,and the reform had shown positive results.The satisfaction with salary increases and salary levels was relatively low,and it was suggested that the government reasonably determine the salary level of public hospitals and establish a scientific and reasonable salary increase mechanism.It will improve supporting reforms and promote equal pay for equal work.

Objective:To construct a clinical decision-making ability indicator system based on evidence-based practice for pediatric nursing interns, and to provide a scientific basis for clinical teaching and evaluation.Methods:A method combining literature analysis, Delphi expert consultation, and empirical research was used. Firstly, a systematic search of Chinese and English databases (2018-2023) was conducted. Literature was screened based on the PICO framework and evidence-based data were extracted, resulting in a preliminary system consisting of 4 primary indicators, 12 secondary indicators, and 39 tertiary indicators. Subsequently, the indicators were revised through two rounds of Delphi expert consultation (25 experts with 19-27 years of work experience). The expert authority coefficients (Cr) were 0.898-0.907 and the Kendall's concordance coefficients were 0.351-0.420 ( P<0.001). Finally, the analytic hierarchy process was used to determine the weights, and the reliability and validity were verified through a questionnaire survey (sample size: 30 participants in preliminary survey and 58 participants in formal survey). Results:The constructed indicator system included 4 primary indicators (weights), 13 secondary indicators, and 42 tertiary indicators. The weights of the primary indicators were as follows: knowledge integration ability (0.300), evidence-based practice ability (0.250), clinical judgment ability (0.280), and ethical decision-making ability (0.170). The importance scores of all items exceeded 4.0 points (out of 5 points), and the coefficients of variation were less than 0.20. The reliability and validity tests showed that the Cronbach's α of the overall scale was 0.89, and the intraclass correlation coefficient was 0.88. The cumulative variance contribution rate of exploratory factor analysis was 69.30%. The confirmatory factor analysis demonstrated a good model fit with a comparative fit index of 0.93 and a root mean square error of approximation of 0.05. Conclusions:This indicator system has high scientificity and practicality, and can provide a reference for the standardized cultivation and evaluation of clinical decision-making ability of pediatric nursing interns. In the future, it is necessary to strengthen advanced evidence-based skills training and long-term application effectiveness tracking.

Objective To investigate the application and effectiveness of a zero-trust network architecture(ZTNA)in a hospital's smart-management platform,providing a practical reference for network-architecture optimization in smart-hospital initiatives.Methods A single-arm mode was involved in the deployment of ZTNA.An encrypted tunnel was established by the zero-trust proxy gateway,and the components for zero-trust terminal security,behavior management,firewall,identity authentication,security operation and analysis center were synergized with the help of a logical bus to form a security protection system of end-to-end trust assessment,dynamic access control,micro-isolation and visualization,and the integration and access to the hospital's intelligent management platform were realized by means of ticket injection.Results ZTNA markedly enhanced data protection for the platform,and significantly improved user experience by simplified authentication and enhanced support for mobile operation.Conclusion ZTNA ensures the security of kinds of hospital business systems,and lays a foundation for large comprehensive hospitals to construct cross-region,cross-institution and multi-center medical information platforms and open data sharing modes.[Chinese Medical Equipment Journal,2025,46(8):50-57]