ObjectiveTo evaluate the anti-inflammatory activity of the novel magnolol ester derivative YW and to investigate its effects on chondrocyte senescence and preliminary mechanisms. MethodsMagnolol and p-methylbenzoic acid were used as raw materials to synthesize the magnolol ester derivative YW （Molecular Formula： C₂₆H₂₄O₃， Molecular Weight： 384.17， HPLC Purity >96%） via DCC/DMAP-catalyzed esterification. Cytotoxicity was assessed using the CCK-8 assay. A lipopolysaccharide （LPS）-induced RAW264.7 macrophage activation model and an interleukin-1β （IL-1β）-induced rat primary chondrocyte model were established. The release and mRNA expression of inflammatory factors including nitric oxide （NO）， IL-1β， tumor necrosis factor-alpha （TNF-α）， and IL-6 were detected by enzyme-linked immunosorbent assay （ELISA）， Griess reagent method， and quantitative real-time PCR （RT-qPCR）. The expression of senescence markers such as inducible nitric oxide synthase （iNOS）， pro-interleukin-1β （pro-IL-1β）， lysine acetyltransferase 7 （KAT7）， cyclin-dependent kinase inhibitor 1A （p21）， and cyclin-dependent kinase inhibitor 2A （p16）， as well as proteins related to chondrocyte extracellular matrix synthesis and catabolism， were analyzed by Western blot （WB）. Molecular docking was performed using Discovery Studio 2019 to validate target binding. ResultsYW exhibited no significant cytotoxicity at concentrations ≤20 μmol/L. YW concentration-dependently inhibited LPS-induced macrophage inflammatory cytokine release， significantly downregulated iNOS， Pro-IL-1β protein， and inflammatory cytokine mRNA expression （P<0.01）. YW stably bound to KAT7 protein （binding energy： -94.2 kcal/mol）； YW downregulated KAT7 and aging marker protein expression in naturally aged and IL-1β-induced chondrocyte models （P<0.01）； YW regulated chondrocyte matrix synthesis and catabolic protein expression in IL-1β-induced chondrocytes （P<0.01）. ConclusionYW inhibits macrophage activation and inflammatory cytokine release while downregulating KAT7 and senescence marker protein expression in chondrocytes， thereby blocking chondrocyte senescence.

Objective: To explore the correlation between parent-child separation experience and non suicidal self injury (NSSI) behavior among junior and senior high school students, so as to provide a reference for the prevention and improvement of NSSI behavior among junior and senior high school students. Methods: Using a stratified cluster random sampling method, 3 114 junior and senior high school students aged 11-19 years were recruited from Chenzhou and Jishou cities in Hunan Province between November 2024 and September 2025. A self designed questionnaire and the Functional Self injury Behavior Assessment Scale were used to collect information on parental labor migration and adolescents NSSI behavior status. Binary Logistic regression model was used to analyse the association between parent-child separation experiences and NSSI behavior among junior and senior high school students, with further stratified analysis by gender. Results: The prevalence rate of NSSI behavior among junior and senior high school students was 9.9%, and the overall incidence of parent-child separation was 48.9%, comprising 17.1% separated from their father only, 5.5% separated from their mother only, and 26.3% separated from both parents. After adjusting for variables such as age, gender, and ethnicity, the results of binary Logistic regression analyses indicated that adolescents with parent-child separation experiences had a higher risk of NSSI behavior ( OR =1.31, 95% CI =1.01-1.69, P <0.05). Compared with those without parent-child separation experiences, adolescents who were separated from their mother only ( OR =1.68, 95% CI =1.03-2.74) or from both parents ( OR =1.41, 95% CI =1.04-1.92) showed significantly increased risks of NSSI behavior (both P <0.05). Conclusions Parent-child separation experiences are associated with an increased risk of NSSI behavior among junior and senior high school students. Strengthened attention should be paid to left behind senior high school students to reduce the occurrence of NSSI in adolescents.

Diabetic cardiomyopathy （DCM） is a common chronic complication of diabetes， categorized as consumptive thirst in traditional Chinese medicine （TCM）， and it subsequently gives rise to chest impediment. DCM is characterized by a complex pathogenesis and exhibits long-term progression with poor prognosis in clinical practice. Astragali Radix， as a medicinal material with edible value， possesses diverse active components including saponins， polysaccharides， and flavonoids. It has the effects of tonifying Qi， elevating Yang， promoting fluid production， nourishing blood， expressing toxin， and expelling pus. Modern pharmacological studies have confirmed that Astragali Radix and its active components exert therapeutic effects in various aspects such as inhibition of inflammation， alleviation of stress injury， regulation of programmed cell death， modulation of glucose and lipid metabolism， inhibition of myocardial fibrosis， and regulation of gut microbiota and metabolites， treating DCM in a multi-component， multi-target， and multi-pathway manner. The compatibility of Astragali Radix exerts both synergistic and antagonistic effects. The compound preparations and extracts of Astragali Radix are widely used in clinical practice， and the development of novel nano and gel materials and extracellular vesicles helps to improve the oral bioavailability， providing more possibilities for the clinical application of Astragali Radix in DCM， though its potential for clinical translation requires ongoing exploration. This review summarizes the TCM theoretical basis of Astragali Radix in the treatment of DCM， and integrates modern pharmacological research results to delve into the effects and mechanisms of the herb combinations， compound preparations， extracts， and new composite materials of Astragali Radix in the treatment of DCM， aiming to provide a reference for in-depth research and new drug development of Astragali Radix for DCM.

Background::Pancreatic adenocarcinoma (PAAD) is an extremely lethal malignancy. Identification of the functional genes and genetic variants related to PAAD prognosis is important and challenging. Previously identified prognostic genes from several expression profile analyses were inconsistent. The regulatory genetic variants that affect PAAD prognosis were largely unknown.Methods::Firstly, a meta-analysis was performed with seven published datasets to systematically explore the candidate prognostic genes for PAAD. Next, to identify the regulatory variants for those candidate genes, expression quantitative trait loci analysis was implemented with PAAD data resources from The Cancer Genome Atlas. Then, a two-stage association study in a total of 893 PAAD patients was conducted to interrogate the regulatory variants and find the prognostic locus. Finally, a series of biochemical experiments and phenotype assays were carried out to demonstrate the biological function of variation and genes in PAAD progression process.Results::A total of 128 genes were identified associated with the PAAD prognosis in the meta-analysis. Fourteen regulatory loci in 12 of the 128 genes were discovered, among which, only rs4887783, the functional variant in the promoter of Ring Finger and WD Repeat Domain 3 ( RFWD3), presented significant association with PAAD prognosis in both stages of the population study. Dual-luciferase reporter and electrophoretic mobility shift assays demonstrated that rs4887783-G allele, which predicts the worse prognosis, enhanced the binding of transcript factor REST, thus elevating RFWD3 expression. Further phenotypic assays revealed that excess expression of RFWD3 promoted tumor cell migration without affecting their proliferation rate. RFWD3 was highly expressed in PAAD and might orchestrate the genes in the DNA repair process. Conclusions::RFWD3 and its regulatory variant are novel genetic factors for PAAD prognosis.

To evaluate the acute lung toxicity of intratracheally instilled nano-TiO2 in Kunming mice, healthy adult male Kunming mice were randomly grouped by their body weight (5 mice in each group). The lungs of mice were intratracheally instilled with 1 or 10 mg/kg x bw of nano-TiO2. The control group was intratracheally instilled with the same volume of physiological saline. After 1 d, 7 d, 14 d and 28 d of exposure, the bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The indices of BALF were examined. Lung tissues were assess histopathologically. The results showed that all indices of 10 mg/kg x bw groups were obviously higher than those of the control group and the group of nano-1 mg/kg x bw, respectively. Activities of lactate dehydrogenase (LDH) on the 1st, 7th, 14th and 28th day post-exposure (pe), the amounts of malodialdehyde (MDA) on the 1st, 7th and, 14th day pe and total protein (TP) on the 1st and 7th day pe as well as the amounts of leukocyte on the 1st and 7th day pe of 10 mg/kg x bw groups were significantly different as compared with controls (P < 0.05). There were no obvious changes observed in the activity of alkaline phosphatase (ALP) within groups (P > 0.05). Histopathological examination revealed that the lungs of 10 mg/kg x bw groups presented marked increase in pulmonary inflammation. Many TiO2 particles were still clearly found in the interstitium at 28 days pe. In contrast, low-dose instillation put forward a low risk potential for producing adverse effects on pulmonary health. We conclude that the inflammatory reaction gradually ceased after 28 days. Under the same experimental condition, the effect of lung injury was severer in high-dose nano-TiO2 than in low-dose nano-TiO2.
Animals ; Bronchoalveolar Lavage Fluid ; cytology ; Lung ; drug effects ; pathology ; Male ; Metal Nanoparticles ; toxicity ; Mice ; Random Allocation ; Titanium ; toxicity ; Toxicity Tests, Acute