Objective: To investigate the mechanism of shed syndecan-4 (sSDC4) in temporomandibular joint osteoarthritis (TMJOA) in rats, aiming to provide experimental evidence for its prevention and treatment. Methods: This study was approved by the Institutional Animal Ethics Committee. Twelve 6-week-old female Sprague Dawley (SD) rats were randomly divided into two groups. They received a single intra-articular injection into the bilateral superior cavity of temporomandibular joint, which consisted of either 50 μL of 4 mg/mL monosodium iodoacetate (TMJOA model group) or 50 μL of phosphate-buffered saline (PBS, control group). After 4 weeks, the mandibular condylar cartilage was harvested for hematoxylin & eosin (H&E) staining, Safranin O-fast green (SO) staining, and type II collagen (Col-Ⅱ) immunohistochemical staining to assess the degree of cartilage degeneration. The synovium of the temporomandibular joint was collected for immunohistochemical staining to detect the expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) to evaluate the degree of synovial inflammation. Synovial fluid from the temporomandibular joint cavity was collected to measure sSDC4 levels by enzyme-linked immunosorbent assay (ELISA). In addition, 12 6-week-old female SD rats were randomly divided into a His-SDC4 group and a control group, receiving injections into the bilateral superior cavity of temporomandibular joint of either 100 ng/mL (50 μL) of His-SDC4 protein or 50 μL of PBS once every 3 days for a total of 28 days. The same experimental procedures were performed for H&E staining, SO staining, and immunohistochemical staining (Col-Ⅱ IL-6, TNF-α) to observe condylar cartilage degeneration and detect synovial inflammation. Rat synovial fibroblasts and condylar chondrocytes were cultured in vitro and randomly divided into a His-SDC4-stimulated (10 ng/mL) group and control group. Perform CCK-8 cytotoxicity assays and observe cellular morphology under optical microscopy, the mRNA expression levels of IL-6 and TNF-α were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and the levels of IL-6 and TNF-α in cell culture supernatants were measured by ELISA. Results: Compared with the control group, the TMJOA group showed decreased condylar cartilage thickness, percentage of SO-positive area, and percentage of Col-Ⅱ-positive area (all P<0.001); an increased synovitis score (P<0.001) and increased percentages of IL-6- and TNF-α-positive cells in the synovium (all P<0.001); and a significant increase in sSDC4 levels in the synovial fluid (P=0.011). Following intra-articular injection of His-SDC4, condylar cartilage thickness, percentage of SO-positive area, and percentage of Col-Ⅱ-positive area all decreased (all P<0.001); the synovitis score increased (P=0.006), and the percentages of IL-6- and TNF-α-positive cells in the synovium increased (all P<0.001). In vitro experiments showed that His-SDC4 stimulation significantly upregulated the expression levels of IL-6 and TNF-α in both synovial fibroblasts and condylar chondrocytes (all P<0.01), and the levels of these two cytokines in the culture supernatants also significantly increased (all P<0.01). Conclusion During TMJOA progression, the level of sSDC4 in the synovial fluid is significantly elevated, which can directly stimulate synovial fibroblasts and condylar chondrocytes to secrete more pro-inflammatory cytokines, forming a vicious cycle that accelerates TMJOA progression.

Objective:To explore independent predictors for poor outcome at 3 months in elderly patients with acute cerebral infarction(ACI)treated with intravenous thrombolysis(IVT), and to develop a nomogram-based predictive model.Methods:This was a retrospective cohort study.Clinical, laboratory and imaging data of 346 elderly patients with ACI treated with IVT from January 2016 to April 2021 in our hospital were collected.Poor outcome was defined as a modified Rankin Scale(mRS)score >2 at 3 months after the stroke.Logistic regression analysis was used to screen for independent factors predicting poor outcome in elderly ACI patients treated with IVT, and a corresponding nomogram model was developed using the R software.The ROC curve, calibration plots and decision curve analysis were used to evaluate discrimination, calibration and clinical application value of the nomogram model.Results:Among 346 candidates, 109 developed a poor outcome, representing a rate of 31.5%.Logistic regression analysis showed that symptomatic hemorrhagic transformation( OR=15.647, 95% CI: 8.913-27.454), stroke severity(moderate stroke, OR=3.322, 95% CI: 1.414-7.811; moderate-severe stroke, OR=8.169, 95% CI: 4.102-16.258; severe stroke, OR=9.653, 95% CI: 5.440-17.121), stroke-associated pneumonia( OR=2.239, 95% CI: 1.134-4.420), and heart failure( OR=2.758, 95% CI: 1.424-5.336)were independent predictors for poor outcome at 3 months in elderly ACI patients treated with intravenous thrombolysis(all P<0.05). With the area under curve(AUC-ROC)value at 0.85(95% CI: 0.80-0.89), the nomogram model, which was composed of the above four predictors, demonstrated good discrimination.On the calibration plot, the mean absolute error was 0.020, indicating that the model had good calibration.Decision curve analysis revealed that the model had good clinical application value. Conclusions:The nomogram model composed of symptomatic hemorrhagic transformation, stroke severity, stroke-associated pneumonia and heart failure may predict poor outcome at 3 months in elderly ACI patients treated with IVT, with high prediction accuracy and high clinical application value.