Osteosarcoma (OS) is the most common primary bone malignancy in the adolescent population. MAFG (v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G) forms a heterodimer with Nrf2 (NF-E2-related factor 2), binding to antioxidant response element (ARE), which is required for Nrf2 signaling activation. We found that MAFG mRNA and protein expression is significantly elevated in human OS tissues as well as in established and primary human OS cells. In human OS cells, MAGF silencing or knockout (KO) largely inhibited OS cell growth, proliferation, and migration, simultaneously inducing oxidative injury and apoptosis activation. Conversely, ectopic overexpression of MAFG augmented OS cell progression in vitro. MicroRNA-4660 (miR-4660) directly binds the 3′ untranslated region (UTR) of MAFG mRNA in the cytoplasm of OS cells. MAFG 3′ UTR luciferase activity and expression as well as OS cell growth were largely inhibited with forced miR-4660 overexpression but augmented with miR-4660 inhibition. In vivo, MAGF short hairpin RNA (shRNA) or forced overexpression of miR-4660 inhibited subcutaneous OS xenograft growth in severe combined immunodeficient mice. Furthermore, MAFG silencing or miR-4660 overexpression inhibited OS xenograft in situ growth in proximal tibia of the nude mice. In summary, MAFG overexpression-driven OS cell progression is inhibited by miR-4660. The miR-4660-MAFG axis could be novel therapeutic target for human OS.

Background: Osteosarcoma was the most common primary bone malignancy in children and adolescents. It was imperative to identify effective prognostic biomarkers for this cancer. This study was aimed to identify potential crucial genes of osteosarcoma by integrated bioinformatics analysis. Methods: Identification of differentially expressed genes from public data gene expression profiles (GSE42352), functional and pathway enrichment analysis, protein–protein interaction (PPI) network construction and module analysis, Cox regression and survival analysis was conducted. Results: Totally 17 co-differential genes were found to be differentially expressed. These genes were enriched in biological processes, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) pathway of inflammatory immune response. PPI network was constructed with 63 differentially expressed genes that co-existed between the test set and the validation set. The area under the receiver operating characteristic curve (AUC value) was 0.855, which indicated that the expression of PODN had a good diagnostic value for osteosarcoma. Furthermore, Cox regression and survival analysis revealed 5 genes were statistically significant. Conclusions: PODN was regarded as a potential biomarker for the diagnosis and prognosis of osteosarcoma, ACTA2, COL6A1, FAP, OLFML2B and COL6A3, can be used as potential prognostic indicators for osteosarcoma.

Studies focusing on bone and joint infections (BJIs) in young infants are rare. Some cases of BJI are accompanied by sepsis. This study aimed to identify the clinical and bacteriological features of sepsis in neonates and young infants with BJIs. Neonates and infants younger than 3 months diagnosed with BJI in the present institution from 2014 to 2021 were retrospectively reviewed. Patient characteristics, clinical data, and outcomes were documented and compared between those with and without sepsis. Twenty-five patients with a mean age of 34.8 days were included. Nine BJI cases had concomitant sepsis (group A), and 16 had BJI without sepsis (group B). Within group A, staphylococcus aureus was the major pathogenic germ (5 cases, of which 4 were of the methicillin-resistant staphylococcus aureus (MRSA) type). There was no statistical difference in male-to-female ratio, age, history of hospitalization, anemia, birth asphyxia, peripheral leukocyte counts, C-reactive protein on admission, and sequelae between groups. Univariate analyses indicated a significant difference in the incidence of septic arthritis (SA) combined with osteomyelitis (OM) (88.9% vs 37.5%), congenital deformities (44.4% vs 0%), and mean duration of symptoms (2.83 days vs 9.21 days) in comparisons between groups A and B. Staphylococcus aureus is the main pathogenic bacteria in BJI cases complicated with sepsis in neonates and young infants. Among infants younger than 3 months diagnosed with BJI, those with concurrent SA and OM, MRSA infection, or congenital deformities are more likely to develop sepsis.

The prevalence of prediabetes among adults in the U.S. is three times higher than that of diabetes, highlighting a greater disease burden. Both diabetes and prediabetes have been demonstrated to be associated with an increased risk of cardiovascular disease (CVD). However, research has primarily focused on diabetes, with limited attention to CVD risk prediction in prediabetes. Emerging 13 metabolic health-related indicators have been proposed to optimize the predictive effect on CVD risk in patients with prediabetes. This study aimed to compare the predictive efficacy of these biomarkers and further develop a nomogram to improve predictive performance of the CVD risk in patients with prediabetes. All eligible participants in the National Health and Nutrition Examination Survey (NHANES) 1999–2020 were enrolled in this study and randomly assigned to the development and validation cohorts in a ratio of 7:3. In the development cohort, the efficacy of 13 indicators used to predict the CVD risk was assessed by receiver operative characteristic (ROC) curves. Independent risk predictors identified by multivariate logistic regression were used to construct a nomogram, and internal and external validation were further implemented. The ROC curve demonstrated that the triglyceride-glucose (TyG) index was an effective predictor of CVD risk [area under the curve (AUC) = 0.694] and exhibited the best predictive performance among the 13 metabolic health-related indices. Based on independent risk factors identified by multivariate logistic regression, the CVD risk nomogram [including age, gender, hypertension, TyG, stress hyperglycemia ratio (SHR), and neutrophil-to-lymphocyte ratio (NLR)] was successfully constructed and validated with good performance (AUCs/C-indexes > 0.70 for all). This study developed a reliable nomogram for predicting CVD risk in patients with prediabetes. The model demonstrated robust performance and offered a simple yet individualized approach for predicting the CVD risk in patients with prediabetes.

Background: The concurrent ipsilateral Tillaux fracture with medial malleolar fracture in adolescents commonly suffer from high-energy injury, making treatment more difficult. The aim of this study was to discuss the mechanism on injury, diagnosis, and treatment of this complex fracture pattern. Methods: The charts and radiographs of six patients were reviewed. The function was assessed by the American Orthopedic Foot and Ankle Society ankle-hindfoot scores. Results: The mean age at operation was 12.8 years. The mean interval from injury to operation was 7.7 days. Five Tillaux fractures and all medial malleolar fractures were shown on AP plain radiographs. One Tillaux fracture and two cases with avulsion of posterolateral tibial aspect were confirmed in axial computerized tomography. There was talar subluxation laterally with medial space widening in three and syndesmotic disruption in one. There were five patients sustaining ipsilateral distal fibular fractures. All fractures, except nonunion in two medial malleolar fractures and in one Tillaux fracture, healed within 6–8 weeks. There was one case of osteoarthritis of ankle joint. The average AOFAS score was 88.7. Conclusions: Computerized tomography is helpful in identifying the fracture pattern. Anatomic reduction and internal fixation of Tillaux and medial malleolar fracture was recommended to restore the articular surface congruity and ankle stability.