Automatic diagnosis of pediatric supracondylar humerus fractures using radiomics-based machine learning.

The aim of this study was to construct a classification model for the automatic diagnosis of pediatric supracondylar humerus fractures using radiomics-based machine learning. We retrospectively collected elbow joint Radiographs of children aged 3 to 14 years and manually delineated regions of interest (ROI) using ITK-SNAP. Radiomics features were extracted using pyradiomics, a python-based feature extraction tool. T-tests and the least absolute shrinkage and selection operator (LASSO) algorithm were used to further select the most valuable radiomics features. A logistic regression (LR) model was trained, with an 8:2 split into training and testing sets, and 5-fold cross-validation was performed on the training set. The diagnostic performance of the model was evaluated using receiver operating characteristic curves (ROC) on the testing set. A total of 411 fracture samples and 190 normal samples were included. 1561 features were extracted from each ROI. After dimensionality reduction screening, 40 and 94 features with the most diagnostic value were selected for further classification modeling in anteroposterior and lateral elbow radiographs. The area under the curve (AUC) of anteroposterior and lateral elbow radiographs is 0.65 and 0.72. Radiomics can extract and select the most valuable features from a large number of image features. Supervised machine-learning models built using these features can be used for the diagnosis of pediatric supracondylar humerus fractures.

Finite element analysis of modified Slongo's external fixation in the treatment of supracondylar humeral fractures in older children.

Older children over 8 years old are at higher risk of elbow joint stiffness after treatment of supracondylar humeral fractures. The objective of this study was to improve the Slongo's external fixation system for treating supracondylar humeral fractures in older children. This would be achieved by increasing fixation strength and providing a theoretical basis through finite element analysis and mechanical testing. A 13-year-old female patient with a history of previous fracture was selected for CT data processing to create a three-dimensional model of the distal humerus fracture. Two internal fixation models were established, using the Slongo's external fixation method with Kirschner wire (Group A) and modifying the Slongo's external fixation (Kirschner wire tail fixation) (Group B). The fracture models were then subjected to mechanical loading analysis using Finite Element Analysis Abaqus 6.14 software to simulate separation, internal rotation, and torsion loads. A PVC humeral bone model was used to create a supracondylar fracture model, and the A and B internal fixation methods were applied separately. The anterior-posterior and torsional stresses were measured using the Bose Electroforce3510 testing system, followed by a comparative analysis. The finite element simulation results showed that under the same tensile, torsion, and inversion forces, the osteotomy model fixed with Kirschner wire at the distal end in Group B exhibited smaller tensile stress and deformation compared to the unfixed osteotomy model in Group A. This indicated that the fixation strength of Group B was superior to that of Group A. According to the test results of the Bose Electroforce3510 testing system, a simple linear regression analysis was conducted using SPSS software. The K values of rotation angle-torque tests and front and rear displacement-stress tests were calculated for Groups A and B, with Group B showing higher values than Group A. The results of this study supported the significantly enhanced biomechanical reliability and stability of fracture fixation in Group B, which utilized the modified Slongo's external fixation (Kirschner wire tail fixation). This optimized method provides a new choice for the clinical treatment of supracondylar humeral fractures in older children, backed by both clinical evidence and theoretical basis.

Kirschner wire versus external fixation in the treatment of proximal humeral fractures in older children and adolescents: a comparative study.

OBJECTIVE: The purpose of this study was to compare the therapeutic effects of Kirschner wire fixation and external fixation in the treatment of proximal humeral fractures in older children and adolescents. METHODS: A retrospective analysis was performed on the clinical data of older children and adolescents who underwent surgery at our institution for proximal humeral fractures between April 2014 and May 2022. One group (n = 28) underwent fracture reduction and Kirschner wire fixation, and the other group (n = 23) underwent external fixation. During the follow-up, the differences in shoulder joint function between the two groups were compared by analysing Quick Disabilities of the Arm, Shoulder, and Hand (Quick DASH) and Constant-Murley scores. Postoperative complications were also recorded. RESULTS: The operation time of the Kirschner wire group was shorter than that of the external fixation group (69.07 ± 11.34 min vs. 77.39 ± 15.74 min, P = 0.33). The time to remove the fixator in the external fixation group was shorter than that in the Kirschner wire group (6.74 ± 1.57 vs. 7.61 ± 1.22, P = 0.032). The Quick DASH score and Constant-Murley score of the patients in the external fixation group were significantly better than those in the Kirschner wire group at 3 months after surgery (5.63 ± 4.33 vs. 8.93 ± 6.40, P = 0.040; 93.78 ± 2.43 vs. 91.75 ± 2.15, P = 0.003). There was no significant difference in the Quick DASH score or Constant-Murley score between the patients in the external fixator group and those in the Kirschner wire group at 9 months after the operation (2.77 ± 3.14 vs. 3.17 ± 3.68, P = 0.683; 97.39 ± 1.80 vs. 96.57 ± 2.15, P = 0.152). The most common complication of the two groups was pin tract infection. The incidence rate of infection was higher in the external fixation group than that in the Kirschner wire group (9 vs. 4, P = 0.043). CONCLUSION: Both Kirschner wire fixation and external fixation of N-H III and IV proximal humeral fractures in older children and adolescents produce good outcomes. External fixation is a preferred surgical treatment option for paediatric proximal humerus fractures because early mobilization of the affected limb can be realized.

Senomorphic agent pterostilbene ameliorates osteoarthritis through the PI3K/AKT/NF-κB axis: an in vitro and in vivo study.

OBJECTIVES: Osteoarthritis (OA) is the most common joint disease in the world. Among the many risk factors for OA, aging is one of the most critical factors. The treatment with senop-associated secretory phenotype (SASP) is one of the important, promising anti-aging strategies at present. Pterostilbene (PTE) is a trans-stilbene compound with anti-tumor, anti-oxidation, anti-inflammatory, and anti-aging pharmacologic activities. The purpose of this study is to explore the therapeutic effects of PTE on articular chondrocyte senescence and OA and its related mechanisms. METHODS: Male Sprague-Dawley rats were operated on with transection of the anterior cruciate ligament (ACLT) and a destabilized medial meniscus (DMM) surgery to establish the OA model and then injected intraperitoneally with PTE (20 mg/kg) for 5 weeks. Finally, rats were sacrificed and knee joints were collected for histologic analysis. Rat chondrocytes were stimulated with interleukin-1ß (IL-1ß) with or without PTE treatment. The therapeutic effects of PTE and related mechanisms were investigated by examining and analyzing relative markers through senescence-associated ß-galactosidase (SA-ß-Gal) assay, cell cycle, qRT-PCR, western blot, bioinformatic analysis, immunofluorescence, and molecular modeling. RESULTS: With in vivo experiments, PTE can significantly reduce the Mankin scores and OARSI scores of the knee joint in ACLT+DMM OA model rats and reduce the interleukin-6 (IL-6) level in the knee lavage fluid. Immunohistochemical staining showed that compared to the OA group, the PTE treatment group had significantly increased expression of collagen type II in articular cartilage, and significantly decreased matrix metalloproteinase 13 (MMP-13) and IL-6, the main SASP proteins, and had expression of p16 and p21, markers of aging in chondrocytes. In vitro, PTE reduced the ratio of SA-ß-Gal positive chondrocytes and G0-G1 phase chondrocytes in IL-1ß-induced rat chondrocytes. PTE significantly inhibited the expression of MMP-13, IL-6, thrombospondin motif 5 (ADAMTS5), p16, and p21, and significantly increased the expression of collagen type II. Bioassay and subsequent western blot showed that PTE significantly inhibited the activation of PI3K/AKT and NF-κB signaling pathways. The results of molecular docking experiments showed that PTE could bind closely to the sites of PI3K protein, thereby inhibiting the phosphorylation of PI3K. CONCLUSIONS: The experimental results indicate that PTE plays an anti-chondrocyte senescence role in the treatment of OA by inhibiting the PI3K/AKT/NF-κB signaling pathway and reducing expression of SASP.

Discovery of First-In-Class Potent and Selective Tropomyosin Receptor Kinase Degraders.

We report compounds 5 (CG416) and 6 (CG428) as two first-in-class tropomyosin receptor kinase (TRK) degraders that target the intracellular kinase domain of TRK. Degraders 5 and 6 reduced levels of the tropomyosin 3 (TPM3)-TRKA fusion protein in KM12 colorectal carcinoma cells and inhibited downstream PLCγ1 signaling at sub-nanomolar concentrations. Both degraders also degraded human wild-type TRKA with similar potency. Interestingly, both degraders, especially 6, showed selectivity for the degradation of endogenous TPM3-TRKA over ectopically expressed ATP/GTP binding protein-like 4 (AGBL4)-TRKB or ETS variant transcription factor 6 (ETV6)-TRKC fusion proteins in KM12 cells. Global proteomic profiling assays demonstrated that 5 is highly selective for the intended target. TPM3-TRKA protein degradation induced by 5 and 6 was further confirmed to be mediated through cereblon and the ubiquitin-proteasome system. Compared with the parental TRK kinase inhibitor, both degraders exhibited higher potency for inhibiting growth of KM12 cells. Moreover, both 5 and 6 showed good plasma exposure levels in mice. Therefore, 5 and 6 are valuable chemical tool compounds for investigating the in vivo function of TRK fusion during tumorigenesis. Our study also paves the way for pharmacological degradation of TRK.