Dual Role of CXCL8 in Maintaining the Mesenchymal State of Glioblastoma Stem Cells and M2-Like Tumor-Associated Macrophages.

PURPOSE: The dynamic interplay between glioblastoma stem cells (GSC) and tumor-associated macrophages (TAM) sculpts the tumor immune microenvironment (TIME) and promotes malignant progression of glioblastoma (GBM). However, the mechanisms underlying this interaction are still incompletely understood. Here, we investigate the role of CXCL8 in the maintenance of the mesenchymal state of GSC populations and reprogramming the TIME to an immunosuppressive state. EXPERIMENTAL DESIGN: We performed an integrative multi-omics analyses of RNA sequencing, GBM mRNA expression datasets, immune signatures, and epigenetic profiling to define the specific genes expressed in the mesenchymal GSC subsets. We then used patient-derived GSCs and a xenograft murine model to investigate the mechanisms of tumor-intrinsic and extrinsic factor to maintain the mesenchymal state of GSCs and induce TAM polarization. RESULTS: We identified that CXCL8 was preferentially expressed and secreted by mesenchymal GSCs and activated PI3K/AKT and NF-κB signaling to maintain GSC proliferation, survival, and self-renewal through a cell-intrinsic mechanism. CXCL8 induced signaling through a CXCR2-JAK2/STAT3 axis in TAMs, which supported an M2-like TAM phenotype through a paracrine, cell-extrinsic pathway. Genetic- and small molecule-based inhibition of these dual complementary signaling cascades in GSCs and TAMs suppressed GBM tumor growth and prolonged survival of orthotopic xenograft-bearing mice. CONCLUSIONS: CXCL8 plays critical roles in maintaining the mesenchymal state of GSCs and M2-like TAM polarization in GBM, highlighting an interplay between cell-autonomous and cell-extrinsic mechanisms. Targeting CXCL8 and its downstream effectors may effectively improve GBM treatment.

A Novel Technique for Resection and Reconstruction of the Temporomandibular Joint by Sliding Vertical Ramus Osteotomy using Only Submandibular Approach.

In this paper, an innovative technique for resection and reconstruction of the temporomandibular joint by sliding vertical ramus osteotomy using only a submandibular approach is presented. Before pulling the posterior mandibular border slightly downward to expose parts of the condyle, the vertical ramus osteotomy was performed. With the help of 3D simulation and surgical templates, the condylectomy was carried out using the ultrasonic osteotome through the submandibular approach. Our technique achieved the desired results while preventing complications of facial nerve paralysis, the occurrence of Frey syndrome, and the preauricular scar. Therefore, we suggest that this surgical method represents an alternative treatment option for temporomandibular joint lesions.

Prediction of placenta accreta spectrum by a scoring system based on maternal characteristics combined with ultrasonographic features.

OBJECTIVE: In order to create a comprehensive scoring system based on maternal characteristics and ultrasonographic features for predicting placenta accreta spectrum (PAS). MATERIALS AND METHODS: This was a retrospective review of pregnant women who underwent routine ultrasound examination in the third trimester of pregnancy from January 2014 to November 2018 were used as a training set to establish the scoring system for PAS prediction while those who underwent examination from January 2019 to December 2019 served as a validation set.. Maternal characteristics including maternal age, parity, previous vaginal deliveries, previous curettage, previous cesarean section (CS), history of hypertension and diabetes mellitus, prenatal body mass index (BMI) were recorded. Ultrasonographic features including abnormal placental lacunae, subplacental hypervascularity, myometrial thinning, placental bulge, bladder wall interruption, location of placenta, placenta previa (yes or not) were recorded. Multivariate analysis was applied to analyze independent risk factors and assess the predictive power of selected parameters predicting PAS. Receiver operating characteristics (ROC) curve was used to evaluate the diagnosis power. RESULTS: Parity, previous curettage and CS were independent risk factors. The best comprehensive scoring system was established as follow: the number of abnormal lacunae ≥3, 2 points; lacuna maximum dimension ≥2 cm, 5 points; subplacental hypervascularity (rich), 1 point; subplacental hypervascularity (extremely rich and disordered), 3 points; bladder wall interruption, 9 points; placental bulge, 9 points; placenta previa, 8 points; anterior placenta, 1 point; previous CS ≥ 1, 1 point; parity ≥ 4, 3 point; previous abortions ≥ 2, 1 point. The area under the ROC curve of the scoring system diagnosing PAS was 0.925. Sensitivity and specificity were 83.3% and 85.7%, respectively. Cross-validation for our model showed that sensitivity, specificity, positive predictive value and negative predictive value of the model in diagnosis of PAS were 82.6%, 81.8%, 82.6% and 81.8%, respectively. Diagnosis of 37 cases were consistent with the "gold standard", and the coincidence rate was 82.2% (37/45). CONCLUSION: The comprehensive scoring system established in this study can effectively diagnose PAS.