MRI-based deep learning and radiomics for prediction of occult cervical lymph node metastasis and prognosis in early-stage oral and oropharyngeal squamous cell carcinoma: a diagnostic study.

INTRODUCTION: The incidence of occult cervical lymph node metastases (OCLNM) is reported to be 20%-30% in early-stage oral cancer and oropharyngeal cancer. There is a lack of an accurate diagnostic method to predict occult lymph node metastasis and to help surgeons make precise treatment decisions. AIM: To construct and evaluate a preoperative diagnostic method to predict occult lymph node metastasis (OCLNM) in early-stage oral and oropharyngeal squamous cell carcinoma (OC and OP SCC) based on deep learning features (DLFs) and radiomics features. METHODS: A total of 319 patients diagnosed with early-stage OC or OP SCC were retrospectively enrolled and divided into training, test and external validation sets. Traditional radiomics features and DLFs were extracted from their MRI images. The least absolute shrinkage and selection operator (LASSO) analysis was employed to identify the most valuable features. Prediction models for OCLNM were developed using radiomics features and DLFs. The effectiveness of the models and their clinical applicability were evaluated using the area under the curve (AUC), decision curve analysis (DCA) and survival analysis. RESULTS: Seventeen prediction models were constructed. The Resnet50 deep learning (DL) model based on the combination of radiomics and DL features achieves the optimal performance, with AUC values of 0.928 (95% CI: 0.881-0.975), 0.878 (95% CI: 0.766-0.990), 0.796 (95% CI: 0.666-0.927) and 0.834 (95% CI: 0.721-0.947) in the training, test, external validation set1 and external validation set2, respectively. Moreover, the Resnet50 model has great prediction value of prognosis in patients with early-stage OC and OP SCC. CONCLUSION: The proposed MRI-based Resnet50 deep learning model demonstrated high capability in diagnosis of OCLNM and prognosis prediction in the early-stage OC and OP SCC. The Resnet50 model could help refine the clinical diagnosis and treatment of the early-stage OC and OP SCC.

Development of PD-1 blockade peptide-cell conjugates to enhance cellular therapies for T-cell acute lymphoblastic leukemia.

Blockade of the interaction of the immune checkpoint receptor programmed cell death protein (PD)-1 and its ligand PD-L1 has been found to be a promising cancer treatment. Our previous studies identified that nABPD1 competed with PD-L1 to bind PD-1. The aim of this study was to evaluate the efficacy and safety of anti-tumor immunotherapy of ICIK cells conjugated with peptides in vivo and in vitro. Here, we synthesized the nABPD1 derivatives SBP1 and SBP2 and showed that their binding efficiency to PD-1-positive improving cytokine-induced killer (ICIK) cells was 98 and 82%, respectively. The cytotoxicity of ICIK cells to T-cell acute lymphoblastic leukemia (T-ALL) cells was increased by conjugating with SBP1 or SBP2, which was 2 times higher than that of ICIK cells alone. Furthermore, mice experiments showed that the fluorescence intensity of leukemia cells in T-ALL xenograft models was reduced by more than 95%, indicating that the peptides enhanced the therapeutic effect in vivo, while morphological evaluations showed that the peptides had no toxicity to important organs. Therefore, peptide-cell conjugates (PCCs) may be a novel method to improve the efficacy of cancer immunotherapy by blocking PD-1 in T-ALL patients.

Resveratrol loaded native silk fiber-sericin hydrogel double interpenetrating bioactive wound dressing facilitates full-thickness skin wound healing.

Wound repair is challenging for traditional wound dressings. New bioactive dressings need to be developed urgently. Herein, we reported a highly bioactive silk protein wound dressing (SPD) with natural silk fiber-sericin hydrogel interpenetrating double network structure, which combines the dual characteristics of natural silk and sericin hydrogel. Silk fiber scaffolds were secreted directly from silkworms bred by regulating their spinning behaviors. Sericin in SPD is obtained by dissolving silkworm cocoons at high temperature and high pressure, while it remains intact activities to self-assemble a hydrogel. To explore the effect of SPD, we first systematically evaluated its physicochemical properties and biological activitiesin vitro. The SPD exhibits high porosity, prominent mechanical strength, pH-responsive degradability, and excellent anti-oxidation and cell compatibility. Besides, SPD can load and maintain long-term drug release. Based on the satisfactory performance of SPDin vitro, effectivein vivotreatment was achieved in a mouse full-thickness wound model, as demonstrated by a significantly accelerated wound healing process, promote the regeneration of hair follicles and sebaceous glands, increased expression of vascular endothelial growth factor, and reduced inflammation. Further, resveratrol was loaded into SPD to enhance the effects of anti-oxidation and anti-inflammation for wound healing. Our investigation shows that SPD with excellent physicochemical and biological properties applied in a murine full-thickness skin wound model resulted in remarkable and efficient acceleration of healing process, which may inspire the design of new, effective, and safer medical materials for tissue regeneration.

A native sericin wound dressing spun directly from silkworms enhances wound healing.

It is attractive and challenging to develop a bioactive dressing based on native nondestructive sericin. Here, a native sericin wound dressing was secreted directly by silkworms bred through regulating their spinning behaviors. To be excited, our first reported wound dressing possesses original unique features of natural sericin, including natural structures and bioactivities. Besides, it has a porous fibrous network structure with a porosity of 75 %, thus achieving excellent air permeability. Moreover, the wound dressing exhibits pH-responsive degradability, softness, and super absorbency properties whose equilibrium water contents are no less than 75 % in various pH conditions. Furthermore, the sericin wound dressing demonstrates high mechanical strength, reaching 2.5 MPa tensile strength. Importantly, we confirmed good cell compatibility of sericin wound dressing that can support cell viability, proliferation, and migration for a long time. When tested in a mouse full-thickness skin wound model, the wound dressing efficiently accelerated the healing process. Our findings suggest that the sericin wound dressing has promising application and commercial value in wound repair.

Nomogram to predict the risk of endoscopic removal failure with forceps/baskets for treating submandibular stones.

BACKGROUND: Endoscopic removal with forceps/baskets is favored in treating submandibular stones due to its minimal invasiveness. However, recent studies have found that endoscopic removal failure (ERF) is not unusual, and stones in such cases still need to be removed with other surgical methods. If the risk of ERF can be predicted preoperatively, it could be helpful for surgeons when choosing the appropriate therapy. AIM: To develop a predictive nomogram for the risk of ERF when treating submandibular stones based on their preoperative clinical features. METHODS: A total of 180 patients with 211 submandibular stones treated from January 2012 to December 2020 were included in the current study. Based on the preoperative clinical features of the stones, independent risk factors for ERF were identified by logistic regression analysis. The stones were then randomly divided into training and testing sets. A nomogram was constructed to predict the risk of ERF using the training set and then validated using both sets. The predictive performance of the nomogram was assessed by calibration curves and the concordance index (C-index). RESULTS: Three independent predictors, location (P = 0.040), transverse diameter (P < 0.001) and longitudinal diameter (P < 0.001) measured on the cone beam computed tomography (CBCT) images of the submandibular stones, were identified and included in the predictive nomogram. Calibration curves of the nomogram showed good agreement between the predicted and observed probabilities in both sets. The C-index in the training set was 0.917 (95%CI, 0.875-0.959) and that in the testing set was 0.925 (95%CI, 0.862-0.989). CONCLUSION: A nomogram based on the location, transverse and longitudinal diameters on CBCT images of submandibular stones showed satisfactory efficacy in predicting the risk of ERF preoperatively when treating submandibular stones.

Osteochondroma of the coronoid process: A case report and review of the literature.

Osteochondroma (OC) is considered the most common tumor of the axial skeleton, although it is relatively uncommon in the craniofacial region. The present study describes an atypical case of OC of the coronoid process. A 34-year-old woman presented with severely limited mouth opening (5 mm) and swelling of the right zygoma. Cone-beam computed tomography (CBCT) revealed a mushroom-shaped outgrowth from the coronoid process to the inner surface of the zygomatic arch, forming a pseudojoint. The patient was treated with coronoidectomy via an intraoral approach. Histopathological examination revealed features suggestive of OC. Subsequently, the patient was able to open their mouth, and there was no evidence of recurrence or post-operative complications in the 21-month follow-up. A review of the literature revealed only 38 histologically proven cases of coronoid OC in the past 30 years (1989-2018). The incidence of the disease was higher in men compared with that in women (male:female, 2.17:1), and the median age at onset was 28.7 years, with a range of 5-57 years. Gradual limitation of mouth opening and facial asymmetry are the most noticeable symptoms. Water's view and submentovertex projection of the zygomatic arch may be useful in identifying the tumor and its association with the zygoma, while CT and CBCT permit a detailed visualization of the location and density of the tumor. Coronoidectomy is the preferred treatment option, and the prognosis is excellent, with no evidence of recurrence or malignant transformation.

Upregulation of interleukin-8 and activin A induces osteoclastogenesis in ameloblastoma.

Ameloblastoma is a common odontogenic benign tumor located in the jaws and is characterized by severe local bone destruction. The current study aimed to investigate the effect of interactions between tumor cells and bone marrow stromal cells (BMSCs) on osteoclast formation in ameloblastoma. The impact of ameloblastoma/BMSC interactions on cytokine production, gene expression and osteoclastogenesis was examined using an immortalized ameloblastoma cell line that the authors' previously established. The results demonstrated that interactions between ameloblastoma cells and BMSCs increased interleukin (IL)­8 and activin A secretion by BMSCs. IL­8 expression in BMSCs was modulated by tumor­derived tumor necrosis factor­α and IL­8 contributed to osteoclast formation not only directly but also by stimulating receptor activator of NF­κB ligand (RANKL) expression in BMSCs. Activin A secretion in BMSCs was stimulated by ameloblastoma cells via cell­to­cell­mediated activation of c­Jun N­terminal kinase activation, acting as a cofactor of RANKL to induce osteoclast formation and function. The present study highlights the critical role of communication between BMSCs and ameloblastoma cells in bone resorption in ameloblastoma.

Role of Salivary Duct Morphology in the Etiology of Chronic Obstructive Parotitis: Statistical Analysis of Sialographic Features and Computational Fluid Dynamics Analysis of Salivary Flow.

PURPOSE: The causes of some cases of chronic obstructive parotitis (COP) without obstructive factors are still unclear. The authors hypothesized that some morphologic features of salivary ducts might contribute to the development of COP. This study investigated the role of salivary duct morphology in the etiology of COP. MATERIALS AND METHODS: The authors designed and implemented a case-and-control study. Cases were defined as patients with COP, diagnosed from September 2014 to May 2017 at the Affiliated Hospital of Stomatology of the Sun Yat-sen University (Guangzhou, China), and controls were healthy participants. The primary predictor variables were the occurrence of an accessory duct (AD), the number of branches uniting to form the Stensen duct (SD), the angle between the AD and the SD, and the angle between branches identified on sialographic computed tomograms. Data from the 2 groups were compared to investigate the association between these variables and COP. The χ2 test, Student t test, and logistic regression were computed, with significance set at a P value less than .05. Fluid dynamics analysis was used to analyze salivary flow field in models of salivary ducts with different morphologic features reconstructed from sialographic computed tomograms. RESULTS: The sample was composed of 39 patients with COP and 18 controls without COP. The 2 groups were not similar for incidences of an AD (71.8 vs 38.9%) and the angle between branches (96.5 ± 26.0° vs 71.5 ± 21.2°). There was no relevant difference between groups in the number of branches and the angle between the AD and the SD. The area of low velocity was larger in the model with the wider angle between branches. CONCLUSIONS: The results suggest that the presence of an AD and a wider angle between duct branches are associated with COP.

Detection of salivary protein biomarkers of saliva secretion disorder in a primary Sjögren syndrome murine model.

Saliva secretion disorder is one of the most common symptoms in primary Sjögren syndrome (pSS). Salivary biomarkers related to saliva secretion disorder were identified in a pSS murine model, NOD/ShiLtJ mouse, using differential proteomic analysis. Candidate biomarkers were screened with Kyoto Encyclopedia of Genes and Genomes pathway analysis and validated in saliva and salivary glands by western blotting and immunohistochemistry (IHC). Biological functions were detected using ingenuity pathway analysis (IPA). We identified 1101 salivary proteins from NOD/ShiLtJ mice and BALB/c mice (control). Catenin alpha-3 (CTNNA3), tyrosine-protein phosphatase non-receptor type 6 (PTPN6), Ras-related C3 botulinum toxin substrate (RAC2), and intermediate conductance calcium-activated potassium channel protein 4 (KCNN4) were screened as candidate biomarkers from 225 significantly dysregulated salivary proteins. These proteins participated in adherens junction or saliva secretion pathway and may be related to saliva secretion disorder. Proteomic analysis revealed that CTNNA3, PTPN6, and RAC2 were dysregulated in saliva and salivary glands and showed satisfactory sensitivity and specificity in receiver-operating characteristic curve; KCNN4 showed no statistical difference. IHC and IPA indicated that CTNNA3 may regulate acinar cell morphology, while PTPN6 and RAC2 promoted lymphocyte adhesion in salivary glands. Thus, CTNNA3, PTPN6, and RAC2 may be related to saliva secretion disorder in pSS.

Clinical and Imaging Findings of Temporomandibular Joint Synovial Chondromatosis: An Analysis of 10 Cases and Literature Review.

PURPOSE: This study investigated clinical and imaging features of synovial chondromatosis (SC) of the temporomandibular joint (TMJ) for use in clinical applications. MATERIALS AND METHODS: We analyzed clinical data from 10 patients with SC of the TMJ in our hospital from 2011 to 2015. We also reviewed and analyzed relevant literature included in the National Center for Biotechnology Information database in the past decade using the search terms "synovial chondromatosis" and "temporomandibular joint." RESULTS: The incidence of SC of the TMJ was higher in female patients than in male patients (male-to-female ratio, 1:2.22). It occurred most often in middle age (mean, 47.2 years). The characteristic symptoms of SC in the TMJ were pain (90.8%), swelling (67.1%), limited ability to open the mouth (68.4%), deviant jaw opening (34.2%), and crepitation (31.6%). Computed tomography (CT) (42.9%) and magnetic resonance imaging (45.4%) were the most common techniques used to assess SC in the TMJ, and cone-beam CT (10.9%) also was used to make preliminary diagnoses based on its imaging findings. Open surgery was the preferred treatment of SC of the TMJ, and the recurrence rate was low. CONCLUSIONS: The main clinical characteristics of SC of the TMJ are pain, swelling, limited mouth opening, joint sounds, and deviant jaw opening. Imaging features include abnormal high-density shadows, condyle hyperostosis or destruction, changes in the temporal bone, and widening of the joint space. Cone-beam CT is useful for diagnosis of SC of the TMJ.