Developing drugs that can effectively block STAT3 activation may serve as one of the most promising strategy for cancer treatment. Currently, there is no putative STAT3 inhibitor that can be safely and effectively used in clinic. In the present study, we investigated the potential of dihydroartemisinin (DHA) as a putative STAT3 inhibitor and its antitumor activities in head and neck squamous cell carcinoma (HNSCC). The inhibitory effects of DHA on STAT3 activation along with its underlying mechanisms were studied in HNSCC cells. The antitumor effects of DHA against HNSCC cells were explored both in vitro and in vivo. An investigation on cooperative effects of DHA with cisplatin in killing HNSCC cells was also implemented. DHA exhibited remarkable and specific inhibitory effects on STAT3 activation via selectively blocking Jak2/STAT3 signaling. Besides, DHA significantly inhibited HNSCC growth both in vitro and in vivo possibly through induction of apoptosis and attenuation of cell migration. DHA also synergized with cisplatin in tumor inhibition in HNSCC cells. Our findings demonstrate that DHA is a putative STAT3 inhibitor that may represent a new and effective drug for cancer treatment and therapeutic sensitization in HNSCC patients.

Adenoid cystic carcinoma (ACC) of the external auditory canal (EAC) is a rare tumor. The present study aimed to describe the clinical features and survival of patients with ACC of the EAC. The present retrospective study included 23 patients (mean age, 51.4±15.4 years; 12 males) diagnosed with ACC of the EAC between January 2010 and September 2017 at The First Affiliated Hospital of The Third Military Medical University (Chongqing, China). The median disease course was 24 months. The presenting features were earache in 16 patients, otorrhea in 7 patients, hearing loss in 5 patients, feeling of aural fullness in 2 patients and EAC mass in 4 patients. Tumor stage was T1 in 13 patients, T2 in 3 patients, T3 in 3 patients and T4 in 4 patients. Among patients with T1 tumors, 5 underwent en bloc external EAC resection; 3 underwent local EAC resection; 1 underwent en bloc EAC resection and superficial parotidectomy; 1 underwent subtotal temporal bone resection for postoperative recurrence; Among patients with T4 tumors, 1 underwent extended temporal bone resection, right parotidectomy, right resection of middle cranial fossa tumors and right resection of temporomandibular joint capsule. 1 underwent subtotal temporal bone resection. Among these 15 patients who underwent surgery, 2 received postoperative radiotherapy, 1 received postoperative chemotherapy, 5 received postoperative chemo-radiotherapy, and 7 did not receive postoperative chemo-radiotherapy. The 3-and 5-year cumulative survival rates of the 23 patients were 47.8% and 17.4%, respectively. Survival may have been improved in patients who received postoperative chemo-radiotherapy and early diagnosis may be the key to improving survival.

Tonotopic differences in the structure and physiological function, e.g., synapse number, membrane properties, Ca 2+ channels, Ca 2+ dependence of exocytosis and vesicle pool replenishment of inner hair cells (IHCs) along the longitudinal cochlear axis have recently been discovered, suggesting different gene expression patterns of IHCs. To determine whether IHCs present different gene expression patterns along the longitudinal cochlear axis, apical and basal IHCs were collected separately using the suction pipette technique from adult mouse cochleae for RNA-seq and genome-wide transcriptome analysis. We found 689 annotated genes showed more than 2-fold increase in expression. Interestingly, 93.4% of the differentially expressed genes (DEGs) was upregulated in apical IHCs. Although a subset of genes that related to IHC machinery and deafness were found to be differentially expressed, a gradient of gene expression was indeed detected in Ocm, Pvalb, Prkd1, Fbxo32, Nme2, and Sncg, which may play putative roles in the Ca 2+ buffering and survival regulation. The expression of these genes was validated by real-time quantitative PCR (RT-qPCR) or immunostaining. We conclude that IHCs from different mouse cochlear longitudinal position have different gene expression profiles. Our data might serve as a valuable resource for exploring the molecular mechanisms underlying different biological properties as well as the survival regulation of IHCs.

Objectives. A more accurate preoperative prediction of lymph node metastasis (LNM) plays a decisive role in the selection of treatment in patients with laryngeal carcinoma (LC). This study aimed to develop a machine learning (ML) prediction model for predicting LNM in patients with LC. Methods. We collected and retrospectively analysed 4887 LC patients with detailed demographical characteristics including age at diagnosis, race, sex, primary site, histology, number of tumours, T-stage, grade, and tumour size in the National Institutes of Health (NIH) Surveillance, Epidemiology, and End Results (SEER) database from 2005 to 2015. A correlation analysis of all variables was evaluated by the Pearson correlation. Independent risk factors for LC patients with LNM were identified by univariate and multivariate logistic regression analyses. Afterward, patients were randomly divided into training and test sets in a ratio of 8 to 2. On this basis, we established logistic regression (LR), k-nearest neighbor (KNN), support vector machine (SVM), extreme gradient boosting (XGBoost), random forest (RF), and light gradient boosting machine (LightGBM) algorithm models based on ML. The area under the receiver operating characteristic curve (AUC) value, accuracy, precision, recall rate, F1-score, specificity, and Brier score was adopted to evaluate and compare the prediction performance of the models. Finally, the Shapley additive explanation (SHAP) method was used to interpret the association between each feature variable and target variables based on the best model. Results. Of the 4887 total LC patients, 3409 were without LNM (69.76%), and 1478 had LNM (30.24%). The result of the Pearson correlation showed that variables were weakly correlated with each other. The independent risk factors for LC patients with LNM were age at diagnosis, race, primary site, number of tumours, tumour size, grade, and T-stage. Among six models, XGBoost displayed a better performance for predicting LNM, with five performance metrics outperforming other models in the training set (AUC: 0.791 (95% CI: 0.776–0.806), accuracy: 0.739, recall rate: 0.638, F1-score: 0.663, and Brier score: 0.165), and similar results were observed in the test set. Moreover, the SHAP value of XGBoost was calculated, and the result showed that the three features, T-stage, primary site, and grade, had the greatest impact on predicting the outcomes. Conclusions. The XGBoost model performed better and can be applied to forecast the LNM of LC, offering a valuable and significant reference for clinicians in advanced decision-making.