Clinical and experimental study of a terahertz time-domain system for the determination of the pathological margins of laryngeal carcinoma.

OBJECTIVE: Laryngeal cancer is a common malignancy in otorhinolaryngological head and neck surgery, accounting for approximately one-third of all head and neck malignancies. Terahertz time-domain spectroscopy (THz-TDS) has recently been found to be useful for the detection of tumors. This study was conducted to investigate the application of THz-TDS in the diagnosis of pathological resection margins of laryngeal cancer. METHODS: Fresh laryngeal cancer tissues from 10 patients with laryngeal cancer were extracted, and after simultaneous HE staining and terahertz imaging, the tumor area, paracancerous area, and normal tissue area of each laryngeal cancer tissue sample were located under a microscope according to the pathological results of HE staining. RESULTS: The shape contours of the tumor region revealed by terahertz imaging maps and HE staining were similar. In the terahertz spectrum in the frequency range of 0.5-1.9 THz, both the absorption coefficient and refractive index values followed the order tumor > para cancer > normal tissue, with statistically significant differences (P < 0.01). When the terahertz frequency was 1.5 THz, the absorption coefficient of terahertz light waves by laryngeal cancer tissue and the percentage of nuclei showed an extremely high positive correlation (P < 0.01, r = 0.971). In the frequency ranges of 0.5-1.2 THz and 1.6-1.9 THz, the absorption coefficients of the highly differentiated group were higher than those of the moderately differentiated group. In the frequency range of 1.2-1.6 THz, the results were reversed, with statistically significant differences (P < 0.05). In the frequency range of 0.5-1.9 THz, the highly differentiated group had a higher refractive index than the moderately differentiated group, with a statistically significant difference (P < 0.05). CONCLUSIONS: THz-TDS can be used to determine the pathological margins of laryngeal cancer based on the absorption coefficient and refractive index, and the magnitudes of the absorption coefficient and refractive index are related to the percentage of nuclei. The degree of differentiation of laryngeal cancer tissue can be assessed by THz-TDS. The study shows that the terahertz time-domain system is promising for applications in the diagnosis of laryngeal cancer, especially for the more accurate identification of intraoperative margins.

Transoral laser microsurgery versus radiotherapy for T1 glottic carcinoma: a systematic review and meta-analysis.

Transoral laser microsurgery (TLM) and radiotherapy (RT) are both accepted treatment modalities for glottic cancer. The objective of the study was to assess the oncologic outcomes and life quality of TLM in comparison with RT for T1 glottic carcinoma. We searched Medline/PubMed, Web of knowledge, EMBASE, the Cochrane Library, the Wiley online library, Springer, Google, China National Knowledge Infrastructure (CNKI), etc. We screened the literature, assessed the quality of the studies, and extracted the relevant data through the establishment of inclusion and exclusion criteria. Meta-analysis was done using the Cochrane collaboration' s RevMan 5.0 for data analysis. A total of 11 studies were included in this meta-analysis. The laryngeal preservation for patients undergoing TLM was significantly better than that for RT (P < 0.00). The laser surgery significantly improved the overall survival of patients with T1 glottic carcinoma (P = 0.04). No statistically significant differences were found between TLM and RT regarding the local control (P = 0.91). The funnel plot demonstrates no apparent publication bias in the overall survival and laryngeal preservation comparison. Our meta-analysis suggested that laser surgery was a preferred method than radiotherapy with respect to significantly better overall survival and laryngeal preservation. But the local control was not significant different. Further prospective randomized controlled studies will be needed.

Single cell RNA sequencing provides novel cellular transcriptional profiles and underlying pathogenesis of presbycusis.

Age-related hearing loss (ARHL) or presbycusis is associated with irreversible progressive damage in the inner ear, where the sound is transduced into electrical signal; but the detailed mechanism remains unclear. Here, we sought to determine the potential molecular mechanism involved in the pathogeneses of ARHL with bioinformatics methods. A single-cell transcriptome sequencing study was performed on the cochlear samples from young and aged mice. Detection of identified cell type marker allowed us to screen 18 transcriptional clusters, including myeloid cells, epithelial cells, B cells, endothelial cells, fibroblasts, T cells, inner pillar cells, neurons, inner phalangeal cells, and red blood cells. Cell-cell communications were analyzed between young and aged cochlear tissue samples by using the latest integration algorithms Cellchat. A total of 56 differentially expressed genes were screened between the two groups. Functional enrichment analysis showed these genes were mainly involved in immune, oxidative stress, apoptosis, and metabolic processes. The expression levels of crucial genes in cochlear tissues were further verified by immunohistochemistry. Overall, this study provides new theoretical support for the development of clinical therapeutic drugs.

Vector dissipative soliton resonance in a fiber laser.

We report on the vector nature of rectangular pulse operating in dissipative soliton resonance (DSR) region in a passively mode-locked fiber laser. Apart from the typical signatures of DSR, the rectangular pulse trapping of two polarization components centered at different wavelengths was observed and they propagated as a group-velocity locked vector soliton. Moreover, the polarization resolved soliton spectra show different spectral distributions. The observed results will enhance the understanding of fundamental physics of DSR phenomenon.

[Risk factors of recurrence and canceration for premalignant vocal fold lesions after surgery].

Objective:To analyze the risk factors of recurrence and canceration for premalignant vocal fold lesions after surgery, and to provide a reasonable basis for preoperative evaluation and postoperative follow-up. Methods:This study retrospective analyzed the relationship between clinicopathological factors and clinical outcome（recurrence, canceration, recurrence-free survival, and canceration-free survival） in 148 patients undergoing surgical treatment in Chongqing General Hospital from 2014 to 2017. Results:The five-year overall recurrence rate was 14.86% and the overall recurrence rate was 8.78%. Univariate analysis showed that smoking index, laryngopharyngeal reflux and lesion range were significantly associated with recurrence（P<0.05）, and smoking index and lesion range were significantly associated with canceration（P<0.05）. Multivariate logistic regression analysis showed that smoking index ≥600 and laryngopharyngeal reflux were independent risk factors for recurrence（P<0.05）, and smoking index ≥600 and lesion range ≥1/2 vocal cord were independent risk factors for canceration（P<0.05）. The mean carcinogenesis interval for the postoperative smoking cessation group was significantly longer（P<0.05）. Conclusion:Excessive smoking, laryngopharyngeal reflux and a wide range of lesions may be related to postoperative recurrence or malignant progression of precancerous lesions in the vocal cord, and further large-scale multi-center prospective randomized controlled studies are needed to clarify the effects of the above factors on recurrence and malignant changes in the future.

Application of an Interpretable Machine Learning Model to Predict Lymph Node Metastasis in Patients with Laryngeal Carcinoma.

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.

l-Carnitine conjugated chitosan-stearic acid polymeric micelles for improving the oral bioavailability of paclitaxel.

A delivery system based on l-carnitine (LC) conjugated chitosan (CS)-stearic acid polymeric micelles has been developed for improving the oral bioavailability of paclitaxel (PTX) through targeting intestinal organic cation/carnitine transporter 2 (OCTN2). Stearic acid grafted chitosan (CS-SA), as micelle skeleton material, was synthesized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. The PTX-loaded micelles were prepared by solvent evaporation-hydration method, and the ligand LC was conjugated onto the micelle surface by anchoring its derivative stearoyl group to the lipophilic core of micelle. The modified polymeric micelles showed regular spherical shapes with small particle size of 157.1 ± 5.2 nm and high drug loading capacity of 15.96 ± 0.20 wt%, and the micelle stability in water was supported by low critical micelle concentration of 14.31 ± 0.21 µg/ml. The drug-loaded micelles presented a slow and incomplete in vitro release, and the pharmacokinetic studies indicated the micelle carriers increased the relative bioavailability of PTX to 165.8% against the commercial formulation. The enhancement effect on intestinal absorption was also confirmed by the intracellular uptake of Caco-2 cells. The proposed micelle carrier system manifested a prospective tool for oral drug delivery.

[Effects of chronic intermittent hypoxia on glucose transporter 4 expression in rat skeletal muscles].

OBJECTIVE: To study the effect of chronic intermittent hypoxia-induced inflammatory cytokines and reoxygenation on glucose transporter 4 (GLUT-4) expression in rat skeletal muscles. METHODS: Twenty-four male Sprague-Dawley rats were randomly assigned to blank control group, chronic intermittent hypoxia (CIH) group, and reoxygenation group. At the end of the experiment, fasting blood glucose (FBG), fasting blood insulin (FINS) and serum inflammatory cytokine levels were measured with glucose oxidase-peroxidase, insulin radioimmunoassay and ELISA, respectively. Homeostasis model assessment (IRI) was used to evaluate insulin resistance in the rats, and GLUT-4 protein expression in the skeletal muscles was measured with Western blotting. RESULTS: Compared with the blank control group, CIH resulted in significantly increased fasting blood glucose, blood insulin levels and insulin resistance index (IRI) (P<0.05); fasting blood glucose was significantly elevated in reoxygenation group (P<0.05). Inflammatory cytokines levels (IL-6 and TNF-α) were significantly higher in CIH group than in the blank control and reoxygenation groups (P<0.05), and were higher in reoxygenation group than in the blank control group. GLUT-4 expression in the skeletal muscles was significantly reduced after CIH (P<0.05) but increased after subsequent reoxygenation (P<0.05). CONCLUSION: CIH can cause increased release of inflammatory cytokines to lower GLUT-4 protein expression in the skeletal muscles, which contributes to insulin resistance in adult rats.

[The effect of oxidative stress on aorta endothelial cell in chronic intermittent hypoxia animal model].

OBJECTIVE: To make a chronic intermittent hypoxia (CIH) animal model and explore the relationships of oxidative stress and the injury of aorta endothelial cell on the CIH rat model. METHOD: Twenty-four sex maturation rat were randomly Divided into unhandled control group(normal feeding for 4 weeks, UC group), CIH group (CIH for 4 weeks), reoxygenation group (normal feeding for 4 weeks after CIH for 4 weeks, RH group). Determined the activity of superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) in blood serum of all groups. Dislodged rat's aorta, observed the appearance of aorta endothelial cell and the expression of endothelial nitric oxide synthase (eNOS). RESULT: Compared with UC group, in CIH group the activities of SOD and NO were significantly lower, but MDA significantly higher (all of P < 0.05 respectively), the appearance of aorta endothelial cell changed, the expressions of eNOS lower. There were not significantly change in UC group and RH group (P > 0.05). CONCLUSION: Oxidative stress played a role in the injury of aorta endothelial cell on ob chronic intermittent hypoxia rat modle.