Abstract Objective The aim of study was to demonstrate that transcutaneous intralesional injection of Triamcinolone Acetonide (TA) under fibrolaryngoscopy could be an option for persistent granulation after Transoral Laser Microsurgery (TLM) in glottic cancer patients. Methods We recruited 32 patients, who had conservative treatment but failed. 20 patients accepted TA injection monthly until the granulation disappeared or did not shrink further. 12 patients chose to closely monitor. Results For the 20 patients, 17 (85.0%) patients’ granulations completely disappeared. 3 (15.0%) patients’ granulations had reduced 80%. For the 12 patients, 3 (25.0%) patients’ granulations disappeared but 9 (75%) patients’ granulations did not have an obvious change. Recurrence was not observed. Conclusion Our experience showed that transcutaneous intralesional TA injection for persistent granulation after TLM through cricothyroid membrane is an efficient, security, harmless and low recurrence method. Especially suitable for huge granulation which blocks the glottis and recur after a second operation.

Abstract Objective MicroRNA-29a-3p has been reported in a variety of cancers, but its role in hypopharyngeal cancer remains unclear. This study was to determine the role of microRNA-29a-3p in the occurrence and development of hypopharyngeal cancer. Methods 40 patients with hypopharyngeal cancer who underwent surgery in the Affiliated Hospital of Jining Medical University from April 2013 to November 2017 were selected for this study. The cancer tissue samples of the patients were collected, and the patients were followed up for three years. The expression of microRNA-29a-3p in tissue samples was detected by in situ hybridization with fluorescent probe, and the relationships among microRNA-29a-3p and clinicopathological factors, postoperative recurrent-metastasis, survival time were studied. Immunohistochemical was used to detect the expression of Ki67 and E-cadherin in tissue samples. Results Combined with HE staining results showed that microRNA-29a-3p expression was relatively high in non-cancer tissue cells (red blood cells and fibroblasts in tumor interstitial vessels), but was relatively low in cancer tissue and cells. According to the follow-up data of 40 patients with hypopharyngeal cancer, tumor size, T-stage, tumor differentiation, postoperative recurrent-metastasis of hypopharyngeal cancer patients were significantly negatively correlated with microRNA-29a-3p (p< 0.05). Immunohistochemica results further confirmed that microRNA-29a-3p was negatively correlated with the expression of Ki67 and E-cadherin. The survival time of patients positively related with microRNA-29a-3p expression (p< 0.05). Moreover, ROC curve analysis showed that the area under the curve of the combined detection of miRNA-29a-3p+Ki67+E-cadherin was larger than that of the single detection of the three indexes. Conclusions The expression of microRNA-29a-3p is closely related to the occurrence, development and prognosis of hypopharyngeal cancer, and it affects the proliferation and invasion. This indicates that microRNA-29a-3p serves as a therapeutic target for the occurrence and development of hypopharyngeal cancer. The evidence of study designs of this study is IV using “Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence”.

Abstract Objective This study aimed to investigate the molecular mechanism of miR-150-5p regulating the malignant biological behavior of Human Epidermoid cancer cell (HEp-2) by targeting peptidyl-prolyl cis/trans isomerase NIMA-Interacting-1 (PIN1). Methods Firstly, qRT-PCR and Western blot were adopted to detect the expression levels of miR-150-5p and PIN1 in cancer tissue and paracancerous tissues of patients with LSCC, and those in human bronchial epithelial cells (16 HBE) and HEp-2. Next, the targeted relationship between miR-150-5p and PIN1 was assessed by bioinformatics website and dual-luciferase reporter assay, followed by their correlation analysis. Besides, after interfering with miR-150-5p or PIN1 expression in HEp-2 cells, CCK-8, cell colony formation assay, and transwell assay were utilized to detect the proliferation, viability, and invasion of cells, respectively. Subsequently, the protein levels of MMP-2, MMP-9, and EMT-related proteins in HEp-2 cells were checked by Western blot. Results Expression of miR-150-5p was down-regulated in LSCC tissues and HEp-2 cells. Moreover, miR-150-5p suppressed proliferation and invasion of HEp-2 cells, affected protein expression related to MMP and EMT, thereby inhibiting development of cancer. The expression of PIN1 was significantly increased in cancer tissues and HEp-2 cells, and there was a targeted relationship and negative correlation between miR-150-5p and PIN1 in cancer tissue. However, overexpression of PIN1 could reverse the effect of miR-150-5p on the proliferation and invasion of HEp-2 cells. Conclusion In a nutshell, there is a targeted relationship between PIN1 and miR-150-5p. Besides, miR-150-5p can inhibit the proliferation and invasion of HEp-2 cells by regulating the expression of PIN1. Level of evidence 3.

Abstract Objective The study aimed to investigate the feasibility of establishing rhinosinusitis model in rats combinated with Lipopolysaccharide (LPS) and merocel sponge. Methods SD (Sprague Dawley) rats that underwent nasal obstruction using Merocel sponge packing, rats with LPS instillation alone, and rats with both nasal obstruction and LPS instillation were used to establish rat models of rhinosinusitis. After the models were established, the nasal symptoms of rats were recorded, the histopathological examination and Transmission Electron Microscopy (TME) of the sinus tissue were performed and the levels of Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6) in the blood were also analyzed. The expressions of Aquaporin-5 (AQP5), Occludin, Toll-Like Receptor-4 (TLR4), Medullary differentiation factor 88 (MyD88) and phosphorylated (p)-p65 protein were detected by Western blot to evaluate the effect and mechanism of the experimental models. Results We found that compared with the control group and LPS group, the sinusitis symptom scores in the Merocel sponge combined with LPS group were significantly increased; the respiratory epithelia of the maxillary sinus were degenerated, cilia were detached, and even inflammatory cell infiltration occurred; the levels of TNF-α and IL-6 were increased; the expression of AQP5 and Occludin protein was decreased; and the expressions of TLR4, MyD88, and p-p65 protein were increased. Conclusion For the first time, we successfully established a rat rhinosinusitis model using Merocel sponge with LPS and explored the possible mechanism of LPS action.

Abstract Objective To evaluate the efficacy and safety of Alternating Chemoradiotherapy (ACRT) using cisplatin and 5-Fluorouracil (5-FU) in patients with nasopharyngeal carcinoma. Methods This was a retrospective study in which patients’ clinical records were reviewed to identify patients with a new diagnosis of nasopharyngeal carcinoma at our institution between January 2005 and January 2019. Thirty-seven eligible patients were identified; of these, the clinical details of 27 patients treated with ACRT were evaluated. Patient outcomes, including overall survival and progression-free survival, and adverse events were assessed. Results Of these initial 37 patients, 1, 10, 13, 10, and 3 were staged as I, II, III, IVA, and IVB, respectively, as defined by the 8th edition of the TNM classification system. Twenty-seven patients received ACRT comprising sequential administration of chemotherapy, radiotherapy (wide field), chemotherapy, radiotherapy (shrinking field), and chemotherapy. The 5-year overall survival and progression-free survival rates were 83.7% and 88.9%, respectively. Treatment compliance was 93%, which is comparable to that of previous reports. Conclusion ACRT using cisplating and 5-fluorouracil was well tolerated with acceptable efficacy. Level of Evidence IVa

Abstract Objective To compare polysomnographic parameters with others from the literature in order to provide more accurate information about Rapid Maxillary Expansion (RME) for treating Obstructive Sleep Apnea (OSA) in children, through raising the question: Is RME a good option for treating OSA in children? Prevention of mouth breathing during children's growth remains a challenge with significant clinical consequences. In addition, OSA induces anatomofunctional changes during the critical period of craniofacial growth and development. Methods The Medline, PubMed, EMBASE, CINAHL, Web of Science, SciELO and Scopus electronic databases were searched up to February 2021 for systematic reviews with meta-analysis in the English language. Among 40 studies on RME for treating OSA in children, we selected seven in which polysomnographic measurements of the Apnea-Hypopnea Index (AHI) had been made. Data were extracted and examined in order to clarify whether any consistent evidence exists for indicating RME as a treatment for OSA in children. Results We found no consistent evidence favoring RME for long-term treatment of OSA in children. All the studies presented considerable heterogeneity due to variability of age and length of follow-up. Conclusion Through this umbrella review, the need for methodologically better studies on RME is supported. Moreover, it can be considered that RME is not recommended for treating OSA in children. Further studies and more evidence identifying early signs of OSA are necessary in order to achieve consistent healthcare practice.

Abstract Objectives We aimed to explore the heterogeneity and differentiation trajectories of epithelial cells and NK/T-cells in Laryngeal Squamous Cell Carcinoma (LSCC). Methods We downloaded the GSE150321 data set containing LSCC01 and LSCC02 samples single cell RNA data from Gene Expression Omnibus. The UMAP analysis was performed to identify the cell subpopulations and cell locations of subpopulations. Seurat package was used to analyze the differential expression of genes. The function of differential expression genes was analyzed using DAVID database. The monocle2 package was used to analyze differentiation trajectories. We used the CellChat package to observe the signaling pathways and ligand-receptor pairs for epithelial cells and NK/T-cells. Results All the LSCC cells were divided into 16 subpopulation that included 7 epithelial cell subsets, 3 T-cell subsets. The function analysis indicated that epithelial cells and NK/T-cells mainly participated in different process, such as cell cycle, immune response, and cell migration. Then, the results of differentiation trajectory indicated that the ability of migration, and the activation of the immune system increases, while the ability of apoptosis, and glucose metabolic process decreases as pseudotime. Migration-related epithelial cells act on all T-cells via the CNTN2-CNTN2 ligand-receptor pair, which suggested that CNTN2 might be an important biomarker for regulating migration of epithelial cells. Conclusions Our study characterized the heterogeneity of LSCC, which provided novel insights into LSCC and identified a new mechanism and target for clinical LSCC threapies. Evidence IV.

Abstract Objectives This study aimed to assess the prevalence of oral lesions in patients living with HIV infection and their association with CD4 count, viral load, and antiretroviral therapy in patients with HIV. Methods A cross-sectional study was conducted on a sample of 161 patients attending the… All the patients were examined for their oral lesions, current CD4 counts, type, and duration of the therapy. Data analyses were carried out using Chi-Square, Student T/Mann-Whitney, and logistic regression tests. Results Oral lesions were observed in 58.39% of patients with HIV. Periodontal disease with 78 (48.45%) or without mobility 79 (49.07%) was observed more frequently, followed by hyperpigmentation of oral mucosa 23 (14.29%), Linear Gingival Erythema (LGE) 15 (9.32%), candidiasis pseudomembranous 14 (8.70%). Oral Hairy Leukoplakia (OHL) was observed only in 3 (1.86%). A relationship between periodontal disease with dental mobility and smoking was found (p = 0.04), as well duration of treatment (p = 1.53e-3) and age (p = 0.02). Hyperpigmentation was related to race (p = 0.01) and smoking (p = 1.30e-6). CD4 count, CD4:CD8 ratio, viral load, or type of treatment were not associated with oral lesions. Logistic regression showed that the duration of treatment has a protective effect on the periodontal disease with dental mobility (OR = 0.28 [−2.27 to −0.25]; p-value = 0.03), independent of age or smoking. To hyperpigmentation, the best model included smoking (OR = 8.47 [1.18-3.10], p = 1.31e-5), without race or type and duration of treatment. Conclusion Among HIV patients undergoing antiretroviral treatment, oral lesions can be observed, predominantly periodontal disease. Pseudomembranous candidiasis and oral hairy leukoplakia were also observed. No relationship was found between associated oral manifestations in HIV patients and the start of the treatment, TCD4+ and TCD8+ cell count, TCD4:TCD8 ratio, or viral load. The data indicate that there is a protective effect of duration of treatment with relation to periodontal disease with mobility and that hyperpigmentation seems to be more related to smoking than type and duration of treatment. Level of evidence Level 3 (OCEBM Levels of Evidence Working Group*. "The Oxford 2011 Levels of Evidence").

Abstract Objective Our study aimed to elucidate the effect of PAI-1 (Plasminogen Activator Inhibitor-1) and t-PA (Tissue-type Plasminogen Activator) in tissue remodeling in nasal polyps patients. Methods Samples were streamed as early Nasal Polyps (eNP, n = 10) and inferior tissue from the same patient, mature Nasal Polyps (mNP, n = 14), and Control group (n = 15), respectively. Immunohistochemistry and immunofluorescence were applied to detect localization. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot were used to measure different levels among three groups. The mNP tissue was cultured in vitro and treated with TGF-β1 (Transforming Growth Factor-beta 1) activator, TGF-β1 inhibitor (SB431542), and PAI-1 inhibitor (TM5275); then Western blot, qRT-PCR, and ELISA were used to assess changes. Results The immunohistochemistry and immunofluorescence showed that PAI-1 expression decreased in eNP and mNP, mainly in epithelium and glands. The transcriptional expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 were lower in eNP than IT while mNP group demonstrated lower mRNA expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 than Control group. In mNP tissue culture in vitro, TGF-β1 activator elevated t-PA, PAI-1, and Collagen1 with higher release of PAI-1 and Collagen1 in supernatant, whereas SB431542 suppressed above reactions; TM5275 lowered transcriptional and protein level of Collagen1 in supernatant. Conclusion Early Nasal polyps’ formation in middle meatus mucous is related with fibrillation system PAI-1/t-PA and tissue remodeling; moreover, nasal polyps’ development is regulated by TGF-β1-mediated PAI-1 reduction. Level of evidence 3b.

Abstract Objectives To determine whether tinnitus negatively impacts the accuracy of sound source localization in participants with normal hearing. Methods Seventy-five participants with tinnitus and 74 without tinnitus were enrolled in this study. The accuracy of sound source discrimination on the horizontal plane was compared between the two participant groups. The test equipment consisted of 37 loudspeakers arranged in a 180° arc facing forward with 5° intervals between them. The stimuli were pure tones of 0.25, 0.5, 1, 2, 4, and 8 kHz at 50 dB SPL. The stimuli were divided into three groups: low frequency (LF: 0.25, 0.5, and 1 kHz), 2 kHz, and high frequency (HF: 4 and 8 kHz) stimuli. Results The Root Mean Square Error (RMSE) score of all the stimuli in the tinnitus group was significantly higher than that in the control group (13.45 ± 3.34 vs. 11.44 ± 2.56, p = 4.115, t < 0.001). The RMSE scores at LF, 2 kHz, and HF were significantly higher in the tinnitus group than those in the control group (LF: 11.66 ± 3.62 vs. 10.04 ± 3.13, t = 2.918, p = 0.004; 2 kHz: 16.63 ± 5.45 vs. 14.43 ± 4.52, t = 2.690, p = 0.008; HF: 13.42 ± 4.74 vs. 11.14 ± 3.68, t = 3.292, p = 0.001). Thus, the accuracy of sound source discrimination in participants with tinnitus was significantly worse than that in those without tinnitus, despite the stimuli frequency. There was no difference in the ability to localize the sound of the matched frequency and other frequencies (12.86 ± 6.29 vs. 13.87 ± 3.14, t = 1.204, p = 0.236). Additionally, there was no correlation observed between the loudness of tinnitus and RMSE scores (r = 0.096, p = 0.434), and the Tinnitus Handicap Inventory (THI) and RMSE scores (r = −0.056, p = 0.648). Conclusions Our present data suggest that tinnitus negatively impacted sound source localization accuracy, even when participants had normal hearing. The matched pitch and loudness and the impact of tinnitus on patients’ daily lives were not related to the sound source localization ability. Level of evidence 4.

Abstract Objective The role of Primary Tumor Volume (PTV) in Nasopharyngeal Carcinoma (NPC) treated with Volumetric Modulated Arc Therapy (VMAT) is still unclear. The aim of this study was to access the effect of PTV in prognosis prediction of nasopharyngeal carcinoma in era of VMAT. Methods Between January 20 and November 2011, 498 consecutive NPC patients with stage I-IVA disease who received VMAT at a single center were retrospectively analyzed. Receiver Operating Characteristic (ROC) was performed to access the cut-off point of PTV. Univariate Kaplan-Meier and multivariate Cox regression analyses were used to evaluate prognostic value for PTV. The Propensity Score Matching (PSM) was used to adjust baseline potential confounders. Results The 5-year Locol-Regional Failure-Free (L-FFR), Distant Failure-Free Survival (D-FFR), Disease-Free Survival (DFS) and Overall Survival (OS) were 90.6%, 83.7%, 71.5% and 79.3%, respectively. Before PSM, the 5-year L-FFR, D-FFR, DFS, OS rates for NPC patients with PTV ≤ 38 mL vs. PTV > 38 mL were 94.1% vs. 90.4% (p= 0.063), 87.9% vs. 76.3% (p< 0.001), 78.5% vs. 58.5% (p< 0.001) and 86.3% vs. 66.7% (p< 0.001) respectively. Multivariate analysis showed PTV was an independent prognostic factor for D-FFS (p= 0.034), DFS (p= 0.002) and OS (p= 0.001). PTV classified was still an independent prognostic factor for OS after PSM (HR = 2.034, p= 0.025. Conclusions PTV had a substantial impact on the prognosis of NPC patients treated with VMAT before and after PSM simultaneously. PTV > 38 mL may be considered as an indicator of the clinical stage of nasopharyngeal carcinoma. Level of evidence III.

Abstract Objective Pediatric orbital blowout fractures can include pathologies that seem mild but require urgent release; serious sequelae can occur with standby surgery or conservative treatment. We sought to validate an algorithm for the treatment of pediatric orbital blowout fractures. Methods This retrospective cohort study included 61 pediatric patients, aged 18 years or younger, treated for pure orbital blowout fractures according to the algorithm from April 1, 2000, to August 31, 2020, at the Japanese Red Cross Asahikawa Hospital. Results There were 52 males (85%). Median age was 14 years (range, 5-18 years). There were 9 patients categorized as needing urgent release, 16 as needing repair, and 36 as needing conservative treatment. Mean follow-up ocular movement was 98.0 (95% Confidence Interval [95% CI], 96.8-99.2). Postoperative diplopia was not observed in 96% (79.6%-99.9%) of patients, better than in previous studies. A higher proportion of patients aged 0-12 years needed urgent repair than those aged 13-18 years (Odds Ratio [OR] = 14.2; 95% CI 1.6-683.4; p= 0.0046). There were no differences in Hess area ratio by age group. Conclusion Clinical results with the algorithm were satisfactory. The algorithm is suitable for treatment of pediatric orbital blowout fractures. Level of evidence 4.

Abstract Objectives The aim of the study was to investigate clinical significance of soluble PD-L1 (sPD-L1) serum level in head and neck cancer and to evaluate its role as a possible prognostic and predictive biomarker. Methods A prospective analysis of sPD-L1 levels in 60 patients diagnosed and treated due to malignant and non-malignant lesions in the region of head and neck was performed in peripheral blood by an ELISA test. Results The range of sPD-L1 in the study group was 0.16-1.63 ng/mL, mean 0.64 ± 0.32. There were no differences in the mean sPD-L1 regarding patients’ age, sex, and the localization of the lesion. Statistically significant difference was revealed in the average sPD-L1 level (p = 0.006) depending on the histopathological advancement of the lesions, 0.704 ± 0.349 and 0.512 ± 0.177 respectively in the malignant and benign group. The separate analysis of laryngeal lesions confirmed statistical difference in sPD-L1 (p = 0.002) for the malignant lesions (0.741 ± 0.353) compared with the benign (0.489 ± 0.175). The sPD-L1 level of 0.765 ng/mL or higher, revealed 35% sensitivity and 95.5% specificity for the diagnosis of head and neck malignant lesions (AUC = 0.664, 95% CI 0.529‒0.8, p-value = 0.039). The 1-year DFS was 83.3% in the group of patients with low sPD-L1 levels (< 0.765 ng/mL) and 53.8% in patients with high sPD-L1 (≥0.765 ng/mL). The 2-year OS were 68% and 69.2% respectively in both groups. The log-rank test confirmed statistically significant prognostic value of sPD-L1 level for 1-year DFS (p-value = 0.035). Conclusions sPD-L1 is a promising prognostic and early recurrence predictive biomarker for head and neck cancers, most significantly for laryngeal lesions. Level of evidence 3.

Abstract Objectives Prominent ear abnormalities affect 5% of the population. A prospective, double-blind study of patients who underwent otoplasty procedures to correct these abnormalities was conducted to compare two surgical techniques. They diverge by the preservation or not of conchal cartilage. Methods The two techniques were compared by measuring the cephalo-auricular and scapho-conchal angles. Measurements were performed in pre and 6-months post-operative periods using alginate molding. Twenty patients were randomly assigned to two groups (with and without cartilage preservation) with 10 participants each. Student’s t-test, Covariance Analysis Model (ANCOVA), and non-parametric Mann-Whitney were used in the statistical analyses. Results A significant reduction in the average of the cephalo-auricular and scapho-conchal angles was observed in both surgical procedures (p < 0.001). However, no significant difference was found between them (p = 0.887). Conclusion The two techniques analyzed in this study fulfilled their objectives. Therefore, further comparative studies are needed to confirm the superiority of one over the other. Level I Evidence obtained from at least one properly designed randomized controlled trial.