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Many studies have investigated factors contributing to large variations in the outcomes of round-window (RW) stimulation but most have focused on the floating mass transducer (FMT). To determine whether results for the FMT hold for a fixed-type transducer (FTT), this study constructs two coupled finite element models of the transducer and the human ear that incorporate the cochlear third windows and inner structures of these two electromagnetic transducers. We use these FE models of the human ear and transducers to investigate the influence of four design parameters and coupling conditions for the transducers, i.e., the support's Young's modulus, the coupling layer's cross sectional area and Young's modulus, and the transducer's cross sectional area. The results show that an increase in the support's Young's modulus reduces the output of the FMT but increases that of the FTT. Reducing the cross sectional area and Young's modulus of the coupling layer significantly increases the low-frequency response of the FMT but slightly reduces that of the FTT. Reducing the cross sectional area of the transducer increases the output of the FMT but reduces that of the FTT. This shows that inner structures of electromagnetic transducers should be considered in the optimal design parameters and coupling conditions for RW stimulation.

Purpose Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors of the head and neck. This study aimed to investigate the crucial genes and regulatory networks involved in the carcinogenesis of NPC using a bioinformatics approach. Methods Five mRNA and two miRNA expression datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and miRNAs (DEMs) between NPC and normal samples were analyzed using R software. The WebGestalt tool was used for functional enrichment analysis, and protein-protein interaction (PPI) network analysis of DEGs was performed using STRING database. Transcription factors (TFs) were predicted using TRRUST and Transcriptional Regulatory Element Database (TRED). Kinases were identified using X2Kgui. The miRNAs of DEGs were predicted using miRWalk database. A kinase-TF-mRNA-miRNA integrated network was constructed, and hub nodes were selected. The hub genes were validated using NPC datasets from the GEO and Oncomine databases. Finally, candidate small-molecule agents were predicted using CMap. Results A total of 122 DEGs and 44 DEMs were identified. DEGs were associated with the immune response, leukocyte activation, endoplasmic reticulum stress in GO analysis, and the NF-κB signaling pathway in KEGG analysis. Four significant modules were identified using PPI network analysis. Subsequently, 26 TFs, 73 kinases, and 2499 miRNAs were predicted. The predicted miRNAs were cross-referenced with DEMs, and seven overlapping miRNAs were selected. In the kinase-TF-mRNA-miRNA integrated network, eight genes (PTGS2, FN1, MMP1, PLAU, MMP3, CD19, BMP2, and PIGR) were identified as hub genes. Hub genes were validated with consistent results, indicating the reliability of our findings. Finally, six candidate small-molecule agents (phenoxybenzamine, luteolin, thioguanosine, reserpine, blebbistatin, and camptothecin) were predicted. Conclusion We identified DEGs and an NPC regulatory network involving kinases, TFs, mRNAs, and miRNAs, which might provide promising insight into the pathogenesis, treatment, and prognosis of NPC.

Esophageal foreign body impaction is the most common cause of endoscopic emergency. However, there are limited available data on delayed endoscopic management of esophageal sharp-pointed food impaction.To investigate cases of esophageal sharp-pointed food impaction with endoscopic removal findings.This single-center retrospective study collected medical records to identify patients with esophageal sharp-pointed food impaction who underwent endoscopic removal between April 2018 and April 2020. The patients were divided into the early (endoscopic removal12 h) and delayed intervention (12 h) cohorts.Overall, 133 and 696 patients received early and delayed intervention, respectively. The success rate of endoscopic foreign body removal was 96.45%. The most common foreign body was fish bone (66.90%), and the most common shape was "I" (56.26%). Patients from the delayed intervention cohort received general anesthesia with a higher risk for perforation, and no foreign body was identified. The duration of endoscopy, distance between the foreign body/wound and the incisor, and longest diameter of the foreign body were not different between the groups. In multivariate analysis, male sex (odds ratio = 1.792 [1.159, 2.771]; P = 0.009), longer duration of impaction (odds ratio = 2.212 [1.121, 4.365]; P = 0.022) and endoscopy (odds ratio = 1.502 [1.253, 1.800]; P 0.001), and longest diameter of the foreign body (odds ratio = 1.632 [1.329, 2.003]; P 0.001) were associated with a higher incidence of perforation in patients with foreign body impaction.Endoscopic removal is a safe and effective treatment method for sharp-pointed food impaction. Delayed endoscopic removal can increase the risk of esophageal perforation.

Stimulating the round window membrane via an active actuator of the middle ear implant, named the reverse stimulation, has become an option to help patients with ossicular chain deformity (OCD) to restore hearing. However, there is still no concise description of how OCD affects reverse stimulation considering the overflow characteristics of third windows. In the present study, an impedance model considering the vestibular and cochlear aqueducts was used to investigate the dynamic response of the cochlea to reverse stimulation under OCD. First, a finite-element (FE) model of the middle ear and the ear canal was used to estimate the changes in reverse middle-ear impedance caused by ossicular chain fixation and ossicular chain interruption. Then, the impedance model was used to predict the reverse transfer function, which characterizes the effect of OCD on the dynamic response of the cochlea. The results show that ossicular chain fixation reduces the reverse stimulation's performance. Moreover, the existence of the third windows complicates the effect of ossicular chain fixation on the reverse stimulation and boosts obviously the reverse stimulation's performance at low frequencies. In contrast, regardless of the existence of third windows, ossicular chain interruption enhances the effect of reverse stimulation.

The inner ear organ is a delicate tissue consisting of hair cells (HCs) and supporting cells (SCs).The mammalian inner ear HCs are terminally differentiated cells that cannot spontaneously regenerate in adults. Epithelial non-hair cells (ENHCs) in the utricle include HC progenitors and SCs, and the progenitors share similar characteristics with SCs in the neonatal inner ear.We applied single-cell sequencing to whole mouse utricles from the neonatal period to adulthood, including samples from postnatal day (P)2, P7 and P30 mice. Furthermore, using transgenic mice and immunostaining, we traced the source of new HC generation.We identified several sensory epithelial cell clusters and further found that new HCs arose mainly through differentiation from Sox9+ progenitor cells and that only a few cells were produced by mitotic proliferation in both neonatal and adult mouse utricles. In addition, we identified the proliferative cells using the marker UbcH10 and demonstrated that in adulthood the mitotically generated HCs were primarily found in the extrastriola. Moreover, we observed that not only Type II, but also Type I HCs could be regenerated by either mitotic cell proliferation or progenitor cell differentiation.Overall, our findings expand our understanding of ENHC cell fate and the characteristics of the vestibular organs in mammals over the course of development.

Objectives During clinical practice, we have detected a few cases of neck abscesses in patients diagnosed with esophageal foreign body impaction (EFB) but without the primary inflammatory disease. However, we do not know if neck abscesses caused by an inflammatory source are more like to be associated with a more severe progression or poorer prognosis. In this study, we aimed to identify differences between these two groups of patients by comparing progression and prognosis. Materials and methods We retrospectively reviewed all patients who underwent neck abscess incisions between January 2011 and March 2022 and divided these patients into two groups: an EFB group and an inflammation group. Data were described by percentages, means, and standard deviations (SDs). Fisher's precision probability test was used to compare differences between the EFB and inflammation groups. Categorical variables were analyzed by Pearson's Chi-squared test. In addition, three factors including hospital days, intensive care unit (ICU) stay, and drainage-tube removal time were used for multivariate analysis to identify independent correlations separately. Results We enrolled a total of 33 patients with neck abscesses who received surgical incisions; the EFB group included 14 (42%) cases, while the inflammatory group included 19 (58%) cases. No significant differences were identified between the two groups in terms of surgery type (with or without mediastinotomy) and postoperative management (negative pressure drainage or postoperative irrigation). There were no significant differences between the two groups in terms of hospital stay, the timing of drainage-tube removal, the risk of ICU admission, and the probability of receiving intubation and tracheotomy. The incidence rate of esophageal perforation differed significantly between the two groups (p Conclusion Patients with neck abscesses associated with EFB and inflammation received the same therapeutic management, and there were no significant differences between these two groups in terms of prognosis. Furthermore, esophageal perforation was found to be irrelevant to the aggravation of neck abscesses, and there was no need for additional surgery to repair a perforated esophagus in patients with neck abscesses. Level of evidence: Retrospective cohort (2b).

Background. Thyroid cancer is the most common endocrine malignancy, with a recent global increase of 20% in age-related incidence. Ultrasonography and ultrasonography-guided fine-needle aspiration biopsy (FNAB) are the most widely used diagnostic tests for thyroid nodules; however, it is estimated that up to 25% of thyroid biopsies are cytologically inconclusive. Molecular markers can help guide patient-oriented and targeted treatment of thyroid nodules and thyroid cancer. Methods. Datasets related to papillary thyroid cancer (PTC) or thyroid carcinoma (GSE129562, GSE3678, GSE54958, GSE138042, and GSE124653) were downloaded from the GEO database and analysed using the Limma package of R software. For functional enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology were applied to differentially expressed genes (DEGs) using the Metascape website. A protein-protein interaction (PPI) network was built from the STRING database. Gene expression, protein expression, immunohistochemistry, and potential functional gene survival were analysed using the GEPIA website, the Human Protein Atlas website, and the UALCAN website. Potential target miRNAs were predicted using the miRDB and Starbase datasets. Results. We found 219 upregulated and 310 downregulated DEGs, with a cut-off ofp<0.01and∣log FC∣>1.5. The DEGs in papillary thyroid cancer were mainly enriched in extracellular structural organisation. At the intersection of the PPI network and Metascape MCODEs, the hub genes in common were identified as FN1, APOE, CLU, and SDC2. In the targeted regulation network of miRNA-mRNA, the hsa-miR-424-5p was found to synchronously modulate two hub genes. Survival analysis showed that patients with high expression of CLU and APOE had better prognosis. Conclusions. CLU and APOE are involved in the molecular mechanism of papillary thyroid cancer. The hsa-miR-424-5p might have the potential to reverse the processes of papillary thyroid cancer by modulating the hub genes. These are potential targets for the treatment of patients with papillary thyroid cancer.

An active actuator of a middle-ear implant coupled to the round window membrane (RWM), which transmits vibration to the cochlea, has been used to compensate for hearing loss in patients. However, various factors affect the coupling condition between the actuator and the RWM, resulting in coupling leakage. In this study, a coupling impedance model of the human ear and the actuator was used to investigate the effect of inefficient coupling during reverse stimulation. First, the three-port circuit network model of the actuator was coupled with the acoustic impedance model of human ear reverse sound transmission. Meanwhile, the inefficient coupling impedance was estimated. Then, the effect of the actuator’s coupling on reverse stimulation was studied by comparing the reverse pressure transfer function. Furthermore, the inefficient coupling’s influence in the ear with middle-ear disorder was also investigated by simulating two typical forms of middle-ear disorder: otosclerosis and ossicular chain disarticulation. The results show that the change of the inefficient coupling impedance plays a significant role during reverse stimulation. Inefficient coupling of the actuator and the RWM deteriorates the cochlear response of reverse stimulation over the entire frequency range. Additionally, the coupling effect of the actuator does not change the influence tendency of middle-ear disorder on reverse stimulation’s performance, but changes the response amplitude of the reverse stimulation.

Introduction The distal end anastomosis is critical to the entire sequential grafts in coronary artery bypass grafting (CABG), but caliber mismatch diminishes the quality of the anastomosis. We aimed to introduce a modified distal end side-to-side (deSTS) anastomosis to handle the size mismatch and compared with classic distal end end-to-side (deETS) anastomosis. Methods From January 2014 to December 2018, 185 patients who underwent off-pump CABG with size mismatched sequential vein grafts (≥3.5 mm) and target coronaries (1.0–1.5 mm) at the distal end anastomoses were included. We retrospectively reviewed the data of the patients, perioperative and follow-up outcomes were analyzed. Results The deSTS group ( n = 67) showed higher anastomotic flow (19.8 ± 8.0 vs 14.9±6.8 mL/min; p < 0.001) and lower pulsatility index (2.7 ± 0.8 vs 3.2 ± 1.0; p = 0.001) than the deETS group ( n = 118). Higher incidence of in-hospital myocardial infarction (MI) was found in the deETS group but without significant difference (9.0% vs. 15.3%; p = 0.220). Kaplan-Meier analysis illustrated a relatively lower MI and major adverse cardiovascular and cerebrovascular events (MACCE) incidence in the deSTS group, and the deSTS group was associated with a reduction in long-term death, MI and MACCE in the adjusted Cox regression model. In addition, relatively higher graft patency was found in the deSTS group. Conclusions The deSTS anastomosis showed superiority in solving size mismatch in sequential CABG, including better intraoperative flow dynamics, ideal long-term graft patency and reduced the incidence of perioperative and follow-up adverse events especially in MI.

Exosomes serve as a crucial mode of communication between tumor-associated macrophages (TAMs) and cancer cells. This study attempted to explore the function of M1-derived exosomes and clarify their specific mechanism in head and neck squamous cell carcinoma (HNSCC). Moreover, the functional roles of M1-derived exosomes and their key molecule long noncoding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) in HNSCC were investigated by conducting a series of in vitro and in vivo experiments. The dual-luciferase test was utilized to clarify the binding capacities between HOTTIP/mRNA and miRNAs. Accordingly, HOTTIP was found to be upregulated in M1-derived exosomes. Meanwhile, the in vitro experiments indicated that M1 exosomes suppressed proliferation, migration and invasion but induced apoptosis of cancer cells. This function was noted to be enhanced by HOTTIP-overexpressed M1 exosomes but was weakened by HOTTIP-knockdown ones, indicating that HOTTIP serves as a key molecule in M1 exosomes. Therefore, the function of HOTTIP in cancer cells was explored, for which overexpression of HOTTIP was found to inhibit proliferation, migration and invasion but induced apoptosis of cancer cells in vitro. A mechanism study further showed that M1 exosomes and HOTTIP activated the TLR5/NF-κB signaling pathway by competitively sponging miR-19a-3p and miR-19b-3p. Furthermore, cancer cells expressing HOTTIP were noted to induce the polarization of both local M1 and M2 macrophages; however, M1 exosomes were observed to reprogram local TAMs into M1 macrophages. More importantly, both cancer cells expressing HOTTIP and M1 exosomes reeducated circulating monocytes to express the M1 phenotype. The corresponding data demonstrated that the M1 exosomal lncRNA HOTTIP suppresses HNSCC progression by upregulating the TLR5/NF-κB signaling pathway through competitively sponging miR-19a-3p and miR-19b-3p. In particular, M1 exosomes and HOTTIP induce the polarization of M1 in circulating monocytes, thus providing novel insight into HNSCC immunotherapy.

The ear canal (EC) is essential for sound transfer and crucial for hearing. Some pathological conditions may modify its morphology, leading to EC sound pressure redistribution, and stapes footplate displacement (FPD) gain alteration. However, no consensus regarding pathological EC and its impact on sound transfer has yet been achieved. To address the effect of morphology of EC on sound pressure redistribution and FPD gain. Varied pathological EC finite element (FE) models were constructed and analyzed based on FE analysis. The results indicated that canal wall down mastoidectomy decreases the second resonance frequency of the EC. The canal wall down mastoidectomy, with conchaplasty increased the first resonance frequency, but decreased the second along with the interval sound pressure gain increased, following which the FPD gain was altered. Stenosis of the EC at the internal portion decreased the second resonance frequency with minimal effect to the first part. When the stenosis moved to the outer portion of the EC, the first resonance frequency decreased, and the second one increased, along with the interval sound pressure gain decreased and FPD gain. Finally, the simplified EC model exerted a minimal effect on sound transfer. The minimal change in EC, such as simplification, straightening, canal wall down mastoidectomy, or enlargement, moderately affects the sound transfer; however, the EC stenosis deteriorates the sound transfer remarkably.

Otitis media is one of the common ear diseases, and its accurate diagnosis can prevent the deterioration of conductive hearing loss and avoid the overuse of antibiotics. At present, the diagnosis of otitis media mainly relies on the doctor's visual inspection based on the images fed back by the otoscope equipment. Due to the quality of otoscope equipment pictures and the doctor's diagnosis experience, this subjective examination has a relatively high rate of misdiagnosis. In response to this problem, this paper proposes the use of faster region convolutional neural networks to analyze clinically collected digital otoscope pictures. First, through image data enhancement and preprocessing, the number of samples in the clinical otoscope dataset was expanded. Then, according to the characteristics of the otoscope picture, the convolutional neural network was selected for feature extraction, and the feature pyramid network was added for multi-scale feature extraction to enhance the detection ability. Finally, a faster region convolutional neural network with anchor size optimization and hyperparameter adjustment was used for identification, and the effectiveness of the method was tested through a randomly selected test set. The results showed that the overall recognition accuracy of otoscope pictures in the test samples reached 91.43%. The above studies show that the proposed method effectively improves the accuracy of otoscope picture classification, and is expected to assist clinical diagnosis.中耳炎是常见的耳科疾病之一，其准确诊断能够预防传导性听力损伤的恶化，以及避免抗生素的过度使用。目前中耳炎诊断主要由医生依据耳镜设备反馈的图像进行目视检查。因耳镜设备图片拍摄质量及医生诊断经验的影响，该主观检查存在较大的误诊率。针对该问题，本文提出采用快速区域卷积神经网络对临床采集的数字耳镜影像进行分析。首先，通过图像数据增强和预处理，扩充了临床耳镜数据集样本数量。然后，根据耳镜图片特征针对性地筛选出卷积神经网络进行特征提取，同时引入特征金字塔网络以进行多尺度的特征提取，增强检测能力。最后，采用锚框尺度优化和超参数调整的快速卷积神经网络进行识别，并通过随机选取的测试集检验该方法的有效性。结果显示，在测试样本中耳镜图片的总体识别准确率达到91.43%。以上研究表明，所提方法有效提高了耳镜图片分类的准确率，有望辅助临床诊断。.

It is difficult to measure the cochlea directly because of the ethical problems and the complexity of cochlear structure. Therefore, finite element model (FEM) can be used as an effective alternative research method. An accurate FEM of the human ear can not only help people understand the mechanisms of sound transmission, but also effectively assess the effects of otologic diseases and guide research on the treatment of hearing loss. In this paper, a three-dimensional (3D) FEM of the human normal cochlea is proposed to study the changes in the biomechanical behavior of the cochlear sensory structure caused by the anterior fissure sclerosis and bottom-turn and apex-turn ossification of the cochlear window. The degree and harm of hearing loss caused by diseases are quantitatively predicted, which can deepen the understanding of the biomechanical mechanism of cochlea, and provide theoretical basis for clinical medicine.

Emerging evidence of significant hearing loss occurring shortly after cisplatin administration in cancer patients has stimulated research into the causes and treatment of this side effect. Although the aetiology of cisplatin-induced hearing loss (CIHL) remains unknown, an increasing body of research suggests that it is associated with excessive generation of intracellular reactive oxygen species (ROS) in the cochlea. Astaxanthin, a xanthophyll carotenoid, has powerful anti-oxidant, anti-inflammatory, and anti-apoptotic properties based on its unique cell membrane function, diverse biological activities, and ability to permeate the blood-brain barrier. In this review, we summarize the role of ROS in CIHL and the effect of astaxanthin on inhibiting ROS production. We focus on investigating the mechanism of action of astaxanthin in suppressing excessive production of ROS.

For achieving flame-retardant AZX912 magnesium alloy with superior mechanical properties, cast ingots were solution-treated at different temperatures of 420–525 °C prior to extrusion at 280 °C. With increasing solution treatment temperature, brittle Al2Ca intermetallic compound changed from a network-like morphology to a spheroidized shape, with an increase in hardness and became unbroken during extrusion. As the solution treatment temperature increased, cracking of Al2Ca particles during tensile deformation tended to be restricted due to hardening and spheroidizing behaviors, and tensile elongation of extruded alloys significantly enhanced from 11.2 to 19.2%. High mechanical strength was maintained with an improvement in ductility when increasing the solution treatment temperature up to 510 °C. The extruded alloy solution-treated at 510 °C exhibited a superior balance between mechanical strength and ductility, with a high ultimate tensile strength of 367 MPa and a good elongation of 16.8%.

Osteoporosis (OP) is common with advancing age. Several studies have shown a strong correlation between OP and otosclerosis. However, no studies have investigated OP of the malleus, incus or stapes in the human middle ear, its effect on middle ear transfer function. Here, we investigate whether these three ossicles develop OP, and how this affects middle ear transfer function. The effect of OP on middle ear transfer function was investigated in simulations based on a finite element (FE) method. First, the FE model used in our previous study was refined, and optimized by introducing viscoelastic properties to selected soft tissues of the middle ear. Then, the FE model was used to simulate OP of the three ossicles and assess its influence on middle ear transfer function. Other possible age-related changes, such as stiffness of the joints or ligaments in the middle ear, were also investigated. The results indicated that OP of the ossicles could increase the high frequency displacement of both the umbo and stapes footplate (FP). However, the stiffness of the middle ear soft tissue can lead to the decrease of middle ear gain at lower frequencies. Furthermore, loosening of these joints or ligaments could increase displacement of the umbo and stapes FP. In conclusion, although age-related hearing loss is most commonly conceived of as sensorineural hearing loss (SNHL), we found that age-related changes may also include OP and changes in joint stiffness, but these will have little effect on middle ear transfer function in elderly people.

In order to study the effect of middle ear malformations on energy absorbance, we constructed a mechanical model that can simulate the energy absorbance of the human ear based on our previous human ear finite element model. The validation of this model was confirmed by two sets of experimental data. Based on this model, three common types of middle ear malformations,为了研究中耳畸形对能量吸收率的影响，本文基于前期所建人耳有限元模型，构建了一个能够模拟人耳能量吸收的力学模型，并利用两组实验数据验证了该模型。基于该模型，通过改变相应组织的结构和材料属性，模拟了砧镫关节缺失、砧骨固定和锤骨固定、镫骨固定这三类常见的中耳畸形；对比分析这三类畸形相应的能量吸收率，研究了中耳畸形对能量吸收率的影响。结果表明：砧镫关节缺失会使能量吸收率在 1 000 Hz 附近显著增大。砧骨固定和锤骨固定会使能量吸收率在低频阶段急剧减小，且在 1 000 Hz 以下低于 10%；与此同时，能量吸收率的峰值移向更高频率。对于这两类中耳畸形，在宽频声导抗测试中具有较为明显的特征。而镫骨固定会使能量吸收率在低频段减小、中频段增大，但变化程度较小，在宽频声导抗测试中无明显特征。本文研究结果或可为临床上中耳畸形的宽频声导抗诊断提供一些理论参考。.

Astaxanthine (AST) has important biological activities including antioxidant and anti-inflammatory effects that could alleviate neurological and heart diseases, but its role in the prevention of cisplatin-induced hearing loss (CIHL) is not yet well understood. In our study, a steady interaction between AST and the E3 ligase adapter Kelch-like ECH-associated protein 1, a predominant repressor of nuclear factor erythroid 2-related factor 2 (NRF2), was performed and tested via computer molecular docking and dynamics. AST protected against cisplatin-induced ototoxicity via NRF2 mediated pathway using quantitative PCR and Western blotting. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential revealed that AST reduced ROS overexpression and mitochondrial dysfunction. Moreover, AST exerted anti-apoptosis effects in mouse cochlear explants using immunofluorescence staining and HEI-OC1 cell lines using quantitative PCR and Western blotting. Finally, AST combined with poloxamer was injected into the middle ear through the tympanum, and the protection against CIHL was evaluated using the acoustic brain stem test and immunofluorescent staining in adult mice. Our results suggest that AST reduced ROS overexpression, mitochondrial dysfunction, and apoptosis via NRF2-mediated pathway in cisplatin-exposed HEI-OC1 cell lines and mouse cochlear explants, finally promoting cell survival. Our study demonstrates that AST is a candidate therapeutic agent for CIHL., Graphical abstract Astaxanthine protects against cisplatin-induced ototoxicity and hearing loss by NRF2 signaling activation that significantly increase the mitochondrial membrane potential and reduce reactive oxygen species.Image 1

Background: Head and neck squamous cell carcinoma (HNSC) is a popular malignancy type that brings about poor prognosis with a low survival rate worldwide. Stanniocalcin 2 (STC2) is a glycosylated peptide hormone and shows the potential to become a new biomarker for the evaluation of malignant tumors. The purpose of this study was to explore the prognostic implications of STC2 and DNA methylation in HNSC and the role of STC2 expression in immune cell infiltration.Methods: STC2 gene expression data were collected from Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases. Univariate and multivariate analyses were employed to screen prognostic risk factors. The relationship between STC2 expression and TP53 mutation in HNSC was explored. TCGA data were utilized to analyze how STC2 expression affected immune cell infiltration in HNSC.Results: STC2 was highly expressed in HNSC patients (P < 0.01), especially those with a lower overall survival rate (P < 0.0001). TP53 mutation might be a risk factor of STC2 overexpression in HNSC (P = 0.0015). STC2 expression was negatively correlated with STC2 methylation (Spearman: -0.43, P < 0.001). Hypermethylation or hypomethylation at the eight CpG sites most related to STC2 expression was identified as independent factors for HNSC prognosis. STC2 was positively correlated with cancer-associated fibroblasts infiltration and associated with the infiltration of various immune cells.Conclusion: STC2 can be regarded as a vital prognostic biomarker of HNSC due to its essential roles in immune cell infiltration.

Background There are limited evidences clarifying the impact of metabolic syndrome (MS) and its components on head and neck cancer (HNC) incidence risk. We explored the correlation between MS, MS components, and the combined effects of MS and C-reactive protein (CRP) and HNC risk. Methods This is a prospective analysis of 474,929 participants from the UK Biobank cohort. Cox proportional hazard regression was utilized to assess the hazard ratio (HR) and 95% confidence interval (CI) and to explore the non-linear correlation between an individual MS component and HNC risk. Results Individuals with MS (HR, 1.05; 95%CI, 0.90–1.22) had no higher HNC risk than those without MS. More MS components showed no higher HNC risk. Nevertheless, hyperglycemia (HR, 1.22; 95%CI, 1.02–1.45) was independently correlated with elevated HNC risk. In a non-linear manner, waist circumference and high-density lipoprotein cholesterol (HDL-C) showed a U-shaped association with HNC risk. Further, piecewise linear model analysis indicated that higher male waist circumference, female waist circumference (≥93.16 cm), blood glucose (≥4.70 mmol/L) and male HDL-C (≥1.26mmo/L), and lower male HDL-C ( Conclusions MS are not correlated with elevated HNC risk. High waist circumference and blood glucose are independent risk factor of HNC incidence. Controlling HDL-C in an appropriate range can get the lowest risk of male HNC. No joint effect of MS and CRP exists in HNC tumorigenesis.

BACKGROUND: While patients with benign paroxysmal positional vertigo (BPPV) commonly develop residual dizziness (RD) after successful repositioning, the factors predictive of RD remain controversial. OBJECTIVE: To identify factors predictive of RD onset in patients with BPPV following successful repositioning. METHODS: This multi-center prospective cohort study enrolled 243 patients with idiopathic BPPV. Vestibular functional and psychological wellbeing assessments administered before repositioning provided the data used to identify factors predictive of RD with a log-binomial model. The endpoint was RD at 1 week after successful repositioning. RESULTS: Of the enrolled patients, 118 reported RD. After adjusting for cofounders, mild [risk ratio (RR), 2.06; 95% confidence interval (CI), 1.39–3.04] or severe (RR, 3.08; 95% CI, 2.17–4.38) anxiety and abnormal vestibular ratio of sensory organization test (RR, 2.68; 95% CI, 1.82–3.95) were identified as risk predictors. Presence of ocular vestibular evoked myogenic potentials responses, either unilateral (RR, 0.55; 95% CI, 0.44–0.69) or bilateral (RR, 0.49; 95% CI, 0.36–0.68), were protective factors. CONCLUSIONS: Anxiety and abnormal balance are significant predictors of RD, while the presence of ocular vestibular evoked myogenic potentials responses predicts against it. These findings may help to improve BPPV outcomes by informing prognoses and guiding treatment strategies. Trial registration: ChiCTR1800018004 (date of registration: 26 August 2018)

To assess the effects of ossicular chain malformations on the performance of bone conduction hearing aids, a human ear finite-element model that includes an ear canal, a middle ear, and a spiral cochlea incorporating the third windows was established. This finite element model was built based on micro-computed tomography scanning and reverse modelling techniques, and the reliability of the finite element model was verified by comparison with reported experimental data. Based on this model, two main types of ossicular chain malformations, i.e., the incudostapedial disconnection and the ossicles fixation, were simulated, and their influences on bone conduction were analyzed by comparing the trans-cochlear-partition differential pressures. The results indicate that the incudostapedial disconnection mainly deteriorates the bone conduction response at mid frequencies. The stapes fixation has the largest effect among the ossicles fixation with the bone conduction stimulation, which also mainly decreases the mid-frequency response of the bone conduction, especially at 2 kHz. As the speech intelligibility has the most important frequency range at the range between 1 kHz and 2.5 kHz, the mid-frequency deterioration caused by ossicular chain malformations should be compensated in optimizing the design of the bone conduction hearing aids. For treating patients with the ossicular chain malformations, especially for the patients who suffer from the stapes fixation, the output of bone conduction hearing aids' actuator in the middle frequency band should be improved.

The vestibular and cochlear aqueducts serve as additional sound transmission paths and produce different degrees of volume velocity shunt flow in cochlear sound transmission. To investigate its effect on forward and reverse stimulations, a lumped-parameter model of the human ear, which incorporates the third windows, was developed. The model combines a transmission-line ear-canal model, a middle-ear model, and an inner-ear model, which were developed previously by different investigators. The model is verified by comparison with experiments. The intracochlear differential-pressure transfer functions, which reflect the input force to the organ of Corti, were calculated. The results show that middle-ear gain for forward sound transmission is greater than the gain for reverse sound transmission. Changes in the cochlear aqueduct impedance have little effect on forward and reverse stimulations. The vestibular aqueduct has little effect on forward stimulation, but increasing its impedance causes deterioration on reverse stimulation below 300 Hz. Decreasing its impedance increases the excitation effect during reverse stimulation over the entire frequency, especially below 1000 Hz. Moreover, compared with the case without the third windows, the presence of the third windows has little effect on forward stimulation. Whereas, it boosts the reverse stimulation's performance below 300 Hz.

A previous study reported that compound 5A, a caffeic acid phenethyl ester (CAPE) analog, exhibited obvious neuroprotective activity, in particular, compound 5A possessed higher stability and membrane permeability than CAPE. CAPE displays antitumour function; therefore, evaluating the antitumour effect of its analog with higher stability and membrane permeability is worthwhile. We first investigated the antitumour activity of compound 5A. We found that compound 5A significantly inhibited the proliferation of tumor cells and showed low cytotoxicity in normal cells. Furthermore, compound 5A was found to induce the cell cycle arrest and apoptosis of CNE2 cells. Through the prediction of SwissTargetPrediction and subsequent confirmation, epidermal growth factor receptor (EGFR) was identified as a target of compound 5A. Compound 5A also influenced the expression of genes downstream of EGFR in nasopharyngeal carcinoma (NPC) cells. Based on these findings, compound 5A inhibits the proliferation of NPC cells by targeting EGFR and may become a new candidate compound for NPC treatment.

As-explosive welded clad plates usually show poor ductility due to heavily deformed microstructures developed after explosive welding (EXW). In this study, the feasibility of improving mechanical properties of an EXWed Mg–6Al–1Zn–1Ca (AZX611)/Al–0.4Mg–0.6Si–0.2Fe (A6005C) (all in wt%) clad plate has been explored by subsequent hot-rolling. Increasing the thickness reduction per pass from 10% to 28% or decreasing the rolling temperature from 430 °C to 250 °C is shown to enhance tensile properties. The joint sheet rolled at 250 °C with a thickness reduction per pass of 28% shows a large fracture elongation of 15%, which is significantly higher than that of the as-EXWed clad plate, 1.2%. Microstructure characterization by means of scanning electron microscope, electron backscatter diffraction and transmission electron microscope reveals that the substantial improvement in ductility is intimately related to a significant reduction of the accumulated strain in AZX611 and A6005C alloy sheets and an elimination of the interface delamination formed during EXW. A certain degree of anisotropic mechanical properties is observed in all sheets regardless of rolling conditions, which can be ascribed to the mechanical anisotropy originated from the AZX611 and A6005C alloy sheets.

miRNAs are among the most important factors that regulate gene expression. According to bioinformatic analysis, miR-365a-3p was predicted to interact with the TET1 mRNA. We predicted that it might affect tumor biological processes through TET1. TET1 interference and miR-365a-3p inhibitor constructs were generated. qRT-PCR was used to verify the expression level of miR-365a-3p and TET1 in Hep-2 and BESB-2B cells. qRT-PCR and Western blot were used to confirm the TET1 expression level in Hep-2 and miR-365a-3p inhibitor cells. Cell proliferation, cell cycle progression and cell invasion were further studied to identify the relationship between TET1 and miR-365a-3p. Luciferase reporter gene assays were used to find the binding site of miR-365a-3p in the 3'-UTR (3'-untranslated region) of the TET1 mRNA. TET1 was weakly expressed in Hep-2 cells and highly expressed in BESB-2B cells, while miR-143-3p and miR-365a-3p were highly expressed in Hep-2 cells and lowly expressed in BESB-2B cells. Inhibiting miR-365a-3p could up-regulate the expression of TET1. The negative effects of miR-365a-3p on cell proliferation, cell cycle progression and cell invasion could be abolished by TET1 interference. The binding site of miR-365a-3p was in the 3'-UTR of the TET1 mRNA. TET1 is one of the targets of miR-365a-3p. miR-365a-3p regulates the biological behavior of laryngeal cancer by down-regulating TET1.

Tensile properties, formability and thermal conductivity of Mg-3Zn-0.5Ca-0.5Al-xMn (x: 0.1–1.5 in wt%) sheet alloys with different Mn contents were investigated. Benefitting from dense Al-Mn nanoscale spherical precipitates, yield strength was significantly enhanced by 39 MPa with increasing the Mn content from 0.1 wt% to 1 wt%. In the meanwhile, excellent formability was maintained with Erichsen values larger than 8 mm. Further increasing the Mn content to 1.5 wt% did not contribute to strengthening due to the formation of coarse β-Mn particles. In spite of larger additive amount, thermal conductivity improved for the 1 wt% Mn added alloy compared to the 0.1 wt% Mn added alloy due to the increased amount of Al-Mn nanoscale spherical precipitates, which reduced a content of Al solute atoms. High strength (average yield strength: 180 MPa), high formability (Erichsen value: 8.5 mm) and high thermal conductivity (133 W/(m K)) were simultaneously achieved in the 1 wt% Mn added alloy.

Poor formability at room temperature (RT) has been the main bottleneck for a wider range of applications of concentrated Mg–Al–Ca(–Zn) sheet alloys. Here, we report that RT stretch formability of concentrated Mg–Al–Zn–Ca alloy sheets can be improved substantially by increasing the final rolling temperature. A Mg–6Al–1Zn–1Ca alloy sheet subjected to 510 °C final rolling shows an index Erichsen (I.E.) value of 7.9 mm, which is significantly higher than that of the same sheet subjected to 450 °C final rolling (4.1 mm). More excitingly, 510 °C final rolled Mg–6Al–1Zn–2Ca (wt%) alloy sheet exhibits a large I.E. value of 8.0 mm which has never been achieved in 2 wt% Ca-containing Mg alloys. A systematic microstructural investigation indicates that the substantial improvement in stretch formability of Mg–6Al–1Zn–xCa (x=1, 2) alloy sheets is mainly associated with weakened basal textures. To clarify the mechanisms responsible for the weak basal textures developed in the high temperature rolled sheets, electron backscatter diffraction (EBSD) assisted slip trace analysis and quasi-in-situ EBSD method were employed. EBSD-assisted slip trace analysis on the side surface of as-rolled Mg–6Al–1Zn–1Ca alloy sheets indicates that the activity of pyramidal slip increases significantly by increasing the final rolling temperature from 450 to 510 °C. During subsequent annealing, grains deformed by pyramidal slip evolve into new recrystallized grains with a wide spectrum of orientations, which plays a key role in the development of the weaker basal texture.

Ag and Ca atoms segregate to grain boundaries (GBs) in a solution treated state, which assists the earlier formation of GB precipitates compared to the grain interior during the early stage of aging. Prolonged aging leads to the growth of GB precipitates, which act as preferred initiation sites for microcracks.

Static recrystallization behavior of Mg-1.5Zn-0.2Ce (wt%) alloy rolled at 480 °C was investigated at different annealing stages using quasi-in-situ electron backscattered diffraction (EBSD) analyses, which were carried out repeatedly in the same region to trace microstructural evolution. In the as-rolled condition, double twins exhibit the highest fraction compared with tensile and compression twins. Double twins mostly exist in deformed grains with basal orientations, and statically recrystallized grains mainly nucleate at the intersections of double twins and pre-existing grain boundaries. Statically recrystallized grains tend to exhibit TD-tilted orientations and grow along double twins to consume adjacent basal-oriented grains. This is the main reason for inducing the change from a RD-split texture to a well-weakened TD-split texture during annealing. The residual unrecrystallized grains with TD-tilted orientations and the growth advantage of TD-tilted grains also enhance the formation of TD-split texture.