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An ultracentrifuge apparatus, which can generate an ultra-strong gravitational field even >1 000 000 (1 million) G (1 G=9.8 m/s[SUP2]) over a wide temperature range up to >500 °C with high stability control, was developed for new materials science research. The system consists of an air turbine motor with ceramic ball bearings and dumper section, a sample rotor with an outer diameter of up to 160 mm, a vacuum chamber, and a heating system. The nonbored rotor and the double-structural dumper bushing are used to raise the maximum rotational speed and to improve the stability. The samples can be heated by radiant heat. A maximum rotational speed of 190 000 rpm using a 70 mm diam rotor was recorded despite a short time where the maximum gravitational field was &gt1 2000 000 G. Long and high-temperature ultracentrifuge experiments using 70 and 80 mm diam rotors made of titanium alloy with rotational speeds of up to 170 000 rpm even at temperatures of over 200 °C for 100 h with ripples of <0.05% and <1°, respectively, were successfully performed, where the maximum gravitational field of the sample was >1 000 000 G. The potential energy and sample volume were increased by factors of >2 and >4, respectively, compared with those in the Kumamoto University study [T. Mashimo, S. Okazaki, and S. Tashiro, Rev. Sci. Instrum. 67, 3170 (1996)]. [ABSTRACT FROM AUTHOR]

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. [Display omitted] [ABSTRACT FROM AUTHOR]

The electromagnetic middle‐ear implant (MEI) is a new type of hearing device for addressing sensorineural and mixed hearing loss. The hearing compensation effect of the MEI varies depending on the transducer stimulation sites. This paper investigates the impact of transducer stimulation sites on MEI performance by analyzing stapes spatial motion. Firstly, we constructed a human‐ear finite element model based on micro‐CT scanning and inverse molding techniques. This model was validated by comparing its predictions of stapes spatial motion and cochlear response with experimental data. Then, stimulation force was applied at four common sites: umbo, incus body, incus long process and stapes to simulate the electromagnetic transducer. Results show that at low and middle frequencies, stapes‐stimulating and incus‐long‐process‐stimulating produce similar spatial motion to normal hearing; at high frequencies, incus‐body‐stimulating produces similar results to normal hearing. The equivalent sound pressure level generated by the stapes piston motion is less sensitive to the stimulation direction than that deduced by the stapes rocking motion. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstracts are not published in this journal [ABSTRACT FROM AUTHOR]

Precipitation hardening provides one of the most common strengthening mechanisms for magnesium (Mg) alloys. Here, we report a new precipitation-hardenable Mg sheet alloy based on the magnesium–silver–calcium system. In a solution treated condition (T4), the strength of Mg–xAg–0.1Ca alloys is enhanced with increasing the Ag content from 1.5 wt.% to 12 wt.%. The Mg–12Ag–0.1Ca (wt.%) alloy sheet shows moderate tensile yield strengths of 193 MPa, 130 MPa, 117 MPa along the rolling direction (RD), 45° and transverse direction (TD) in the T4-treated condition. Subsequent artificial aging at 170 °C for 336 h (T6) increases the tensile yield strengths to 236 MPa, 163 MPa and 143 MPa along the RD, 45° and TD, respectively. This improvement in the tensile yield strength by the T6 treatment can be ascribed to the formation of AgMg4 precipitates lying on the {11 2 ¯ 0}ɑ and pyramidal planes. Our finding is expected to stimulate the development of precipitation-hardenable Mg–Ag-based wrought alloys with high strength. [ABSTRACT FROM AUTHOR]

Low flame resistance and inferior mechanical properties are critical issues in widening applications of wrought magnesium alloys as a structural component. To address these issues, the present authors attempted to develop a flame-resistant magnesium–silver-based sheet alloy with excellent room temperature (RT) formability. It was found that the ignition temperature of Mg–1.5 wt%Ag–x wt.%Ca alloy was significantly increased with increasing the Ca content up to 2 wt%. The 2 wt% Ca-containing alloy exhibited a non-flammability characteristic upon 1000 °C due to the formation of compact and dense CaO film on the surface. Strength and in-plane yield anisotropy were enhanced with increasing the Ca content, which were mainly associated with a finer microstructure and a denser distribution of Mg 2 Ca second phase particles. In contrast, stretch formability was decreased with increasing the Ca content due to an increased number of the Mg 2 Ca particles. A compositionally optimized Mg–1.5Ag–1Ca (wt.%) alloy showed a high ignition temperature of 912.5 °C with a large index Erichsen value of 7.8 mm at RT. • The flame-resistance of Mg–1.5Ag–xCa alloys is significantly improved with increasing the Ca content. • Strength and in-plane yield anisotropy of Mg–1.5Ag–xCa alloys are enhanced with increasing the Ca content. • Mg–1.5Ag–xCa (x = 0.1, 0.5, 1, and 2 wt%) alloys show weak and ring-like basal textures. • Mg–1.5Ag–1Ca (wt.%) alloy exhibits a high ignition temperature of 912.5 °C with a large index Erichsen value of 7.8 mm. [ABSTRACT FROM AUTHOR]

This work investigated effects of silver (Ag) content on the microstructure, texture and mechanical properties of magnesium–silver–calcium alloys by a combined experimental and numerical approach. A series of ternary magnesium–silver–calcium alloys with Ag concentrations between 0.3 and 12 wt% were prepared by hot-extrusion, hot-rolling followed by annealing. As-rolled sheets showed rolling direction split textures with double peaks irrespective of the Ag content. A new component where (0002) basal poles tilted from the normal direction toward the transverse direction (TD) appeared when the Ag content was increased to 1 wt% after annealing. The Mg–xAg–0.1Ca (x = 0.3, 1, 2 and 3) alloys showed excellent room temperature (RT) formability, which could be mainly ascribed to weak basal textures developed after annealing. When the Ag content was increased to 6 wt%, a weak TD-split texture with a homogeneous fine-grained microstructure was developed, which resulted in excellent RT formability and high strength. In contrast, the Mg–12Ag–0.1Ca alloy showed much lower RT formability and ductility in comparison with Mg–Ag–Ca alloys with lower Ag concentrations due to the presence of coarse AgMg 4 particles. Visco-plastic self-consistent simulation results revealed that the activity of prismatic slip was increased with increasing the Ag content and the enhanced activity of prismatic during rolling may partially lead to the formation of TD-split texture in the formable Mg–Ag–Ca alloys during annealing. • Mg–xAg–0.1Ca (x = 0.3, 1, 2, 3, 6 and 12 wt%) alloys showed weak basal textures. • Mg–0.1Ca alloys with Ag no more than 3 wt% showed excellent formability. • A Mg–6Ag–0.1Ca (wt.%) alloy exhibited a high strength and excellent formability. • Activity of prismatic slip increased with increasing Ag content. [ABSTRACT FROM AUTHOR]

Effects of scandium (Sc) content on microstructures and mechanical properties of a Mg–1.5Zn (wt.%) alloy have been systematically investigated. Mg–1.5Zn alloys with Sc content no more than 0.3 wt% showed large index Erichsen (I.E.) values, an indicator of stretch formability, over than 8 mm due to weak basal textures. Further increase in Sc content up to 1.5 wt% led to a gradual decline in the stretch formability and a Mg–1.5Zn–1.5Sc alloy showed the lowest I.E. value of 4.2 mm. Detailed microstructural characterization of the Mg–1.5Zn–1.5Sc alloy revealed that the poor stretch formability was associated with a combined effect of strong basal texture, un-recrystallized matrix grains and a dense distribution of ScZn and Sc second phase particles. On the other hand, tensile properties, in particular tensile yield strength (TYS) and r-value were almost identical along the rolling direction (RD) and the transverse direction (TD) for a Mg–1.5Zn–0.1Sc alloy. Higher TYS and r-value along the RD than the TD were observed in a Mg–1.5Zn–0.3Sc alloy, while opposite results were obtained in Mg–1.5Zn–1.0Sc and Mg–1.5Zn–1.5Sc alloys. Different plastic anisotropy trends observed in Mg–1.5Zn–xSc (x = 0.1–1.5) alloys could be ascribed to their distribution of crystallographic orientations. • Microalloying addition of Sc to a Mg–Zn alloy led to the formation of weak texture. • Mg–1.5Zn alloys with Sc no more than 0.3 wt% showed excellent formability. • A Mg–1.5Zn–0.1Sc (wt.%) alloy did not show a plastic anisotropy. • A Mg–1.5Zn–0.3Sc (wt.%) alloy exhibited a unique quadruple basal texture. [ABSTRACT FROM AUTHOR]

A newly developed magnesium sheet alloy, Mg–1.5Ag–0.1Ca in wt.%, shows a large index Erichsen value of 8.6 mm with a large average elongation to failure of 33% at room temperature (RT). The excellent RT formability and ductility are associated with a weak ring-like basal texture. [ABSTRACT FROM AUTHOR]

In this study, the microstructures, mechanical properties, and ignition temperatures of hot-rolled Mg-1.5Zn-X (X: Ca and/or Sr) alloys were investigated. The Mg-1.5Zn, Mg-1.5Zn–1Ca and Mg-1.5Zn–1Sr alloys had the mean grain sizes of 56.1 μm, 8.7 μm, and 18.5 μm, respectively. This indicates that Ca addition exerts a stronger effect on grain refinement than Sr addition. Both Ca and Sr additions significantly weakened the basal texture to approximately one-quarter in intensity for the annealed sheets. Ca-containing alloys exhibited texture splitting in the transverse direction, while Sr-containing alloys tended to maintain it in the rolling direction after annealing. The Ca and Sr additions improved the mechanical strength considerably due to grain refinement, which overcompensated for the influence of texture softening. Meanwhile, benefiting from the weakened textures, the 1% Ca and Sr additions remarkably increased the Erichsen values from 3.8 to 8.0 and 7.1, respectively. However, further addition resulted in the deterioration of both tensile ductility and stretch formability due to the cracking of secondary-phase particles. Ca addition had a better effect on enhancing the flame-retardant property than Sr addition, and 2% Ca and Sr additions increased the ignition temperature from 629 °C to 800 °C and 720 °C, respectively. [ABSTRACT FROM AUTHOR]

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) [ABSTRACT FROM AUTHOR]

Background: The stria vascularis (SV), located in the lateral wall of the cochlea, maintains cochlear fluid homeostasis and mechanoelectrical transduction (MET) activity required for sound wave conduction. The pathogenesis of a number of human inheritable deafness syndromes, age related hearing loss, drug-induced ototoxicity and noise-induced hearing loss results from the morphological changes and functional impairments in the development of the SV. In this study, we investigate the implications of intercellular communication within the SV in the pathogenesis of sensorineural hearing loss (SNHL). We aim to identify commonly regulated signaling pathways using publicly available single-cell transcriptomic sequencing (scRNA-seq) datasets. Methods: We analyzed scRNA-seq data, which was derived from studying the cochlear SV in mice with SNHL compared to normal adult mice. After quality control and filtering, we obtained the major cellular components of the mouse cochlear SV and integrated the data. Using Seurat's FindAllMarkers and FindMarkers packages, we searched for novel conservative genes and differential genes. We employed KEGG and GSEA to identify molecular pathways that are commonly altered among different types of SNHL. We utilized pySCENIC to discover new specific regulatory factors in SV subpopulation cells. With the help of CellChat, we identified changes in subpopulation cells showing similar trends across different SNHL types and their alterations in intercellular communication pathways. Results: Through the analysis of the integrated data, we discovered new conserved genes to SV specific cells and identified common downregulated pathways in three types of SNHL. The enriched genes for these pathways showing similar trends are primarily associated with the Electron Transport Chain, related to mitochondrial energy metabolism. Using the CellChat package, we further found that there are shared pathways in the incoming signaling of specific intermediate cells in SNHL, and these pathways have common upstream regulatory transcription factor of Nfe2l2. Combining the results from pySCENIC and CellChat, we predicted the transcription factor Nfe2l2 as an upstream regulatory factor for multiple shared cellular pathways in IC. Additionally, it serves as an upstream factor for several genes within the Electron Transport Chain. Conclusion: Our bioinformatics analysis has revealed that downregulation of the mitochondrial electron transport chain have been observed in various conditions of SNHL. E2f1, Esrrb, Runx1, Yy1, and Gata2 could serve as novel important common TFs regulating the electron transport chain. Adm has emerged as a potential new marker gene for intermediate cells, while Itgb5 and Tesc show promise as potential new marker genes for marginal cells in the SV. These findings offer a new perspective on SV lesions in SNHL and provide additional theoretical evidence for the same drug treatment and prevention of different pathologies of SNHL. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Small amounts of transition elements: Ti, Mn, Fe, Co, and Ni, have been added to a Mg–0.1Ca (wt%) alloy to elucidate their additions on the microstructure and room temperature (RT) mechanical properties. Only Ni was effective in weakening the texture intensity and thus led to the improvement in RT formability and ductility, whereas the other elements were basically no effect. The microstructural characterization by high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) in conjunction with energy-dispersive X-ray spectrometry (EDS) and numerical simulation using a grain boundary (GB) phase model indicates that the Ca and Ni co-segregated to the GB of the Ni-containing alloy, while the GB of the other alloys was enriched with Ca only. Further investigations by a correlative electron backscatter diffraction and STEM-EDS reveal that the transverse direction (TD) oriented GBs had significantly lower concentration of Ca and Ni compared to the basal-oriented GBs, which resulted in the development of the TD-split texture in the Ni-containing alloy. A compositionally optimized Mg–0.1Ca–0.1Ni (wt%) alloy showed a large index Erichsen value of 8.5 mm in the sheet form, and exhibited a high tensile yield strength of 238 MPa with a moderate fracture elongation of 14% in the form of an extruded rod. Due to the addition of small amounts of alloying elements, the newly developed Mg–0.1Ca–0.1Ni alloy had an excellent thermal conductivity of 154 W/(m·K) which is even higher than that of a commercial 5052 Al alloy. [Display omitted] [ABSTRACT FROM AUTHOR]

• The expression of Histidine decarboxylase (HDC) is clarified in the inner ear hair cells. • HDC−/− mice with endogenous histamine deficiency exhibit increased susceptibility to cisplatin-induced hearing loss. • Exogenous histamine can alleviate cisplatin-induced ototoxicity in HDC−/− mice. • Disruption of HDC/histamine/H 1 R signaling enhances the susceptibility of inner ear hair cells to cisplatin. Cisplatin (CDDP) is extensively utilized in the management of diverse types of cancers, but its ototoxicity cannot be ignored, and clinical interventions are not ideal. Histidine decarboxylase (HDC) is the exclusive enzyme for histamine synthesis. Anti-histamine receptor drugs are ubiquitously employed in the therapeutics of allergies and gastrointestinal diseases. Yet, the specific role of histamine and its signaling in the inner ear is not fully understood. This study utilized cisplatin treated mice and HEI-OC1 auditory hair cell line to establish a cisplatin-induced ototoxicity (CIO) model. Histidine decarboxylase knockout (HDC−/−) mice and histamine receptor 1 (H 1 R) antagonist were utilized to investigate the influence of HDC/histamine/H 1 R signaling on ototoxicity. The results identified HDC and H 1 R expression in mouse hair cells. Transcriptomics indicated that the expression levels of oxidative stress-related genes in the cochlea of HDC−/− mice increased. Furthermore, histamine deficiency or suppression of H 1 R signaling accelerated HC ferroptosis, a pivotal factor underlying the aggravation of CIO in vivo and in vitro, conversely, the supplementation of exogenous histamine reversed these deleterious effects. Mechanistically, this study revealed that the malfunction of HDC/histamine/H 1 R signaling induced upregulation of NRF2 expression, accompanied by the upregulation of ACSL4 and downregulation of GPX4 expression, which are major regulatory factors of ferroptosis. In summary, histamine deficiency may induce hair cell death by regulating the H 1 R pathway and exacerbate CIO. Our findings have indicated a potential therapeutic target for CIO. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusions: Overall, our findings expand our understanding of ENHC cell fate and the characteristics of the vestibular organs in mammals over the course of development. [ABSTRACT FROM AUTHOR]

• The mechanical properties of dilute Mg-Zn-Ca alloy sheets were investigated. • The addition of more than 0.3 wt% Zn significantly improved the RT formability. • VPSC simulation was conducted to clarify the cause of the change in RT formability. • The increase in IE value can be attributed to the formation of TD-split texture. • The efficient scheme for parameter fitting of VPSC simulation was proposed. The relationship between Zn content and room temperature (RT) mechanical properties of dilute Mg- x Zn-0.1Ca (x = 0.1, 0.2,0.3, 0.5, 1.5, 2.5 in wt%) alloy sheets was investigated. The index Erichsen (IE) value, an indicator of stretch formability, was found to increase significantly from 6.6 mm to 8.4 mm by increasing the Zn content from 0.2 wt% to 0.3 wt%. Visco-Plastic Self-Consistent (VPSC) simulation revealed there was no apparent difference in the relative activity of deformation modes in Mg-0.2Zn-0.1Ca and Mg-0.3Zn-0.1Ca alloys. On the other hand, electron back-scattered diffraction observation showed that a component having basal poles tilted towards the transverse direction (TD) began to appear when 0.3 wt% of Zn was added, and the typical TD-split texture was developed when the Zn content was increased to more than 1.5 wt%. Therefore, the rapid improvement of RT formability observed in this study can be attributed to the formation of TD-split texture. In addition to this, the efficient scheme for parameter fitting required to use VPSC simulation was also proposed in this study. [ABSTRACT FROM AUTHOR]

Background: 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. Aims: To investigate cases of esophageal sharp-pointed food impaction with endoscopic removal findings. Methods: 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 removal <12 h) and delayed intervention (>12 h) cohorts. Results: 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. Conclusions: Endoscopic removal is a safe and effective treatment method for sharp-pointed food impaction. Delayed endoscopic removal can increase the risk of esophageal perforation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Poor cold formability, poor corrosion resistance, and high cost of alloying elements are longstanding barriers to the widespread use of the lightest structural metal, viz. magnesium (Mg). Here, we report that both the room-temperature (RT) stretch formability and corrosion resistance of the commercially used pure Mg could be significantly improved by adding trace amounts of copper (Cu) and calcium (Ca). The mechanical properties were characterized by Erichsen cupping and tensile tests, while the corrosion properties were evaluated by immersion in saline solution. The significant enhancement in the RT stretch formability is associated with the weakened basal texture and refined microstructure, whereas the substantial improvement in the corrosion resistance is related to the strong Fe-removal ability induced mainly by Ca addition and formation of a protective surface film enriched with Cu and Ca. Owing to the trace amounts of the alloying elements, the resultant alloy also showed excellent thermal conductivity, which was almost two times higher than that of the most commonly used Mg alloy (AZ31: Mg–3Al–1Zn in wt.%). These findings are expected to stimulate the development of high-performance Mg alloys that can be used in portable electronic devices, automobile electronics, and household appliances. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Cardiac blunt trauma clinically presents as a spectrum of injuries of varying severity. However, the diagnosis of complications of remote myocardial trauma is often challenging, especially if the patient forgets to mention a remote history of chest trauma., Case Summary: In this study, we present a patient who recently experienced traumatic myocardial dissection and interventricular septal rupture, alongside three patients exhibiting a mimic double-chambered left ventricle, indicative of prior remote myocardial trauma potentially associated with myocardial dissecting tear., Discussion: Patients with recent severe myocardial injury are detectable through cardiac imaging. However, forgotten remote myocardial trauma can lead to adverse myocardial remodelling, heart failure, and arrhythmias. Long-term myocardial remodelling can obscure initial myocardial imaging characteristics, posing challenges in interpretation. Our case series suggests that remote myocardial trauma may be more prevalent than commonly thought of in clinical practice., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Age-related hearing loss (ARHL), is a pervasive health problem worldwide. ARHL seriously affects the quality of life and reportedly leads to social isolation and dementia in the elderly. ARHL is caused by the degeneration or disorders of cochlear hair cells and auditory neurons. Numerous studies have verified that genetic factors contributed to this impairment, however, the mechanism behind remains unclear. In this study, we analyzed an mRNA expression dataset (GSE49543) from the GEO database. Differentially expressed genes (DEGs) between young control mice and presbycusis mice were analyzed using limma in R and weighted gene co-expression network analysis (WGCNA) methods. Functional enrichment analyses of the DEGs were conducted with the clusterProfiler R package and the results were visualized using ggplot2 R package. The STRING database was used for the construction of the protein-protein interaction (PPI) network of the screened DEGs. Two machine learning algorithms LASSO and SVM-RFE were used to screen the hub genes. We identified 54 DEGs in presbycusis using limma and WGCNA. DEGs were associated with the synaptic vesicle cycle, distal axon, neurotransmitter transmembrane transporter activity in GO analysis, and alcoholic liver disease, pertussis, lysosome pathway according to KEGG analyses. PPI network analysis identified three significant modules. Five hub genes (CLEC4D, MS4A7, CTSS, LAPTM5, ALOX5AP) were screened by LASSO and SVM-RFE. These hub genes were highly expressed in presbycusis mice compared with young control mice. We screened DEGs and identified hub genes involved in ARHL development, which might provide novel clues to understanding the molecular basis of ARHL.

In order to explore the hearing loss resulting from exposure to continuous or intermittent loud noise. A three-dimensional liquid-solid coupling finite element model of spiral cochlea was established. The reliability of the model was verified, and the stress and amplitude of the basilar membrane of the pivotal structure in cochlea were analyzed. The results show that under the action of the same high-pressure sound, the preferential fatigue area of the cochlear high-frequency area mainly causes fatigue in the cochlear. The safer area is a sound pressure level below 70 dB, while one above 90 dB accelerates damage to the ear.

Problem: Artificial intelligence has been widely investigated for diagnosis and treatment strategy design, with some models proposed for detecting oral pharyngeal, nasopharyngeal, or laryngeal carcinoma. However, no comprehensive model has been established for these regions., Aim: Our hypothesis was that a common pattern in the cancerous appearance of these regions could be recognized and integrated into a single model, thus improving the efficacy of deep learning models., Methods: We utilized a point-wise spatial attention network model to perform semantic segmentation in these regions., Results: Our study demonstrated an excellent outcome, with an average mIoU of 86.3%, and an average pixel accuracy of 96.3%., Conclusion: The research confirmed that the mucosa of oral pharyngeal, nasopharyngeal, and laryngeal regions may share a common appearance, including the appearance of tumors, which can be recognized by a single artificial intelligence model. Therefore, a deep learning model could be constructed to effectively recognize these tumors., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Routine echocardiography using a standard-frequency ultrasound probe has insufficient spatial resolution to clearly visualize the parietal pericardium (PP). High-frequency ultrasound (HFU) has enhanced axial resolution. The aim of this study was to use a commercially available high-frequency linear probe to evaluate apical PP thickness (PPT) and pericardial adhesion in both normal pericardium and pericardial diseases., Methods: From April 2002 to March 2022, 227 healthy individuals, 205 patients with apical aneurysm (AA) and 80 patients with chronic constrictive pericarditis (CP) were recruited to participate in this study. All subjects underwent both standard-frequency ultrasound and HFU to image the apical PP (APP) and pericardial adhesion. Some subjects underwent computed tomography (CT)., Results: Apical PPT was measured using HFU and found to be 0.60 ± 0.01 mm (0.37-0.87 mm) in normal control subjects, 1.22 ± 0.04 mm (0.48-4.53 mm) in patients with AA, and 2.91 ± 0.17 mm (1.13-9.01 mm) in patients with CP. Tiny physiologic effusions were observed in 39.2% of normal individuals. Pericardial adhesion was detected in 69.8% of patients with local pericarditis due to AA and 97.5% of patients with CP. Visibly thickened visceral pericardium was observed in six patients with CP. Apical PPT measurements obtained by HFU correlated well with those obtained by CT in those patients with CP. However, CT could clearly visualize the APP in only 45% of normal individuals and 37% of patients with AA. In 10 patients with CP, both HFU and CT demonstrated equal ability to visualize the very thickened APP., Conclusions: Apical PPT measured using HFU in normal control subjects ranged from 0.37 to 0.87 mm, consistent with previous reports from necropsy studies. HFU had higher resolution in distinguishing local pericarditis of the AA from normal individuals. HFU was superior to CT in imaging APP lesions, as CT failed to visualize the APP in more than half of both normal individuals and patients with AA. The fact that all 80 patients with CP in our study had significantly thickened APP raises doubt regarding the previously reported finding that 18% of patients with CP had normal PPT., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Some experiments can't be realized because the cochlea's Corti is the most delicate and complex sensory organ. In this paper, some typical and special behavioral characteristics in the process of sensation were found in medical clinic. Based on the interdisciplinary principles of medicine, physics and biology, a real numerical simulation model of Corti is established. On the basis of verifying the correctness of the model, the mechanism corresponding to these typical and special behavior characteristics in the process of sensation is explored through simulation calculation and analysis. This study provides theoretical and applied basis for people to better understand the sound sensing mechanism, and provides a numerical simulation platform for further analyzing Corti's sensing mechanism and good clinical application., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

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 < 0.001). However, there were no significant differences in terms of other preoperative or postoperative comorbidities. The multivariate analysis revealed that the application of mediastinotomy (HR = 0.216 [0.049, 0.963]; p = 0.044) was correlated with a longer stay in the hospital. The time from symptoms to surgery was associated with a longer drainage tube removal time (HR = 0.392 [0.159, 0.967]; P = 0.042) and longer ICU stay (OR = 79.754[1.513, 4203.182]; P = 0.03)., 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)., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

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., (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

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.

Disorders pertaining to 5-methylcytosine (m5C) modifications are involved in the pathological process of many diseases. However, the effect of m5C on the tumorigenesis and progression of oral squamous cell carcinoma (OSCC) remains unclear. In this study, we integrated the genomic and clinical data of 558 OSCC samples to comprehensively evaluate m5C modification patterns. Based on 16 m5C methylation regulators, two m5C modification clusters were identified with distinct tumor immune microenvironment (TIME) characteristics and prognosis in OSCC. We then performed weighted gene co-expression network analysis (WGCNA) to identify m5C modification cluster-related modules. Genes in the selected module were chosen to construct the m5Cscore scoring system for evaluating m5C modification pattern in individual OSCC patients. Patients with a high m5Cscore had higher immune, stromal, and ESTIMATE scores; lower tumor purity score; lower immune activity; and higher tumor mutational burden. The overall survival rate and progression-free survival rate were markedly worse and the tumor recurrence rate was higher in OSCC patients with a high m5Cscore. Furthermore, patients with oral leukoplakia who also had a high m5Cscore had a higher risk of deterioration to OSCC. This study demonstrated that m5C modification patterns might affect the TIME in OSCC. m5Cscore may provide a new approach for predicting the prognosis and progression of OSCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gao, Chen, Sugimoto, Mizuta, Zhou, Kishimoto, Huang and Omori.)

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., Competing Interests: The author reports no conflicts of interest in this work., (© 2021 Gao et al.)

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 (<1.26mmo/L) were correlated with higher HNC risk. Increased CRP (≥1.00mg/dL) elevated HNC risk and individuals with MS and CRP≥1.00mg/dL had the highest HNC risk (HR, 1.29; 95%CI, 1.05-1.58). But no joint effect between MS and CRP was detected (p-interaction=0.501)., 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.

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, i . e . incudostapedial joint defect, incus fixation and malleus fixation, and stapes fixation, were simulated by changing the structure and material properties of the corresponding tissue. Then, the effect of these three common types of middle ear malformations on energy absorbance was investigated by comparing the corresponding energy absorbance. The results showed that the incudostapedial joint defect significantly increased the energy absorbance near 1 000 Hz. The incus fixation and malleus fixation dramatically reduced the energy absorbance in the low frequency, which made the energy absorbance less than 10% at frequencies lower than 1 000 Hz. At the same time, the peak of energy absorbance shifted to the higher frequency. These two kinds of middle ear malformations had obvious characteristics in the wideband acoustic immittance test. In contrast, the stapes fixation only reduced the energy absorbance in the low frequency and increased energy absorbance in the middle frequency slightly, which had no obvious characteristic in the wideband acoustic immittance test. These results provide a theoretical reference for the wideband acoustic immittance diagnosis of middle ear malformations in clinic.

Electromagnetic middle ear implants (MEIs), which use the mechanical vibration of their implanted transducers to treat hearing loss, have emerged to overcome the limitations of conventional hearing aids. Several reports have indicated that the electromagnetic MEI's performance changed with different stimulation sites of the transducer. The aim of this study was to analyze the influence of the transducers' stimulation sites on the electromagnetic MEIs' performance. To aid this investigation, a human ear finite-element model was developed from micro-CT images of an adult's right ear. The validity of the model was confirmed by comparing the model-derived results with experimental data. Then, stimulation forces, which simulate ideal electromagnetic transducers, were respectively applied at five typical coupling sites: the umbo, incus body, incus long process, the round window, and the stapes. The stimulation sites' influence on the electromagnetic MEI's performance was studied by analyzing their corresponding basilar membrane displacements. The results show that stimulation of the round window with a force produces more cochlear stimulation than equal force stimulation of the umbo, incus body, incus long process and the stapes, though the superiority of the round window depends on its smaller area compared to the stapes footplate. Among the forward stimulation, the stapes is the optimal stimulation site for the electromagnetic transducer regarding its hearing compensation's efficiency. The performance of the umbo stimulation is comparable to that of the incus-long-process stimulation. Driving the incus body is less efficient than stimulating the other forward driving sites. Additional, using the stapes response to evaluate the forward stimulation gives results similar to those deduced by the basilar membrane response; in contrast, for the round-window stimulation, the evaluation result based on the stapes response is prominently less than the one calculated by the basilar membrane response, especially in the mid-high frequency range., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., (© 2020 Wiley Periodicals, Inc.)

Objective: To study the effects of typical middle ear lesions on bone conduction, and to provide a theoretical basis for the optimized design of bone conduction hearing aids. Method: A finite element model including the middle ear and cochlea was established by using micro-CT scanning date from a case of adult male human-cadaver temporal bone. The reliability of the model was verified by comparison with relevant experimental data. Based on this model, the effects of several typical middle ear lesions on bone conduction were analyzed. Result: With the increase of tympanic membrane mass, the basilar membrane response at the frequency range of 0.25 kHz to 1 kHz was reduced, and the maximum decrease was 6.9 dB at the frequency of 0.5 kHz. The incus fixation reduced basilar membrane response at the frequency range of 0.2 kHz to 1 kHz, with the maximum decrease of 12.0 dB at 0.75 kHz. The ossicular chain disruption reduced the response of basilar membrane at the frequency range of 1 kHz to 4 kHz, which the decrease was 5.0 dB at 1.5 kHz in the case of incudomallear joint disruption and 11.0 dB at 2 kHz in the case of incudostapedial joint disruption. Conclusion: The results showed that the increased mass of the tympanic membrane and incus fixation mainly reduced the response of bone conduction at the low frequencies. The ossicular chain disruption mainly reduced the response of bone conduction at the middle frequencies. Moreover, the deterioration of incudostapedial disruption was more obvious., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: The etiology of Takayasu arteritis (TA) is unknown; however, a possible relationship between streptococcal infection and TA has been proposed. This study aimed to identify the clinical features and cardiac valvular involvement in untreated TA patients with an elevated antistreptolysin O (ASO) titer., Methods: In this retrospective study, the clinical characteristics and features of valvular involvement were compared in TA patients with or without an elevated ASO titer., Results: Of the 74 untreated TA patients, 13 patients were found have elevated ASO titers (17.6%). Mitral insufficiency was the most common in patients with elevated ASO (69.2%, 9/13), followed by aortic valve insufficiency (46.2%, 5/13) and tricuspid insufficiency (46.2%, 5/13), which were no significantly different than that in normal ASO group. The proportions of moderate to severe mitral (30.8% vs 1.6%, p = 0.000) and tricuspid valve (15.4% vs 1.64%, p = 0.023) insufficiency in the ASO positive group were significantly higher than those in the ASO negative group. The odds of mitral regurgitation in patients with elevated ASO titers were 3.9 times higher than those in the group with normal ASO titers (p = 0.053, OR = 3.929, 95% confidence interval [CI]: 0.983-15.694). Furthermore, the risk of moderate to severe mitral insufficiency in patients with elevated ASO titers was 41.6 times higher than that in patients with normal ASO titers (p = 0.002, OR = 41.600, 95% CI: 3.867-447.559)., Conclusions: An increase in ASO titer is related to valvular involvement in TA and is closely linked to mitral insufficiency.