Identification of mRNA expression profiles and their characterization in age-related hearing loss.

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.

Identification of common stria vascularis cellular alteration in sensorineural hearing loss based on ScRNA-seq.

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.

Factors Influencing the Fasting Time in Adult Patients After the Endoscopic Management of Sharp Esophageal Foreign Bodies.

Background: Sharp esophageal foreign body (SEFB) impaction can cause varying degrees of damage to the esophagus. There are few studies analyzing the postoperative fasting time in SEFB patients. Methods: We retrospectively collected 835 SEFB patients. According to the fasting time after the endoscopic removal (ER) of SEFBs, the patients were divided into two groups: short fasting time (SFT, fasted ≤24 h) and long fasting time (LFT, fasted >24 h). Results: There were 216 and 619 patients in the SFT and LFT group, respectively. The average age of the SFT group (52.97 years) was younger than that of the LFT group (55.96 years) (p = 0.025). The LFT group had lower proportion of duration of impaction (DOI) within 12 hours (14.2% vs 22.2%, p = 0.006) and erosion rates (89.0% vs 94.0%, p = 0.034) as well as higher proportion of esophageal perforation (19.5 vs 6.5%, p = 0.010) and patients who got intravenous anesthesia (63.78% vs 31.9%, p = 0.000) than the SFT group. The longest diameter of the foreign body (Lmax) in the LFT group (2.60 ± 1.01 cm) was greater than that in the SFT group (2.41 ± 0.83 cm; p = 0.01). Multivariate regression analysis found that age (OR = 1.726[1.208-2.465], p = 0.003), DOI (OR = 1.793[1.175-2.737], p = 0.007), Lmax (OR = 1.477[1.033-2.111], p = 0.032), perforation (OR = 3.698[2.038-6.710]; p < 0.01) and intravenous anesthesia (OR = 3.734[2.642-5.278]; p < 0.01) were the independent factors that prolonged fasting time in patients with SEFBs, while esophageal mucosal erosion (OR = 0.433[0.229-0.820]; p = 0.01) was the influencing factor leading to shortened fasting time. Conclusion: For the first time, we analyzed factors influencing the fasting time after ER in SEFB patients. Age, DOI, Lmax, perforation and intravenous anesthesia were risk factors for a prolonged postoperative fasting time.

Point-wise spatial network for identifying carcinoma at the upper digestive and respiratory tract.

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.

Evaluation of Pericardial Thickening and Adhesion Using High-Frequency Ultrasound.

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.

Behavioral characteristics in sensing mechanism of the Corti.

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.

Study of fatigue damage to the cochlea.

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.

Distal end side-to-side anastomosis of sequential coronary bypass for size mismatched saphenous vein grafts and coronary arteries.

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.

A comparison of patients with neck abscesses caused by esophageal foreign body impaction vs. inflammatory disease: a retrospective study.

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).

The heterogeneity of mammalian utricular cells over the course of development.

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.

M1 macrophage-derived exosomes and their key molecule lncRNA HOTTIP suppress head and neck squamous cell carcinoma progression by upregulating the TLR5/NF-κB pathway.

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.

Astaxanthine attenuates cisplatin ototoxicity in vitro and protects against cisplatin-induced hearing loss in vivo.

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.

Effects of design and coupling parameters on the performance of electromagnetic transducers in round-window stimulation.

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.

Delayed Endoscopic Management of Esophageal Sharp-Pointed Food Impaction: An Analysis of 829 Cases in China.

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.

Effect of ossicular chain deformity on reverse stimulation considering the overflow characteristics of third windows.

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.

Morphology of human ear canal and its effect on sound transmission.

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.

Case report: Multiple biventricular aneurysms in arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is a genetic disease characterized by fibro-fatty myocardial replacement and is clinically associated with malignant ventricular arrhythmias and sudden cardiac death. It presents a major diagnostic and therapeutic challenge due to its complex clinical presentation and multiparametric diagnostic scoring system that includes structural, histological, and electrocardiographic data. A 57-year-old man with a history of palpitation and premature ventricular contractions (PVC) experienced syncope and sustained ventricular tachycardia at a rate of 213 bpm, which was successfully rescued by synchronized cardioversion. Multiple ventricular aneurysms were found in the right ventricular free wall and the left ventricular apical regions, as well as mild biventricular systolic dysfunction, according to echocardiography and high-frequency ultrasound. The genetic analysis revealed the following desmoplakin genes, chr6-7585274-7585275, NM_004415, exon24, and c.7780delT (p.S2594Pfs*9), a heterozygous and likely pathogenic mutation, as the mutation sites in the patient and his 24-year-old daughter. During the 21-month follow-up, the patient did not experience syncope or pre-syncope symptoms while on ß-blocker (bisoprolol) therapy. Among the multimodality imaging techniques of the ACM, late gadolinium enhancement on cardiac magnetic resonance (CMR) is accepted as a more objective indicator of myocardial fibrosis. Left ventricular systolic dysfunction, fibrosis on CMR, and frequent PVC are the primary and most sensitive clinical signs of desmoplakin cardiomyopathy. However, echocardiography continues to be the most commonly used imaging modality for assessing focal ventricular movement and structural abnormalities. The pathological characteristics of arrhythmogenic cardiomyopathy of the right ventricular anterior free wall and apical regions near the transducer can be better shown using high-frequency linear ultrasound with a higher resolution.

[Research on computer aided diagnosis of otitis media based on faster region convolutional neural network].

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.

The RNA Methylation Modification 5-Methylcytosine Impacts Immunity Characteristics, Prognosis and Progression of Oral Squamous Cell Carcinoma by Bioinformatics Analysis.

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.

Identification of Novel Kinase-Transcription Factor-mRNA-miRNA Regulatory Network in Nasopharyngeal Carcinoma by Bioinformatics Analysis.

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.