Publications by authors named "Yiqing Zheng"

138 Publications

Autophagy-dependent Ferroptosis Contributes to Cisplatin-Induced Hearing Loss.

Toxicol Lett 2021 Jul 21. Epub 2021 Jul 21.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Department of Hearing and Speech Science, Xinhua College, Sun Yat-sen University, Guangzhou, China. Electronic address:

Cisplatin-induced hearing loss is a common side effect of cisplatin chemotherapy, for which clinical therapy remains unavailable. Apoptosis of hair cells is considered the primary cause of cisplatin-induced ototoxicity; however, inhibiting apoptosis can only partially restore cisplatin-induced hearing loss. Therefore, auditory cell death caused by cisplatin damage requires further study. Ferroptosis, a novel form of regulated cell death, has been shown to play a role in the mechanism of cisplatin toxicity. In this study, we observed proferroptotic alterations (lipid peroxidation and impaired antioxidant capacity) in the cochleae of C57BL/6 mice after cisplatin damage, verifying the induction of ferroptosis. Using the HEI-OC1 cell line, we observed that cisplatin induced proferroptotic alterations and activated ferritinophagy (specific autophagy pathway). Employing chloroquine, we confirmed that the blockage of autophagy remarkably alleviated cisplatin-induced ferroptosis in HEI-OC1 cells; therefore, the induction of ferroptosis in cisplatin-treated auditory cells was dependent on the activation of autophagy. In addition, the ferroptosis inhibitor ferrostatin-1 and iron chelator deferoxamine significantly attenuated cisplatin-induced cytotoxicity in HEI-OC1 cells and cochlear explants. Moreover, pharmacologically inhibiting ferroptosis using ferrostatin-1 significantly decreased the auditory cell loss and, notably, attenuated hearing loss in C57BL/6 mice after cisplatin damage. Collectively, these findings indicate that autophagy-dependent ferroptosis plays an integrated role in the mechanism of cisplatin-induced hearing loss.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxlet.2021.07.010DOI Listing
July 2021

Development and validation of a novel ferroptosis-related gene signature for predicting prognosis and immune microenvironment in head and neck squamous cell carcinoma.

Int Immunopharmacol 2021 Jun 12;98:107789. Epub 2021 Jun 12.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Department of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China. Electronic address:

Ferroptosis plays an important role across variable cancer types. However, few studies have focused on the prognostic patterns of ferroptosis-related genes in HNSCC. Cohorts with mRNA expression profiles, as well as corresponding clinical data of HNSCC patients from published studies, were collected and consolidated from public databases. We performed random survival forest analysis, Kaplan-Meier (KM) analysis of best combinations, and Cox regression analysis on 231 ferroptosis-related genes to construct a gene signature in the discovery cohort (TCGA), and later validated it in the validation cohort (GEO). The 7-gene signature was constructed to stratify patients into two groups according to their level of risk. Poorer overall survival (OS) was detected in the high risk (HRisk) group than in the low risk (LRisk) group in both the TCGA cohort (P < 0.0001, HR = 1.71, 95%CI:1.41-2.07) and the GEO cohort (P < 0.001, HR = 1.68, 95%CI:1.32-2.13). The risk score was identified as an independent predictive factor of OS in multivariate Cox regression analyses (HR > 1, P < 0.0001) in both cohorts. The signature's predictive capacity was proven by the time-dependent receiver operating characteristic (ROC) curve analysis and nomogram analysis. Functional enrichment analysis revealed that immunosuppressive pathways such as matrix extracellular space, and (transforming growth factor-β)TGF-β were enriched. The HRisk group was strongly associated with upregulation of both cancer-related pathways and stromal scores, while higher proportions of anti-tumor immune cells and immune signatures were enriched in the LRisk group. In conclusion, the signature based on 7 ferroptosis-related genes could be applicable for predicting the prognosis of HNSCC, indicating that ferroptosis may be a potential therapeutic target for HNSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2021.107789DOI Listing
June 2021

Efficacy of Repetitive Transcranial Magnetic Stimulation (rTMS) for Tinnitus: A Retrospective Study.

Ear Nose Throat J 2021 Jun 15:1455613211016896. Epub 2021 Jun 15.

Department of Hearing and Speech Science, Xinhua College, Sun Yat-sen University, Guangzhou, China.

Objective: Current studies still find insufficient evidence to support the routine use of repetitive transcranial magnetic stimulation (rTMS) in tinnitus. This study aimed to assess response of tinnitus to treatment with rTMS and identify factors influencing the overall response.

Methods: Between January 2016 and May 2017, 199 tinnitus patients were identified from a retrospective review of the electronic patient record at the Sun Yat-sen Memorial Hospital. All patients received rTMS treatment. Their clinicodemographic profile and outcomes, including the tinnitus handicap inventory (THI) and visual analog scale (VAS) scores, were extracted for analysis.

Results: Regarding the THI results, 62.3% of all patients responded to rTMS. The analysis of the VAS score revealed an overall response rate of 66.3%. Both percentages were close to the patient's subjective assessment result, of 63.8%. Patients with tinnitus of less than 1-week duration had the highest response rate to rTMS in terms of either THI/VAS scores or the patient's subjective assessment of symptoms. Tinnitus duration was recognized as a factor influencing the overall response to the treatment.

Conclusions: Repetitive transcranial magnetic stimulation treatment is effective for patients with tinnitus, but its efficacy is affected by tinnitus duration. Tinnitus patients are advised to attend for rTMS as soon as possible since therapy was more effective in those with a shorter duration of disease of less than 1 week.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/01455613211016896DOI Listing
June 2021

Modulation of NAD biosynthesis activates SIRT1 and resists cisplatin-induced ototoxicity.

Toxicol Lett 2021 Oct 4;349:115-123. Epub 2021 Jun 4.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China; Department of Hearing and Speech-Language Science, Xinhua College, Guangzhou, China. Electronic address:

Cisplatin, the most widely used platinum-based anticancer drug, often causes progressive and irreversible sensorineural hearing loss in cancer patients. However, the precise mechanism underlying cisplatin-associated ototoxicity is still unclear. Nicotinamide adenine dinucleotide (NAD), a co-substrate for the sirtuin family and PARPs, has emerged as a potent therapeutic molecular target in various diseases. In our investigates, we observed that NAD level was changed in the cochlear explants of mice treated with cisplatin. Supplementation of a specific inhibitor (TES-1025) of α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), a rate-limiting enzyme of NADde novo synthesis pathway, promoted SIRT1 activity, increased mtDNA contents and enhanced AMPK expression, thus significantly reducing hair cells loss and deformation. The protection was blocked by EX527, a specific SIRT1 inhibitor. Meanwhile, the use of NMN, a precursor of NAD salvage synthesis pathway, had shown beneficial effect on hair cell under cisplatin administration, effectively suppressing PARP1. In vivo experiments confirmed the hair cell protection of NAD modulators in cisplatin treated mice and zebrafish. In conclusion, we demonstrated that modulation of NAD biosynthesis via the de novo synthesis pathway and the salvage synthesis pathway could both prevent ototoxicity of cisplatin. These results suggested that direct modulation of cellular NAD levels could be a promising therapeutic approach for protection of hearing from cisplatin-induced ototoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxlet.2021.05.013DOI Listing
October 2021

Reduced Functional Connectivity in Children With Congenital Cataracts Using Resting-State Electroencephalography Measurement.

Front Neurosci 2021 14;15:657865. Epub 2021 Apr 14.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Objectives: Numerous task-based functional magnetic resonance imaging studies indicate the presence of compensatory functional improvement in patients with congenital cataracts. However, there is neuroimaging evidence that shows decreased sensory perception or cognition information processing related to visual dysfunction, which favors a general loss hypothesis. This study explored the functional connectivity between visual and other networks in children with congenital cataracts using resting state electroencephalography.

Methods: Twenty-one children with congenital cataracts (age: 8.02 ± 2.03 years) and thirty-five sex- and age-matched normal sighted controls were enrolled to investigate functional connectivity between the visual cortex and the default mode network, the salience network, and the cerebellum network during resting state electroencephalography (eyes closed) recordings.

Result: The congenital cataract group was less active, than the control group, in the occipital, temporal, frontal and limbic lobes in the theta, alpha, beta1 and beta2 frequency bands. Additionally, there was reduced alpha-band connectivity between the visual and somatosensory cortices and between regions of the frontal and parietal cortices associated with cognitive and attentive control.

Conclusion: The results indicate abnormalities in sensory, cognition, motion and execution functional connectivity across the developing brains of children with congenital cataracts when compared with normal controls. Reduced frontal alpha activity and alpha-band connectivity between the visual cortex and salience network might reflect attenuated inhibitory information flow, leading to higher attentional states, which could contribute to adaptation of environmental change in this group of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnins.2021.657865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079630PMC
April 2021

Xylitol enhances synthesis of propionate in the colon via cross-feeding of gut microbiota.

Microbiome 2021 03 18;9(1):62. Epub 2021 Mar 18.

School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, 310018, China.

Background: Xylitol, a white or transparent polyol or sugar alcohol, is digestible by colonic microorganisms and promotes the proliferation of beneficial bacteria and the production of short-chain fatty acids (SCFAs), but the mechanism underlying these effects remains unknown. We studied mice fed with 0%, 2% (2.17 g/kg/day), or 5% (5.42 g/kg/day) (weight/weight) xylitol in their chow for 3 months. In addition to the in vivo digestion experiments in mice, 3% (weight/volume) (0.27 g/kg/day for a human being) xylitol was added to a colon simulation system (CDMN) for 7 days. We performed 16S rRNA sequencing, beneficial metabolism biomarker quantification, metabolome, and metatranscriptome analyses to investigate the prebiotic mechanism of xylitol. The representative bacteria related to xylitol digestion were selected for single cultivation and co-culture of two and three bacteria to explore the microbial digestion and utilization of xylitol in media with glucose, xylitol, mixed carbon sources, or no-carbon sources. Besides, the mechanisms underlying the shift in the microbial composition and SCFAs were explored in molecular contexts.

Results: In both in vivo and in vitro experiments, we found that xylitol did not significantly influence the structure of the gut microbiome. However, it increased all SCFAs, especially propionate in the lumen and butyrate in the mucosa, with a shift in its corresponding bacteria in vitro. Cross-feeding, a relationship in which one organism consumes metabolites excreted by the other, was observed among Lactobacillus reuteri, Bacteroides fragilis, and Escherichia coli in the utilization of xylitol. At the molecular level, we revealed that xylitol dehydrogenase (EC 1.1.1.14), xylulokinase (EC 2.7.1.17), and xylulose phosphate isomerase (EC 5.1.3.1) were key enzymes in xylitol metabolism and were present in Bacteroides and Lachnospiraceae. Therefore, they are considered keystone bacteria in xylitol digestion. Also, xylitol affected the metabolic pathway of propionate, significantly promoting the transcription of phosphate acetyltransferase (EC 2.3.1.8) in Bifidobacterium and increasing the production of propionate.

Conclusions: Our results revealed that those key enzymes for xylitol digestion from different bacteria can together support the growth of micro-ecology, but they also enhanced the concentration of propionate, which lowered pH to restrict relative amounts of Escherichia and Staphylococcus. Based on the cross-feeding and competition among those bacteria, xylitol can dynamically balance proportions of the gut microbiome to promote enzymes related to xylitol metabolism and SCFAs. Video Abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40168-021-01029-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977168PMC
March 2021

WDPCP Modulates Cilia Beating Through the MAPK/ERK Pathway in Chronic Rhinosinusitis With Nasal Polyps.

Front Cell Dev Biol 2020 1;8:630340. Epub 2021 Feb 1.

Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Cilia loss and dysfunction is one of the typical pathological features of chronic rhinosinusitis with nasal polyps (CRSwNP). Tryptophan-aspartic acid (W-D) repeat containing planar cell polarity effector (WDPCP) has been proven to be an essential element for ciliogenesis in human nasal epithelium, but its role in the beating of cilia remains unclear. In this study, we sought to investigate the role of WDPCP and its underlying mechanism behind the dysfunction in the beating of cilia in nasal polyp tissue. We demonstrated WDPCP expression in the epithelium of nasal polyps. We also investigated the MAPK/ERK pathway in primary human sinonasal epithelial cells to explore the function of WDPCP. The air-liquid interface culture system was used as a model to verify the role of WDPCP and the MAPK/ERK pathway in the beating of cilia. With the dysfunction of cilia beating, we observed a low expression of WDPCP in the epithelium of nasal polyp tissues. Within the study, we found that WDPCP was critical for mitochondrial biogenesis and mitochondrial function in human sinonasal epithelial cells, possibly due to the activation of the MAPK/ERK pathway. The mitochondrial dysfunction caused by U0126 or lacking WDPCP could be partially recovered by dexamethasone. The low expression of WDPCP in nasal epithelium could affect mitochondria via the MAPK/ERK pathway, which may contribute to the dysfunction in the beating of cilia in CRSwNP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2020.630340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882705PMC
February 2021

Vitamin B12 Enriched in Spinach and its Effects on Gut Microbiota.

J Agric Food Chem 2021 Feb 9;69(7):2204-2212. Epub 2021 Feb 9.

School of Food Science and Bioengineering, Zhejiang Gongshang University, Hangzhou 310018, China.

Meat and fermented foods are the main source of vitamin B12 (cobalamin) for human beings. Therefore, daily cobalamin intake is a big problem for vegans. In this study, cyanocobalamin (CNCBL) was added to the culture broth for cobalamin enrichment in spinach. After 36 h of cultivation, the accumulated CNCBL in the spinach leaves (wet weight) was as high as 0.48% (concentration), and the leaves still contained 0.94 ± 0.11 μg/g CNCBL after boiling, which could provide consumer daily requirement of CNCBL. Because CNCBL supplementation had adverse effects on gut microbiota, this study focused on the effect of the combination of spinach and CNCBL on gut microbiota as well. After the boiled leaves were passed through an gastrointestinal tract simulation system, it was found that the spinach protected CNCBL against the low-pH gastric acid. Moreover, compared with the CNCBL supplement group, the relative abundances of and increased, and the relative abundance of Proteobacteria, especially spp., reduced. Analysis of short-chain fatty acids (SCFAs) showed that cobalamin-rich spinach was positively correlated with , propionate, and butyrate. The results showed that the method of enriching spinach with CNCBL was effective and had beneficial effects on gut microbiota and SCFAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.0c07597DOI Listing
February 2021

Investigating the use of a two-stage attention-aware convolutional neural network for the automated diagnosis of otitis media from tympanic membrane images: a prediction model development and validation study.

BMJ Open 2021 01 21;11(1):e041139. Epub 2021 Jan 21.

Department of Otolaryngology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China

Objectives: This study investigated the usefulness and performance of a two-stage attention-aware convolutional neural network (CNN) for the automated diagnosis of otitis media from tympanic membrane (TM) images.

Design: A classification model development and validation study in ears with otitis media based on otoscopic TM images. Two commonly used CNNs were trained and evaluated on the dataset. On the basis of a Class Activation Map (CAM), a two-stage classification pipeline was developed to improve accuracy and reliability, and simulate an expert reading the TM images.

Setting And Participants: This is a retrospective study using otoendoscopic images obtained from the Department of Otorhinolaryngology in China. A dataset was generated with 6066 otoscopic images from 2022 participants comprising four kinds of TM images, that is, normal eardrum, otitis media with effusion (OME) and two stages of chronic suppurative otitis media (CSOM).

Results: The proposed method achieved an overall accuracy of 93.4% using ResNet50 as the backbone network in a threefold cross-validation. The F1 Score of classification for normal images was 94.3%, and 96.8% for OME. There was a small difference between the active and inactive status of CSOM, achieving 91.7% and 82.4% F1 scores, respectively. The results demonstrate a classification performance equivalent to the diagnosis level of an associate professor in otolaryngology.

Conclusions: CNNs provide a useful and effective tool for the automated classification of TM images. In addition, having a weakly supervised method such as CAM can help the network focus on discriminative parts of the image and improve performance with a relatively small database. This two-stage method is beneficial to improve the accuracy of diagnosis of otitis media for junior otolaryngologists and physicians in other disciplines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-041139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825258PMC
January 2021

Cigarette smoking promotes keratinocyte malignancy via generation of cancer stem-like cells.

J Cancer 2021 1;12(4):1085-1093. Epub 2021 Jan 1.

The Cancer Center, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian 350001, China.

: Cigarette smoking is involved in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). However, the underlying molecular mechanisms of cigarette smoking-induced HNSCC carcinogenesis are unclear and may involve cancer stem-like cell generation. We examined the effects of cigarette smoke condensate (CSC) on the formation of cancer stem-like cells, which are rich in octamer-binding transcription factor (OCT)-4, inhibitor of differentiation 1 (ID1), nuclear factor (NF)-κB, and B lymphoma Mo-MLV insertion region 1 homolog (BMI-1). : We used , , and archival human HNSCC tissue analysis to evaluate the effects of CSC on cancer stem-like cell formation. We found that CSC regulated OCT-4 expression, which subsequently regulated ID1 and NF-κB, at the promoter, mRNA, and protein levels . Furthermore, OCT-4 knockdown with siRNA reduced ID1 expression. ID1 and NF-κB synergistically increased the expression of BMI-1 and stimulated keratinocyte sphere generation. , ID1 and NF-κB acted together to generate malignant xenograft tumors, which were aggressive locally and systemically metastatic. Clinical data confirmed that ID1- and NF-κB-positive patients had poor clinical outcomes and 5-year disease-free survival. : Our data suggest that smoking cigarettes promoted cancer stem-like cell generation in the head and neck area via the OCT-4/ID1/NF-κB/BMI-1 signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.50746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797662PMC
January 2021

Glucose Protects Cochlear Hair Cells Against Oxidative Stress and Attenuates Noise-Induced Hearing Loss in Mice.

Neurosci Bull 2021 May 7;37(5):657-668. Epub 2021 Jan 7.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.

Oxidative stress is the key determinant in the pathogenesis of noise-induced hearing loss (NIHL). Given that cellular defense against oxidative stress is an energy-consuming process, the aim of the present study was to investigate whether increasing energy availability by glucose supplementation protects cochlear hair cells against oxidative stress and attenuates NIHL. Our results revealed that glucose supplementation reduced the noise-induced formation of reactive oxygen species (ROS) and consequently attenuated noise-induced loss of outer hair cells, inner hair cell synaptic ribbons, and NIHL in CBA/J mice. In cochlear explants, glucose supplementation increased the levels of ATP and NADPH, as well as attenuating HO-induced ROS production and cytotoxicity. Moreover, pharmacological inhibition of glucose transporter type 1 activity abolished the protective effects of glucose against oxidative stress in HEI-OC1 cells. These findings suggest that energy availability is crucial for oxidative stress resistance and glucose supplementation offers a simple and effective approach for the protection of cochlear hair cells against oxidative stress and NIHL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12264-020-00624-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099978PMC
May 2021

Accelerated anaerobic biodecolorization of sulfonated azo dyes by magnetite nanoparticles as potential electron transfer mediators.

Chemosphere 2021 Jan 20;263:128048. Epub 2020 Aug 20.

Nantong Key Laboratory of Intelligent and New Energy Materials, School of Chemistry and Chemical Engineering, Nantong University, Nantong, 222100, China. Electronic address:

Anaerobic decolorization of azo dyes has been evidenced to be an economical and effective pretreatment method, but its generally limited by the low decolorization efficiency, especially for biodecolorization sulfonated azo dyes. In this study, magnetite nanoparticles (MNPs) as a conductive material, was coupled into anaerobic system for enhancing decolorization of sulfonated azo dyes, i.e., methyl orange (MO), with technology feasibility and system stability emphasized. The results showed that the anaerobic decolorization capacity was significantly enhanced with addition of MNPs (at dose of 1 g/L), where the efficiencies of MO decolorization and aromatic amines formation were as high as 97.28 ± 0.78 % and 99.44 ± 0.25%, respectively. In addition, both electron transport system activity and sludge conductivity were also significantly improved, suggesting that a direct extracellular electron transfer had been successfully established via MNPs as RMs. Under continuous-flow experiments, addition of MNPs not only improved anaerobic system resistance environmental stress (e.g., high MO concentration, low hydraulic retention time and low co-substance concentration) but also accelerated sludge granulation. The relative abundance of functional species related to dissimilatory iron reduction and MO biodegradation were also enriched under MNPs stimulation. The observed long-term stable performance suggests the full-scale application potential of this coupled system for treatment of wastewater containing sulfonated azo dyes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2020.128048DOI Listing
January 2021

Hemagglutinin stalk-based monoclonal antibody elicits broadly reactivity against group 1 influenza A virus.

Virol J 2020 12 7;17(1):191. Epub 2020 Dec 7.

MOE International Joint Collaborative Research Laboratory for Animal Health and Food Safety & Jiangsu Engineering Laboratory of Animal Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.

Background: Influenza virus remains a continuous and severe threat to public health worldwide, and its prevention and treatment have always been a major international issue. Because of its ability to evade immune surveillance through rapid antigenic drift and antigenic shift, broad-spectrum vaccines seem increasingly important.

Methods: A mAb named 3C12 from an immortalized hybrid cell was generated via immunizing mice with HA2 protein from A/chicken/Anhui/BRI99/2016 (AH/BRI99/16, H9N2) generated by prokaryotic expression. Then, its broad-spectrum activity was analyzed by WB and IFA. Next, the minimal linear epitope was identified via analyzing the reaction of a series of HA truncations with 3C12. Finally, the protective effects of 3C12 were evaluated in vitro and in vivo infection experiments.

Results: The mAb could react with the viruses of subtypes H1, H2, H5, H8, H9, H12, H13, H16, and HA protein of H18 in group 1, but failed to react with viruses in group 2. The minimal linear epitope targeted by the mAb was NAELLVL in full length of HA and localized in the C-helix region of HA2 (residue 95-101, HA2 numbering). What's more, the mAb 3C12 inhibited H1, H2, H5, H8, H9, H12, H13 and H16 virus-replication in vitro and also has shown effectiveness in preventing and treating disease in mice challenged with lethal dose of AH/BRI99/16 (H9N2) virus in vivo. These results suggested that the broadly reactive anti-HA stem mAb 3C12 exhibited prophylactic and therapeutic efficacy.

Conclusions: Here, we have demonstrated that the linear epitope identified in this study could be a novel target for developing broad-spectrum influenza diagnostics or vaccine design, and the HA2-based monoclonal antibody is indeed a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12985-020-01458-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720065PMC
December 2020

Bleomycin A5 suppresses Drp1‑mediated mitochondrial fission and induces apoptosis in human nasal polyp‑derived fibroblasts.

Int J Mol Med 2021 01 23;47(1):346-360. Epub 2020 Nov 23.

Department of Otorhinolaryngology‑Head and Neck Surgery, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510000, P.R. China.

Intralesional injection of bleomycin‑A5 (BLE‑A5) is a novel treatment for nasal polyps. Our previous study clarified that BLE‑A5 could induce nasal polyp‑derived fibroblast (NPDF) apoptosis in nasal polyps. However, the detailed mechanisms are still unclear. The present study aimed to determine the effects of BLE‑A5 on NPDF mitochondrial dynamics and provide a theoretical basis for the local application of BLE‑A5 to treat nasal polyps. In the present study, an in vitro nasal polyp tissue culture model was used to define the BLE‑A5 target cell type in nasal polyps. NPDF primary cell culture was used to study the effects of BLE‑A5 on the mitochondrial dynamic‑related mechanism. The results showed that BLE‑A5 treatment of NPDFs caused mitochondrial‑mediated apoptosis. Dynamin‑related protein 1 (Drp1) was shown to be altered in BLE‑A5‑treated NPDFs. Drp1 knockdown increased the sensitivity of NPDFs to BLE‑A5 and exacerbated mitochondrial dysfunction. BLE‑A5 decreased cyclin B1‑CDK1 complex‑mediated phosphorylation of Drp1 and inhibited Drp1‑mediated mitophagy in NPDFs. Overall, the present study concluded that BLE‑A5 mainly induces NPDF apoptosis in nasal polyps. BLE‑A5 regulates the mitochondria by inhibiting Drp1 activation, resulting in NPDF mitochondrial dynamic disorder and apoptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ijmm.2020.4797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723402PMC
January 2021

Alterations of brain activity and functional connectivity in transition from acute to chronic tinnitus.

Hum Brain Mapp 2021 02 13;42(2):485-494. Epub 2020 Oct 13.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou City, Guangdong Province, China.

The objective of this study was to investigate alterations to brain activity and functional connectivity in patients with tinnitus, exploring neural features in the transition from acute to chronic phantom perception. Twenty-four patients with acute tinnitus, 23 patients with chronic tinnitus, and 32 healthy controls were recruited. High-density electroencephalography (EEG) was used to explore changes in brain areas and functional connectivity in different groups. When compared with healthy subjects, acute tinnitus patients had a significant reduction in superior frontal cortex activity across all frequency bands, whereas chronic tinnitus patients had a significant reduction in the superior frontal cortex at beta 3 and gamma frequency bands as well as a significant increase in the inferior frontal cortex at delta-band and superior temporal cortex at alpha 1 frequency band. When compared to the chronic tinnitus group, the acute tinnitus group activity was significantly increased in the middle frontal and parietal gyrus at the gamma-band. Functional connectivity analysis showed that the chronic tinnitus group had increased connections between the parahippocampus gyrus, posterior cingulate cortex, and precuneus when compared with the healthy group. Alterations of local brain activity and connections between the parahippocampus gyrus and other nonauditory areas appeared in the transition from acute to chronic tinnitus. This indicates that the appearance and development of tinnitus is a dynamic process involving aberrant local neural activity and abnormal connectivity in multifunctional brain networks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776005PMC
February 2021

Features of Nuclear Export Signals of NS2 Protein of Influenza D Virus.

Viruses 2020 09 29;12(10). Epub 2020 Sep 29.

MOE Joint International Research Laboratory of Animal Health and Food Safety, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.

Emerging influenza D viruses (IDVs), the newest member in the genus family, which can infect and transmit in multiple mammalian species as its relatives the influenza A viruses (IAVs). Additional studies of biological characteristics of IDVs are needed; here, we studied the characteristics of IDV nonstructural protein 2 (NS2), which shares the lowest homology to known influenza proteins. First, we generated reassortant viruses via reverse genetics to analyze the segment compatibility and gene interchangeability between IAVs and IDVs. Next, we investigated the locations and exact sequences of nuclear export signals (NESs) of the IDV NS2 protein. Surprisingly, three separate NES regions were found to contribute to the nuclear export of an eGFP fusion protein. Alanine scanning mutagenesis identified critical amino acid residues within each NES, and co-immunoprecipitation experiments demonstrated that their nuclear export activities depend on the CRM1-mediated pathway, particularly for the third NES (136-146aa) of IDV NS2. Interestingly, the third NES was important for the interaction of NS2 protein with CRM1. The findings in this study contribute to the understanding of IDV NS2 protein's role during nucleocytoplasmic transport of influenza viral ribonucleoprotein complexes (vRNPs) and will also facilitate the development of novel anti-influenza drugs targeting nuclear export signals of IDV NS2 protein.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v12101100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600798PMC
September 2020

Transcriptomic analysis highlights cochlear inflammation associated with age-related hearing loss in C57BL/6 mice using next generation sequencing.

PeerJ 2020 19;8:e9737. Epub 2020 Aug 19.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Background: In our aging society, age-related hearing loss (AHL) is the most common sensory disorder in old people. Much progress has been made in understanding the pathological process of AHL over the past few decades. However, the mechanism of cochlear degeneration during aging is still not fully understood.

Methods: Next generation sequencing technique was used to sequence the whole transcriptome of the cochlea of C57BL/6 mice, a mouse model of AHL. Differentially expressed genes (DEGs) were identified using the Cuffdiff software. GO and KEGG pathway enrichment analyses of the DEGs were implemented by using the GOseq R package and KOBAS software, respectively.

Results: A total of 731 genes (379 up- and 352 down-regulated) were revealed to be differentially expressed in the cochlea of aged mice compared to the young. Many genes associated with aging, apoptosis, necroptosis and particularly, inflammation were identified as being significantly modulated in the aged cochlea. GO and KEGG analyses of the upregulated DEGs revealed that the most enriched terms were associated with immune responses and inflammatory pathways, whereas many of the downregulated genes are involved in ion channel function and neuronal signaling. Real-time qPCR showed that HO treatment significantly induced the expression of multiple inflammation and necroptosis-related genes in HEI-OC1 cells.

Conclusion: Using next generation sequencing, our transcriptomic analysis revealed the differences of gene expression pattern with age in the cochlea of C57BL/6 mice. Our study also revealed multiple immune and inflammatory transcriptomic changes during cochlear aging and provides new insights into the molecular mechanisms underlying cochlear inflammation in AHL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.9737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443093PMC
August 2020

Aberrant Functional and Causal Connectivity in Acute Tinnitus With Sensorineural Hearing Loss.

Front Neurosci 2020 30;14:592. Epub 2020 Jun 30.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Purpose: The neural bases in acute tinnitus remains largely undetected. The objective of this study was to identify the alteration of the brain network involved in patients with acute tinnitus and hearing loss.

Methods: Acute tinnitus patients ( = 24) with hearing loss and age-, sex-, education-matched healthy controls ( = 21) participated in the current study and underwent resting-state functional magnetic resonance imaging (fMRI) scanning. Regional homogeneity and amplitude of low-frequency fluctuation were used to investigate the local spontaneous neural activity and functional connectivity (FC), and Granger causality analysis (GCA) was used to analyze the undirected and directed connectivity of brain regions.

Results: Compared with healthy subjects, acute tinnitus patients had a general reduction in FC between auditory and non-auditory brain regions. Based on FC analysis, the superior temporal gyrus (STG) revealed reduced undirected connectivity with non-auditory brain regions including the amygdala (AMYG), nucleus accumbens (NAc), the cerebellum, and postcentral gyrus (PoCG). Using the GCA algorithm, increased effective connectivity from the right AMYG to the right STG, and reduced connectivity from the right PoCG to the left NAc was observed in acute tinnitus patients with hearing loss. The pure-tone threshold was positively correlated with FC between the AMYG and STG, and negatively correlated with FC between the left NAc and the right PoCG. In addition, a negative association between the GCA value from the right PoCG to the left NAc and the THI scores was observed.

Conclusion: Acute tinnitus patients have aberrant FC strength and causal connectivity in both the auditory and non-auditory cortex, especially in the STG, AMYG, and NAc. The current findings will provide a new perspective for understanding the neuropathophysiological mechanism in acute tinnitus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnins.2020.00592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340148PMC
June 2020

Eustachian tube dysfunction in patients with house dust mite-allergic rhinitis.

Clin Transl Allergy 2020 15;10:30. Epub 2020 Jul 15.

Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.

Background: One of the important pathogeneses of eustachian tube dysfunction (ETD) is nasal inflammatory disease. The prevalence of allergic rhinitis (AR) in adults ranges from 10 to 30% worldwide. However, research on the status of eustachian tubes in AR patients is still very limited.

Methods: This prospective controlled cross-sectional study recruited 59 volunteers and 59 patients with AR from Sun Yat-sen Memorial Hospital. Visual analogue scale (VAS) scores for AR symptoms and seven-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) scores were collected for both groups. Nasal endoscopy, tympanography and eustachian tube pressure measurement (tubomanometry, TMM) were used for objective assessment. All AR patients underwent 1 month of treatment with mometasone furoate nasal spray and oral loratadine. Then, the nasal condition and eustachian tube status were again evaluated.

Results: TMM examination revealed that 22 patients (39 ears, 33.1%) among the AR patients and 5 healthy controls (7 ears, 5.9%) had abnormal eustachian pressure. Twenty-two AR patients (37.3%) and 9 healthy controls had an ETDQ-7 score ≥ 15. With regard to nasal symptoms of AR, the VAS scores of nasal obstruction were correlated with the ETDQ-7 scores, and the correlation coefficient was r = 0.5124 (< 0.0001). Nasal endoscopic scores were also positively correlated with ETDQ-7 scores, with a correlation coefficient of 0.7328 (< 0.0001). After 1 month of treatment, VAS scores of nasal symptoms, endoscopic scores and ETDQ-7 scores were significantly decreased in AR patients (< 0.0001), and TMM examination also suggested that eustachian tube function was significantly improved after treatment (< 0.0001).

Conclusions: AR patients, especially those with severe nasal obstruction, could have ETD. The local conditions of the pharyngeal orifices of the eustachian tubes are closely related to the symptoms of ETD. After treatment with nasal glucocorticoids and oral antihistamines, eustachian tube function can significantly improve as nasal symptoms subside. Chinese Clinical Trial Registery (ChiCTR2000029071) Registered 12 January 2020-Retrospectively registered, http://www.chictr.org.cn/edit.aspx?pid=48328&htm=4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13601-020-00328-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362452PMC
July 2020

Clinical significance of COL1A1 and COL1A2 expression levels in hypopharyngeal squamous cell carcinoma.

Oncol Lett 2020 Jul 7;20(1):803-809. Epub 2020 May 7.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China.

Alterations in collagen type I α1 (COL1A1) and collagen type I α 2 (COL1A2) expression levels have been reported to predict prognosis in various types of cancer. However, the effect of these biomarkers on hypopharyngeal squamous cell carcinoma (HPSCC) is yet to be fully elucidated. The present study aimed to explore the prognostic significance of COL1A1 and COL1A2 expression levels in HPSCC. The expression levels of COL1A1 and COL1A2 in 67 patients with HPSCC were examined using an immunohistochemical assay in a tissue microarray. The associations between COL1A1/COL1A2 expression levels and patient clinicopathological features were analyzed using ANOVA, Pearson's χ or Fisher's exact test. The Cox proportional hazard models and Kaplan-Meier survival analysis with log-rank tests were used to analyze the significance of COL1A1/COL1A2 as prognostic markers for patients with HPSCC. As a result, immunohistochemical staining revealed that COL1A1 was positively expressed in all cases, among which 40.3% were strong positive, while COL1A2 was positively expressed in 76.1% of the HPSCC cases with 6.0% of the samples exhibiting strong staining. Further analysis revealed no significant association between the expression levels of COL1A1/COL1A2 and other clinicopathological features. Cox regression analysis revealed that a high COL1A2 expression level predicted a high locoregional recurrence and a less favorable disease-free survival rate (P=0.042 and 0.020, respectively). Overall, the present study indicated that COL1A2 expression levels may have value as a prognostic indicator in HPSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2020.11594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285875PMC
July 2020

Acoustic and Aerodynamic Analyses of the Voice of Prelingually Deaf Young Men After Cochlear Implantation.

J Voice 2020 May 16. Epub 2020 May 16.

Department of Otorhinolaryngology-Head and Neck Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. Electronic address:

Objective: The purpose of this study was to characterize the acoustic and aerodynamics of the voice of young men with prelingual deafness after cochlear implantation (CI) to provide a theoretical basis for their rehabilitation after CI.

Methods: The CI group included 17 young men with prelingual deafness who implanted cochlear at 18-24 years old. The control group included 17 normally hearing young men at the same age. The 10-item Voice Handicap Index, acoustic parameters, and aerodynamic parameters were evaluated.

Results: For the acoustic parameters, the F0, SDF0, and Jitter of the CI group were higher than those of the Control group, and these differences were statistically significant. Additionally, The difference in mean shimmer and mean NHR values between the CI group and the Control group was not statistically significant For the aerodynamic parameters, the subglottal pressure and aerodynamic power of the CI group were significantly higher than those of the Control group, whereas the MPT was significantly shorter.

Discussion: Due to excessive stress on the laryngeal muscle and limited pneumo-phono-articulatory coordination, the young men in the CI group had a thin voice and poor voice control and muscle coordination, and they exhibited excessive laryngeal resistance. We propose that after CI, in addition to regular hearing and speech rehabilitation, voice training is also extremely important for prelingually deaf young men.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvoice.2020.03.007DOI Listing
May 2020

Nrf2 activation protects auditory hair cells from cisplatin-induced ototoxicity independent on mitochondrial ROS production.

Toxicol Lett 2020 Oct 16;331:1-10. Epub 2020 May 16.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Department of Hearing and Speech Science, Sun Yat-sen University, Guangzhou, China. Electronic address:

Cisplatin is a well-known and commonly used chemotherapeutic agent. However, cisplatin-induced ototoxicity limits its clinical use. Previous studies have shown an important role of reactive oxygen species (ROS) accumulation in the pathogenesis of cisplatin-induced ototoxicity. In many cell types, the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant response element (ARE) protect against oxidative stress by suppressing ROS. Here our results showed that cisplatin injury reduced Nrf2 expression and inhibited Nrf2 translocation in HEI-OC1 cells and Nrf2 activator tert-butylhydroquinone (TBHQ) rescued hair cells from cisplatin induced apoptosis by suppressing the total cellular ROS accumulation. Moreover, we found that decreased ROS accumulation induced by TBHQ didn't depend on mitochondrial derived ROS production, indicating that Nrf2 activation alleviated cisplatin induced oxidative stress and apoptosis through mitochondrial-independent ROS production. Therefore, we provide a potential strategy of prevention and treatment for cisplatin-induced ototoxicity by Nrf2 activation. In conclusion, Nrf2 activation protects auditory hair cells from cisplatin-induced ototoxicity through suppressing the total cellular ROS levels which arise from sources other than mitochondria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxlet.2020.04.005DOI Listing
October 2020

Diminished self-monitoring in hallucinations - Aberrant anterior insula connectivity differentiates auditory hallucinations in schizophrenia from subjective tinnitus.

Asian J Psychiatr 2020 Aug 7;52:102056. Epub 2020 May 7.

Psychological Applications Research Center, Guangdong Key Laboratory of Mental Health and Cognitive Science, School of Psychology, South China Normal University, Guangzhou, China. Electronic address:

Auditory hallucinations in schizophrenia (SCZ-AH) and subjective tinnitus (TN) are two conditions that share a superficial resemblance, namely the presence of phantom sounds produced by the brain. A crucial difference between them lies in the self-processing of the phantom signals, which is intact in TN patients but lost in SCZ-AH. Our study sets out to investigate the potential neural mechanisms for this crucial psychotic symptom of SCZ-AH under the framework of self. We gathered resting-state fMRI data from three participant groups: SCZ-AH, TN and healthy controls. Focusing on predefined self-related regions-of-interest, we found that SCZ-AH had reduced degree centrality in the right anterior insula (rAI) compared to both TN and healthy controls. Further functional connectivity analysis showed a reduced connectivity between the rAI and right superior temporal gyrus. Our finding indicates that compromised self-processing in SCZ-AH could be due to aberrant connectivity in rAI, which interacted with the decreased connectivity between rAI and auditory cortex, and jointly contributed to the misattribution of the source of the phantom sound. Our findings provided preliminary evidence for the neural mechanism of self-disorder underlying SCZ-AH, and could provide implications for investigating other modalities of hallucinations in schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajp.2020.102056DOI Listing
August 2020

Yap-lin28a axis targets let7-Wnt pathway to restore progenitors for initiating regeneration.

Elife 2020 04 30;9. Epub 2020 Apr 30.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

The sox2 expressing (sox2) progenitors in adult mammalian inner ear lose the capacity to regenerate while progenitors in the zebrafish lateral line are able to proliferate and regenerate damaged HCs throughout lifetime. To mimic the HC damage in mammals, we have established a zebrafish severe injury model to eliminate both progenitors and HCs. The expressing () HC precursors were the main population that survived post severe injury, and gained sox2 expression to initiate progenitor regeneration. In response to severe injury, was activated to upregulate transcription. Severe-injury-induced progenitor regeneration was disabled in or mutants. In contrary, overexpression of initiated the recovery of sox2 progenitors. Mechanistically, microRNA acted downstream of to activate Wnt pathway for promoting regeneration. Our findings that lin28a is necessary and sufficient to regenerate the exhausted sox2 progenitors shed light on restoration of progenitors to initiate HC regeneration in mammals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.55771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250571PMC
April 2020

Event-Related Potential Evidence of Enhanced Visual Processing in Auditory-Associated Cortex in Adults with Hearing Loss.

Audiol Neurootol 2020 22;25(5):237-248. Epub 2020 Apr 22.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital and Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China,

Objective: The present study investigated the characteristics of visual processing in the auditory-associated cortex in adults with hearing loss using event-related potentials.

Methods: Ten subjects with bilateral postlingual hearing loss were recruited. Ten age- and sex-matched normal-hearing subjects were included as controls. Visual ("sound" and "non-sound" photos)-evoked potentials were performed. The P170 response in the occipital area as well as N1 and N2 responses in FC3 and FC4 were analyzed.

Results: Adults with hearing loss had higher P170 amplitudes, significantly higher N2 amplitudes, and shorter N2 latency in response to "sound" and "non-sound" photo stimuli at both FC3 and FC4, with the exception of the N2 amplitude which responded to "sound" photo stimuli at FC3. Further topographic mapping analysis revealed that patients had a large difference in response to "sound" and "non-sound" photos in the right frontotemporal area, starting from approximately 200 to 400 ms. Localization of source showed the difference to be located in the middle frontal gyrus region (BA10) at around 266 ms.

Conclusions: The significantly stronger responses to visual stimuli indicate enhanced visual processing in the auditory-associated cortex in adults with hearing loss, which may be attributed to cortical visual reorganization involving the right frontotemporal cortex.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000505608DOI Listing
May 2021

Efficacy of an Integrative Treatment for Tinnitus Combining Music and Cognitive-Behavioral Therapy-Assessed With Behavioral and EEG Data.

Front Integr Neurosci 2020 7;14:12. Epub 2020 Apr 7.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Chronic tinnitus is a prevalent condition that could cause severe negative impact on an individual's life. However, there has not been an established treatment due to a limited understanding of the pathophysiology of this multifarious disorder. In this study, we tested the efficacy of an integrative treatment, combining music therapy with cognitive-behavioral therapy (CBT). We collected three groups of patients receiving three different treatments: Music-CBT, music therapy and CBT. We used both subjective (i.e., questionnaires) and objective (i.e., resting-state EEG data) measurements to assess the behavioral and neural changes brought upon by the treatments. Analyses of the subjective measurements found a significant improvement of scale scores in Music-CBT and CBT, but not in the Music group. Analysis of the EEG data further showed increased powers in alpha and theta band after the Music-CBT treatment, and increased gamma power after CBT, whereas no significant difference was found for the music therapy. Further source localization analysis of alpha and theta changes in the Music-CBT group found that primary sources of the changes were located at auditory processing regions such as superior temporal gyrus, and higher emotional and cognitive processing regions such as ventromedial prefrontal cortex (vMPFC), lateral prefrontal cortex and parahippocampus. These results indicated that Music-CBT was effective in improving tinnitus symptoms on both a behavioral and neural level, which is more robust than the music therapy or CBT alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnint.2020.00012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155387PMC
April 2020

Modified Postauricular Incision for Preservation of the Lesser Occipital Nerve and the Great Auricular Nerve in Ear Surgery.

ORL J Otorhinolaryngol Relat Spec 2020;82(3):150-162. Epub 2020 Mar 23.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Objective: To describe the feasibility of preserving the lesser occipital nerve (LON) and the great auricular nerve (GAN) in postauricular incision in ear surgery.

Methods: The distribution of the LON and the GAN was first identified in human cadavers. Then a clinical study was performed in 34 patients who underwent middle ear surgery between September 2016 and January 2017. Patients were divided into the conventional incision group and the modified incision group, according to incision types, and underwent sensory testing and subjective evaluation of auricular numbness after surgery at different times.

Results: Most frequently, the auricular branches of the LON went into the postauricular groove at the same height of inferior crus of antihelix. The vertical dimension from the intersection of the highest auricular branch of the GAN and postauricular groove to intertragic notch ranged from 5.7 to -4.2 mm. Preservation of the LON and the GAN reduced sensory loss in the modified incision group compared to the conventional incision group.

Conclusion: Preservation of the LON and the GAN with modified postauricular incision can reduce postoperative auricular numbness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000506209DOI Listing
April 2021

Impact of visual signals on axial segmental control during walking in patients with vestibular disorder and healthy persons.

J Biomech 2020 05 25;104:109712. Epub 2020 Feb 25.

Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; Department of Hearing and Speech Science, Xinhua College, Sun Yat-sen University, Guangzhou, People's Republic of China. Electronic address:

Head and trunk control during standing in patients with vestibular disorder may depend on intact visual signal to override vestibular disturbance. It is unknown if such process during walking would change. Therefore, the aims of this study were to quantify (1) head and trunk control in healthy participants (HPs) and patients with unilateral vestibular hypofunction (UVH) during walking with and without visual manipulation; and (2) the correlation/association between vestibular function and head/trunk control during walking with visual manipulation in patients. Seventeen UVH patients and 15 HPs completed all the tests. They participated in the caloric test, which was used to examine vestibular function, and walked on a treadmill with and without visual manipulation. Head and trunk angular displacement and velocity were primary outcome measures, deviation of center of mass and step variability were secondary. Head roll angular displacement (7.38° ± 1.38 [mean ± SE] v.s. 12.95° ± 1.48, p = 0.004) and head-trunk correlation (in the pitch/sagittal plane: 0.22 ± 0.05 v.s. 0.38 ± 0.05, roll/frontal plane: 0.35 ± 0.06 v.s. 0.55 ± 0.06, p < 0.05) were significantly lower in patients compared to HPs. Head pitch angular velocity (8.58°/s ± 2.17 v.s. 14.23°/s ± 1.22, p = 0.026) and step width variability (0.075 ± 0.010 v.s. 0.083 ± 0.009, p = 0.04) increased with visual manipulation only in patients. No significant correlation/association was found between vestibular function and head/trunk control. Lower head-trunk correlation in patients suggests an independent head-trunk control strategy in response to vestibular impairment. Visual input could be used by patients to compensate for vestibular disturbance for head control and foot placement. Severe UVH may not lead to worse postural control compared to mild disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbiomech.2020.109712DOI Listing
May 2020

Comparison of 2 Ear Molding Systems for Nonsurgical Management of Newborn Auricular Deformities.

Ear Nose Throat J 2020 Feb 7:145561320901398. Epub 2020 Feb 7.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Congenital auricular deformities are common diseases in newborn infants. We compared the efficacy of 2 ear molding systems in the nonsurgical management of newborn auricular deformities in Chinese infants.

Methods: A total of 462 newborns with auricular deformities were treated with either the EarWell or the LiangEar ear molding systems. The posttreatment outcome was graded as excellent, fair, and poor. The differences in effectiveness between the 2 ear molding systems and factors that may affect the posttreatment outcome were analyzed.

Results: Both ear molding systems showed substantial efficacy in the treatment of newborn auricular deformities. The effective rate was comparable between the EarWell and the LiangEar systems for 4 types of auricular deformities (cryptotia, prominent ear, helical rim abnormality, and cup ear), while the costs for the LiangEar systems were half as much as that for the EarWell systems. Multivariate regression analysis showed that earlier time points at treatment initiation, less severe auricular deformities, treatment duration, and breastfeeding were the most significant predictive factors for a better outcome.

Conclusion: Our findings demonstrate that using the EarWell and the LiangEar systems are both optimal nonsurgical approaches for treatment of most newborn auricular deformities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0145561320901398DOI Listing
February 2020

Inhibition of DRP-1-Dependent Mitophagy Promotes Cochlea Hair Cell Senescence and Exacerbates Age-Related Hearing Loss.

Front Cell Neurosci 2019 17;13:550. Epub 2019 Dec 17.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

: Mitochondrial dysfunction is considered to contribute to the development of age-related hearing loss (AHL). The regulation of mitochondrial function requires mitochondrial quality control, which includes mitophagy and dynamics. Dynamin-related Protein 1 (DRP-1) is believed to play a central role in this regulation. However, the underlying mechanism of DRP-1 in AHL remains unclear. Here, we examined whether the decline of DRP-1-dependent mitophagy contributes to the development of AHL. : We induced cellular and cochlear senescence using hydrogen peroxide (HO) and evaluated the level of senescence through senescence-associated β-galactosidase staining. We evaluated mitophagy levels fluorescence imaging and Western Blotting of LC3II and P62. Mitochondrial function was assessed by ATP assay, mtDNA assay, and JC-1. : We found that both the expression of DRP-1 and the mitophagy level decreased in senescent cells and aged mice. DRP-1 overexpression in HEI-OC1 cells initiated mitophagy and preserved mitochondrial function when exposed to HO, while cells with DRP-1 silencing displayed otherwise. Moreover, inhibition of DRP-1 by Mdivi-1 blocked mitophagy and exacerbated hearing loss in aged C57BL/6 mice. : These results indicated that DRP-1 initiated mitophagy, eliminated mitochondrial dysfunction, and may protect against oxidative stress-induced senescence. These results provide a potential therapeutic target for AHL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fncel.2019.00550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929675PMC
December 2019
-->