Publications by authors named "Haidi Yang"

65 Publications

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

Analysing wideband absorbance immittance in normal and ears with otitis media with effusion using machine learning.

Sci Rep 2021 May 20;11(1):10643. Epub 2021 May 20.

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

Wideband Absorbance Immittance (WAI) has been available for more than a decade, however its clinical use still faces the challenges of limited understanding and poor interpretation of WAI results. This study aimed to develop Machine Learning (ML) tools to identify the WAI absorbance characteristics across different frequency-pressure regions in the normal middle ear and ears with otitis media with effusion (OME) to enable diagnosis of middle ear conditions automatically. Data analysis included pre-processing of the WAI data, statistical analysis and classification model development, and key regions extraction from the 2D frequency-pressure WAI images. The experimental results show that ML tools appear to hold great potential for the automated diagnosis of middle ear diseases from WAI data. The identified key regions in the WAI provide guidance to practitioners to better understand and interpret WAI data and offer the prospect of quick and accurate diagnostic decisions.
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http://dx.doi.org/10.1038/s41598-021-89588-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137706PMC
May 2021

Application of Ketoreductase in Asymmetric Synthesis of Pharmaceuticals and Bioactive Molecules: An Update (2018-2020).

Chem Rec 2021 Jul 9;21(7):1611-1630. Epub 2021 Apr 9.

Department of Chemistry, Engineering Center of Catalysis and Synthesis for Chiral Molecules, Fudan University, Shanghai Engineering Research Center of Industrial Asymmetric Catalysis of Chiral Drugs, 220 Handan Road, Shanghai, 200433, P. R. China.

With the rapid development of genomic DNA sequencing, recombinant DNA expression, and protein engineering, biocatalysis has been increasingly and widely adopted in the synthesis of pharmaceuticals, bioactive molecules, fine chemicals, and agrochemicals. In this review, we have summarized the most recent advances achieved (2018-2020) in the research area of ketoreductase (KRED)-catalyzed asymmetric synthesis of chiral secondary alcohol intermediates to pharmaceuticals and bioactive molecules. In the first part, synthesis of chiral alcohols with one stereocenter through the bioreduction of four different ketone classes, namely acyclic aliphatic ketones, benzyl or phenylethyl ketones, cyclic aliphatic ketones, and aryl ketones, is discussed. In the second part, KRED-catalyzed dynamic reductive kinetic resolution and reductive desymmetrization are presented for the synthesis of chiral alcohols with two contiguous stereocenters.
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http://dx.doi.org/10.1002/tcr.202100062DOI Listing
July 2021

Metformin alleviates cisplatin-induced ototoxicity by autophagy induction possibly via the AMPK/FOXO3a pathway.

J Neurophysiol 2021 04 24;125(4):1202-1212. Epub 2021 Feb 24.

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

Cisplatin is an antitumor drug that is widely used for the treatment of various solid tumors. Unfortunately, patients are often troubled by serious side effects, especially hearing loss. Up to now, there have been no clear and effective measures to prevent cisplatin-induced ototoxicity in clinical use. We explored the role of autophagy and the efficacy of metformin in cisplatin-induced ototoxicity in cells, zebrafish, and mice. Furthermore, the underlying molecular mechanism of how metformin affects cisplatin-induced ototoxicity was examined. In in vitro experiments, autophagy levels in HEI-OC1 cells were assessed using fluorescence and Western blot analyses. In in vivo experiments, whether metformin had a protective effect against cisplatin ototoxicity was validated in zebrafish and C57BL/6 mice. The results showed that cisplatin induced autophagy activation in HEI-OC1 cells. Metformin exerted antagonistic effects against cisplatin ototoxicity in HEI-OC1 cells, zebrafish, and mice. Notably, metformin activated autophagy and increased the expression levels of the adenosine monophosphate-activated protein kinase (AMPK) and the transcription factor Forkhead box protein O3 (FOXO3a), whereas cells with AMPK silencing displayed otherwise. Our findings indicate that metformin alleviates cisplatin-induced ototoxicity possibly through AMPK/FOXO3a-mediated autophagy machinery. This study underpins further researches on the prevention and treatment of cisplatin ototoxicity. Cisplatin is an antitumor drug that is widely used for the treatment of various solid tumors. Up to now, there have been no clear and effective measures to prevent cisplatin-induced ototoxicity in clinical use. We investigated the protective effect of metformin on cisplatin ototoxicity in vitro and in vivo. Our findings indicate that metformin alleviates cisplatin-induced ototoxicity possibly through AMPK/FOXO3a-mediated autophagy machinery. This study underpins further researches on the prevention and treatment of cisplatin ototoxicity.
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http://dx.doi.org/10.1152/jn.00417.2020DOI Listing
April 2021

[Analysis of related factors between sudden sensorineural hearing loss and serum indices base on artificial intelligence and big data].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2020 Nov;34(11):977-980

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

The etiology and pathophysiologic mechanism of sudden sensorineural hearing loss are undefined. We will use artificial intelligence and big data methods to explore the correlation between sudden sensorineural hearing loss and serum indices. A total of 1218 patients with sudden deafness admitted to Sun Yat-sen Memorial Hospital were selected as the experimental group, 95 861 healthy subjects were randomly selected as the control group at the same period. Serum biochemical indexes in two groups were collected and analyzed by TreeNet and CART machine learning algorithms, to screen out highly correlated indicators with sudden sensorineural hearing loss and dig out a set of clinical features for people with high risk of sudden sensorineural hearing loss. It was found that high prevalence rate of sudden sensorineural hearing loss is related to eosinophils, reticulocyte and fibrinogen. The areas under the receiver operator characteristic curves(ROC-AUC) were exploited to evaluate the prediction performance of TreeNet model. Overall the TreeNet model has provided high predictive ability by ROC curve, achieving AUC of 0.99, both recall and accuracy rate of 99.90%. There is significant difference between sudden deadness and normal people in serum biochemical indexes. Eosinophil is the first important indicator to distinguish sudden sensorineural hearing loss. Treenet model has important referenced significance for the screening and diagnosis of sudden sensorineural hearing loss.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2020.11.004DOI Listing
November 2020

Repetitive transcranial magnetic stimulation on chronic tinnitus: a systematic review and meta-analysis.

BMC Psychiatry 2020 11 23;20(1):547. Epub 2020 Nov 23.

Department of Otolaryngology, The First Affifiliated Hospital of Jinan University, 601 Huangpu Avenue, Guangzhou, 510632, China.

Background: Although the clinical efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) in the treatment of chronic tinnitus have been frequently examined, the results remain contradictory. Therefore, we performed a systematic review and meta-analysed clinical trials examining the effects of rTMS to evaluate its clinical efficacy and safety.

Methods: Studies of rTMS for chronic tinnitus were retrieved from PubMed, Embase, and Cochrane Library through April 2020. Review Manager 5.3 software was employed for data synthesis, and Stata 13.0 software was used for analyses of publication bias and sensitivity.

Results: Twenty-nine randomized studies involving 1228 chronic tinnitus patients were included. Compared with sham-rTMS, rTMS exhibited significant improvements in the tinnitus handicap inventory (THI) scores at 1 week (mean difference [MD]: - 7.92, 95% confidence interval [CI]: - 14.18, - 1.66), 1 month (MD: -8.52, 95% CI: - 12.49, - 4.55), and 6 months (MD: -6.53, 95% CI: - 11.406, - 1.66) post intervention; there were significant mean changes in THI scores at 1 month (MD: -14.86, 95% CI: - 21.42, - 8.29) and 6 months (MD: -16.37, 95% CI: - 20.64, - 12.11) post intervention, and the tinnitus questionnaire (TQ) score at 1 week post intervention (MD: -8.54, 95% CI: - 15.56, - 1.52). Nonsignificant efficacy of rTMS was found regarding the THI score 2 weeks post intervention (MD: -1.51, 95% CI: - 13.42, - 10.40); the mean change in TQ scores 1 month post intervention (MD: -3.67, 95% CI: - 8.56, 1.22); TQ scores 1 (MD: -8.97, 95% CI: - 20.41, 2.48) and 6 months (MD: -7.02, 95% CI: - 18.18, 4.13) post intervention; and adverse events (odds ratios [OR]: 1.11, 95% CI: 0.51, 2.42). Egger's and Begg's tests indicated no publication bias (P = 0.925).

Conclusion: This meta-analysis demonstrated that rTMS is effective for chronic tinnitus; however, its safety needs more validation. Restrained by the insufficient number of included studies and the small sample size, more large randomized double-blind multi-centre trials are needed for further verification.
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http://dx.doi.org/10.1186/s12888-020-02947-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684956PMC
November 2020

The immune and metabolic changes with age in giant panda blood by combined transcriptome and DNA methylation analysis.

Aging (Albany NY) 2020 11 7;12(21):21777-21797. Epub 2020 Nov 7.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.

Giant panda () is an endangered mammalian species. Exploring immune and metabolic changes that occur in giant pandas with age is important for their protection. In this study, we systematically investigated the physiological and biochemical indicators in blood, as well as the transcriptome, and methylation profiles of young, adult, and old giant pandas. The white blood cell (WBC), neutrophil (NEU) counts and hemoglobin (HGB) concentrations increased significantly with age (young to adult), and some indicators related to blood glucose and lipids also changed significantly with age. In the transcriptome analysis, differentially expressed genes (DEGs) were found in comparisons of the young and adult (257), adult and old (20), young and old (744) groups. Separation of the DEGs into eight profiles according to the expression trend using short time-series expression miner (STEM) software revealed that most DEGs were downregulated with age. Functional analysis showed that most DEGs were associated with disease and that these DEGs were also associated with the immune system and metabolism. Furthermore, gene methylation in giant pandas decreased globally with age, and the expression of , , , and showed a highly negative correlation with their degree of methylation. These results indicate that the giant panda's immune function improves gradually with age (young to adult), and that changes in the methylation profile are involved in the effects of age on immune and metabolic functions. These results have important implications for the understanding and conservation of giant pandas.
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http://dx.doi.org/10.18632/aging.103990DOI Listing
November 2020

Altered Topological Patterns of Gray Matter Networks in Tinnitus: A Graph-Theoretical-Based Study.

Front Neurosci 2020 27;14:541. Epub 2020 May 27.

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

Objective: Tinnitus is a prevalent hearing disorder, which could have a devastating impact on a patient's life. Functional studies have revealed connectivity pattern changes in the tinnitus brains that suggested a change of network dynamics as well as topological organization. However, no studies have yet provided evidence for the topological network changes in the gray matter. In this research, we aim to use the graph-theoretical approach to investigate the changes of topology in the tinnitus brain using structural MRI data, which could provide insights into the underlying anatomical basis for the neural mechanism in generating phantom sounds.

Methods: We collected 3D MRI images on 46 bilateral tinnitus patients and 46 age and gender-matched healthy controls. Brain networks were constructed with correlation matrices of the cortical thickness and subcortical volumes of 80 cortical/subcortical regions of interests. Global network properties were analyzed using local and global efficiency, clustering coefficient, and small-world coefficient, and regional network properties were evaluated using the betweenness coefficient for hub connectivity, and interregional correlations for edge properties. Between-group differences in cortical thickness and subcortical volumes were assessed using independent sample -tests, and local efficiency, global efficiency, clustering coefficient, sigma, and interregional correlation were compared using non-parametric permutation tests.

Results: Tinnitus was found to have increased global efficiency, local efficiency, and cluster coefficient, indicating generally heightened connectivity of the network. The small-world coefficient remained normal for tinnitus, indicating intact small-worldness. Betweenness centrality analysis showed that hubs in the amygdala and parahippocampus were only found for tinnitus but not controls. In contrast, hubs in the auditory cortex, insula, and thalamus were only found for controls but not tinnitus. Interregional correlation analysis further found in tinnitus enhanced connectivity between the auditory cortex and prefrontal lobe, and decreased connectivity of the insula with anterior cingulate gyrus and parahippocampus.

Conclusion: These findings provided the first morphological evidence of altered topological organization of the brain networks in tinnitus. These alterations suggest that heightened efficiency of the brain network and altered auditory-limbic connection for tinnitus, which could be developed in compensation for the auditory deafferentation, leading to overcompensation and, ultimately, an emotional and cognitive burden.
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http://dx.doi.org/10.3389/fnins.2020.00541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267018PMC
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.
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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.
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http://dx.doi.org/10.1016/j.ajp.2020.102056DOI Listing
August 2020

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

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

Data on diet and growth by giant panda in zoo Negara, Malaysia.

Data Brief 2020 Apr 2;29:105082. Epub 2020 Jan 2.

Institute of Tropical Biodiversity and Sustainable Development, Universiti Malaysia Terengganu, 21030, Kuala Nerus, Malaysia.

In this data article we present the determinations of the diet preference and growth of a pair of the giant panda, (David, 1869) from Zoo Negara Malaysia. Once considered as endangered, the captive giant pandas were given with nine species of local bamboo in separate indoor enclosures. We recorded data between May 25, 2014 and December 31, 2016 and analysed it based on food preference, the pattern toward food consumption and body weights using SPSS v25.0 (IBM, USA). Data on the bamboo preference, daily average bamboo provided and consumed, and factors predicting of body weight per individual are reported in this article. The data highlight correlation between panda growth (kg) to the part of bamboo consumed (kg) and exhibit the pattern of preferred part of food (i.e.: either the leaf, culm or shoots of bamboo variety) for panda consumptions. The food consumption toward the body weight was modelled using logistic regression analysis to help determine the pattern of food consumption and body weight of giant panda in the future and based on regression model 1, only consumed variable is significance to the model.
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http://dx.doi.org/10.1016/j.dib.2019.105082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971374PMC
April 2020

Computer-aided diagnosis of laryngeal cancer via deep learning based on laryngoscopic images.

EBioMedicine 2019 Oct 5;48:92-99. Epub 2019 Oct 5.

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

Objective: To develop a deep convolutional neural network (DCNN) that can automatically detect laryngeal cancer (LCA) in laryngoscopic images.

Methods: A DCNN-based diagnostic system was constructed and trained using 13,721 laryngoscopic images of LCA, precancerous laryngeal lesions (PRELCA), benign laryngeal tumors (BLT) and normal tissues (NORM) from 2 tertiary hospitals in China, including 2293 from 206 LCA subjects, 1807 from 203 PRELCA subjects, 6448 from 774 BLT subjects and 3191 from 633 NORM subjects. An independent test set of 1176 laryngoscopic images from other 3 tertiary hospitals in China, including 132 from 44 LCA subjects, 129 from 43 PRELCA subjects, 504 from 168 BLT subjects and 411 from 137 NORM subjects, was applied to the constructed DCNN to evaluate its performance against experienced endoscopists.

Results: The DCCN achieved a sensitivity of 0.731, a specificity of 0.922, an AUC of 0.922, and the overall accuracy of 0.867 for detecting LCA and PRELCA among all lesions and normal tissues. When compared to human experts in an independent test set, the DCCN' s performance on detection of LCA and PRELCA achieved a sensitivity of 0.720, a specificity of 0.948, an AUC of 0.953, and the overall accuracy of 0.897, which was comparable to that of an experienced human expert with 10-20 years of work experience. Moreover, the overall accuracy of DCNN for detection of LCA was 0.773, which was also comparable to that of an experienced human expert with 10-20 years of work experience and exceeded the experts with less than 10 years of work experience.

Conclusions: The DCNN has high sensitivity and specificity for automated detection of LCA and PRELCA from BLT and NORM in laryngoscopic images. This novel and effective approach facilitates earlier diagnosis of early LCA, resulting in improved clinical outcomes and reducing the burden of endoscopists.
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http://dx.doi.org/10.1016/j.ebiom.2019.08.075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838439PMC
October 2019

Retraction notice to "miR-34a/Bcl-2 signaling pathway contributes to age-related hearing loss by modulating hair cell apoptosis" [Neurosci. Lett. 661 (November) (2017) 51-56].

Neurosci Lett 2019 08 5;707:134290. Epub 2019 Jun 5.

Department of Otolaryngology-HNS, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Rd., Guangzhou, 510120, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, China.

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http://dx.doi.org/10.1016/j.neulet.2019.134290DOI Listing
August 2019

SIRT1 protects cochlear hair cell and delays age-related hearing loss via autophagy.

Neurobiol Aging 2019 08 15;80:127-137. Epub 2019 Apr 15.

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 Science, Xinhua College, Sun Yat-sen University, Guangzhou, China. Electronic address:

Age-related hearing loss (AHL) is typically caused by the irreversible death of hair cells (HCs). Autophagy is a constitutive pathway to strengthen cell survival under normal or stress condition. Our previous work suggested that impaired autophagy played an important role in the development of AHL in C57BL/6 mice, although the underlying mechanism of autophagy in AHL still needs to be investigated. SIRT1 as an important regulator involves in AHL and is also a regulator of autophagy. Thus, we hypothesized that the modulation between SIRT1 and autophagy contribute to HC death and the progressive hearing dysfunction in aging. In the auditory cell line HEI-OC1, SIRT1 modulated autophagosome induction because of SIRT1 deacetylating a core autophagy protein ATG9A. The deacetylation of ATG9A not only affects the autophagosome membrane formation but also acts as a sensor of endoplasmic reticulum (ER) stress inducing autophagy. Moreover, the silencing of SIRT1 facilitated cell death via autophagy inhibition, whereas SIRT1 and autophagy activation reversed the SIRT1 inhibition media cell death. Notably, resveratrol, the first natural agonist of SIRT1, altered the organ of Corti autophagy impairment of the 12-month-old C57BL/6 mice and delayed AHL. The activation of SIRT1 modulates the deacetylation status of ATG9A, which acts as a sensor of ER stress, providing a novel perspective in elucidating the link between ER stress and autophagy in aging. Because SIRT1 activation restores autophagy with reduced HC death and hearing loss, it could be used as a strategy to delay AHL.
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http://dx.doi.org/10.1016/j.neurobiolaging.2019.04.003DOI Listing
August 2019

Modulation of miR-34a/SIRT1 signaling protects cochlear hair cells against oxidative stress and delays age-related hearing loss through coordinated regulation of mitophagy and mitochondrial biogenesis.

Neurobiol Aging 2019 07 27;79:30-42. Epub 2019 Mar 27.

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. Electronic address:

Mitophagy and mitochondrial biogenesis are 2 pathways that regulate mitochondrial content and metabolism maintaining cellular homeostasis. The imbalance between these opposing processes impairs mitochondrial function and is suggested to be the pathophysiological basis of a variety of neurodegenerative diseases and aging. Here we investigated the role of mitophagy and mitochondrial biogenesis in oxidative damage to the cochlear hair cells and age-related hearing loss. In cultured mouse House Ear Institute-Organ of Corti 1 hair cells, oxidative stress activated mitophagy but inhibited mitochondrial biogenesis and impaired mitochondrial function. Pharmacological inhibition of miR-34a/SIRT1 signaling enhanced mitophagy, mitochondrial biogenesis, and attenuated House Ear Institute-Organ of Corti 1 cell death induced by oxidative stress. In the cochlea of C57BL/6 mice, mitophagy and mitochondrial biogenesis were both upregulated during aging. Long-term supplementation with resveratrol, a SIRT1 activator, not only improved the balance between mitophagy and mitochondrial biogenesis but also significantly reduced age-related cochlear hair cell loss, spiral ganglion neuron loss, stria vascularis atrophy, and hearing threshold shifts in C57BL/6 mice. Moreover, SIRT1 overexpression or miR-34a deficiency both attenuated age-related cochlear hair cell loss and hearing loss in C57BL/6 mice. Our findings reveal that imbalance between mitophagy and mitochondrial biogenesis contributes to cochlea hair cell damage caused by oxidative stress and during aging. Coordinated regulation of these 2 processes by miR-34a/SIRT1 signaling might serve as a promising approach for the treatment of age-related cochlear degeneration and hearing loss.
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http://dx.doi.org/10.1016/j.neurobiolaging.2019.03.013DOI Listing
July 2019

Sirtuin 1 and Autophagy Attenuate Cisplatin-Induced Hair Cell Death in the Mouse Cochlea and Zebrafish Lateral Line.

Front Cell Neurosci 2018 14;12:515. Epub 2019 Jan 14.

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

Cisplatin-induced ototoxicity is one of the major adverse effects in cisplatin chemotherapy, and hearing protective approaches are unavailable in clinical practice. Recent work unveiled a critical role of autophagy in cell survival in various types of hearing loss. Since the excessive activation of autophagy can contribute to apoptotic cell death, whether the activation of autophagy increases or decreases the rate of cell death in CDDP ototoxicity is still being debated. In this study, we showed that CDDP induced activation of autophagy in the auditory cell HEI-OC1 at the early stage. We then used rapamycin, an autophagy activator, to increase the autophagy activity, and found that the cell death significantly decreased after CDDP injury. In contrast, treatment with the autophagy inhibitor 3-methyladenine (3-MA) significantly increased cell death. In accordance with results, rapamycin alleviated CDDP-induced death of hair cells in zebrafish lateral line and cochlear hair cells in mice. Notably, we found that CDDP-induced increase of Sirtuin 1 (SIRT1) in the HEI-OC1 cells modulated the autophagy function. The specific SIRT1 activator SRT1720 could successfully protect against CDDP-induced cell loss in HEI-OC1 cells, zebrafish lateral line, and mice cochlea. These findings suggest that SIRT1 and autophagy activation can be suggested as potential therapeutic strategies for the treatment of CDDP-induced ototoxicity.
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http://dx.doi.org/10.3389/fncel.2018.00515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339946PMC
January 2019

Prevalence and factors associated with tinnitus: data from adult residents in Guangdong province, South of China.

Int J Audiol 2018 12 27;57(12):892-899. Epub 2018 Sep 27.

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

There is a lack of national studies on tinnitus in China and data based on a large sample size from multiple areas of the country. A cross-sectional study was carried out in Guangdong province from October 2015 to February 2016. In the study, tinnitus was defined as the presence of ringing, buzzing or other sounds in the ears in the past one year. Fourteen districts in Guangdong Province were selected as the first-level cluster by using the sampling method of probability proportional to size (PPS). Two sub-districts in each first-level cluster were randomly selected as the second-level cluster by PPS method. The sample consisted of 3705 eligible people aged over 18 years old, which were also selected by the PPS methods. The prevalence of tinnitus was 10.4% in Guangdong Province. Age, region, educational background, hearing impairment, ear trauma, otitis media and self-health report were the main risk factors for tinnitus. Tinnitus is a common condition and a large population suffers from tinnitus in Guangdong province, south of China. Greater public awareness and understanding of the associated factors are required for further interventions of prevention and management of tinnitus in China.
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http://dx.doi.org/10.1080/14992027.2018.1506169DOI Listing
December 2018

Deviant Dynamics of Resting State Electroencephalogram Microstate in Patients With Subjective Tinnitus.

Front Behav Neurosci 2018 22;12:122. Epub 2018 Jun 22.

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

Given the importance of central reorganization and tinnitus, we undertook the current study to investigate changes to electroencephalogram (EEG) microstates and their association with the clinical symptoms in tinnitus. High-density (128 channel) EEG was used to explore changes in microstate features in 15 subjects with subjective tinnitus and 17 age-matched controls. Correlations between microstate parameters and subjective tinnitus symptoms were also analyzed. An increased presence of class A microstate and decreased presence of class D microstate were found in coverage and lifespan of microstate parameters in the tinnitus patients. Syntax analysis also demonstrated an aberrant pattern of activity, with reduced transitions from class D to class B in tinnitus patients. Moreover, a significant positive correlation of tinnitus loudness with increased lifespan of microstate class C was found. Significant differences in temporal characteristics and syntax of the EEG microstate classes were found at rest between tinnitus patients and the healthy subjects. Our study indicates that EEG microstates may provide a possible valuable method to study large-scale brain networks, which may in turn be beneficial to investigation of the neurophysiological mechanisms behind tinnitus.
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http://dx.doi.org/10.3389/fnbeh.2018.00122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024160PMC
June 2018

Human-Pathogenic Enterocytozoon bieneusi in Captive Giant Pandas (Ailuropoda melanoleuca) in China.

Sci Rep 2018 04 26;8(1):6590. Epub 2018 Apr 26.

The Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, 611100, China.

Human and animal infections of Enterocytozoon bieneusi (E. bieneusi) have consistently been reported worldwide, garnering public attention; however, the molecular epidemiology of E. bieneusi in the giant panda remains limited. We surveyed captive giant pandas in China for the presence of E. bieneusi by using PCR and sequence analysis of the ribosomal internal transcribed spacer (ITS) revealing a 34.5% positive rate, with seven known genotypes (SC02, EpbC, CHB1, SC01, D, F, and Peru 6) and five novel genotypes (SC04, SC05, SC06, SC07, and SC08) identified. We similarly analyzed water samples, and E. bieneusi was detected in two samples, with genotype SC02 identified. Phylogenetic analysis revealed that CHB1 did not cluster with any recognized group, while the remaining genotypes belonged to group 1. The predominance of zoonotic group 1 genotypes indicates a public health threat that giant pandas could spread E. bieneusi to humans. The identification of E. bieneusi in water samples suggests giant pandas could contribute to water contamination. Effective control measures are therefore needed to minimize the contamination of the water and prevent a human microsporidiosis outbreak.
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http://dx.doi.org/10.1038/s41598-018-25096-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920105PMC
April 2018

Logistic regression analysis of factors influencing the effectiveness of intensive sound masking therapy in patients with tinnitus.

BMJ Open 2017 Nov 15;7(11):e018050. Epub 2017 Nov 15.

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

Objectives: To investigate factors influencing the effectiveness of intensive sound masking therapy on tinnitus using logistic regression analysis.

Design: The study used a retrospective cross-section analysis.

Participants: 102 patients with tinnitus were recruited at the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, China.

Intervention: Intensive sound masking therapy was used as an intervention approach for patients with tinnitus.

Primary And Secondary Outcome Measures: Participants underwent audiological investigations and tinnitus pitch and loudness matching measurements, followed by intensive sound masking therapy. The Tinnitus Handicap Inventory (THI) was used as the outcome measure pre and post treatment. Multivariate logistic regression was performed to investigate the association of demographic and audiological factors with effective therapy.

Results: According to the THI score changes pre and post sound masking intervention, 51 participants were categorised into an effective group, the remaining 51 participants were placed in a non-effective group. Those in the effective group were significantly younger than those in the non-effective group (P=0.012). Significantly more participants had flat audiogram configurations in the effective group (P=0.04). Multivariable logistic regression analysis showed that age (OR=0.96, 95% CI 0.93 to 0.99, P=0.007), audiometric configuration (P=0.027) and THI score pre treatment (OR=1.04, 95% CI 1.02 to 1.07, P<0.001) were significantly associated with therapeutic effectiveness. Further analysis showed that patients with flat audiometric configurations were 5.45 times more likely to respond to intervention than those with high-frequency steeply sloping audiograms (OR=5.45, 95% CI 1.67 to 17.86, P=0.005).

Conclusion: Audiometric configuration, age and THI scores appear to be predictive of the effectiveness of sound masking treatment. Gender, tinnitus characteristics and hearing threshold measures do not seem to be related to treatment effectiveness. A further randomised control study is needed to provide evidence of the effectiveness of prognostic factors in tinnitus interventions.
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http://dx.doi.org/10.1136/bmjopen-2017-018050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695311PMC
November 2017

Population genetics of Enterocytozoon bieneusi in captive giant pandas of China.

Parasit Vectors 2017 Oct 18;10(1):499. Epub 2017 Oct 18.

The Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Sichuan Province, China.

Background: Most studies on Enterocytozoon bieneusi are conducted based on the internal transcribed spacer (ITS) region of the rRNA gene, whereas some have examined E. bieneusi population structures. Currently, the population genetics of this pathogen in giant panda remains unknown. The objective of this study was to determine the E. bieneusi population in captive giant pandas in China.

Results: We examined 69 E. bieneusi-positive specimens from captive giant pandas in China using five loci (ITS, MS1, MS3, MS4 and MS7) to infer E. bieneusi population genetics. For multilocus genotype (MLG) analysis of E. bieneusi-positive isolates, the MS1, MS3, MS4, and MS7 microsatellite and minisatellite loci were amplified and sequenced in 48, 45, 50 and 47 specimens, respectively, generating ten, eight, nine and five types. We successfully amplified 36 specimens and sequenced all five loci, forming 24 MLGs. Multilocus sequence analysis revealed a strong and significant linkage disequilibrium (LD), indicating a clonal population. This result was further supported by measurements of pairwise intergenic LD and a standardized index of association (I ) from allelic profile data. The analysis in STRUCTURE suggested three subpopulations in E. bieneusi, further confirmed using right's fixation index (F ). Subpopulations 1 and 2 exhibited an epidemic structure, whereas subpopulation 3 had a clonal structure.

Conclusions: Our results describe E. bieneusi population genetics in giant pandas for the first time, improving the current understanding E. bieneusi epidemiology in the studied region. These data also benefit future studies exploring potential transmission risks from pandas to other animals, including humans.
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http://dx.doi.org/10.1186/s13071-017-2459-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648467PMC
October 2017

Activation of miR-34a impairs autophagic flux and promotes cochlear cell death via repressing ATG9A: implications for age-related hearing loss.

Cell Death Dis 2017 10 5;8(10):e3079. Epub 2017 Oct 5.

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

Age-related hearing loss is a major unresolved public health problem. We have previously elucidated that the activation of cochlear miR-34a is correlated with age-related hearing loss in C57BL/6 mice. A growing body of evidence points that aberrant autophagy promotes cell death during the development of multiple age-related diseases. The aim of this study was to investigate the role of miR-34a-involved disorder of autophagy in the pathogenesis of age-related hearing loss. Our results showed that miR-34a expression was markedly upregulated in the aging cochlea accompanied with impairment of autophagic flux. In the inner ear HEI-OC1 cell line, miR-34a overexpression resulted in an accumulation of phagophores and impaired autophagosome-lysosome fusion, and led to cell death subsequently. Notably, autophagy-related protein 9A (ATG9A), an autophagy protein, was significantly decreased after miR-34a overexpression. Knockdown of ATG9A inhibited autophagy flux, which is similar to the effects of miR-34a overexpression. Moreover, ursodeoxycholic acid significantly rescued miR-34a-induced HEI-OC1 cell death by restoring autophagy activity. Collectively, these findings increase our understanding of the biological effects of miR-34a in the development of age-related hearing loss and highlight miR-34a as a promising therapeutic target for its treatment.
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http://dx.doi.org/10.1038/cddis.2017.462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680584PMC
October 2017

The protective effect of autophagy on ischemia/reperfusion-induced hearing loss: implications for sudden hearing loss.

Neuroreport 2017 Dec;28(17):1157-1163

Departments of aOtolaryngology bEmergency, Sun Yat-sen Memorial Hospital cInstitute of Hearing and Speech-Language Science dDepartment of Hearing and Speech Science, Xinhua College, Sun Yat-Sen University, Guangzhou, China.

The present study aimed to determine the effects of ischemia/reperfusion (IR) injury for the carotid system on hearing, particularly, the role of autophagy in this process. Sixty-three Sprague-Dawley rats were divided randomly into three groups: sham surgery animals (S), temporary carotid artery occlusion (ischemia) for 30 min (I30), and temporary carotid artery occlusion for 60 min (I60). Auditory brainstem response measurements were performed on mice. After 72 h of reperfusion, the microcirculation was measured in mice after ischemia injury. Immunofluorescence was used to examine the expression of caspase-3 and light chain 3B in the cochlear sections. Temporary carotid artery occlusion lasting for 30 (I30) or 60 min (I60) caused significant hearing loss in the ischemia phase. Following a recovery during the postreperfusion phase, the temporal threshold shift occurred in the I30 group, whereas a permanent threshold shift occurred in the I60 group. Moreover, both microcirculation and autophagy affected hearing 24 h after reperfusion, whereas at 72 h, autophagy works as an intrinsic cellular process that protects against death from the IR effect. These results suggest that the sooner the reperfusion, the better the hearing recovery. In conclusion, autophagy promotes cell survival in the cochlea; however, excessive IR damage counteracts the beneficial potential of autophagy protection and leads to a permanent threshold shift.
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http://dx.doi.org/10.1097/WNR.0000000000000897DOI Listing
December 2017

The miR-34a/Bcl-2 Pathway Contributes to Auditory Cortex Neuron Apoptosis in Age-Related Hearing Loss.

Audiol Neurootol 2017 18;22(2):96-103. Epub 2017 Aug 18.

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

Hypothesis: The miR-34a/Bcl-2 signaling pathway may play a role in the mechanisms related to age-related hearing loss (AHL) in the auditory cortex.

Background: The auditory cortex plays a key role in the recognition and processing of complex sound. It is difficult to explain why patients with AHL have poor speech recognition, so increasing numbers of studies have focused on its central change. Although micro (mi)RNAs in the central nervous system have recently been increasingly reported to be associated with age-related diseases, the molecular mechanisms of AHL in the auditory cortex are not fully understood.

Methods: The auditory brainstem response was used to assess the hearing ability of C57BL/6 mice, and q-PCR, immunohistochemistry, and Western blotting were used to detect the expression levels of miR-34a and Bcl-2 in the mouse auditory cortex. TUNEL and DNA fragmentation were adopted to detect the apoptosis of neurons in the auditory cortex. To verify the relationship of miR-34a and Bcl-2, we transfected an miR-34a mimic or miR-34a inhibitor into primary auditory cortex neurons.

Results: In this study, miR-34a/Bcl-2 signaling was examined in auditory cortex neurons during aging. miR-34a and apoptosis increased in the auditory cortex neurons of C57BL/6 mice with aging, whereas an age-related decrease in Bcl-2 was determined. In the primary neurons of the auditory cortex, miR-34a overexpression inhibited Bcl-2, leading to an increase in apoptosis. Moreover, miR-34a knockdown increased Bcl-2 expression and diminished apoptosis.

Conclusion: Our results support a link between age-related apoptosis in auditory cortex neurons and miR-34a/Bcl-2 signaling, which may serve as a potential mechanism of the expression of AHL in the auditory cortex.
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http://dx.doi.org/10.1159/000454874DOI Listing
August 2018

miR-34a/Bcl-2 signaling pathway contributes to age-related hearing loss by modulating hair cell apoptosis.

Neurosci Lett 2017 Nov 26;661:51-56. Epub 2017 Jul 26.

Department of Otolaryngology-HNS, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen university, 107 Yanjiang West Rd, Guangzhou 510120, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, China.

MicroRNAs, such as miR-34, have been reported to influence age-related diseases. In this study, we explored the role of the miR-34a/Bcl-2 signaling pathway in age-related hearing loss (AHL). Using an AHL mouse model (C57BL/6), we found that the expression of miR-34a in the cochlea increased with age, whereas expression of Bcl-2 decreased. Increasing the amount of a miR-34a mimetic in a mouse auditory cell line (HEI-OC1) inhibited Bcl-2, leading to enhanced apoptosis; in contrast, miR-34a inhibition produced the opposite effect. Our results support a link between age-related cochlear hair cell apoptosis and miR-34a/Bcl-2 signaling. The latter may thus serve as a potential target for AHL therapy.
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http://dx.doi.org/10.1016/j.neulet.2017.07.044DOI Listing
November 2017
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