Objectives:The protection of spiral ganglion neurons (SGNs) is crucial for hearing loss. Exendin-4 has been shown to have neuroprotective effects in several neurological disorders. Therefore, this study aimed to investigate the effect of the glucagon-like protein-1 receptor (GLP-1R) agonist exendin-4 on kanamycin-induced injury in mouse SGNs in vitro.Materials and Methods:In this study, GLP-1R expression in SGNs was verified by immunofluorescence and immunohistochemical staining. In vitro-cultured SGNs and the organ of Corti were exposed to kanamycin with or without exendin-4 treatment. The cell survival rate was measured using the cell counting kit-8 assay, and the damage to auditory nerve fibers (ANF) projecting radially from the SGNs was evaluated using immunofluorescence staining. Reactive oxygen species (ROS) content was determined by flow cytometry, and glutathione peroxidase (GSH-Px) content, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content were determined by spectrophotometry. Protein expression of nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) was detected using western blotting.Results:GLP-1R was expressed in SGNs. Treatment with 1 mM kanamycin for 24 hr induced SGN damage. Exendin-4 (100 nM) had a protective effect against kanamycin-induced SGN cell injury, improved cell survival rate, reduced nerve fiber injury, increased SOD activity and GSH-Px level, and reduced MDA and ROS contents. The Nrf2/HO-1 pathway was activated.Conclusion:Exendin-4 alleviates oxidative damage and exerts neuroprotective effects in kanamycin-induced SGN injury through the Nrf2/HO-1 signaling pathway. Exendin-4 has the potential to prevent or treat hearing loss due to SGN damage.

目的 对一个遗传性非综合征型耳聋家系的临床特征进行分析并鉴定其致聋基因突变,同时在大规模耳聋人群队列中对鉴定出的致病性突变致中国人群耳聋的特征进行分析.方法 完善家系成员的问卷调查、听力学检查、体格检査等临床检查,同时采集血液样本,通过耳聋相关基因的大规模平行测序(MPS)和生物信息学分析进行致病基因鉴定.总结及分析鉴定出的致病性突变在中国耳聋基因研究战略联盟(CDGC)耳聋数据库中的检出情况.结果 在一个早发性极重度感音神经性耳聋家系中鉴定出MYO15A基因NM_016239.4:c.8182C>G(p.Arg2728Gly)/c.9861C>T(p.Gly3287=)复合杂合突变,为该家系耳聋患者的致聋原因.其中MYO15A基因c.9861C>T(p.Gly3287=)同义突变通过改变剪接导致基因功能缺陷,其在中国广西壮族人群中次要等位基因频率为0.2％(3/1438),在其他人群及公共数据库中均未检出.结论 研究确定了MYO15A基因c.9861C>T(p.Gly3287=)在中国非综合征型耳聋患者中的致病性,该突变在中国广西壮族自治区富集明显.通过研究强调了在致病基因鉴定时,高频与同义突变并非过滤的绝对指标,尤其是在某些地区富集格外明显的突变,应格外注意.

BACKGROUND We aimed to explore the correlation between patients' sigmoid sinusoidal tinnitus (SST) and low-frequency sensorineural hearing loss (LFSHL) and illustrate the underlying mechanism. MATERIAL AND METHODS Seven healthy volunteers with normal hearing were subjected to 125-, 250-, and 500-Hz pure sound and different white noise-masking intensities. A retrospective analysis was made on the clinical data and postoperative follow-up data of 59 patients with SST in the First Affiliated Hospital of Chongqing Medical University. The patients' sex, age, chief complaints, affected site, concomitant symptoms, course of disease, pure-tone audiometry (PTA) results, tinnitus discomfort loudness scale results, imaging examination, and complications were collected. RESULTS The results of the simulation experiment showed that the threshold of each frequency segment was higher after noise masking than before masking; the intensity of noise masking was positively correlated with hearing loss, and the changes of the hearing threshold of the 3 frequencies before and after masking were statistically significant (P<0.05). Fifty-nine patients with SST were documented between January 2015 and January 2020. After the operation, their low-frequency hearing was recovered to normal; 11 cases had significantly alleviated tinnitus and 9 cases were cured. CONCLUSIONS SST often causes corresponding pseudo-low-frequency hearing loss due to the noise-masking effect. The center frequency of tinnitus appears not to be 250-Hz or 500-Hz octave frequency of PTA, barring the detection of the pseudo-hearing loss in the audiometry chart of most patients. Surgery positively affects patients with SST, and the pseudo-LFSHL can be completely recovered after the operation as a result of tinnitus elimination.

1 病例资料 患者,女,9岁,汉族.自幼右耳耳廓畸形并外耳道闭锁.5岁时因腹痛就诊于当地医院,腹部超声检查发现右侧肾缺如,患儿发育较同龄人一致,智力正常,言语发育好.患儿为第一胎,同卵双胎之一,孕38周足月生产,出生时体重2.55kg,出生无缺氧史,无明显黄疸等.其孪生姐姐无耳廓畸形及肾缺如.母亲孕5月有感染史,无特殊用药,无糖尿病等代谢疾病史.父亲左足第四、第五趾并趾畸形,简单查体未发现听力障碍及颜面部畸形,未行相关听力学检查.否认耳廓畸形、耳聋及肾缺如家族史.

目的 分析一个遗传性耳聋家系的临床特征及致病基因,总结该致病位点的临床表型及特点,为该家系遗传咨询提供依据.方法 对该家系成员进行详细病史询问、体格检查,完善相关听力学及影像学检查;抽取部分家系成员的外周静脉血,利用已知耳聋基因目标区域高通量测序技术和Sanger测序验证,进行耳聋致病基因的鉴定与分析.结果 该家系临床均表现为极重度非综合征型感音神经性语前聋,经检测发现该家系中先证者及其母亲、弟、妹均携带WFS1基因c.2051C>T(p.A684V)杂合突变,Sanger测序验证该基因突变基因型和听力表型共分离,符合常染色体显性遗传特征.结论 WFS1基因c.2051C>T(p.A684V)杂合突变为该家系耳聋致病原因,进一步验证了c.2051C>T突变可能为WFS1基因在中国人群中的热点突变,不同于欧美人群,该致病突变在中国人群中主要临床表型为语前非综合征型感音神经性聋.

Objective: To analyze the clinical characteristics and identify the causative gene of a case with congenital deafness. Methods: Detailed medical history and clinical examination of a 4-year-old male child with congenital deafness were conducted in the First Affiliated Hospital of Army Military Medical University in June 2016. He was diagnosed with sensorineural deafness. The venous blood of the child and his parents was drawn, and genomic DNA was extracted. Proband's DNA was performed with targeted capture of high-throughput sequencing, then Sanger sequencing was used to verify the suspected mutation and segregation in this pedigree. According to the genetic diagnosis of the proband's deafness, ophthalmic examinations were performed. Genetic prenatal diagnosis was performed when the proband's mother was pregnant again. Results: The patient was detected with p.Trp1466Ter/p.Tyr2042Ter compound heterozygous mutations of MYO7A gene with targeted high-throughput sequencing. The mutation of p.Trp1466Ter was a reported mutation, while p.Tyr2042Ter has not been reported. In addition to congenital deafness, retinitis pigmentosa was also found by ophthalmologic examination, and the patient was clinically diagnosed with Usher syndrome type 1. Amniocentesis and fetal DNA sequencing were performed on the repregnancy fetus of this family at 18 weeks of gestation. The heterozygous mutation of MYO7A gene p.Tyr2042Ter was found, and the other allele was the wild type, indicating that the child will not exhibit clinical manifestations of Usher syndrome type 1. Indeed, the second child passed neonatal hearing screening. Conclusions: The clinical features and genetic variants were delineated in this family with Usher syndrome type 1. The results of the current study have enriched the phenotype and genotype data of the disease and provided a basis for genetic counseling.

Background: There is no effective treatment for idiopathic tinnitus. Both acoustic therapy and acupuncture have been used in the treatment of idiopathic tinnitus, but the clinical efficacy is quite different. For there is no clinical study combining the 2, the purpose of this randomized controlled trial is to evaluate the effectiveness and safety of acoustic therapy combined with acupuncture in the treatment of idiopathic tinnitus. Methods: This is a prospective randomized controlled trial to study the effectiveness and safety of acoustic therapy combined with acupuncture in the treatment of idiopathic tinnitus, and is approved by the clinical research ethics committee of our hospital. The patients are randomly divided into one of 2 treatment options: (A) acoustic therapy combined with acupuncture group and (B) simple acupuncture group. Patients, doctors, nurses, and data collection assistants are blinded to group allocation. Observation indicators include: 1. Tinnitus Disability Scale; 2. Loudness visual analog scale; 3. Adverse reactions. Data is analyzed using the statistical software package SPSS version 25.0 (Chicago, IL). Discussion: This protocol will evaluate the efficacy and safety of acoustic therapy combined with acupuncture in the treatment of idiopathic tinnitus. The results of this experiment will provide clinical evidence for the use of acoustic therapy combined with acupuncture in the treatment of idiopathic tinnitus. Ethics and dissemination: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval was not required. OSF Registration number: DOI 10.17605/OSF.IO/87VFB.

Abstract Background Hearing loss is a common disease globally, and more than 50% of the cases are genetic. Autosomal recessive nonsyndromic hearing loss (ARNSHL) is one of the most common types of hereditary hearing loss. Here, a novel MYO15A missense mutation was identified in a Chinese family with ARNSHL, using targeted genetic sequencing and Sanger sequencing. Case presentation: A 6-year-old girl with congenital nonsyndromic sensorineural deafness was presented from the First Affiliated hospital of Chongqing Medical University, China. We used targeted region sequencing, Sanger sequencing, functional prediction, and three-dimensional protein structure modeling to identify and verify the genes responsible for deafness in the family. Conclusions We found pathogenic compound heterozygous mutations in MYO15A, including a novel missense mutation, c.6353T > C (p.Leu2118Pro). It could provide help not only for genetic counseling but also for further understanding of the functional role of MYO15A mutations.

BackgroundHearing loss is a common disease globally, and more than 50% of the cases are genetic. Autosomal recessive nonsyndromic hearing loss (ARNSHL) is one of the most common types of hereditary hearing loss. Here, a novel MYO15A missense mutation was identified in a Chinese family with ARNSHL, using targeted genetic sequencing and Sanger sequencing.Case presentation:A 6-year-old girl with congenital nonsyndromic sensorineural deafness was presented from the First Affiliated hospital of Chongqing Medical University, China. We used targeted region sequencing, Sanger sequencing, functional prediction, and three-dimensional protein structure modeling to identify and verify the genes responsible for deafness in the family.ConclusionsWe found pathogenic compound heterozygous mutations in MYO15A, including a novel missense mutation, c.6353T > C (p.Leu2118Pro). It could provide help not only for genetic counseling but also for further understanding of the functional role of MYO15A mutations.

Objectives: Sudden sensorineural hearing loss (SSNHL) is an emergency disease with undefined pathogenesis in the otolaryngology department. In our previous study, we found patients with SSNHL had lower serum concentration of Matrix metalloprotease 9 (MMP-9) than healthy controls, and the result was accordant with auto-immune diseases. This study aimed to reveal the correlation between changes in serum MMP-9 concentration following treatment with the outcomes of patients and to provide further evidence that immune disorder was the main pathogenesis of SSNHL. Design, setting, and participants: Fifty-two patients with SSNHL, hospitalized in The First Affiliated Hospital of Chongqing Medical University from March 2019 to August 2019, were enrolled. The serum concentration of MMP-9 was detected by enzyme-linked immunosorbent assay (ELISA). Main outcome measure: The mean concentration of MMP-9 before treatment was compared with the post-treatment concentration by the Mann-Whitney U test. The correlations between favorable outcomes of patients and clinical characteristics were measured with the Chi-squared test and binary multiple logistic regression analysis. Results: In treatment responders, mean serum concentration was elevated from 106.85±41.40ng/ml to 144.03±37.65 ng/ml following treatment (P＜0.001), while in non-responders it decreased from 132.09±59.21 ng/ml to 106.82±49.93 ng/ml (P=0.142). Changes in MMP-9 concentration was the only factor associated with favorable outcomes (P=0.008, OR=5.13, 95% CI: 1.53-17.28). Conclusions: Elevated MMP-9 concentration is a potential prognosis biomarker in patients with SSNHL. These findings are in line with auto-immune diseases and indicate immune disorder is mainly pathogenesis in SSNHL. Keywords Sudden sensorineural hearing loss; Matrix metalloprotease 9; Immune disorder; prognosis; Enzyme-linked immunosorbent assay

目的 分析老年性突发性耳聋的流行病学特征及其预后关系,为提高疗效提供临床思路.方法 回顾性分析2015年1月～2018年12月重庆医科大学附属第一医院突发性聋患者中≥65岁的临床病例229例(241耳),描述其流行病学特征,并探讨其与疗效的相关性.结果 老年突发性聋占所有突发性聋患者的10.7％.229例老年突发性聋患者中,初诊时间≤14 d的172例、＞14 d的57例;听力下降前后出现耳鸣者189例,以持续性嗡嗡声为主;有耳闷者85例;有眩晕或者头晕者80例;无明显诱因者占91.3％、有感冒病史者占4.4％、有劳累、压力大、情绪波动因素者占3％、其他因素占1.3％;伴高血压病者121例;伴糖尿病者65例;伴冠心病者42例;伴高血压、糖尿病、冠心病任一基础疾病者146例,占63.8％.241例患耳中,按耳聋程度分级:轻度27耳、中度44耳、重度67耳、极重度103耳;按听力曲线类型分类:低频下降型6耳、高频下降型24耳、平坦型111耳和全聋型100耳.老年突发性聋患者的性别、是否伴耳鸣、耳闷、头晕或眩晕对临床总有效率的影响不具有统计学意义(P＞0.05);不同初诊时间、不同听力曲线类型与患者的临床总有效率比较,差异有统计学意义(P＜0.05),即初诊时间越长,疗效越差.高频听力损失患者的疗效较全聋型差.结论 老年突发性聋患者虽多伴有基础疾病,但是否伴基础疾病与疗效无明显相关性,在就诊及时的情况下,临床总有效率较高,且高频听力损失患者的预后较全聋型差.

音调性耳鸣是一种耳鸣频率可以被匹配出来的主观性耳鸣.目前大部分主观性耳鸣尚无有效的治疗方法,但针对音调性耳鸣的一种新的治疗方法——个性化切迹音乐治疗被提出,其疗效值得期待.本文就个性化切迹音乐治疗音调性耳鸣的原理、方法、临床疗效等进行综述,探讨其存在的问题及临床应用前景.