Umbilical cord-derived mesenchymal stromal cells (UCMSCs) have potential applications in regenerative medicine. UCMSCs have been demonstrated to repair tissue damage in many inflammatory and degenerative diseases. We have previously shown that UCMSC exosomes reduce nerve injury-induced pain in rats. In this study, we characterized UCMSC exosomes using RNA sequencing and proteomic analyses and investigated their protective effects on cisplatin-induced hearing loss in mice. Two independent experiments were designed to investigate the protective effects on cisplatin-induced hearing loss in mice: (i) chronic intraperitoneal cisplatin administration (4 mg/kg) once per day for 5 consecutive days and intraperitoneal UCMSC exosome (1.2 μg/μL) injection at the same time point; and (ii) UCMSC exosome (1.2 μg/μL) injection through a round window niche 3 days after chronic cisplatin administration. Our data suggest that UCMSC exosomes exert protective effects in vivo. The post-traumatic administration of UCMSC exosomes significantly improved hearing loss and rescued the loss of cochlear hair cells in mice receiving chronic cisplatin injection. Neuropathological gene panel analyses further revealed the UCMSC exosomes treatment led to beneficial changes in the expression levels of many genes in the cochlear tissues of cisplatin-injected mice. In conclusion, UCMSC exosomes exerted protective effects in treating ototoxicity-induced hearing loss by promoting tissue remodeling and repair.

Incomplete partition type III (IP-III) is a relatively rare inner ear malformation that has been associated with a POU3F4 gene mutation. The IP-III anomaly is mainly characterized by incomplete separation of the modiolus of the cochlea from the internal auditory canal. We describe a 71-year-old woman with profound sensorineural hearing loss diagnosed with an IP-III of the cochlea that underwent cochlear implantation. Via targeted sequencing with a non-syndromic gene panel, we identified a heterozygous c.934G > C p. (Ala31Pro) pathogenic variant in the POU3F4 gene that has not been reported previously. IP-III of the cochlea is challenging for cochlear implant surgery for two main reasons: liquor cerebrospinalis gusher and electrode misplacement. Surgically, it may be better to opt for a shorter array because it is less likely for misplacement with the electrode in a false route. Secondly, the surgeon has to consider the insertion angles of cochlear access very strictly to avoid misplacement along the inner ear canal. Genetic results in well describes genotype-phenotype correlations are a strong clinical tool and as in this case guided surgical planning and robotic execution.

UNASSIGNED: No cochlear otosclerosis in infants with congenital bilateral SNHL has been reported.
UNASSIGNED: We report an infant male with bilateral cochlear otosclerosis, suggesting that cochlear otosclerosis may be a congenital disease and to further analyze the etiology of and genetic expression in congenital bilateral cochlear otosclerosis. We also describe the clinical characteristics and experience of patients with bilateral cochlear otosclerosis treated with cochlear implants (CIs).
UNASSIGNED: Seven patients, including an infant, who were diagnosed with cochlear otosclerosis underwent CI surgery. Their medical records, audiological and radiological results, surgical procedures, and CI outcomes were collected and reviewed.
UNASSIGNED: The median age at hearing loss was 38 years, ranging from 0 to 47 years. The child had bilateral hearing loss at birth and received a CI at 1 year of age. He also had growth retardation and was diagnosed with 3q+/3p- syndrome. All patients (8 ears) had better postoperative auditory performance than that preoperatively.
UNASSIGNED: Although cochlear otosclerosis often starts at middle age and progresses slowly, it may be a congenital disease that is related to chromosome abnormality. This disease presents with SNHL or MHL, and treatment with a CI is beneficial.

Bilateral sensorineural deafness and unilateral cochlear ossification have rarely been described in patients with chronic myeloid leukemia (CML). A 21-year-old man presented to a hospital with right-sided sudden hearing loss and tinnitus. He was diagnosed with CML. Five days later, sudden hearing loss appeared in the other ear. Abnormality of the right-sided inner ear structure was revealed by preoperative magnetic resonance imaging; honeycomb-like cochlear ossification was observed during cochlear implant surgery in the right ear. The patient\'s auditory performance exhibited significant improvement after bilateral cochlear implantation in our hospital. Hematological disorders must be considered in patients with sensorineural hearing loss. Cochlear implantation is feasible in patients with CML who exhibit sensorineural deafness, but cochlear ossification should be carefully evaluated by means of preoperative imaging examinations.

Objective: To investigate the characteristics of cochleo-vestibular dysfunction in patients with profound sudden deafness, and the prognosis of inner ear hemorrhage. Methods: From January 2017 to December 2018, 92 inpatients with profound sudden sensorineural hearing loss were enrolled in the Department of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University. Our studied patients included 47 males and 45 females, aged 20-78 (39.3±6.1) years. According to the results of inner ear magnetic resonance imaging (MRI), the patients were divided into two groups: inner ear hemorrhage group and non-inner ear hemorrhage group. The clinical features, vestibular tests and audiological examination results during follow up were compared between the two groups. SPSS 22.0 software was used for statistical analysis. Results: The inner ear hemorrhage group consisted of 32 cases (34.8%, 32/92), all of whom complained of vertigo (100%, 32/32). Simultaneous vertigo attack and hearing loss occurred in 78.1% of this group (24/32). Neither semicircular canals function, nor cervical vestibular evoked myogenic potential (c-VEMP), nor ocular vestibular evoked myogenic potential (o-VEMP) in the affected side was normal (100%, 32/32). The rates of benign paroxysmal positional vertigo (BPPV) and disequilibrium were 37.5% (12/32) and 25.0% (8/32) respectively. Hearing improved in 28.1% (9/32) two weeks after treatment, and became stable at one month\'s follow up. In 60 cases without inner ear hemorrhage, 58.3% of them (35/60) experienced vertigo, which occurred simultaneously with hearing loss in 21 patients (60%, 21/35). The abnormal rates of semicircular canals function, c-VEMP and o-VEMP were 71.6% (43/60), 78.3% (47/60) and 66.7% (40/60), respectively. The incidence of BPPV was 16.7% (10/60) and 8.3% (5/60) in cases with disequilibrium. Hearing improved in 58.3% (35/60) two week after treatment, and became stable at three months\' follow up. Significant difference was found in either vertigo rate, or simultaneous vertigo/hearing loss rate, or abnormal c-VEMP/o-VEMP rates, or accompanying BPPV, or disequilibrium rates between the two groups (P<0.05 each). Moreover, we observed better hearing recovery in non-inner ear hemorrhage group in the two weeks, one month, three months and six months\' follow up, when compared with those in inner ear hemorrhage groups (P<0.05 each). Conclusions: Inner ear hemorrhage is associated with more severe cochlea-vestibular lesion and poorer prognosis, in comparison to the non-inner ear hemorrhage,in patients with profound sudden sensorineural hearing loss.
目的： 观察极重度突发性聋患者耳蜗及前庭功能变化特点，探讨内耳出血对患者预后的影响。 方法： 2017年1月至2018年12月在中山大学附属第一医院耳鼻咽喉科住院治疗的极重度突聋患者92例，其中男47例、女45例，年龄20~78岁，平均（39.3±6.1）岁。根据内耳磁共振成像（MRI）检查结果将其分成内耳出血组和非内耳出血组，比较两组患者临床特征、前庭功能检查及听力学检查随访结果。应用SPSS 22.0软件进行统计学处理。 结果： 92例患者中，内耳出血组32例（34.8%，32/92），其眩晕发生率为100%（32/32），眩晕与听力下降同时出现的比率为78.1%（24/32），患侧半规管功能、颈源性前庭诱发肌源性电位（cervical vestibular evoked myogenic potentials，c-VEMP）和眼源性前庭诱发肌源性电位（ocular vestibular evoked myogenic potentials，o-VEMP）异常率均为100%（32/32），良性阵发性位置性眩晕（BPPV）的发生率为37.5%（12/32），失平衡发生率为25.0%（8/32）；治疗后14 d听力改善有效率为28.1%（9/32），治疗后30 d听力变化稳定。非内耳出血组60例（65.2%，60/92），眩晕发生率为58.3%（35/60），眩晕与听力下降同时出现的比率为60%（21/35），患侧半规管功能、c-VEMP、o-VEMP的异常率分别为71.6%（43/60）、78.3%（47/60）和66.7%（40/60），BPPV发生率为16.7%（10/60），失平衡发生率为8.3%（5/60）；治疗后14 d有效率为58.3%（35/60），治疗后90 d听力变化稳定。两组患者在眩晕发生率、眩晕与听力下降同时出现的比率，患侧半规管功能、c-VEMP及o-VEMP异常率、BPPV发生率、失平衡发生率，治疗后14 d有效率、治疗后14 d、30 d、90 d、180 d平均听阈，差异均有统计学意义，P值均<0.05。 结论： 内耳出血所致极重度突聋患者与非内耳出血极重度突聋患者相比，前庭和耳蜗功能损伤重，恢复效果差。.

Objective: The aging model of guinea pigs induced by D-galactose was set up to investigate the changes of BK(Ca) expression and function on cochlear pericytes and their relationship with age-related hearing loss. Methods: Thirty healthy 8-week-old guinea pigs were randomly divided into three groups, with 10 in each group: D-galactose aging model group, subcutaneous injection of D-galactose (500 mg/kg) daily for 6 weeks; saline control group, the same amount of saline was injected into the neck of the aging model group for 6 weeks; the blank control group, no treatment was performed. The threshold of auditory brainstem response (ABR) was detected. The content of BK(Ca) in the perivascular cells of the guinea pig cochlear cells was detected by immunofluorescence technique. The changes of peripheral current density and BK(Ca) current were detected by patch clamp technique. The data were analyzed by GraphPad Prism software. Results: Compared with the saline group and the control group, the ABR threshold and the amplitude of the wave I were significantly decreased in the aging model group, and the difference was statistically significant (P<0.01). Compared with the control group, the expression of BK(Ca) in the vascular pericytes of guinea pigs in the aging model group was significantly reduced (1.00±0.08 vs 0.27±0.03,the difference was statistically significant P<0.01), and the cell current density and BK(Ca) net current value were also significantly reduced with statistically significant (P<0.01). Conclusions: D-galactose can successfully induce guinea pig aging model, in which BK(Ca) expression decreases and net current value decreases in pericytes of cochlear striavascularis, and changes in BK(Ca) expression and function may be related to age-related hearing loss.
目的： 探讨豚鼠D-半乳糖衰老模型耳蜗血管纹周细胞大电导钙激活钾离子通道（large conductance calcium-activated potassium channels，BK(Ca)）的表达和功能变化及其与年龄相关性听力损失的关系。 方法： 30只8周龄健康豚鼠按完全随机法分为三组，每组10只：D-半乳糖衰老模型组，每天颈部皮下注射D-半乳糖（500 mg/kg），连续6周；生理盐水对照组：每天颈部皮下注射与衰老模型组同体积生理盐水，连续6周；空白对照组：不做任何处理。造模结束后检测各组豚鼠听性脑干反应（auditory brainstem response, ABR）阈值；通过免疫荧光技术检测各组豚鼠耳蜗血管纹周细胞上BK(Ca)的表达情况；利用膜片钳技术检测周细胞电流密度及BK(Ca)电流的变化情况。数据采用GraphPad Prism软件进行统计分析。 结果： 与生理盐水组和对照组相比，衰老模型组豚鼠ABR阈值升高且Ⅰ波振幅明显降低，差异均具有统计学意义（P值均<0.01)。与对照组相比，衰老模型组豚鼠血管纹周细胞上BK(Ca)的表达明显减少（1.00±0.08 vs 0.27±0.03,差异有统计学意义，P<0.01)，周细胞电流密度和BK(Ca)净电流值亦明显减小（差异均具有统计学意义，P值均<0.01)。 结论： D-半乳糖可成功诱导豚鼠衰老模型，其耳蜗血管纹周细胞上BK(Ca)表达下降、净电流值减小，BK(Ca)表达和功能的变化可能与年龄相关性听力损失有关。.

Copy number variation is an extensively studied cause of hereditary diseases. However, its role in hereditary sensorineural deafness has been rarely reported. Using targeted sequencing, SNP array and qPCR, we found a novel 622.2 kb duplication of 6q14.1 in a patient with congenital sensorineural hearing loss and cochlear aplasia. The duplication included MYO6 and IMPG1 genes. FISH study confirmed that this duplication was inherited from the patient\'s mosaic mother.

The TLR-4/NF-κB signaling pathway is involved in innate immunity and inflammation induced by trauma. The present study aimed to investigate possible TLR-4/NF-κB signaling pathway activation in the cochlea associated with acoustic trauma that might induce cochlear inflammation. A total of 72 rats were exposed to white noise at 120 dB SPL for 8 h per day repeated over 2 successive days. Auditory brainstem responses (ABR) were measured in animals before noise exposure and 0 d (PE0), 1 d (PE1), 3 d (PE3), 7 d (PE7), and 14 d (PE14) after noise exposure. At each defined time point, animals were sacrificed, and cochleae were collected to evaluate the expression levels of TLR4, MyD88, cytoplasmic NF-κB p65, IκBα, TNF-α, and IL-1β using western blotting and NF-κB p65 transcriptional activity using an NF-κB p65 Transcription Factor Assay Kit. Cochlear localizations of TLR-4, TNF-α and IL-1β were analyzed using immunohistochemistry in paraffin-embedded slices. The nuclear translocation of NF-κB p65 was evaluated using immunofluorescence staining in paraffin-embedded slices. DNA fragmentation was measured with a TUNEL assay in paraffin-embedded slices. We found a stable permanent threshold shift after noise exposure. After noise exposure, expression levels of TLR-4, MyD88, IκBα, TNF-α, and IL-1β were significantly upregulated (PE3); DNA binding activity of NF-κB p65 was also significantly enhanced (PE3), while the cytoplasmic NF-κB p65 levels were unchanged. TLR-4, TNF-α, and IL-1β immunostaining intensities were substantially enhanced in spiral ganglion cells and spiral ligament fibrocytes after noise exposure (PE3). In conclusion, the results of this study indicate that the TLR-4/NF-κB signaling pathway is activated in noise-exposed cochleae and that it participates in noise-induced cochlear inflammation.

Waardenburg syndrome (WS) is the consequence of an inherited autosomal dominant mutation which causes the early degeneration of intermediate cells of cochlear stria vascularis (SV) and profound hearing loss. Patients with WS may also experience primary vestibular symptoms. Most of the current WS studies did not discuss the relationship between WS and abnormal vestibular function. Our study found that a spontaneous mutant pig showed profound hearing loss and depigmentation. MITF-M, a common gene mutation causes type WS which affect the development of the intermediate cell of SV, was then identified for animal modeling.
In this study, the degeneration of vestibular hair cells was found in pigs with MITF-M. The morphology of hair cells in vestibular organs of pigs was examined using electron microscopy from embryonic day E70 to postnatal two weeks. Significant hair cell loss in the mutant saccule was found in this study through E95 to P14. Conversely, there was no hair cell loss in either utricle or semi-circular canals.
Our study suggested that MITF-M gene mutation only affects hair cells of the saccule, but has no effect on other vestibular organs. The study also indicated that the survival of cochlear and saccular hair cells was dependent on the potassium release from the cochlear SV, but hair cells of the utricle and semi-circular canals were independent on SV.

OBJECTIVE: The timing of CI for postmeningitic deafness is controversial and differential outcomes have been reported. To review and share our surgical and auditory outcomes.
METHODS: 17 patients with ossified cochleas who received CI were enrolled. Clinical data including the cause of cochlear ossification, preoperative examination, onset of deafness, age at implantation, surgical findings, and relevant auditory outcomes was analysed.
RESULTS: Cochlear ossification was observed in 53% of patients with HRCT, whereas the corresponding value for MRI was 59%. Patients in both stage I and II received complete insertion of the electrode array, however, stage III patients only received partial insertion. 1 patient in stage II received bilateral CI. Hearing tests showed increased average hearing threshold for stage III patients than those in stage I and II (P < 0.05). CAP scores were much lower for stage III patients than those in stage I and II (P < 0.05). Postlingual deafness patients showed higher SIR scores than prelingual deafness children (P < 0.05).
CONCLUSIONS: HRCT and MRI have comparable value in predicting the occurrence of ossification in cochleas. We recommend fast surgical intervention in the patients with bilateral profound postmeningitic deafness. If possible, bilateral cochlear implantation is recommended.