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Objective To study the characteristics of voltage gated potassium channel (Kv) subunit expression in rat spiral ganglion neurons(SGNs) after hypoxia. Methods SGNs were isolated and cultured in SD rats on 3-5 d after decapitated. The rats were divided into the control group and experiment group (anoxic treatment for 24 h),and then total RNA was extracted. The real-time fluorescence quantitative polymerase chain reaction (qPCR) was used to detect the mRNA expression characteristics of caspase-3,Kv1. 1, Kv1. 2 and Kv3. 1α subunits. Results After anoxic treatment for 24 h,caspase-3 mRNA expression in rat spiral ganglion neurons was increased; meanwhile the expressions of Kv1.1, Kv1.2 and Kv3.1α mRNA in these neurons were also up-regulated, compared with the control group, which were increased by 3. 71,3. 59,4. 33 times respectively. Conclusion Severe hypoxia can significantly up-regulate the expression of voltage gated potassium channel Kv mRNA in primary auditory ganglion neurons, which may be one of the mechanism of anoxia affecting hearing. [ABSTRACT FROM AUTHOR]

Objective: To analyze the application of direct cochlear nerve monitoring technology-cochlear nerve action potential (CNAP) monitoring in resection of vestibular schwannoma (VS) and to compare with which in microvascular decompression (MVD) of hemifacial spasm (HFS), in order to provide reference for identification of the cochlear nerve during VS resection surgery and predicting postoperative hearing preservation. Methods: From June 2018 to March 2022, patients with facial spasm and vestibular schwannoma who underwent retrosigmoid approach surgery at the Chinese PLA General Hospital were collected. Before surgery, there were a total of 11 HFS patients and 30 VS patients. Before surgery, the former had hearing level of class A(AAO-HNS), while the latter had serviceable hearing (AAO-HNS class A-B), with a maximum tumor diameter of≤20 mm. CNAP combined with Auditory Brainstem Response (ABR) monitoring was performed during surgery. SPSS 23.0 software was used to analyze the differences of ABR and CNAP parameters between the two groups. Results: The preoperative ABR test in the VS group showed that the latency of wave V and I-V interval were significantly prolonged compared to the HFS group ( t =8.36, P <0.001; t =4.61, P <0.001).In VS group, all tumors were totally removed with preserved facial nerve function (House-Brackmann grade Ⅰ-Ⅱ). The serviceable hearing preservation rate was 63.3%. In the HFS group, the initial CNAP waveforms were triphasic and biphasic, with N1 wave latency of (4.32±0.37) ms and amplitude of 25.20 [15.63, 35.40]μV. The distribution of CNAP waveforms before tumor resection in the VS group was the same as that in the HFS group, and which in the hearing preservation group after surgery was also the same. Compared with the HFS group, the latency of N1 wave was prolonged ( t =2.670, P =0.011; t =4.584, P <0.001), and the amplitude of N1 wavein the VS group before tumor resection was lower ( Z =-3.001, P =0.003). The amplitude of N1 wave in the hearing preservation group after surgery was 20.20 [6.23, 40.90] μV,which was significantly higher than that before tumor resection ( Z =-2.133, P =0.033), but there was no statistically significant difference compared to the HFS group ( Z =-0.495, P =0.621). Conclusions: The reference range of CNAP in normal hearing population can be preliminarily obtained by the analysis of CNAP in MVD surgery. The latency of N1 wave in VS patients is prolonged and the amplitude of N1 wave is decreased due to tumor compression. The CNAP waveform combined with the change of N1 wave amplitude can provide reference for intraoperative mapping of the cochlear nerve and prediction of postoperative hearing preservation.

Objective To investigate the role of β-catenin, the core protein of canonical Wnt/β-catenin signaling, in the inner-ear development and polarity regulation. Methods β-catenin was conditionally deleted from precursor cells of inner-ear sensory epithelium (Sox2-positive cells) in embryonic mice. Morphological changes of the inner ear were observed. Immunofluorescence staining was performed to basilar membranes, utricles and saccules to observe the hair-cell changes in arrangement and polarity. Results Compared with the control group, knock-out of β-catenin in Sox2-positive cells resulted in smaller otic vesicles, cochleas and vestibules, and fewer hair cells(HCs) in vestibular sensory epithelium (P<0.01). Stereocilium showed misorientation and kinocillia had a change in location and quantity in the cochlea. Scattered misorented HCs were also observed in the vestibule. Conclusionsβ-catenin is crucial for the development of inner ear and polarity manipulation of HCs in mice. The canonical Wnt/β-catenin signaling may be involved in the regulation of cochlea extension and planar cell polarity (PCP) of inner ear, which is known to be controlled by non-canonical Wnt/PCP signaling. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impacts of cochlear implant (CI) electrode on cochlear function in a guinea pig model, and provide reliable animal model for cochlear implant research. Methods: Eight guinea pigs with normal hearing were selected, four guinea pigs were administered with a single dose of kanamycin followed by furosemide to establish deaf group, while the other four were administered with saline as control group. After ABR and DPOAE tests, the eight animals underwent electrode-insertion surgery on their left ears. Results: In deaf group, ABR threshold shifts in the fiequency range 4, 8, 16, and 32 kHz on the operative sides were gradually decreased with time, and the differences among the 24 h, 48 h and 72 h were statistically insignificant (P ＞ 0.05). In control group, ABR threshold shifts in these frequency range on the operative side were gradually decreased with time as well, and the differences among the 24 h, 48 h and 72 h were statistically significant only in 32 kHz (P ＜ 0.05). In deaf group, the DPOAE could not be elicited before and after the surgery; in control group, the DPOAE could be elicited before the surgery, but absent after the surgery. 72 h after the surgery, the electrodes were surrounded with tissue and fixed well, and no inflammatory response was observed. Conclusion: A guinea pig cochlear electrode implantation model with kanamycin-induced deafness was successfully established, which could provide experimental basis for the study of temporal bone pathological changes after cochlear implantation. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the responsiveness of cochlear nerve to electrical stimulation in patients with cochlear nerve deficiency(CND), to compare their results with those measured in implanted children with normal-sized cochlear nerves, and to investigate the characteristics of the cochlear nerve injury of children with CND. Methods: Participants were children who underwent cochlear implantation at Shandong Provincial ENT Hospital from January 2012 to January 2020, including CND group and control group. The CND group included 51 subjects (male:20; female: 31) who were diagnosed with CND and had normal cochlea. For the CND group, four children had been bilaterally implanted, the mean implantation age was (2.7±1.5) years old. The control group included 21 subjects (male:10; femal:11) who had normal-sized cochlear nerve and normal cochlea. For the control group, all children had been unilaterally implanted except one, and the mean implantation age was (3.0±1.9)years old. Three subjects in the CND group used CI422 electrode arrays, and all the other subjects used CI24RECA/CI512 electrode arrays. The electrically evoked compound action potentials (ECAP) had been tried to record for each electrode using Custom Sound EP software (v. 4.3, Cochlear Ltd.) at least six months post first activation. Furthermore, ECAP amplitude growth functions (AGF) were measured at multiple electrode locations across the electrode array. Generalized linear mixed effect models with the subject group and electrode location as the fixed effects and subjects as the random effect were used to compare results of ECAP measurements. Results: In the control group, ECAP could been recorded at all electrodes (100%), but it could only be recorded in 71% (859/1 210) electrodes in the CND group. Additionally, the percentage of electrodes with measurable ECAP decreased from electrode 1 to electrode 22 in the CND group. Compared to the control group, the ECAP thresholds significantly increased, the ECAP amplitudes and AGF slopes significantly decreased, and the ECAP latency significantly increased in the CND group ( P <0.01). GLMM showed that the stimulating site had a significant effect on the ECAP threshold, maximum amplitude, and AGF slope ( P <0.01), but had no significant effect on the ECAP latency ( P >0.05) in the CND group. However, the stimulating site had no significant effects on the ECAP measurements in the control group. Furthermore, the functional status of cochlear nerve varied greatly among CND group. From electrode 1 to electrode 22, the ECAP thresholds gradually increased, the ECAP maximum amplitudes and AGF slopes gradually decreased in the CND group. Conclusion: Compared with patients with normal-sized cochlear nerve, not only the number of residual spinal ganglion neurons reduce,but also the function of spinal ganglion neurons damages in CND patients. The degree of cochlea nerve deterioration varies greatly among CND patients. Generally, the deterioration of cochlear nerve tends to increase from the basal to the apical site of the cochlea.

Objective: To report the experience of using CT-guided cochlear implant surgery in difficult cases such as severe inner ear deformities and anatomical abnormalities, and to discuss the application value of intraoperative CT-assisted localization in difficult cases of cochlear implant surgery. Methods: Retrospectively analyzed the clinical data of 23 cases of difficult cochlear implant surgery cases completed by our team with the assistance of intraoperative CT, and collected their medical data, including preoperative imaging manifestations, surgical conditions, and intraoperative imaging images for evaluation. Results: During the study period, 23 difficult cases（27 ears） underwent cochlear implantation under the guidance of intraoperative CT, and 4 cases were bilaterally implanted. Including 6 cases of incomplete segmentation type Ⅰ（IP-Ⅰ）, 1 case of incomplete segmentation type Ⅱ（IP-Ⅱ）, 10 cases of incomplete segmentation type Ⅲ（IP-Ⅲ）, 3 cases of common cavity deformity（CC） and 3 cases of cochlear ossification after meningitis. Facial nerve anatomy was abnormal in 9 cases, cerebrospinal fluid "blowout" was serious in 14 cases, electrode position was abnormal in 3 cases requiring intraoperative adjustment of electrode position, anatomical difficulties required intraoperative CT to assist in finding anatomical landmarks in 2 cases, and electrodes were not fully implanted in 3 cases. Conclusion: When faced with difficult cases with challenging and complex temporal bone anatomy, intraoperative CT can accurately evaluate the electrode position and provide intraoperative anatomical details, allowing immediate adjustment of the electrode position if necessary, providing safety guarantee for difficult cases of cochlear implant surgery and ensure accurate implantation of electrodes., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Electrode array misplacement is a rare complication of cochlear implant. This article reports an 11-year-old boy who was mistakenly implanted the cochlear electrode array into the superior semicircular canal during the initial cochlear implant. After the diagnosis was confirmed, he underwent a second cochlear implant and the electrode array were successfully implanted into the cochlea. This article conducted a systematic review of the literature on electrode array misplacement, and the causes of electrode array misplacement were analyzed from different implantation position., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To investigate the application of cochlear nerve action potential (CNAP) monitoring in the resection of vestibular schwannoma, especially evaluating its significance for hearing preservation. Methods: From April 2018 to December 2021, 54 patients with vestibular schwannoma who underwent resection via retrosigmoid approach were collected in Chinese PLA General Hospital. Before surgery, all patients had effective hearing (AAO-HNS grade C or above). Brainstem auditory evoked potential (BAEP) combined with CNAP monitoring was performed during surgery. The CNAP monitoring was combined with continuous monitoring and cochlear nerve mapping. And patients were divided into hearing preservation group and non-preserved group according to postoperative AAO-HNS grade. SPSS 23.0 software was used to analyze the differences of CNAP and BEAP parameters between the two groups. Results: A total of 54 patients completed intraoperative monitoring and data collection, including 25 males (46.3%) and 29 females (53.7%), aged 27-71 years with an average age of 46.2 years. The maximum tumor diameter were (18.1±5.9) mm (range 10-34 mm). All tumors were totally removed with preserved facial nerve function (House-Brackmann grade I-II). The hearing preservation rate of 54 patients was 51.9% (28/54). During surgery, the V wave extraction rate of BAEP waveform was 85.2% (46/54) before tumor resection, 71.4% (20/28) in the hearing preservation group after tumor resection, and disappeared in the hearing preservation group (0/26). CNAP waveform was elicited in 54 patients during operation. Differences were found in the distribution of CNAP waveforms after tumor resection. The waveforms of the hearing-preserving group were triphasic and biphasic, while those in the non-preserving group were low-level and positive. For hearing preservation group, the amplitude of N1 wave after tumor resection was significantly higher than that before tumor resection[14.45(7.54, 33.85)μV vs 9.13(4.88, 23.35)μV, P =0.022]; However, for the non-preserved group, the amplitude of N1 wave after tumor resection was significantly lower than that before tumor resection [3.07(1.96, 4.60)μV vs 6.55(4.54, 9.71)μV, P =0.007]; After tumor resection, the amplitude was significantly higher than that of the unreserved group [14.45(7.54, 33.85)μV vs 3.07(1.96, 4.60)μV, P <0.001]. Conclusions: BAEP combined with CNAP monitoring is conducive to intraoperative hearing protection, and the application of cochlear nerve mapping can prompt the surgeon to avoid nerve injury. The waveform and N1 amplitude of CNAP after tumor resection have a certain value in predicting postoperative hearing preservation status.

Objective: To summarize the clinical characteristics of children undergoing surgery of cochlear reimplantation, focus on various problems and management in cochlear reimplantation, in order to avoid related problems in surgery of cochlear reimplantation and the initial implantation. Methods: A total of 32 children who underwent cochlear reimplantation in Peking University Third Hospital from July 2018 to July 2022 were retrospectively analyzed, and the duration from the initial implantation was from 1 year to 8 years. The cochlear implant mapping was performed 4 weeks after the operation, and the auditory performance was evaluated. Results: Special intraoperative issues included 32 cases with bone and soft tissue hyperplasia at various sites（2 cases with obvious bone hyperplasia in cochlear window, 1 case with obvious bone hyperplasia in subperiosteal tunnel of wire）, 5 cases with bone defects in important structures（including the posterior wall of the external auditory canal, the facial nerve canal, and the subperiosteal pocker of the receiver-stimulator）, 1 case with cholesteatoma, 4 cases with other lesions or foreign bodies, 4 cases with abnormal position of the electrodes（migration or reversal）. All operations were successfully completed without complications. Postoperative recoveries were smooth. Conclusion: In the initial cochlear implantation, attention should be paid to retain residual hearing as much as possible, fully consider the possibility of postoperative bone hyperplasia, avoid large amounts of non-absorbable adhesive materials, avoid bone defects in important structures（such as facial nerve canal or posterior wall of the external auditory canal）, pay attention to the depth and orientation of electrode implantation. The possibility of "hidden injury" mentioned above should be fully considered in surgery of cochlear reimplantation to avoid new injury or complication., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective To observe the expression of protein phosphates 1 nuclear targeting subunit (PNUTS) in the cochlea of D- galactose induced ageing mice. Methods Twenty Kunming mice, six weeks old, cleaning degree, were randomly divided into two groups, control group and D-galactose group, ten mice for each group. Mice in D-galactose group were administrated with D-galactose at a dose of 800 mg/(kg·d) by subcutaneous injection for eight weeks. Mice in control group were injected with the same volume of saline. After eight weeks, auditory brainstem responses (ABR) were collected to test the hearing thresholds of mice. Western blot assay was used to detect expressions of PNUTS and p53 protein. The expression and distribution of PNUTS in the cochlear Corti, spiral ganglion and striavascularis cells were observed by immunohistochemical (IHC) staining. Results There were no significant differences in ABRs at 8, 12 and 24 kHz between two groups. Protein expressions of PNUTS were located in the cochlear hair cells, spiral ganglion cells and striavascularis cells, and the expression level of cochlea was significantly decreased in D-galactose group than that in control group (P < 0.05). The expression level of p53 protein was significantly increased in D-galactose group than that in control group (P < 0.01). Conclusion PNUTS is expressed in the normal mouse cochlea, and which is down-regulated in the cochlea of ageing mice induced by D-galactose. [ABSTRACT FROM AUTHOR]

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Objective: To explore the feasibility of using the threshold of neural response telemetry（NRT） to guide postoperative machine adjustment by analyzing the regularity and correlation between the threshold of subjective behavior test and NRT in cochlear implant patients with normal cochlear morphology and inner ear malformation. Methods: Thirty cochlear implant patients with normal cochlear morphology and 12 cochlear implant patients with inner ear malformation were selected for NRT test and subjective behavior test, respectively. Electrode 1 representing high frequency, electrode 11 representing medium frequency and electrode 22 representing low frequency were selected to analyze the correlation between NRT threshold and T value and C value. Results: The mean NRT threshold values of the cochlear normal group and the inner ear malformation group were both greater than T value, close to and slightly smaller than C value. The T value, C value and NRT threshold of the inner ear malformation group were slightly higher than those of the cochlear normal group. The NRT thresholds of high, middle and low frequency bands were significantly correlated with C and T values in the normal cochlear group and the inner ear malformation group. Compared with the normal cochlear group, the regression coefficients B of NRT threshold and T value in the high, medium and low frequency groups were 20.90%, 3.02%, 9.68%, and the K coefficients were 13.01%, 3.92%, 5.28%. The regression coefficients B of NRT threshold and C value of the two groups were 15.74%, 2.51%, 0.53%, and K were 14.44%, 0.24%, 4.09%, respectively. It can be seen that the correlation between NRT threshold and T value and C value of the two groups was significantly different in the high frequency band, but similar in the low and middle frequency band. Conclusion: The NRT threshold is significantly correlated with the threshold of subjective behavior test. The linear regression equation obtained can be used to guide the cochlear implant tuning machine, especially for the high frequency band T and C values of patients with inner ear malformation implantation. Different regression equations should be used to estimate the T and C values of patients with normal cochlea, so as to obtain more accurate T and C values., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

The cochlea is the most precise mechanical component in a human body. With frequencies from dozens to thousands of Hertz, acoustic signals can be processed by the cochlea and captured by the sensory hair cells on the basilar membrane (BM). Experimental research shows that sound waves of different frequencies are scattered at different positions along the basilar membrane as a natural Fourier filter. Based on Manoussaki's D fluid-solid coupling model for the spiral cochlear basilar membrane and in addition according to the longitudinal gradients of the cochlear duct height and the BM stiffness, a dispersion equation for the acoustic wave propagation along the basilar membrane was deduced. The influences of the duct height and the BM stiffness on the dispersion characteristics were analyzed. It is found that existence of the cochlear endolymph greatly increases the low-frequency signal processing ability, and the capture frequency reduces with the decreases of both the BM stiffness and the duct height. Finally, examples of human, gerbil and guinea pig were empirically studied for verification. Frequency-position diagrams corresponding to the animals respectively were obtained to prove the correctness of the proposed dispersion model, and reveal the relationship between the biological adaptability and the function of cochlear dispersion. This study is not only beneficial to understanding of the cochlear function but also promising to lay a theoretical basis for the development and design of sound sensors. [ABSTRACT FROM AUTHOR]

High level noise can damage cochlear hair cells, auditory nerve and synaptic connections between cochlear hair cells and auditory nerve, resulting in noise-induced hearing loss (NIHL). Recent studies have shown that animal cochleae have circadian rhythm, which makes them different in sensitivity to noise throughout the day. Cochlear circadian rhythm has a certain relationship with brain-derived neurotrophic factor and glucocorticoids, which affects the degree of hearing loss after exposure to noise. In this review, we summarize the research progress of the regulation of cochlear sensitivity to noise by circadian rhythm and prospect the future research direction.

Hearing loss is one of the most common chronic developmental diseases.The available studies have demonstrated that the occurrence and development of hearing loss is closely related to oxidative damage caused by oxidative stress.Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase,NOX) contribute to the production of reactive oxygen and are classified into seven subtypes (NOX1,NOX2,NOX3,NOX4,NOX5,DUOX1,and DUOX2).To explore the relationship between oxidative stress and hearing loss,this paper reviews the latest research progress in the pathological mechanism of NOX-mediated oxidative stress and hearing loss.

Objective: To analyze the objective test results of the pure-tone audiogram （PTA）, extended high-frequency audiometry （EHFA）, distortion product otoacoustic emission （DPOAE）, auditory brainstem response（ABR）, and electrocochleogram （ECochG） in patients with unilateral acute tinnitus, summarize their characteristics and explore their clinical application value in hidden hearing loss. Methods: PTA, DPOAE, ABR, and ECochG tests were performed in 33 patients with unilateral acute tinnitus as the chief complaint. The detection rate and response amplitude of each DPOAE frequency, incubation period, and interval of ABR waves and -SP/AP in ECochG were analyzed. Results: ①The thresholds of PTA at 0.25-8 kHz in both ears were in the normal range （ P >0.05）, and the thresholds of PTA at 9-16 kHz in affected ears were higher than those in healthy ears （ P <0.001）; ②There was statistical significance in the detection rate and response amplitude of DPOAE at 3, 4, 6, 8 kHz between ears （ P <0.05）; ③The incubation period of ABR Ⅰ wave in affected ears was （1.55±0.17） ms, that in the healthy ear was （1.50±0.14） ms, among them, the incubation period of ABR Ⅰ wave in the affected ear was longer than that in the healthy ear, and the difference was statistically significant （ P <0.05）; ④In ECochG, there was no significant difference in -SP amplitude between ears （ P >0.05）, but there was a significant difference in AP amplitude and -SP/AP amplitude between ears （ P <0.05）. Conclusion: EHFA, DPOAE, ABR, and ECochG have clinical significance in evaluating cochlear function in tinnitus patients., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To study the protective effects of metformin on noise-induced hearing loss (NIHL) and its differential protein omics expression profile. Methods: In January 2021, 39 male Wistar rats were randomly divided into control group, noise exposure group and metformin+noise exposure group, with 13 rats in each group. Rats in the noise exposure group and metformin+noise exposure group were continuously exposed to octave noise with sound pressure level of 120 dB (A) and center frequency of 8 kHz for 4 h. Rats in the metformin+noise exposure group were treated with 200 mg/kg/d metformin 3 d before noise exposure for a total of 7 d. Auditory brainstem response (ABR) was used to test the changes of hearing thresholds before noise exposure and 1, 4, 7 d after noise exposure in the right ear of rats in each group. Tandem mass tag (TMT) quantitative proteomics was used to identify and analyze the differentially expressed protein in the inner ear of rats in each group, and it was verified by immunofluorescence staining with frozen sections. Results: The click-ABR thresholds of right ear in the noise exposure group and metformin+noise exposure group were significantly higher than those in the control group 1, 4, 7 d after noise exposure ( P <0.05) . The click-ABR threshold of right ear in the metformin+noise exposure group were significantly lower than that in the noise exposure group ( P <0.05) . Compared with the noise exposure group, 1035 up-regulated proteins and 1145 down-regulated proteins were differentially expressed in the metformin+noise exposure group. GO enrichment analysis showed that the significantly differentially expressed proteins were mainly involved in binding, molecular function regulation, signal transduction, and other functions. Enrichment analysis of KEGG pathway revealed that the pathways for significant enrichment of differentially expressed proteins included phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway, focal adhesion, diabetic cardiomyopathy, mitogen, and mitogen-activated protein kinase (MAPK) signaling pathway. Immunofluorescence experiments showed that compared with the noise exposure group, the fluorescence intensity of insulin-like growth factor 1 receptor (IGF1R) in the metformin+noise exposure group was increased, and the fluorescence intensity of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1) was decreased. Conclusion: Noise exposure can lead to an increase in rat hearing threshold, and metformin can improve noise-induced hearing threshold abnormalities through multiple pathways and biological processes.

Objective: To examine the expression of tight-junction connexin ZO-1 in the stria vascularis tissue of the cochlea by using spontaneous endolymphatic hydrops animal model constructed with PHEX gene mutant mice, and to analyze the dynamic changes of the gene mutant mice in pathology, imaging, and hearing function., Methods: Male Hyp-Duk/Y mice with PHEX gene mutation were selected as the experimental group at three time points, 21 days post birth (P21), 90 days post birth (P90) and 120 days post birth (P120), and wild-type male mice of the same ages were selected as the control groups. The cochlear sections were HE-stained in order to observe whether endolymphatic hydrops was present or absent and to assess its severity. The expression of connexin ZO-1 in both groups was evaluated through immunohistochemical staining of cochlear sections. Auditory-evoked brainstem response (ABR) was induced in both groups at P90 and gadolinium-enhanced MRI was conducted in vivo to observe the middle-order endolymphatic dilatation of cochlea in experimental and control mice aged P21, P90 and P120., Results: HE staining of pathological sections of PHEX Hyp-Duk/Y mice aged P90 and P120 showed increased endolymphatic hydronephrosis. The level of striae ZO-1 in PHEX Hyp-Duk/Y mice aged P90 and P120 was significantly lower than that of the controls of the same age ( P <0.05). The expression level of ZO-1 was significantly negatively correlated with the degree of endolymphatic hydronephrosis ( r =-0.939, P <0.01). The bilateral ABR threshold of PHEX Hyp-Duk/Y mice aged P90 was higher than that of the wild-type mice of the same age, and the mutant mice showed asymmetric hearing loss on both sides. Severe endolymphatic hydronephrosis was observed in PHEX Hyp-Duk/Y mice aged P90 and P120 through in vivo MRI gadolinium imaging., Conclusion: PHEX Hyp-Duk/Y can be used as a sound model for basic research of Ménière's disease. Compared with wild-type mice, PHEX Hyp-Duk/Y mice showed decreased expression of connexin protein ZO-1, which damaged the function of the blood-labyrinth barrier in stria vascularis, and was involved in the formation of endolymphatic hydrops. 7.0 T MRI gadolinium imaging can be used to observe the changes of severe endolymphatic hydrops in mice in vivo , providing imaging basis for the diagnosis of Ménière's disease., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Objective: To investigate whether large conductance calcium-activated potassium channel (BK(Ca)) was involved in the migration of pericytes (PC) in the mice of senile cochlear stria vascularis capillaries PC. Methods: C57BL/6J mice were divided into 3-month ( n =10) and 12-month groups ( n =10). Auditory brainstem response (ABR) was used to test the hearing threshold of each group. The immunofluorescence was used to detect the expression changes of osteopontin (OPN) and β-BK(Ca) channels on cochlear stria vascularis PC. The morphological changes of perivascular cells in cochlea were observed by transmission electron microscope (TEM). Cell experiment: The PC, which were in the stria vascularis of the cochlea were primary cultured and identified. A cell senile model was made with D-gal. The appropriate intervention concentration of low galactose (D-gal) was determined by CCK8. β-galactosidase (SA-β-gal) staining was used to evaluate the cell decrept level. The change of BK(Ca) channels current on PC were recorded by whole cell patch clamp technique. The expression of BK(Ca) channels on PC was detected by immunofluorescence. The migration and invasion ability of two groups were detected by using Scratch test and Transwell. The levels of OPN and β-BK(Ca) channels were detected by Western blot. SPSS 22.0 software was used to analyze the data. Results: The ABR threshold in the 12-month group was higher than 3-month group ( t =12.66, P <0.01). In the 12-month group, the expression of β-BK(Ca) channel was lower and the expression of OPN was increased ( t =14.64, P <0.01; t =20.73, P <0.01). In TEM, cochlear stria vascularis PC were tightly connected to endothelial cells in 3-month group, while PC were loosely connected to endothelial cells or PC soma were separated from the capillary in 12-month group. Cell experiment: The positive rate of PC in the primary cultured cochlear stria vascularis is above 95%. Compared with the SA-β-gal stained cells in the control group, the positive rate of 15 mg/ml D-gal intervention PC was 85% ( t =36.90, P <0.01). Whole cell patch clamp BK(Ca) channels current decreased in the D-gal group compared with the young group PC ( t =12.18, P <0.05). The OPN expression in the senile group was higher than control group ( t =16.30, P <0.01), while the β-BK(Ca) channels expression was decreased ( t =11.98, P <0.01; t =15.72, P <0.05), and migration ability raised ( t =7.91, P <0.01; t =7.59, P <0.01). After intervened of BK(Ca) channels specific blocker IBTX in the D-gal group, the expression of OPN and migration were increased ( t =4.26, P <0.05; t =5.88, P <0.01; t =21.97, P <0.01). Conclusion: PC migration capacity were increased during the senile period, and the expression of β-BK(Ca) channel was decreased. The administration of IBTX, a specific blocker of BK(Ca) channel, at the cell level could increase the migration capacity, suggesting that BK(Ca) might be involved in the migration of PC in the stria vascularis of the aging cochlea.

For cochlear implant training and robotic cochlear implant experiments, the design method of scalable scala tympani model was proposed. The mathematical model of the cochlea was used as the central curve of scala tympani channel. Referring to the clinical anatomy data, the contour of the scala tympani cross-section was approximated as an ellipse. The profile was placed along the central curve, and the angle was adjusted to determine the position and orientation of the profile in three dimensions such that the central curve passes through its center. The data was imported into Matlab to generate a three-dimensional mathematical model of scala tympani, which can be expanded by setting different scale factors. The virtual scala tympani model was generated in SolidWorks, and the 2:1 fully transparent scala tympani model were fabricated by 3D printing to replace the specimen for experiment.

Objective: To study the changes in the permeability of the blood labyrinth barrier of the aging cochlea in mice, and to establish a non-contact co-culture model of endothelial cells (EC) and pericytes (PC) to furtherly investigate the cochlear stria vascularis microvascular pericytes impact on the permeability of endothelial cells. Methods: C57BL/6J mice were divided into two groups, three months old as young group, 12 months old as senile group. Cell experiment was divided into four groups, EC group, EC+PC co-culture group, D-gal+EC group and D-gal+EC+PC co-culture group. Auditory brainstem response (auditory brain response, ABR) was used to detect the auditory function of the two groups of mice. Evans blue staining was applied to detect the permeability of the cochlear blood labyrinth barrier of the two groups of mice. Transmission electron microscopy was used to observe the ultrastructure of blood labyrinth barrier endothelial cells, pericytes and tight junctions in the two groups of mice. Immunohistochemistry was used to detect the expression levels of tight junction proteins in the stria vascularis of the cochlea of the two groups of mice. Transwell chamber was used to detect the permeability of endothelial cells. Western blot and immunofluorescence technology were used to detect the expression level of tight junction protein on endothelial cells. SPSS 20.0 software was used to analyze the data. Results: Compared with the young group, the ABR threshold of the aging group was significantly increased, the latency of wave I was prolonged ( t =10.25, P <0.01; t =5.61, P <0.05), the permeability of the cochlear blood labyrinth barrier was increased and the expression of tight junction protein on the vascular stria was decreased ( P <0.05). The cochlear ultrastructure showed that the cochlear vascular stria microvascular lumen was deformed, the basement membrane thickened and the tight junction gap between endothelium enlarged. The positive rate of ECs and PCs in primary culture was more than 95%. The cells induced by 15 g/L D-gal were determined to be senescent cells. Compared with EC group, the expression of tight junction protein in endothelial cells of D-gal+EC group decreased（ t =7.42， P <0.01； t =13.19， P <0.05）and the permeability increased ( t =11.17, P <0.01). In the co-culture group, the expression of tight junction protein between endothelial cells in EC+PC co-culture group and D-gal+EC+PC co-culture group increased and the permeability decreased. Conclusions: In aging mice, the permeability of cochlear blood labyrinth barrier will increase and the level of tight junction protein will decrease; in aging state, cochlear vascular stria microvascular pericytes may affect endothelial cell permeability by regulating the expression of tight junction protein.

Tinnitus is one of the most common clinical symptoms of otology, and its pathogenesis is still unclear. The mechanism of tinnitus has been studied through a cognitive progress from the periphery （cochlea） to auditory center to the limbic system. Auditory peripheral lesions, such as damages to ribbon synapses, may form excitatory deafferentation, then it induces the auditory center to start the compensatory gain, leading to an increase in excitatory response; If the damage is further aggravated, it may cause continuous enhancement of central gain effect, hyperexcitability may occur and leading to tinnitus. Besides, the limbic system may be involved in the maintenance or exacerbation of tinnitus symptoms. This paper reviews the recent researches on tinnitus mechanism and auditory center plasticity., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

As isolated anatomical position, limited labyrinthine artery supply, and blood-labyrinth barrier hampers systemic drug delivery to the inner ear. The efficient concentration of drug treatment is unsatisfactory and there's possible side effects after systemic administration. Intratympanic injection of drug can bypass the blood-labyrinth and permeated to the hair cells or synaptic area via the round-or oval window of the cochlea. Efficacy and safety of pharmacotherapy has become increasingly relied on the inner ear delivery carrier system. The goal of this review focus on the anatomical barrier that need to be overcome in the intratympanic applications, the improvement of drug retention and specific targets, and the safety of novel drug carriers, these emerging strategies of local drug delivery promise novel and better guidance for the clinical application., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: The aim of this study is to analyze the clinical features of cochlear migraine. Methods: The clinical data of cases of cochlear migraine were collected, and the clinical symptoms and hearing examination results were analyzed. Results: The ratio of male to female patients with cochlear migraine was 1∶3.1; the peak incidence was between 30 to 60 years old; the clinical symptoms were tinnitus in 61 people（70%）, mild hearing loss in 52 people（60%）, aural fullness in hyperacusis in 13 people（15%）, auditory allergy in 9 people（10%） and otalgia in 5 people（6%）; the audiology characteristic was that 61.5%（32/52） of patients with hearing loss showed mild high-frequency neurological hearing loss, 34.6%（18/52） of patients showed mild low-frequency neurological hearing loss, and 3.8%（2/52） of patients showed full-frequency mild neurological hearing loss; the effective rate of tinnitus treatment was 57.4%, the effective rate of hearing loss was 71.2%, and the effective rate of aural fullness was 69.2%, the effective rate of hyperacusis is 66.7% and the effective rate of otalgia is 60.0%. Conclusion: The clinical characteristics of cochlear migraine are summarized, which provides a basis for the intervention of anti-migraine treatment programs for inner ear diseases., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To study the changes of proliferation and oxidation indexes of Cochlear hair cell line (HEI-OC1 cells) exposed to ethylbenzene. Methods: From July to December 2019, 11 groups with ethylbenzene concentrations of 0, 30, 60, 90, 300, 600, 900 μmol/L and 3, 6, 9, 10 mmol/L, were used to determine the proliferation activity of HEI-OC1 cells exposed to ethylbenzene for 24 hours, and the cells were treated with 0, 1, 2, 4, 8, 16, 32, 64 mmol/L ethylbenzene for 24 hours, then the 50% inhibitory concentration of ethylbenzene was calculated. After HEI-OC1 cells were exposed to 0, 6, 9 and 12 mmol/L ethylbenzene for 24 hours, the malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were measured. Results: Compared with 0 mmol/L concentration group, the survival rate of HEI-OC1 cells at 6, 9, 12 mmol/L concentration was significantly decreased ( P <0.01) . The 50% inhibitory concentration of ethylbenzene on HEI-OC1 cells was 12.86 mmol/L ( R (2)=99.05) . There were significant differences in SOD and GSH-Px activity in HEI-OC1 cells treated with ethylbenzene at different concentrations (0, 6, 9, 12 mmol/L) for 24 hours ( F =65.11, 6.48, 22.85, P <0.05) . Compared with 0 mmol/L concentration group, the MDA content of HEI-OC1 cells was significantly increased in 9 and 12 mmol/L concentration groups, the SOD activity was significantly decreased in 12 mmol/L concentration group, and the GSH-Px activity was significantly decreased in 6 and 12 mmol/L concentration groups. Conclusion: Ethylbenzene can inhibit the proliferation of HEI-OC1 cells and cause oxidative damage.

Objective: To investigate the distribution of common inner ear and internal auditory canal malformations in children with single-sided deafness（SSD） ,and to explore the imaging etiology of SSD by comparing the quantitative parameters of key bone structures between deaf and normal ears in children with congenital SSD. Method: Forty children with SSD diagnosed in the Second Hospital of Lanzhou University from September 2016 to March 2019 were collected. All of them underwent HRCT examinations of temporal bone . The area of bone island, the width of vestibular, the width of internal auditory canal, the height of cochlear and the width of cochlear basal axis were measured. Paired t test was used to compare the difference between the hearing abnormality and normal hearing in children with SSD. Result: The rate of inner ear deformity was 62.5% in SSD group,the most common deformity was cochlear nerve canal deformity, 20 cases （50.0%） of cochlear canal stenosis and 3 cases （7.5%） of cochlear canal atresia.The second most common deformity was internal auditory canal deformity, including 5 cases （12.5%） of internal auditory canal stenosis and 1 case （2.5%） of internal auditory canal atresia. Other malformations included 1 case（2.5%） of RO, 2 cases （5.0%） of incomplete partition （IP） type II and 1 case （2.5%） of enlargement of vestibular aqueduct （EVA）. There are no significant difference in the measured results of the key structures of the inner ear between two groups except the width of cochlear nerve canal, internal auditory canal and the area of bone island. Conclusion: The main inner ear deformities in children with SSD are cochlear nerve canal stenosis and inner auditory canal stenosis. HRCT of temporal bone has high diagnostic value for inner ear deformities in children with SSD., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To observe the effects of estrogen on cochlear spiral ganglia cell apoptosis in aged C57BL/6J mice, and to explore the possible mechanism of estrogen's protective effects on senile deafness. Methods: Forty C57BL/6J mice were divided into the following four groups (10 mice/group): 3 m group (3 months old group), 12 m group (12 months old sham operation group); In the 12 m OVX group (ovariectomized at 12 months), bilateral oophorectomy was performed at the age of 9 months and normal feeding was performed until the age of 12 months.The 12m OVX+E2 group (estrogen intervention group) underwent bilateral oophorectomy at 9 months of age. After the one-month washout period, mice in the other groups were treated with estrogen at the dose of 100 μg/(kg·d) by subcutaneous injection, lasting 2 months to 12 months old. Mice in the other groups were fed normally.Blood samples were collected from the tail vein at the end of the treatment in 12 m OVX+E2 group. Enzyme-linked immunosorbent assays (ELISAs) was used to determine the serum estrogen levels. Auditory brainstem response (ABR) was used to detect the changes of hearing threshold in each group.Mice were anesthetized with 2% pentobarbital sodium. Bilateral cochlea was extracted after neck amputation and paraffin-embedded sections were performed.Hematoxylin eosin (HE) staining was used to observe the morphological changes in the cochlea spiral ganglion neurons (SGN), and TUNEL staining was used to observe the apoptosis of SGN. The expression levels of Caspase-3, Bax and Bcl-2 mRNA of the apoptotic proteins in cochlear spiral ganglion were measured by real-time fluorescence quantitative PCR (QRT-PCR). Results: Compared with the 3 m group, the hearing threshold of the 12 m group was improved, the loss of spiral ganglion cells was aggravated, and the apoptosis of the cells was increased( P ＜0.01). After removal of the ovaries, the hearing threshold of the mice in the 12 m OVX group was higher than that in the 12 m control group ( P ＜0.01), and this increased threshold was accompanied by an increased loss of spiral ganglion cells, and increased apoptosis ( P ＜0.01). Meanwhile, the mRNA levels of apoptotic protein Caspase-3 and Bax were increased ( P ＜0.01), while the mRNA level of anti-apoptotic protein Bcl-2 was decreased ( P ＜0.01). After exogenous estrogen was given to the 12 m OVX+E2 group, the hearing threshold was lower than that in 12 m OVX group( P ＜0.01). At the same time, the apoptosis of helical ganglion cells was reduced, the mRNA levels of Caspase-3 and Bax were decreased ( P ＜0.01), and the Bcl-2 mRNA level was increased ( P ＜0.01). Conclusion: Estrogen inhibited apoptosis of cochlear spiral ganglion cells in aged C57BL/6J mice ,thus achieving a protective effect on presbycusis.

Objective: Primary cultured cochlear stria vascularis endothelial cells (ECs) of guinea pig were used to investigate the expression changes of TMEM16A and its effect on apoptosis and senescence of ECs in the cochlear stria vascularis. Methods: Primary cultured ECs in the cochlear stria vascularis were used to establish aging models according to CCK-8 and SA-β-galactosidase. Senescent cells were randomly divided into senescent group (P12), DMSO group (P12+DMSO), T16Ainh-A01 group (P12+T16Ainh-A01). Immunofluorescence and Western blot were used to detect the expression of TMEM16A in ECs. Flow cytometry was used to detect the apoptotic rate. Western blot was used to detect the protein expressions of Bax, Bcl-2 and cleaved casepase-3 in each group. Results: The positive rate of primary cultured cochlear stria vascularis ECs was above 95%, and the 12th generation cochlear stria vascularis ECs were determined as the senescence group, and the expression of TMEM16A in protein and fluorescence was increased ( P ＜0.05). After intervention with T16Ainh-A01 for 24 h, the protein expressions of Bax and cleaved casepase-3 were down-regulated ( P ＜0.01), the protein expression of Bcl-2 was increased ( P ＜0.05), the apoptotic rate and the positive rate of SA-β-gal were down-regulated ( P ＜0.01). Conclusion: It was found that apoptosis and TMEM16A expression were increased in cochlear stria vascularis senescent ECs, TMEM16A specific blocker T16Ainh-A01 could reduce the apoptosis and senescence in ECs of the cochlear stria vascularis. These results suggest that TMEM16A may participate in apoptosis and senescence of ECs in the cochlear stria vascularis.

Objective: To determine the cell types composing blood-labyrinth barrier in stira vascularis of cochlear lateral wall, analyze the distribution of these composing cells in blood-labyrinth barrier, and to investigate the relationship between perivascular-resident macrophages （PVMs）, endothelial cells and pericytes in blood-labyrinth barrier. Method: Cochlear lateral wall tissues were harvested from adult GFP-transgenic mice（C57BL/6）. Then the isolated whole stria vascularis tissue was scanned at 0.5 um intervals on the Z axis by two-photon confocal microscope and a 3D-structure of stria vascularis was reconstructed to observe the distribution of capillaries in blood-labyrinth barrier. Cochlear stria vascularis isolated from Balb/c mice was stained by mulit-immunofluorescence and then 3D real time deconvolution of stria vascularis was performed by Imaris software to investigate the distribution of PVMs and pericytes, and their contacting with basement membrane of capillaries was also observed. The ultrastructure of endothelial cells, pericytes and PVMs in blood-labyrinth barrier was observed using transmission electron microscope. Result: The vessels in stria vascularis are parallel to modiolus, distinct from that in spiral ligament which are perpendicular to modiolus. Numerous pericyts in stria vascularis are ensheathed by a vascular basement membrane shared with endothelial cells and closely attaching to the lateral wall of endothelial cells, while PVMs are located outside basement membrane of capillaries. Unlike pericytes that surround one capillary, PVMs branch to connect with more than one capillary. Conclusion: Serial layers on the Z axis scanned by two-photon confocal microscope and a 3D-structure reconstructed by Imaris 3D deconvolution helps to display the micro structure of capillaries in cochlear lateral wall clearly, which could be applied to analyze the 3D structure and function of blood-labyrinth barrier. PVMs in stria vascularis contact with more than one vessel through cytoplasmic processes, suggesting that PVMs may play a more significant role than pericytes in the integrity of blood-labyrinth barrier., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To compare intact dissection and segmented dissection of cochlear surface preparation in adult mice. Methods: From February to March, 2019, Six adult C57BL/6 mice were randomly divided into 2 groups: one group (3 mice) for the intact dissection while the other group (3 mice) for the segmented dissection. Cochlear hair cells were labeled with phalloidin for evaluation of the integrity of the basilar membrane. Results: The basilar membranes can be completely dissected from the cochlea by two approaches. The average dissection time is (16.33±1.86)min with the intact dissection approach while (23.66±3.88) min with the segmented dissection( t= -4.173, P= 0.002). Immunofluorescence analysis showed all cochlear hair cells werevisible and intact in two groups. Conclusion: Cochlear basilar membrane can be dissected intact in a short time through both approaches. The approaches selection is dependent on the purpose of experiment and operators' experience.

Objective: The research is to study the expression and distribution of matrix metalloproteinase (MMPs)-2 and -9 in the guinea pig cochlea after noise exposure, and to explore the role of MMPs in the blood-labyrinth-barrier (BLB). In addition, the role of MMPs inhibitor doxycycline in noise-induced BLB trauma was studied as well, which provides the basis for further studies and prophylaxis of noise-induced hearing loss. Methods: A total of 45 healthy adult guinea pigs were randomly divided into the control group (15 received intraperitoneal injection of 0.9% saline for 4 consecutive days), the noise-exposure group (15 exposed by 120 dB SPL white noise for 4 h per day for continuous 2 d, intraperitoneal injection of normal saline for 4 consecutive days) and the noise-exposure + doxycycline group (15 exposed by 120 dB SPL white noise exposure for 4 h per day for 2 consecutive days, and intraperitoneal injection of doxycycline 50 mg/kg/d for 4 consecutive days), respectively. Immunofluorescence staining, western blot, and real-time quantitative PCR were used to analyze the distribution and differential expression of MMP-2 and -9 in the stria vascularis of guinea pigs in comparison with the normal control group, noise only group, and noise & doxycycline treatment group. Immunofluorescence staining was used to observe the changes in tight junction (TJ) protein ZO-1 in stria vascularis in three groups and to investigate the effect of acoustic injury on TJs. And ABR tests were utilized to detect the hearing function of guinea pigs in the three groups. Intravenous Evans blue was administrated intravenously as an indicator of vascular leakage among three groups to study the changes in BLB permeability in context of acoustic injury. SPSS 22.0 was used for statistical analysis. Results: There was no significant difference in hearing function between the noise-exposure group and the noise & doxycycline group two hours after noise exposure. After seven, 14 and 28 days noise exposure, the hearing recovery of the noise & doxycycline treatment group was significantly greater than that of the noise-exposure group ( P <0.05) . Immunofluorescence staining showed that there was only a small amount of MMP-2 and -9 in the stria vascular in the normal control group, and ZO-1 showed dense linear expression. While, in the noise-explore group, MMP-2 and -9 in the stria vascular was significantly elevated ( P <0.05), and the configuration of ZO-1 became loose and discontinuous. However, the MMP-2 and -9 in the noise & doxycycline treatment group were not significantly different from the normal control group ( P >0.05), which were significantly less than that in the noise-exposure group, and just a little break of ZO-1 was observed, however, the overall structure remained dense. The leakage of Evans blue from stria vascular capillary in the noise-exposure group was significantly increased, and the difference between the other two groups did not show any statistical significance ( P >0.05). Conclusions: The damage of tight junction structure induced by MMP-2 and -9 may play an important role in BLB destruction. In addition, doxycycline can inhibit MMPs secretion, thereby, to some extent, protecting the integrity of BLB from acoustic injury, and contributing to the long-term hearing recovery.

Summary Since the first cochlear implant was developed and used in clinical practice, many patients with profound deafness have returned to the world of sound, with the development of modern large-scale integrated circuits and the in-depth study of the anatomical pathophysiology of cochlea, deaf patients have been continuously benefited from it. Electrode is one of the core parts of cochlea implants, the design of the electrode and the placement of the electrode are important factors for patients to benefit from cochlea implantation. Postoperative starting up and debugging are also crucial. Through debugging, the electric stimulation level of each channel can be optimized, which is of great significance for postoperative rehabilitation effect, the magnitude of electrode impedance plays an important role in starting up and debugging. At present, there is no unified conclusion about the relationship between the electrode position and the electrode impedance value. Only when the implanted position and the electrode impedance are normal, can the implanted electrode function be better played., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To determine the extent of transfection and expression of adeno-associated virus (AAV) serotype 9 (AAV9) in the cochleae of mice at different ages. Methods: AAV9-green fluorescent protein (GFP) was inoculated into the cochlea of mice via the round window membrane (RWM) or through cochleostomy at different ages. Four groups were divided according to ages and injection sites: P1SM group, AAV9-GFP was delivered to the scala media by cochleostomy at postnatal day 1; P1RW group, AAV9-GFP was delivered to the scala tympani via RWM at postnatal day 1; P9RW group: AAV9-GFP was injected through RWM at postnatal day 9; and P30RW group, adult mice (P30) were injected through RWM. GFP expression in cochlear whole mount was analyzed and auditory brainstem response (ABR) tests were conducted one month after virus injection (for each animal, only left cochlea was injected and the right side was used as a control). GraphPad Prism 5 statistical software was used for data analysis. Results: All of inner hair cells (IHCs) and most of outer hair cells (OHCs) were transfected via two approaches at P1 injection. There was no significant difference in ABR threshold between injected ears and untreated ears ( P> 0.05). All of the IHCs and parts of OHCs (69% in apical turn) were transfected via RWM at P9. The strongest GFP expression was observed near the apical turn. Cochlear inoculation via RWM at P30 led to transgene expression in only IHCs. The ABR threshold of injected ears in P9RW group and P30RW group was significantly higher than that of contralateral ears ( P< 0.01). Conclusions: AAV9 can be highly expressed in the inner and outer hair cells of the cochlea and hearing sensitivity can be preserved if virus injections are performed in neonatal mice. After AAV9 is transfected into the inner ear of adult mice, it is only expressed in the inner hair cells, which leads to the increase of the ABR response threshold of mice. Transfection efficiency is significant higher in neonate mice than in P9 and adult mice.

Acid-sensing ion channels are a class of extracellular H(+) activated cation channels, belonging to the amiloride-sensitive epithelial Na(+) channel/degenerin (ENaC/DEG) superfamily. During extracellular acidification, the channels are activated and produce corresponding action potential. Acid-sensing ion channels are extensively expressed in the peripheral and central nervous system. It plays an important in synaptic plasticity, mechanical sensation, injury sensation related to acidosis of local tissues, acid reception and retinal regulation. This article reviews the expression, biological characteristics and functions of acid-sensing ion channels in cochlea, vestibular tissue and auditory center, so as to improve the understanding of physiology and pathophysiology of auditory system.

Objective: To observe the position of the electrode in the cochlea following cochlear implantation by cone beam computed tomography (CBCT). Methods: Twenty-five children who received cochlear implantation and CBCT examinations in the Department of Otorhinolaryngology Head and Neck Surgery from the Second Hospital of Shandong University between January 2016 and December 2017 were selected. There were 15 males (17 ears) and 10 females (10 ears). The age ranged from 0.5 to 7.0 years old, with a median age of 1.6 years. 23 patients with unilateral implantation and two patients with bilateral implantation. The implants were all Med-El standard 12-electrode contact arrays. The CBCT was used to determine the position of the electrode in the cochlea, the distance between the electrode contacts and modiolus, and intracochlear insertion length of the electrode arrays. SPSS Statistics, version 22.0 was used for data processing and statistical analysis. Results: CBCT images could clearly demonstrate the structure of round window, oval window, modiolus, osseous cochlear duct, osseous spiral lamina, and electrodes. The electrode arrays of all the children were fully implanted into the cochlea. 26 of the electrode arrays were located in the scala tympani and one of them was inserted into the scala vestibular. The mean intracochlear insertion length of the electrode arrays was 30.23 (95 %CI , 30.04-30.71) mm. The distance between the electrode contacts and modiolus gradually increased at the 1-4th electrode contacts and reached the maximum at the 4th electrode contacts with an average of 1.10 mm (95 %CI , 1.02 to 1.18 mm), and then gradually decreased from the 5th electrode contacts. Conclusions: CBCT can clearly show cochlear fine structures and therefore accurately assess the electrode position following cochlear implantation.

Objective: To analyse the characteristics of the revision cochlear implantation （RCI）patients，the cause of the cochlear malfunction，and the choice of RCI operative approach. Method: A total of 39 patients with RCI were enrolled in this study. The cochlear use time, cause of failure and reoperation procedure are recorded and analyzed retrospectively. Result: There were 39 patients accepted cochlear reoperation，the ages ranges from 1 to 28，average age was 7.8 years, median age was 5 years old. The cochlear use time ranges from 1 month to 7 years，average was 2.2 years, median time was 1 year. Thirty-seven patients underwent RCI,30 cases right side and 7 cases left side. The reason of RCI contains device failure (28 cases)，infection (5 cases)，incorrect electrode implantation (3 cases)，facial nerve stimulation (2 cases)，and electrode prolapse (1 case).The choice of RCI procedure was dependent on the first operation procedure,contains facial nerve recess approach (35 cases) and mastoid approach (2 cases).Contralateral implantation was performed in 5 cases, the rest were ipsilateral. Conclusion: RCI has a variety causes and the common reason is trauma and device failure，the RCI should be completed as early as possible to avoid the ossified cochlear and hearing or speech stagnation，the electrode implantation through previous approach is the best method., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: This study aimed to investigate the P19ink4d expression in cochlea of mice model with noise induced hearing loss and the role of P19ink4d in the degeneration of inner ear cells. It also searched for P19ink4d gene alterations in patients with profound sensorineural deafness. Method: CBA/J mice were exposed to broad band noise at 101 dB SPL for 2 hours, auditory brainstem response (ABR) were examined to confirm noise lead to the permanent threshold shift. Immunohistochemical staining, Western blotting, and real-time polymerase chain reaction (PCR) were performed on cochlear tissues, to elucidate changes in P19ink4d expression in mice after noise exposure. For clinical evaluation, 400 children from unrelated families with severe or profound sensorineural hearing loss (SNHL) were recruited, genomic DNA was obtained from the patients and was subjected to DNA microarray to screen mutations in 4 most common genes. The sample that carried none of the common mutant alleles were subjected to PCR and sequenced to detect mutations in P19ink4d gene. Result: The ABR threshold shift of mice in the experimental group significantly increased after noise exposure and was higher than that in the null-noise group. The ABR of 1 day post noise was least among experimental groups and there is no statistical different between ABR of 7 days and 14 days post noise. The missing of outer hair cells occurred after noise exposure, while the inner hair cells hardly miss. It was found that the P19ink4d expression increased significantly in the inner ear cells 3 hours after noise exposure, then recovered in 24 hours. Western blot indicated that the amount of P19ink4d increased transitorily 3-6 h after the noise. However, no mutation existed within the coding exons of P19ink4d in the patients with profound sensorineural deafness. Conclusion: The results support the concept that P19ink4d may play an important role in the pathogenesis and development of noise induced hearing loss., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Nowadays, more than 300 000 deaf people around the world benefit from cochlea implantation. With the extension of cochlear implantation indications, it has become a research focus for how to apply the anti-inflammatory and anti-fibrotic drugs safely and effectively to better retain residual hearing, as well as to protect hair cells and the spiral ganglion cells from apoptosis. Due to the blood-labyrinth barrier, perioperative systemic steroids are often unable to achieve satisfactory drug concentration in the inner ear. Also, given that higher doses of steroids will cause more serious side effects and sometimes steroids are strictly limited to apply on some patients with certain diseases, the attention has been attracted on topical drug delivery to the inner ear. In this review, the methods of topical drug delivery to the inner ear are divided into four categories: transtympanic injection of liquid solutions, tympanic implantation of drug delivery systems, intracochlear injection and modified implant electrode. The results in each category and up to date progress are reviewed.

Objective: To explore ways of evaluating morphological information of cochlea electrode in post cochlear implantation patients, and so as to make sure its value of clinical usage. Method: A series of 52 patients who were diagnosed as severe to profound sensorineural hearing loss and received cochlear implantation were admitted. All the patients had cone-beam CT scanning of the operated side 1 or 2 days after operation. The software of NNT Viewer was used to proceed original DICOM data of CBCT scanning in order to evaluate the morphological information. A comparative study in recognizing the numbers of anatomic structures was carried out between CBCT and X-ray. Result: All the 52 patients successfully received cochlear implantation as well as CBCT scanning.The cochlear implantation was implanted bilaterally at the same time in 3 patients, left side implantation in 13 patients and 36 cases in right side. There are four ways of evaluating the morphological information of electrode in cochlea post-operatively, including mode of Panorex, mode of MPR, mode of 3D-Ceph and 3D-Bone. A comprehensive evaluation can be achieved by the using of these four methods. The numbers of anatomic structures distinguished by CBCT is far more than X-ray. Conclusion: The evaluating methods of CBCT scanning is flexible and diverse, the CBCT scanning have unique values in clinical usage.

Objective: To investigate the values of electrocochleograph（ECochG）in patients with OSAHS. Method: ECochG was performed in 31 (62 ears) OSAHS patients (moderately 5 cases, severely 26 cases) and 28 healthy adults (56 ears). AP latency ，AP amplitude and SP/AP were measured and analyzed. Result: There was no difference between the two groups in SP/AP amplitude ratio（ P >0.05） while both AP latency（ P <0.05） and AP amplitude（ P <0.05） were significantly different. Conclusion: ECochG can confirm the damage of cochlear and auditory nerve near the cochlear segment in patients with moderate to severe OSAHS., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To explore the relation between distortion products and frequency tuning charateristics in cochlear basilar membrane. Method: Time variances curves of distortion products and frequency tuning curves of basilar membrane response were measured by laser interferometery in situ guinea pig cochlea. Result: Response sensitivity and tuning sharpness of basilar membrane response decreased with distortion product amplitude and become most low and flat when distortion products disappeared. Conclusion: Distortion products in cochlea are related with hearing sensitivity and frequency tuning. They are indicator whether function of cochlear hearing sensitivity enhancing and frequency tuning sharpening is still at work., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Pulsatile tinnitus (PT) is relatively rare, which accounts for approximately 4% of patients with tinnitus. It originates from mostly vascular structures within the cranial cavity, head and neck region or thoracic cavity, and is transmitted to the cochlear by bony or vascular structures and the blood flow, stimulating patient's hearing. It can be the patient's subjective feelings, there can be objective performance.Vascular PT is more common than non-vascular PT. Vascular PT can be further classified by vessel of origin as arterial and venous ones, and the latter is more commonly seen clinically.It's rhythm is synchronous with patients' pulse, and its tinnitus frequency is less than 600 Hz. The cause of pulsatile tinnitus is complex and diverse, and 56 cases are reported in the literature. Objective tinnitus or somatosensory, associated with tympanic membrane myoclonus, ear blood flow changes adjacent to blood vessels and other in vivo factors. While subjective tinnitus lacks a clear source of the body. PT's pathogenesis has not been fully understood yet, so intensive study targeting PT is of great importance. This review focuses on the pathophysiological mechanisms,etiology,clinical manifestation, diagnosis and progress of treatment of vascular PT., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To study the effect of early administration exogenous BDNF on the morphology and function of conditional knockout Cx26 mice cochlea. Method: Conditional knockout Cx26 mice was chosen as animal model, early after birth (P0-P2) exogenous BDNF (rAAV mediated BDNF plasmid, AAV-BDNF) was injected through scala media. Expression of BDNF in the cochlea was observed by western-blot, the growth promoting effect of nerve fibers was detected by IHC; 2 m after injection, the protective effect of BDNF on corti and spiral ganglion cells were detected by resin section; animal hearing were tested by ABR. Result: ①Exogenous BDNF could be well expressed in the inner ear; ②Exogenous BDNF has a good effect on the growth of cochlea nerve fiber; ③Exogenous BDNF could protect the morphology of organ of corti; to count the number of spiral ganglion cells, using the density value of top-turn in non-injected ear as the standard unit, the values of middle and basal turn in injected ear were 0.81±0.02, 0.65±0.02, compared with non-injected ears, both statistically significant difference could be found, indicates that exogenous BDNF can effectively improve the number of spiral ganglion cells. ④By calculating the ABR threshold of different frequencies of the injected and non-injected ear, there was no statistical difference between them. Indicates that exogenous BDNF has no effect on improving the function of cochlea. Conclusion: The protective effect of early administration exogenous BDNF was effective in the cochlea and spiral ganglion cells of conditional knockout Cx26 mice, but no protective effect for auditory function., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To study the variation of the electrode impedance in different periods after cochlear implantation performed with round window insertion in steroid deposition, and to provide the basis for the postoperative debugging of the speech processor. Method: Detected the electrode impedance of 47 cochlear receivers after operation in steroid deposition from September 2014 to October 2015, compared the impedance values between different periods, and different groups according to their locations. Result: The average impedance of all the electrodes and the 3 subgroups are low after implantation (period A0), peaked at the first month (period A1), then decreased slowly, and then turned to be stable at the sixth month (period A3); the impedance values were no significantly different between the sixth month (period A3) and the twelfth month (period A4) while were significantly different between each of other two periods ( P <0.05); the apical group had the highest impedance and the basal group had the lowest impedance in all the 5 periods. Conclusion: The local use of steroid can decrease the impedance of the electrode after implantation. The impedance value were the low during operation, peaked at the first month, then decreased slowly, and turned to be stable at the sixth month. As a result, the cochlear implant should be debugged at regular intervals in 6 months after operation to obtain the best hearing status., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Neurotrophin-3 (NT-3) attracted increasing attention about NTFs researches in recent years. But the mechanism of promoting the development of neurons and neurite extension is not clear. Recombinant human NT-3 or NT-3 gene is commonly used in the treatment of peripheral and central neurons system damage. When rats are born, the cochlear is not mature yet. It is a suitable experimental animal for studying the morphological and functional development of the peripheral auditory pathway. It was found that NT-3 could promote the survival, growth, division and extension of the cochlear neurons in rats. To make clear the role of NT-3 in the development of spiral ganglion in the rat cochlear will be of significance for the treatment of nervous hearing loss by NT-3 in the future., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To observe the morphological changes on cochlear hair cells of rats in simulated weightlessness and inboard noise and to investigate the different changes in three turns of hair cells., Methods: Thirty-two healthy SD rats, all males, were randomly divided into four groups: control group, weightlessness group, noise group and weightlessness+noise groups (n=8). Then rats were exposed to -30° head down tilt as simulated weightlessness and inboard noise including steady-state noise which was (72±2) dB SPL and impulse noise up to 160 dB SPL in spaceship environment. The control group was kept in normal condition for 8 weeks. Bilateral auditory brainstem response (ABR) thresholds were tested before and after exposure respectively, and immunofluorescence staining and scanning electron microscopy (SEMs) of basilar membrane were applied after exposure., Results: ABR threshold shifts of each group were higher after exposure. There was difference between ABRs of the experiment groups before and after exposure (P<0.05). IF showed that the inner hair cells (IHCs) missing was the main damage in the basal turn of weightlessness group, the hair cells in the middle turn were swell and in the top turn, the hair cells were not clear. In noise group, the main loss happened in the outer hair cells (OHCs) of the outermost layer. In weightlessness+noise group, the nuclear missing in the basal turn was apparent, and mainly happened at the outermost layer. Meanwhile, the missing of hair cells in the middle turn and top turn was seen at the innermost layer. SEM showed that the cilia in the basal turn of weightlessness group were serious lodging, and occasional absence. Furthermore, the basal cilia in noise group became lodged and absent, and the other two turns were seriously missing. And in weightlessness+noise group, the cilia missing in the basal turn was apparently seen. The damage degree of the four groups: weightlessness+noise group>noise group>weightlessness group>control group and the damage degree of the four turns of hair cells: basal turn>mid turn>top turn., Conclusion: The rats exposed to the above environment for 2 weeks displayed obvious changes in cochlea morphology, and the weightlessness +noise group had the most obvious damage.

Objective: To discuss the possible reasons for cerebrospinal fluid (CSF) gusher in cochlear implantation (CI) with inner ear abnormality. Method: A retrospective analysis was performed on 340 cases who underwent CI from January 2013 to December 2016 in Division of Otology, Otorhinolaryngology Hospital, the First Affiliated Hospital of Zhengzhou University. Among them, 96 cases had inner ear abnormalities. Imaging examinations were performed on these patients, and classification of inner ear malformation was done according to the results. Results: Among the cases with inner ear abnormality, 9.4% (9/96) suffered from CSF gusher during CI. The inner ear abnormalities were found to be as follows: 3 cases had incomplete partition type Ⅰ; 1 case had incomplete partition type Ⅰ with semicircular canal dysplasia; 1 case had common cavity deformity; 1 case had enlarged vestibular aqueducts and common cavity deformity; 2 cases had Mondini deformity. All of these cases had bony defect in the fundus of the internal acoustic meatus observed on CT scans. Another case was type 1 cochlear aqueduct with round window aplasia. Conclusions: Defects in the modiolus or fundus of the internal acoustic meatus is the main reason for CSF gusher during CI. A patent cochlear aqueduct is another possible reason.