Assessments of Subjective Visual Gravity and Spontaneous Nystagmus in Patients With Vestibular Neuritis.

OBJECTIVE: This study aimed to assess the correlation between the spontaneous nystagmus (SN) and the subjective visual vertical/horizontal (SVV/SVH) among patients with vestibular neuritis (VN) at the different head positions. STUDY DESIGN: Case-control study. SETTING: Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine. METHODS: This study evaluated the SVV/SVH in both healthy subjects and patients with VN. These evaluations were performed in 5 different head positions: upright, 45° tilt to the left, 90° tilt to the left, 45° tilt to the right, and 90° tilt to the right. Additionally, the intensity of SN, as measured by slow-phase velocity, was recorded. RESULTS: In patients with VN, a significant correlation was observed between SN and SVV/SVH in an upright position. The intensity of SN was higher when the head was tilted 90° toward the affected side compared to other positions. The SVV/SVH displayed an ipsiversive shift, when the head was tilted toward both the lesion and unaffected sides, exhibiting a contraversive direction. Furthermore, the changes in position-induced SN were consistent with the displacements of SVV and SVH caused by head tilt. CONCLUSION: The presence of SN in patients with VN was observed to vary across different head position. These variations could potentially be attributed to the diverse activation patterns of the mechanical properties of otolith organs that are induced by head tilts.

[An analysis of clinical efficacy of microvascular decompression for 21 inpatients suffering from primary hemifacial spasm].

Objective:To assess the effectiveness of microvascular decompression（MVD） in treating inpatients suffering from primary hemifacial spasm（HFS）. Methods:A total of 21 inpatients with HFS underwent MVD. The clinical effect was follow up evaluated according to the clinical symptoms until post operative 6 months. Results:The effective rate of MVD for 1 day, 14 days, 1 month, 3 months and 6 months post-operation was 95.2%, 100%, 100%, 100% and 100%, respectively.one patient had transient tinnitus and the symptom disappeared within 6 days postoperatively.one patient developed postoperative incomplete facial paralysis（HB grade IV facial nerve function, grade Ⅱ） and recovered 6 days after surgery; There was no cerebrospinal fluid leakage, intracranial infection, death or disability occurred during follow-up. Conclusion:Microvascular decompression is a safe and effective method for the treatment of primary hemifacial spasm, which is worthy of clinical promotion.

Inhibition of CISD1 attenuates cisplatin-induced hearing loss in mice via the PI3K and MAPK pathways.

Cisplatin is an effective chemotherapeutic drug for different cancers, but it also causes severe and permanent hearing loss. Oxidative stress and mitochondrial dysfunction in cochlear hair cells (HCs) have been shown to be important in the pathogenesis of cisplatin-induced hearing loss (CIHL). CDGSH iron sulfur domain 1 (CISD1, also known as mitoNEET) plays a critical role in mitochondrial oxidative capacity and cellular bioenergetics. Targeting CISD1 may improve mitochondrial function in various diseases. However, the role of CISD1 in cisplatin-induced ototoxicity is unclear. Therefore, this study was performed to assess the role of CISD1 in cisplatin-induced ototoxicity. We found that CISD1 expression was significantly increased after cisplatin treatment in both HEI-OC1 cells and cochlear HCs. Moreover, pharmacological inhibition of CISD1 with NL-1 inhibited cell apoptosis and reduced mitochondrial reactive oxygen species accumulation in HEI-OC1 cells and cochlear explants. Inhibition of CISD1 with small interfering RNA in HEI-OC1 cells had similar protective effects. Furthermore, NL-1 protected against CIHL in adult C57 mice, as evaluated by the auditory brainstem response and immunofluorescent staining. Mechanistically, RNA sequencing revealed that NL-1 attenuated CIHL via the PI3K and MAPK pathways. Most importantly, NL-1 did not interfere with the antitumor efficacy of cisplatin. In conclusion, our study revealed that targeting CISD1 with NL-1 reduced reactive oxygen species accumulation, mitochondrial dysfunction, and apoptosis via the PI3K and MAPK pathways in HEI-OC1 cell lines and mouse cochlear explants in vitro, and it protected against CIHL in adult C57 mice. Our study suggests that CISD1 may serve as a novel target for the prevention of CIHL.

Comparison of two endoscopic perichondrium-cartilage graft underlay myringoplasty for large perforations: a randomized controlled trial.

OBJECTIVE: The objective of this study was to compare the graft outcomes and complications of two endoscopic perichondrium-cartilage graft techniques for repairing large perforations. STUDY DESIGN: Single center blinded randomized controlled trial. MATERIALS AND METHODS: 61 large perforations more than 50% of TM area were prospectively randomized to undergo the free perichondrium and free cartilage graft group (FPFC, n = 31) or perichondrium partial attachment the cartilage graft group (PPAC, n = 30). The primary outcome measures were the operation time; secondary outcome measures were the graft success rate and hearing gain at 12 months postoperatively and postoperative complications. RESULTS: All patients completed follow-up of 12 months. The mean operation time was 38.2 ± 2.3 min in the FPFC group and 37.4 ± 5.6 min in the PPAC group (P = 0.658). At postoperative 3 months, the graft success rates were 96.7% in the FPFC group and 93.3% in the PPAC group (P = 0.976). At postoperative 12 months, the graft success rates were 96.7% in the FPFC group and 83.3% in the PPAC group (P = 0.182). However, the residual and re-perforation rate with no infection was 0.0% (0/31) in the FPFC group and 16.7% (5/30) in the PPAC group (P = 0.056). No significant between-group differences were observed pre- (P = 0.842) or post- (P = 0.759) operative air bone gap (ABG) values or mean ABG gain (P = 0.886). However, granular myringitis has been noted in 6.5% in the FPFC group and in 3.3% in the PPAC group. CONCLUSIONS: This study suggested that 12-month graft success and hearing gain were comparable between the perichondrium free and partial attachment the cartilage graft techniques, nevertheless, partial attachment technique could increase residual and re-perforations.

Comparison of healing of acute total tympanic membrane perforation between rats with and without excision of the mallear handle.

Objective: We compared the histological changes and hearing restoration during the healing of acute total tympanic membrane (TM) perforations between Sprague-Dawley (SD) rats with and without excision of the mallear handle. Materials and methods: Bilateral, acute, and total TM perforations were created in 36 male SD rats. The mallear handle was preserved in the left ear (handle-preserved ear [HPE]) and excised from the right ear (handle-excised ear [HEE]). Endoscopical examination, auditory brainstem response (ABR) thresholds, histopathological, and scanning electron microscope (SEM) analysis were performed. Results: Endoscopic photographs showed that all perforations in the 18 SD rats were closed. The mean closure times were 6.83 ± 0.85 and 8.50 ± 0.71 days in the HPE and HEE groups, respectively (p < .001). SEM images showed radial arrangement of fiber bundles in a single direction in HPEs, although normal arrangement was not achieved. In contrast, HEEs showed disorganized arrangement. At 1 month after perforation closure, the ABR thresholds at high frequencies were significantly higher in the HEE group than in the HPE group (p = .029 and p = .017 for 16 and 32 kHz, respectively). Additionally, the changes in ABR threshold were significantly different at high frequencies (p = .011 and p = .017 for 16 and 32 kHz, respectively) before and 1 month after perforation closure between the HPE and HEE groups, although the differences were not statistically significant at the remaining frequencies. Conclusion: Although the malleus handle may not affect the closure of total perforation in SD rats, it contributes to accelerate the perforation closure by possible guide the migration of proliferative epithelial cell on the upper halves of the annulus. Additionally, resection of the malleus handle impairs high frequency hearing recovery following spontaneous closure of the TM.

Redistribution of the astrocyte phenotypes in the medial vestibular nuclei after unilateral labyrinthectomy.

Astrocytes are highly heterogeneous and involved in different aspects of fundamental functions in the central nervous system (CNS). However, whether and how this heterogeneous population of cells reacts to the pathophysiological challenge is not well understood. To investigate the response status of astrocytes in the medial vestibular nucleus (MVN) after vestibular loss, we examined the subtypes of astrocytes in MVN using single-cell sequencing technology in a unilateral labyrinthectomy mouse model. We discovered four subtypes of astrocytes in the MVN with each displaying unique gene expression profiles. After unilateral labyrinthectomy, the proportion of the astrocytic subtypes and their transcriptional features on the ipsilateral side of the MVN differ significantly from those on the contralateral side. With new markers to detect and classify the subtypes of astrocytes in the MVN, our findings implicate potential roles of the adaptive changes of astrocyte subtypes in the early vestibular compensation following peripheral vestibular damage to reverse behavioral deficits.

Comparison of perichondrium-cartilage double and single underlay myringoplasty for subtotal perforations: a randomized controlled trial.

OBJECTIVE: The objective of this study was to compare graft outcome, operation time and surgical complications of the double and single perichondrium-cartilage underlay techniques for repairing subtotal tympanic membrane (TM) perforations. MATERIALS AND METHODS: Patients with unilateral subtotal perforations undergoing myringoplasty were prospectively randomized to undergo DPCN or SPCN. The operation time, graft success rate, audiometric outcomes, and complications were compared between these groups. RESULTS: In total, 53 patients with unilateral subtotal perforations were included (DPCN group, 27; SPCN group, 26).All patients completed 6 months of follow-up. The mean operation time was 41.2 ± 1.8 min in the DPCN group and 37.2 ± 5.4 min in the SPCN group, the difference was not significant (p = 0.613).The graft success rates were 96.3% (26/27) in the DPCN group and 73.1% (19/26) in the SPCN group, the difference was significant (p = 0.048). During the period of follow-up, residual perforation was found at postoperative in one (3.7%) in the DPCN group, while cartilage graft slipped (graft lateralization) in 2 (7.7%) and residual perforation in 5 (19.2%) were found in the SPCN group, the difference of residual perforation was not significant among two group (p = 0.177).In addition, no significant between-group differences were observed pre- (p = 0.741) or post- (p = 0.687) operative ABG values or mean ABG gain (p = 0.659) (Table 2).The functional success rates (postoperative ABG ≤ 20 dB) were 85.2% (23/27) in the DPCN group and 73.1% (19/26) in the SPCN group (p = 0.454). CONCLUSION: Although similar functional result and operation time can be obtained with double perichondrium-cartilage underlay technique compared to the single perichondrium-cartilage underlay technique for endoscopic closure of subtotal perforations, double unerlay technique offers better anatomical result with minimum complications.

TMEM30A is essential for hair cell polarity maintenance in postnatal mouse cochlea.

BACKGROUND: Phosphatidylserine is translocated to the inner leaflet of the phospholipid bilayer membrane by the flippase function of type IV P-tape ATPase (P4-ATPase), which is critical to maintain cellular stability and homeostasis. Transmembrane protein 30A (TMEM30A) is the ß-subunit of P4-ATPase. Loss of P4-ATPase function causes sensorineural hearing loss and visual dysfunction in human. However, the function of TMEM30A in the auditory system is unclear. METHODS: P4-ATPase subtype expression in the cochlea was detected by immunofluorescence staining and quantitative real-time polymerase chain reaction (qRT-PCR) at different developmental stages. Hair cell specific TMEM30A knockout mice and wild-type littermates were used for the following functional and morphological analysis. Auditory function was evaluated by auditory brainstem response. We investigated hair cell and stereocilia morphological changes by immunofluorescence staining. Scanning electron microscopy was applied to observe the stereocilia ultrastructure. Differentially expressed transcriptomes were analyzed based on RNA-sequencing data from knockout and wild-type mouse cochleae. Differentially expressed genes were verified by qRT-PCR. RESULTS: TMEM30A and subtypes of P4-ATPase are expressed in the mouse cochlea in a temporal-dependent pattern. Deletion of TMEM30A in hair cells impaired hearing onset due to progressive hair cell loss. The disrupted kinocilia placement and irregular distribution of spectrin-α in cuticular plate indicated the hair cell planar polarity disruption in TMEM30A deletion hair cells. Hair cell degeneration begins at P7 and finishes around P14. Transcriptional analysis indicates that the focal adhesion pathway and stereocilium tip-related genes changed dramatically. Without the TMEM30A chaperone, excessive ATP8A2 accumulated in the cytoplasm, leading to overwhelming endoplasmic reticulum stress, which eventually contributed to hair cell death. CONCLUSIONS: Deletion of TMEM30A led to disrupted planar polarity and stereocilia bundles, and finally led to hair cell loss and auditory dysfunction. TMEM30A is essential for hair cell polarity maintenance and membrane homeostasis. Our study highlights a pivotal role of TMEM30A in the postnatal development of hair cells and reveals the possible mechanisms underlying P4-ATPase-related genetic hearing loss.

Aucubin protects mouse cochlear hair cells from cisplatin-induced ototoxicity via activation of the PI3K/AKT/STAT3 pathway.

Cisplatin is commonly used to treat cancers and is associated with a significant risk of irreversible sensorineural hearing loss. However, no effective preventive strategies are available for cisplatin-induced HL. Therefore, significant efforts have been made to discover new drugs protecting cochlear hair cells from cisplatin-induced damage. We found that a new phytochemical, aucubin, attenuated cisplatin-induced apoptosis, the production of reactive oxygen species, and mitochondrial dysfunction in House Ear Institute Organ of Corti 1 cells and cochlear hair cells. Moreover, aucubin attenuated cisplatin-induced sensorineural hearing loss and hair cells loss in vivo. Furthermore, RNA sequencing analysis revealed that the otoprotective effects of aucubin were mainly mediated by increased STAT3 phosphorylation via the PI3K/AKT pathway. Inhibition of the STAT3 signaling pathway with the inhibitor S3I-201 or siRNA disrupted the protective effects of aucubin on cisplatin-induced apoptosis. In conclusion, we identified an otoprotective effect of aucubin. Therefore, aucubin could be used to prevent cisplatin-induced ototoxicity.

[Research progress on non-surgical treatment of vestibular schwannomas].

At present, the main treatment for vestibular schwannomas is surgery. Considering the risk of multiple complications from surgery and the subjective and objective conditions of patients, a non-surgical treatment modality, namely stereotactic radiotherapy, has gradually been included in the treatment of vestibular schwannomas. Studies have shown that Gamma Knife therapy has a more prominent therapeutic effect on smaller tumors and can alleviate facial nerve disorders caused by space occupying of tumor mass. Cyberknife not only has a better effect on tumor control, but also has an ideal retention rate for patients' auditory function. Proton beam therapy has also been gradually applied to the treatment of vestibular schwannomas, but the effect of treatment remains to be further studied. Drug therapy includes a variety of target inhibitors and anti-angiogenic drugs. At present, drug treatment focuses more on preclinical research. This article reviews the clinical research of various radiotherapy and the progress of drug treatment.

The Spectrum of Vestibular Disorders Presenting With Acute Continuous Vertigo.

Objective: To explore the composition of vestibular disorders presenting with the acute vestibular syndrome (AVS). Methods: We performed a case analysis of 209 AVS patients between January 2016 and December 2020. These patients were grouped into different disorder categories according to the relevant diagnostic criteria. Results: We classified the 209 patients into 14 disorder categories, including 110 cases of vestibular neuritis, 30 of idiopathic sudden sensorineural hearing loss with vertigo, 17 of the first attack of continuous vertigo with migraine, 15 of Ramsay Hunt syndrome, 11 of acute labyrinthitis secondary to chronic otitis media, 8 of vestibular schwannoma, 6 of posterior circulation infarction and/or ischemia, 3 of cerebellar abscess secondary to chronic otitis media, 3 of AVS caused by trauma or surgery, 2 of AVS with down-beating nystagmus, 1 of multiple sclerosis of the medulla oblongata, 1 of epidermoid cyst of the posterior cranial fossa, 1 of a probable acute otolithic lesion, and 1 of AVS without measurable vestibular dysfunction. Conclusion: When a group of disorders present with AVS, characteristic clinical manifestations and imaging help with an accurate diagnosis.

Genome-Wide Association Study of Obstructive Sleep Apnea and Objective Sleep-related Traits Identifies Novel Risk Loci in Han Chinese Individuals.

Rationale: Previous genetic studies of obstructive sleep apnea (OSA) have limitations in terms of precise case definition, integrated quantitative traits, and interpretation of genetic functions; thus, the heritability of OSA remains poorly explained. Objectives: To identify novel genetic variants associated with OSA and objective sleep-related traits and to explore their functional roles. Methods: A genome-wide association study was performed in 20,590 Han Chinese individuals (5,438 OSA and 15,152 control samples). Human samples and point mutation knockin mice were used for follow-up investigation of gene functions. Measurements and Main Results: Two characteristic study-wide significant loci (P < 2.63 × 10-9) for OSA were identified: the PACRG intronic variant rs6455893 on 6q26 (odds ratio [OR] = 1.62; 95% confidence interval [CI], 1.39-1.89; P = 6.98 × 10-10) and the missense variant rs3746804 (p.Pro267Leu) in the riboflavin transporter SLC52A3 on 20p13 (OR = 0.83; 95% CI, 0.79-0.88; P = 7.57 × 10-10). In addition, 18 genome-wide significant loci associated with quantitative OSA and objective sleep-related traits were identified, 5 of which exceeded the study-wide significance threshold. Rs3746804 was associated with elevated serum riboflavin concentrations, and the corresponding mutation in mice increased riboflavin concentrations, suggesting that this variant may facilitate riboflavin uptake and riboflavin-dependent physiological activity. Conclusions: We identified several novel genome-wide significant loci associated with OSA and objective sleep-related traits. Our findings provide insight into the genetic architecture of OSA and suggest that SLC52A3 might be a therapeutic target, whereas riboflavin might be a therapeutic agent.

A Deep Learning Model for Three-Dimensional Nystagmus Detection and Its Preliminary Application.

Symptoms of vertigo are frequently reported and are usually accompanied by eye-movements called nystagmus. In this article, we designed a three-dimensional nystagmus recognition model and a benign paroxysmal positional vertigo automatic diagnosis system based on deep neural network architectures (Chinese Clinical Trials Registry ChiCTR-IOR-17010506). An object detection model was constructed to track the movement of the pupil centre. Convolutional neural network-based models were trained to detect nystagmus patterns in three dimensions. Our nystagmus detection models obtained high areas under the curve; 0.982 in horizontal tests, 0.893 in vertical tests, and 0.957 in torsional tests. Moreover, our automatic benign paroxysmal positional vertigo diagnosis system achieved a sensitivity of 0.8848, specificity of 0.8841, accuracy of 0.8845, and an F1 score of 0.8914. Compared with previous studies, our system provides a clinical reference, facilitates nystagmus detection and diagnosis, and it can be applied in real-world medical practices.

A reduced form of nicotinamide riboside protects the cochlea against aminoglycoside-induced ototoxicity by SIRT1 activation.

BACKGROUND: Nicotinamide adenine dinucleotide (NAD+), a coenzyme that plays crucial roles in many cellular processes, is a potential therapeutic target for various diseases. Dihydronicotinamide riboside (NRH), a novel reduced form of nicotinamide riboside, has emerged as a potent NAD+ precursor. Here, we studied the protective effects and underlying mechanism of NRH on aminoglycoside-induced ototoxicity. METHODS: Auditory function and hair-cell (HC) morphology were examined to assess the effects of NRH on kanamycin-induced hearing loss. The pharmacokinetic parameters of NRH were measured in plasma and the cochlea using liquid chromatography tandem mass spectrometry. NAD+ levels in organ explant cultures were assessed to compare NRH with known NAD+ precursors. Immunofluorescence analysis was performed to detect reactive oxygen species (ROS) and apoptosis. We analyzed SIRT1 and 14-3-3 protein expression. EX527 and resveratrol were used to investigate the role of SIRT1 in the protective effect of NRH against kanamycin-induced ototoxicity. RESULTS: NRH alleviated kanamycin-induced HC damage and attenuated hearing loss in mice. NRH reduced gentamicin-induced vestibular HC loss. Compared with NAD and NR, NRH produced more NAD+ in cochlear HCs and significantly ameliorated kanamycin-induced oxidative stress and apoptosis. NRH rescued the aminoglycoside-induced decreases in SIRT1 and 14-3-3 protein expression. Moreover, EX527 antagonized the protective effect of NRH on kanamycin-induced HC loss by inhibition of SIRT1, while resveratrol alleviated HC damage caused by EX527. CONCLUSIONS: NRH ameliorates aminoglycoside-induced ototoxicity by inhibiting HC apoptosis by activating SIRT1 and decreasing ROS. NRH is an effective therapeutic option for aminoglycoside-induced ototoxicity.

Single-Cell RNA-Seq Reveals Heterogeneity of Cell Communications between Schwann Cells and Fibroblasts within Vestibular Schwannoma Microenvironment.

Vestibular schwannomas (VSs), which develop from Schwann cells (SCs) of the vestibular nerve, are the most prevalent benign tumors of the cerebellopontine angle and internal auditory canal. Despite advances in treatment, the cellular components and mechanisms of VS tumor progression remain unclear. Herein, single-cell RNA-sequencing was performed on clinically surgically isolated VS samples and their cellular composition, including the heterogeneous SC subtypes, was determined. Advanced bioinformatics analysis revealed the associated biological functions, pseudotime trajectory, and transcriptional network of the SC subgroups. A tight intercellular communication between SCs and tumor-associated fibroblasts via integrin and growth factor signaling was observed and the gene expression differences in SCs and fibroblasts were shown to determine the heterogeneity of cellular communication in different individuals. These findings suggest a microenvironmental mechanism underlying the development of VS.

Long-lasting and Sex-dependent Effects of Postweaning Swimming Exercise on Social Dominance in Adult Mice.

Increasing evidence has shown that early life events exert long-lasting effects on brain function and mental diseases. Exercise has been proven to have many positive effects on behaviors, such as reducing anxiety- and depression-like behaviors and alleviating cognitive impairment. However, the long-lasting and even short-term effects of regular swimming exercise on social dominance remain unclear. The purpose of this study was to investigate the potential effects of postweaning swimming exercise on social dominance and metabolic adaptation in adult mice. Three-week-old mice performed 1 h of swimming exercise in warm water for 4 weeks. A series of behavioral tests, such as the social dominance test (SDT), open field test (OFT), and forced swim test (FST), were conducted. Behavioral test results showed that both male and female mice in the swimming group had a higher rank than those in the sedentary group in the SDT of early adulthood, while only female mice in the swimming group maintained the social dominance in late adulthood. There was no difference between the swimming and sedentary groups in anxiety- and depression-like behaviors. Metabolomics analysis showed that there were alterations in particular metabolites and signaling pathways after one month of swimming exercise, including sphingolipid metabolism, neuroactive ligand-receptor interaction and caffeine metabolism. In conclusion, our results provide the first evidence that postweaning swimming exercise has long-lasting and sex-dependent effects on social dominance, which may be caused by metabolic adaptation.

Changes of Vestibular Symptoms in Menière's Disease After Triple Semicircular Canal Occlusion: A Long-Term Follow-Up Study.

BACKGROUND: The clinical efficacy of triple semicircular canal occlusion (TSCO) and vestibular nerve resection (VNS) for patients with Ménière's disease has been unclear. OBJECTIVE: To explore changes in vestibular symptoms after TSCO and its advantages compared to the classical operation of VNS in patients with Menière's disease. METHODS: In total, 36 patients with Menière's disease performed TSCO or VNS at Shanghai Jiao Tong University Affiliated Sixth People's Hospital, China from May 2005 to July 2021, and all of them were enrolled in our study. Twelve of them underwent TSCO, 23 underwent VNS, and 1 had both treatments. We compared the demographic parameters, clinical symptoms, and selected test results between the two surgical methods. Ten patients each who underwent TSCO and VNS completed the follow-up. We collected and compared data pertaining to changes in vestibular symptoms. RESULTS: No significant difference in demographic parameters, clinical symptoms, or auditory or vestibular test results was detected between the two groups preoperatively. The TSCO group with vertigo as the main complaint experienced less residual paroxysmal dizziness after surgery than the VNS group (P = 0.020). Also, 57% of the patients in the VNS group had unsteadiness after surgery, while no such problems were reported in the TSCO group (P = 0.025). CONCLUSIONS: Our study shows that TSCO controls vertigo in most Menière's disease patients, and also has the advantage of lower rates of postoperative paroxysmal dizziness and unsteadiness than VNS. Thus, TSCO may be an effective surgery for refractory Menière's disease.

Overexpression of XIAP inhibits cisplatin-induced hair cell loss.

Cisplatin is a platinum-containing drug with ototoxicity commonly used clinically and has significant efficacy against a variety of solid tumors. One of the most important mechanisms of ototoxicity is that cisplatin induces apoptosis of hair cells. According to relevant literature, X-linked inhibitor of apoptosis protein (XIAP, anti-apoptotic protein) could inhibit the apoptotic pathway. We hypothesized that this protein might protect cochlear hair cells from cisplatin-induced injury. To figure it out, we treated cochlea of normal mice with various concentrations of cisplatin to observe the response and morphology of hair cells and determine a reasonable concentration. Next, Western Blot and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) experiments were conducted to make an investigation about the expression of XIAP protein and mRNA. In addition, we constructed and identified XIAP overexpressing mice. Finally, we treated cochlear tissues of normal and overexpressing mice with cisplatin to investigate the cyto-protection of XIAP on hair cells, respectively. It was found that 50 µmol/L cisplatin resulted in significant loss and disorganization of hair cells, while simultaneously downregulating the protein and mRNA of XIAP. In XIAP overexpressing mice, the loss and disorganization of hair cells were significantly lessened. These results showed that XIAP can lessen cisplatin-induced hair cell loss and play a role in otoprotection.

Comparison of endoscopic over-underlay technique with and without packing for repairing chronic perforation.

OBJECTIVE: This study was performed to compare the efficacy of the endoscopic modified cartilage over-underlay technique with and without packing for repairing chronic tympanic membrane (TM) perforations. METHODS: A total of 70 cases of chronic TM perforation were randomly allocated to endoscopic modified cartilage over-underlay myringoplasty groups with (n = 35) and without (n = 35) packing. The graft success rate and hearing outcomes were compared between the two groups. In addition, neovascularization scores were subjectively obtained. RESULTS: At 12 months postoperatively, the difference in graft success rate between the packing and no-packing groups was not significant (94.3% vs. 100.0%, P = 0.473). In addition, there were no significant differences between the two groups in the pre- or postoperative air-bone gap (ABG) (15.18 ± 2.73 vs. 15.07 ± 4.02, P = 0.623 and 8.63 ± 3.03 vs. 8.52 ± 4.50, P = 0.591) or mean ABG gain (6.56 ± 3.23 vs. 6.54 ± 2.83, P = 0.751). However, the average operating times were 43.6 ± 7.1 and 32.7 ± 2.1 min in the packing and no-packing groups, respectively (P < 0.001). CONCLUSIONS: Surgical and hearing outcomes were comparable between patients with chronic TM perforation treated using the endoscopic modified over-underlay technique with and without packing. However, without packing, the procedure was less invasive and had a shorter operating time.

Trehalose protects against cisplatin-induced cochlear hair cell damage by activating TFEB-mediated autophagy.

Cisplatin is a widely used chemotherapeutic agent for the treatment of various tumors, but its side effects limit its application. Ototoxicity, a major adverse effect of cisplatin, causes irreversible sensorineural hearing loss. Unfortunately, there are no effective approaches to protect against this damage. Autophagy has been shown to exert beneficial effects in various diseases models. However, the role of autophagy in cisplatin-induced ototoxicity has been not well elucidated. In this study, we aimed to investigate whether the novel autophagy activator trehalose could prevent cisplatin-induced damage in the auditory cell line HEI-OC1 and mouse cochlear explants and to further explore its mechanisms. Our data demonstrated that trehalose alleviated cisplatin-induced hair cell (HC) damage by inhibiting apoptosis, attenuating oxidative stress and rescuing mitochondrial dysfunction. Additionally, trehalose significantly enhanced autophagy levels in HCs, and inhibiting autophagy with 3-methyladenine (3-MA) abolished these protective effects. Mechanistically, we showed that the effect of trehalose was attributed to increased nuclear translocation of transcription factor EB (TFEB), and this effect could be mimicked by TFEB overexpression and inhibited by TFEB gene silencing or treatment with cyclosporin A (CsA), a calcineurin inhibitor. Taken together, our findings suggest that trehalose and autophagy play a role in protecting against cisplatin-induced ototoxicity and that pharmacological enhancement of TFEB-mediated autophagy is a potential treatment for cisplatin-induced damage in cochlear HCs and HEI-OC1 cells.