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.

Detecting epidemiological relevance of adenoid hypertrophy, rhinosinusitis, and allergic rhinitis through an Internet search.

PURPOSE: This study aimed to detect the epidemiological relevance between adenoid hypertrophy (AH) and rhinosinusitis, and AH and allergic rhinitis (AR) through an Internet search. METHODS: Internet search query data from January 2011 to December 2019 in China were retrieved from the Baidu Index (BI). Spearman's correlation coefficients were used to detect the correlation among the search volumes of AH, rhinosinusitis, and AR. We also collected search data from the first 5 months of 2020, when quarantine was implemented in China due to the coronavirus disease 2019 epidemic. Then, we compared the search data to those obtained during the same period in 2019 to assess the effects of isolation on AH and AR. RESULTS: Statistically significant relevance was found between the search variations of AH and rhinosinusitis during 2011-2019 (R = 0.643, P < 0.05). However, the relationship between AH and AR was weak (R = - 0.239, P < 0.05) and that between rhinosinusitis and AR (R = - 0.022, P > 0.05) was not relevant. The average monthly search volume of AH and rhinosinusitis had a strong correlation (R = 0.846, P < 0.01), but AH and AR and rhinosinusitis and AR were not correlated (R = - 0.350, P > 0.05; R = - 0.042, P > 0.05, respectively). AH and rhinosinusitis search volumes decreased consistently during the first 5 months of 2020 (isolation), whereas that for AR increased during January-February. CONCLUSION: AH had an epidemiological relationship with rhinosinusitis, which was not consistent with AR. The decrease in public gathering effectively reduced the morbidities of AH and rhinosinusitis but not those of AR.

Anxiety and depression in patients with nasal septal deviation.

OBJECTIVE: Nasal septal deviation (NSD) has a significant impact on patients' quality of life; however, there have been limited studies examining the psychological status of NSD patients. In this study, symptoms of depression and anxiety were investigated between NSD patients and controls using a self-report questionnaire. METHODS: A case-control study design was used to evaluate the psychological burden of NSD in patients who visited the general hospital. The control group comprised of ENT outpatients without a history of chronic nasal disease. The Zung Self-rating Anxiety/Depression Scale (SDS/SAS) was used to evaluate the prevalence and severity of anxiety and depression between the NSD and control group. RESULTS: Seventy-six patients with NSD and 79 control patients were enrolled in the study. We found that depression and anxiety, as well as the co-morbidity of depression with anxiety, were more common in the NSD group in comparison to the control (39.5% vs 22.8%, p = 0.025; 38.2% vs 15.2%, p = 0.001; and 27.6% vs 11.4%, p = 0.011, respectively). The average SDS and SAS score was higher in NSD patients compared to controls (SDS: 49.7 ± 13.1 vs 45.2 ± 10.4, p = 0.019 and SAS: 48.1 ± 11.6 vs 41.3 ± 9.3, p < 0.001, respectively), and NSD patients were found to have more severe levels of anxiety and depression. CONCLUSION: Depression and anxiety are more common and severe in patients with NSD. Therefore, psychological distress should be taken into consideration during the diagnostic and therapeutic process for patients with NSD.

Delayed Diagnosis and Treatment of Cerebrospinal Fluid Leakage in Current Practice.

As delayed diagnosis and treatment of cerebrospinal fluid (CSF) leakage are common in current practice, this study was performed to determine associated factors and discuss appropriate strategies to deal with these problems. A retrospective analysis of all cases of CSF leakage in our hospital from 2007 to 2018, including 41 patients with CSF rhinorrhea and 5 with CSF otorhinorrhea, was performed. Symptoms, associated diseases, misdiagnoses, history of skull base repair surgical, previous medical costs, and number of hospital visits before visiting our institution were reviewed. The diagnoses, surgical reconstruction methods, and prognoses of the patients were analyzed. In 18 patients, CSF leakage was spontaneous, in 14 the cause was trauma, and in the remaining 14 the origin was iatrogenic. Twelve patients had been misdiagnosed with allergic rhinitis, rhinosinusitis, or otitis media. Twelve cases had intracranial infection and 14 suffered airway infection. Six had undergone unsuccessful craniotomy, endonasal endoscopic surgery, or ear surgery for treatment of CSF leakage before visiting our institute. This resulted in an average of 5.13 ±â€Š1.32 referrals and medical costs of up to 20,795.7 ±â€Š4553.80 RMB. The success rate was 97.83% after repairing CSF fistulae in our hospital. The septal floor flap (SFF) method (based on ethmoidal arteries) to treat CSF rhinorrhea showed a success rate of 100% in 12 patients. Therefore, early localization, clinical diagnosis, and appropriate repair surgery can avoid the occurrence of delayed events. Pedicled flaps, including SFF, are recommended to manage challenging CSF rhinorrhea.

The Key Transcription Factor Expression in the Developing Vestibular and Auditory Sensory Organs: A Comprehensive Comparison of Spatial and Temporal Patterns.

Inner ear formation requires that a series of cell fate decisions and morphogenetic events occur in a precise temporal and spatial pattern. Previous studies have shown that transcription factors, including Pax2, Sox2, and Prox1, play important roles during the inner ear development. However, the temporospatial expression patterns among these transcription factors are poorly understood. In the current study, we present a comprehensive description of the temporal and spatial expression profiles of Pax2, Sox2, and Prox1 during auditory and vestibular sensory organ development in mice. Using immunohistochemical analyses, we show that Sox2 and Pax2 are both expressed in the prosensory cells (the developing hair cells), but Sox2 is later restricted to only the supporting cells of the organ of Corti. In the vestibular sensory organ, however, the Pax2 expression is localized in hair cells at postnatal day 7, while Sox2 is still expressed in both the hair cells and supporting cells at that time. Prox1 was transiently expressed in the presumptive hair cells and developing supporting cells, and lower Prox1 expression was observed in the vestibular sensory organ compared to the organ of Corti. The different expression patterns of these transcription factors in the developing auditory and vestibular sensory organs suggest that they play different roles in the development of the sensory epithelia and might help to shape the respective sensory structures.

Distinct severity stages of obstructive sleep apnoea are correlated with unique dyslipidaemia: large-scale observational study.

BACKGROUND: Dyslipidaemia is an intermediary exacerbation factor for various diseases but the impact of obstructive sleep apnoea (OSA) on dyslipidaemia remains unclear. METHODS: A total of 3582 subjects with suspected OSA consecutively admitted to our hospital sleep centre were screened and 2983 (2422 with OSA) were included in the Shanghai Sleep Health Study. OSA severity was quantified using the apnoea-hypopnea index (AHI), the oxygen desaturation index and the arousal index. Biochemical indicators and anthropometric data were also collected. The relationship between OSA severity and the risk of dyslipidaemia was evaluated via ordinal logistic regression, restricted cubic spline (RCS) analysis and multivariate linear regressions. RESULTS: The RCS mapped a nonlinear dose-effect relationship between the risk of dyslipidaemia and OSA severity, and yielded knots of the AHI (9.4, 28.2, 54.4 and 80.2). After integrating the clinical definition and RCS-selected knots, all subjects were regrouped into four AHI severity stages. Following segmented multivariate linear modelling of each stage, distinguishable sets of OSA risk factors were quantified: low-density lipoprotein cholesterol (LDL-C), apolipoprotein E and high-density lipoprotein cholesterol (HDL-C); body mass index and/or waist to hip ratio; and HDL-C, LDL-C and triglycerides were specifically associated with stage I, stages II and III, and stages II-IV with different OSA indices. CONCLUSIONS: Our study revealed the multistage and non-monotonic relationships between OSA and dyslipidaemia and quantified the relationships between OSA severity indexes and distinct risk factors for specific OSA severity stages. Our study suggests that a new interpretive and predictive strategy for dynamic assessment of the risk progression over the clinical course of OSA should be adopted.

The Importance of Acoustic Temporal Fine Structure Cues in Different Spectral Regions for Mandarin Sentence Recognition.

OBJECTIVES: To study the relative contribution of acoustic temporal fine structure (TFS) cues in low-, mid-, and high-frequency regions to Mandarin sentence recognition. DESIGN: Twenty-one subjects with normal hearing were involved in a study of Mandarin sentence recognition using acoustic TFS. The acoustic TFS information was extracted from 10 3-equivalent rectangular bandwidth-wide bands within the range 80 to 8858 Hz using the Hilbert transform and was assigned to low-, mid-, and high-frequency regions. Percent-correct recognition scores were obtained with acoustic TFS information presented using one, two, or three frequency regions. The relative weights of the three frequency regions were calculated using the least-squares approach. RESULTS: Results indicated that the mean percent-correct scores for sentence recognition using acoustic TFS were nearly perfect for stimuli with all three frequency regions together. Recognition was approximately 50 to 60% correct with only the low- or mid-frequency region but decreased to approximately 5% correct with only the high-frequency region of acoustic TFS. The mean weights of the low-, mid-, and high-frequency regions were 0.39, 0.48, and 0.13, respectively, and the difference between each pair of frequency regions was statistically significant. CONCLUSION: The acoustic TFS cues in low- and mid-frequency regions convey greater information for Mandarin sentence recognition, whereas those in the high-frequency region have little effect.

Elevated low-density lipoprotein cholesterol is independently associated with obstructive sleep apnea: evidence from a large-scale cross-sectional study.

BACKGROUND: Lipid metabolism disorder is recognized to be associated with obstructive sleep apnea (OSA); however, inconsistent results have been reported. The aim of this study was to evaluate the association between lipid profile and OSA with adjustments for multiple confounding factors. METHODS: In total, 2983 subjects were recruited from the Shanghai Sleep Health Study (SSHS) during 2007-2013. Data for overnight polysomnography (PSG) parameters, serum lipids, fasting blood glucose, insulin levels, and anthropometric measurements were collected. Multivariable logistic regression analyses were used to determine the correlation between lipid profile and OSA with adjustments for confounders including lipids, age, gender, Epworth sleepiness scale, body mass index, waist/hip ratio, glucose, insulin resistance, hypertension, and smoking. RESULTS: The prevalence of hyper total cholesterol (TC), hyper triglycerides, hypo high-density lipoprotein cholesterol, hyper low-density lipoprotein cholesterol (LDL-C), hyper apolipoprotein (apo) A-I, and hyper apoB differed significantly between the non-OSA and OSA patients. Without considering the interaction across different lipids, TC, LDL-C, and apoB were independently associated with OSA in primary multivariable logistic regression analyses; the odds ratios (ORs) and 95 % confidence intervals (CIs) were 1.262 (1.109-1.438), 1.432 (1.233-1.664), and 5.582 (2.643-11.787), respectively. However, only LDL-C (OR = 1.430, 95 % CI = 1.221-1.675) was found to be an independent risk factor for OSA in further multivariable logistic regression analyses. CONCLUSIONS: We demonstrated that patients with OSA had a higher percentage of dyslipidemia than subjects without OSA. Of the various components in serum lipid, only LDL-C was independently associated with OSA.

Detection of eustachian tube openings by tubomanometry in adult otitis media with effusion.

Otitis media with effusion (OME) is a common disease and eustachian tube (ET) dysfunction is widely known to be related to the incidence of OME; however, objective evaluation tools for ET function are lacking. To evaluate ET openings by tubomanometry (TMM) in adult patients with otitis media with effusion (OME), the ET patency of 123 ears, including 63 ears of OME patients and 60 control ears, were tested using TMM and tympanometry. ET patency was evaluated by the R value and ET score, and was compared to the tympanogram results. The eustachian tube dysfunction questionnaire (ETDQ-7) was used to assess the severity of the symptoms in OME patients. The results showed that the rates of restricted opening or blocked ET under pressures of 30, 40, and 50 mbar by TMM testing were 10, 5, and 0 %, respectively (control group) and 76.19, 66.7, and 57.97 %, respectively (OME group) (p < 0.05 for all pressure groups). However, the rates were 77.42, 71.97, and 61.29 % in the type B tympanogram group, and 75, 62.5, and 46.87 % in the type C tympanogram group; no significant difference was found at each testing pressure (p = 0.821, 0.246, and 0.516; respectively) between these tympanogram groups. The mean ETDQ-7 score in OME patients was 16.40 ± 10.72, which was significantly negatively correlated with the ET score at 30 and 40 mbar (30 mbar: correlation coefficient -0.29, p = 0.025; 40 mbar: correlation coefficient -0.28; p = 0.030), but not at 50 mbar (correlation coefficient -0.013, p = 0.924). These findings showed that ET blockage or delayed opening were found in most adult patients with OME when evaluated by this innovative and semi objective TMM, testing pressures should be considered when assessing the results of TMM in OME patients.

Comparison of cochlear cell death caused by cisplatin, alone and in combination with furosemide.

Establishment of appropriate animal models is an important step in exploring the mechanisms of drug-induced ototoxicity. In the present study, using guinea pigs we compared cochlear lesions induced by cisplatin administered in two regimens: consecutive application alone and in combination with furosemide. The effects of furosemide alone were also evaluated; it was found to cause temporary hearing loss and reversible damage to the stria vascularis. Consecutive application of cisplatin alone appeared to be disadvantageous because it resulted in progressive body weight loss and higher mortality compared to the combined regimen, which used a smaller cisplatin dose. The combined regimen resulted in comparable hearing loss and hair cell loss but a markedly lower mortality. However, their coadministration failed to cause similar damage to spiral ganglion neurons (SGN), as seen in animals that received cisplatin alone. This difference suggests that the combined regimen did not mimic the damage to cochlear neuronal innervation caused by the clinical application of cisplatin. The difference also suggests that the SGN lesion is not caused by cisplatin entering the cochlea via the stria vascularis.

Comparison of the healing mechanisms of human dry and endogenous wet traumatic eardrum perforations.

This prospective study aimed to assess the spontaneous healing mechanisms of human dry and endogenous wet traumatic tympanic membrane perforations (TMPs). A total of 106 patients with traumatic TMPs were included. Based on the presence or absence of endogenous bloody or watery exudates on the residual eardrum and/or at perforation margins, 73 perforations were classified as dry perforations and the remaining 33 as endogenous wet perforations. In 65 of the 73 dry perforations, centripetal migration of an epithelial layer was the first event seen during the spontaneous healing process, which was followed by growth and migration of the other two layers (i.e., the fibrous layer and the inner mucous layer). In the remaining eight dry perforation cases, outward epithelial migration was observed on the side of the perforation edge. In the 33 endogenous wet perforations, closure seemed to start with growth of the fibrous layers which were then covered by the migrating epithelium. Within the first week after injury, only 16.3 ± 6.7 % of the perforation area healed in the dry perforation cases, whereas 82.2 ± 13.9 % of the perforation area healed in the wet perforation cases; the difference was significant (P < 0.01). These observations suggest that different mechanisms may be involved in spontaneous healing of dry and wet traumatic TMPs in humans, thereby resulting in differences in healing time and healing outcome.

Delayed diagnosis and treatment of benign paroxysmal positional vertigo associated with current practice.

The purposes of this study were to demonstrate the current status of benign paroxysmal positional vertigo (BPPV) management and the advantages of repositioning maneuvers as well as to facilitate the accurate and efficient diagnosis and management of BPPV. Of 131 participants with severe dizziness/vertigo who were examined and treated, 31 (23.7%) fulfilled the diagnostic criteria for BPPV. All patients in the study had a diagnosis of BPPV confirmed by their history, typical subjective symptom reports, and characteristic positional nystagmus during the Dix-Hallpike test and/or roll test. All participants were comprehensively interviewed regarding their medical history, characteristics of the first attack of vertigo, associated symptoms, previous financial costs, and number of hospital visits. The average duration from the appearance of the first symptoms until a final diagnostic positional maneuver was >70 months. On average, patients visited hospitals more than eight times before the final diagnosis due to initial visits to inappropriate departments, including neurology, emergency, orthopaedic surgery, and Traditional Chinese Medicine, with a corresponding average financial cost of more than 5,000 RMB. The canalith repositioning procedure (CRP) was effective in 80.65% of patients after the first repositioning maneuver. Our data demonstrated that despite the significant prevalence of BPPV, delays in diagnosis and treatment frequently occur, which have both cost and quality-of-life impacts on both patients and their caregivers. The CRP is very effective for patients with BPPV. It is important for patients to pay more attention to the impact of BPPV on their lives and recognize its nature to ensure compliant follow-up in otolaryngology.

Emerging roles of circular RNAs in regulating the hallmarks of thyroid cancer.

Thyroid cancer is a prevalent endocrine malignancy with increasing incidence in recent years. Although most thyroid cancers grow slowly, they can become refractory, leading to a high mortality rate once they exhibit recurrence, metastasis, resistance to radioiodine therapy, or a lack of differentiation. However, the mechanisms underlying these malignant characteristics remain unclear. Circular RNAs, a type of closed-loop non-coding RNAs, play multiple roles in cancer. Several studies have demonstrated that circular RNAs significantly influence the development of thyroid cancers. In this review, we summarize the circular RNAs identified in thyroid cancers over the past decade according to the hallmarks of cancer. We found that eight of the 14 hallmarks of thyroid cancers are regulated by circular RNAs, whereas the other six have not been reported to be correlated with circular RNAs. This review is expected to help us better understand the roles of circular RNAs in thyroid cancers and accelerate research on the mechanisms and cure strategies for thyroid cancers.

Global burden of head and neck cancers from 1990 to 2019.

Head and neck cancer (HNC) exerts a significant healthcare burden worldwide. Insufficient data impedes a comprehensive understanding of its global impact. Through analysis of the 2019 Global Burden of Disease (GBD) database, our secondary investigation unveiled a surging global incidence of HNC, yet a decline in associated mortality and disability-adjusted life years (DALYs) owing to enhanced prognosis. Particularly noteworthy is the higher incidence of escalation among females compared to males. Effective resource allocation, meticulous control of risk factors, and tailored interventions are imperative to curtail mortality rates among young individuals afflicted with HNC in underprivileged regions, as well as in elderly individuals grappling with thyroid cancer.

Store-Operated Ca2+ Channels Contribute to the Generation of Ca2+ Waves in Interdental Cells in the Cochleae.

Cochlear calcium (Ca2+) waves are vital regulators of the cochlear development and establishment of hearing function. Inner supporting cells are believed to be the main region generating Ca2+ waves that work as internal stimuli to coordinate the development of hair cells and the mapping of neurons in the cochlea. However, Ca2+ waves in interdental cells (IDCs) that connect to inner supporting cells and spiral ganglion neurons are rarely observed and poorly understood. Herein, we reported the mechanism of IDC Ca2+ wave formation and propagation by developing a single-cell Ca2+ excitation technology, which can easily be accomplished using a two-photon microscope for simultaneous microscopy and femtosecond laser Ca2+ excitation in any target individual cell in fresh cochlear tissues. We demonstrated that the store-operated Ca2+ channels in IDCs are responsible for Ca2+ wave formation in these cells. The specific architecture of the IDCs determines the propagation of Ca2+ waves. Our results provide the mechanism of Ca2+ formation in IDCs and a controllable, precise, and noninvasive technology to excite local Ca2+ waves in the cochlea, with good potential for research on cochlear Ca2+ and hearing functions.

Adenoid lymphocyte heterogeneity in pediatric adenoid hypertrophy and obstructive sleep apnea.

Introduction: Adenoid hypertrophy is the main cause of obstructive sleep apnea in children. Previous studies have suggested that pathogenic infections and local immune system disorders in the adenoids are associated with adenoid hypertrophy. The abnormalities in the number and function of various lymphocyte subsets in the adenoids may play a role in this association. However, changes in the proportion of lymphocyte subsets in hypertrophic adenoids remain unclear. Methods: To identify patterns of lymphocyte subsets in hypertrophic adenoids, we used multicolor flow cytometry to analyze the lymphocyte subset composition in two groups of children: the mild to moderate hypertrophy group (n = 10) and the severe hypertrophy group (n = 5). Results: A significant increase in naïve lymphocytes and a decrease in effector lymphocytes were found in severe hypertrophic adenoids. Discussion: This finding suggests that abnormal lymphocyte differentiation or migration may contribute to the development of adenoid hypertrophy. Our study provides valuable insights and clues into the immunological mechanism underlying adenoid hypertrophy.

A Flexible Thermocouple Film Sensor for Respiratory Monitoring.

A novel flexible thermocouple film sensor on a polyimide substrate is proposed that is simple and flexible for monitoring the respiratory signal. Several thermocouples were connected in series and patterned on the polyimide substrate, and each one is formed by copper and a constant line connected to each other at two nodes. The respiratory signal was measured by the output voltage, which resulted from the temperature difference between the hot and cold junctions. The sensors were fabricated with surface-microfabrication technology with three sputtering steps. The measurement results showed that the peak voltage decreased by 90% in the case of apnea compared with normal breathing. The sensor has potential application for wearable detection of sleep apnea hypopnea syndrome (OSAHS).

Oriented Growth of Neural Stem Cell-Derived Neurons Regulated by Magnetic Nanochains.

Neural stem cell therapy has become a promising cure in the treatment of neurodegenerative disorders. Owing to the anisotropy of the nervous system, the newly derived neurons need not only the functional integrity but also the oriented growth to contact with the partner cells to establish functional connections. So the oriented growth of the newly derived neurons is a key factor in neural stem cell-based nerve regeneration. Nowadays, various biomaterials have been applied to assist in the oriented growth of neural stem cell-derived neurons. However, among these biomaterials, the magnetic materials applied in guiding the neuronal growth are still fewer than the other materials, such as the fibers. So in this work, we developed the magnetic nanochains to guide the oriented growth of neural stem cell-derived neurons. With the guidance of the magnetic nanochains, the seeded neural stem cells exhibited a good arrangement, and the neural stem cell-derived neurons showed well-oriented growth with the orientation of the nanochains. We anticipated that the magnetic nanochains would have huge potential in stem cell-based nerve regeneration.

Tetrandrine Prevents Neomycin-Induced Ototoxicity by Promoting Steroid Biosynthesis.

Aminoglycoside antibiotics are widely used for the treatment of serious acute infections, life-threatening sepsis, and tuberculosis, but all aminoglycosides cause side effects, especially irreversible ototoxicity. The mechanisms underlying the ototoxicity of aminoglycosides need further investigation, and there are no effective drugs in the clinic. Here we showed that tetrandrine (TET), a bioactive bisbenzylisoquinoline alkaloid derived from Stephania tetrandra, ameliorated neomycin-induced cochlear hair cell injury. In both in vitro and in vivo experiments we found that TET administration significantly improved auditory function and reduced hair cell damage after neomycin exposure. In addition, we observed that TET could significantly decrease oxidative stress and apoptosis in hair cells after neomycin exposure. Finally, RNA-seq analysis suggested that TET protected against neomycin-induced ototoxicity mainly by promoting steroid biosynthesis. Collectively, our results provide pharmacological evidence showing that TET may be a promising agent in preventing aminoglycosides-induced ototoxicity.

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.