Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Her...Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Here,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory mechanisms.We established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 hours.We found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with tranylcypromine.The noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with saline.These findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell loss.Additionally,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy pathway.Tranylcypromine treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)production.In conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing function.These findings suggest that inhibiting lysine-specific demethylase 1 is a potential therapeutic strategy for preventing hair cell loss and noise-induced hearing loss.展开更多
Cochlear implantation(CI)is currently recognized as the most effective treatment for severe to profound sensorineural deafness and is considered one of the most successful neural prostheses.Since its inception in 1961...Cochlear implantation(CI)is currently recognized as the most effective treatment for severe to profound sensorineural deafness and is considered one of the most successful neural prostheses.Since its inception in 1961,cochlear implantation has expanded its range of applications to encompass younger newborns,older people,and individuals with unilateral hearing loss.In addition,it has improved its surgical methods to minimize the occurrence of complications.Furthermore,notable advancements have been made in the design of electrodes,techniques for speech processing,and software for programming.Nevertheless,inflammation,fibrosis,and even ossification are observed in the cochlea of nearly all cochlear implant(CI)patients.These tissue responses might have a negative impact on the performance of the implants,residual hearing,and the results of post-operative CI rehabilitation.Animal models are significant translational tools that offer essential preclinical data for possible therapeutics.Thus,this study concentrates on the existing animal models used for cochlear implantation,highlights the advancements made in research,and offers insights into potential future research areas.展开更多
Purpose: To analyze the effect of right versus left long-term single-sided deafness(SSD) on sound source localization(SSL), discuss the necessity of intervention and treatment for SSD patients, and analyze the therape...Purpose: To analyze the effect of right versus left long-term single-sided deafness(SSD) on sound source localization(SSL), discuss the necessity of intervention and treatment for SSD patients, and analyze the therapeutic effect of long-term unilateral cochlear implantation(UCI) from the perspective of SSL.Methods: This study included 25 patients with SSD, 11 patients with UCI, and 30 participants with normal hearing(NH). Their SSL ability was tested by obtaining their average root mean square(RMS) error values of SSL test.Results: The results showed that the RMS error value of SSD, UCI and NH groups were 52.26 ± 20.25°, 69.84 ±12.14° and 4.27 ± 2.66°, respectively. The ability of SSL was better in the SSD-L group than that in the SSD-R group, and no significant difference existed in the SSD-R and the UCI group.Conclusion: When bilateral deafness patients select unilateral treatment, right-side cochlear implantation may be more beneficial in terms of SSL, which means that the central auditory cortex in long-term SSD patients is affected differently based on which side their deafness occurs.展开更多
Subjective tinnitus is the most common type of tinnitus, which is the manifestation of pathologicalactivities in the brain. It happens in a substantial portion of the general population and brings significantburden to...Subjective tinnitus is the most common type of tinnitus, which is the manifestation of pathologicalactivities in the brain. It happens in a substantial portion of the general population and brings significantburden to the society. Severe subjective tinnitus can lead to depression and insomnia and severely affectspatients’ quality of life. However, due to poor understanding of its etiology and pathogenesis, treatmentof subjective tinnitus remains challenging. In recent decades, a growing number of studies have shownthat subjective tinnitus is related to lesion-induced neural plasticity of auditory and non-auditory centralsystems. This article reviews cellular mechanisms of neural plasticity in subjective tinnitus to providefurther understanding of its pathogenesis.展开更多
Objective: To understand the crucial role of the klotho gene in hearing development in mouse models.Methods: PCR was used to identify CBA mice with different genotypes, i.e. WT, heterozygous(klotho +/-)or homozygous(k...Objective: To understand the crucial role of the klotho gene in hearing development in mouse models.Methods: PCR was used to identify CBA mice with different genotypes, i.e. WT, heterozygous(klotho +/-)or homozygous(klotho-/-). Mice phenotype and weight were recorded postnatal 25 days(P-25) and auditory brainstem responses(ABR) were used to determine auditory function at P-60.Results: klotho-/-mice tended to have smaller size, lighter weight and higher ABR thresholds at P-60,showing early onset age-related hearing loss(ARHL).Conclusion: Heterozygous and homozygous klotho deficient mice exhibit different degrees of hearing loss at young age, with homozygous mice(klotho-/-) showing more severe hearing loss. Our results indicate that persisted expression of klotho protein in the inner ear may potentially delay the onset of ARHL and play an important role in the protection of auditory function.展开更多
Cell-cell junctions in the cochlea are highly complex and well organized. The role of these junctions is to maintain structural and functional integrity of the cochlea. In this review, we describe classification of ce...Cell-cell junctions in the cochlea are highly complex and well organized. The role of these junctions is to maintain structural and functional integrity of the cochlea. In this review, we describe classification of cell junction-associated proteins identified within the cochlea and provide a brief overview of the function of these proteins in adherent junctions, gap junctions and tight junctions. Copyright ? 2016, PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).展开更多
The development of auditory synapses is a key process for the maturation of heating function. However, it is still on debate regaralng wnemer the development of auditory synapses is dominated by acquired sound stimula...The development of auditory synapses is a key process for the maturation of heating function. However, it is still on debate regaralng wnemer the development of auditory synapses is dominated by acquired sound stimulations. In this review, we summarize relevant publications in recent decades to address this issue. Most reported data suggest that extrinsic sound stimulations do affect, but not govern the development of periphery auditory synapses. Overall, periphery auditory synapses develop and mature according to its intrinsic mechanism to build up the synaptic connections between sensory neurons and/or interneurons.展开更多
Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness.The rapid development of nanodrug delivery systems based on hydrogel has provided a new...Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness.The rapid development of nanodrug delivery systems based on hydrogel has provided a new opportunity.Among them,thermo-sensitive hydrogels promote the development of new dosage form for intratympanic injection.This smart biomaterial could transform to semisolid phase when the temperature increased.Thermo-sensitive hydrogel nanodrug delivery system is expected to achieve safe,efficient,and sustained inner ear drug administration.This article introduces the key techniques and the latest progress in this field.展开更多
Mini pig models are large mammals and their ears are more similar with human beings in structure and development than other animals.However,the study on porcine ears is still in the initial stage and there is no descr...Mini pig models are large mammals and their ears are more similar with human beings in structure and development than other animals.However,the study on porcine ears is still in the initial stage and there is no description of an ideal operation approach to endocochlear potential and potassium ion concentration measurements.In this article,we describe a pre-auricular surgical approach to access the middle and inner ear for endocochlear potential and potassium ion concentration measures in mini pig models.Ten one-week old normal mini pigs were used in the study.The bulla of the temporal bone was accessed via a pre-auricular approach for endocochlear potential and potassium ion concentration measurements.The condition of the animals during the first post—experiment 24 h was observed.One animal died during surgery.The preauricular approach improved protection and preservation of relevant nervous and vascular elements including the facial nerve and carotid artery.So,the pre-auricular approach can be used for endocochlear potential and potassium ion concentration measurements with improved nerve and artery preservation mini pigs.展开更多
Objective: The aim of this study was to improve muscle flaps and to evaluate surgical outcomes with the use of a novel specialized retractor, which is a surgical instrument used to locate and shape a bony seat for min...Objective: The aim of this study was to improve muscle flaps and to evaluate surgical outcomes with the use of a novel specialized retractor, which is a surgical instrument used to locate and shape a bony seat for minimally invasive cochlear implantation.Methods: 50 patients aged 1 e75 years with sensorineural hearing loss who required cochlear implantation were recruited. A small incision(<3 cm) was made, and the novel specialized retractor was used in the study group during cochlear implantation. The incision length, surgical outcomes and operative time were recorded and analyzed.Results: The incision length, total operative time and drilling bony time were shorter in the study group than in the control group(P < 0.05, respectively). All patients recovered well after the surgery without any severe complications.Conclusion: The use of a novel specialized retractor standardized the surgical processes of cochlear implantation. The retractor helped locate and control the size of the bony well during bone drilling. The tool reduced the technical difficulty and improved the efficacy of this minimally invasive operation.展开更多
Object： To identify transcript variants and expression patterns of porcine Mitf. Materials and methods： A pairwise BLAST search at NCBI database was performed to deduce the structure of porcine Mitf gene. Subsequent...Object： To identify transcript variants and expression patterns of porcine Mitf. Materials and methods： A pairwise BLAST search at NCBI database was performed to deduce the structure of porcine Mitf gene. Subsequently, 5＇ RACE and fluorescent quantitative RT-PCR were used to analyze the expression pattern of porcine Mitf in different tissues. Results： Four transcript variants of porcine Mitf, MITF-A, MITF-H, MITF-M and MITF-SUS were identified, all sharing high homology with those in humans, except Mitf-SUS.Conclusion： The sequence of porcine Mitf appear highly homologous to human MITF. However, only 4 transcript variants of porcine Mitf were identified in these minipigs, less than the 9 transcript variants in human MITF.展开更多
Objective:To report detection of vestibular-evoked myogenic potentials (VEMPs) in the miniature pig. Methods:Potentials evoked by 1000 Hz tone bursts were recorded from neck extensor muscles and the masseter muscles i...Objective:To report detection of vestibular-evoked myogenic potentials (VEMPs) in the miniature pig. Methods:Potentials evoked by 1000 Hz tone bursts were recorded from neck extensor muscles and the masseter muscles in normal adult Bama miniature pigs anesthetized with 3%pentobarbital sodium and Carbachol II. Results:The latency of the first positive wave P from neck extensor muscles was 7.65 ± 0.64 ms, with an amplitude of 1.66 ± 0.34 uv and a rate of successful induction of 75%at 80 dB SPL. The latency of potentials evoked from the masseter muscles was 7.60 ± 0.78 ms, with an amplitude of 1.31 ± 0.28 uv and a rate successful induction of 66%at 80 dB SPL. Conclusion:The latencies and thresholds of VEMPs recorded from the neck extensor muscle and the masseter muscle appear to be comparable in normal adult Bama miniature pigs, although the amplitude recorded from the neck extensor muscle seems to be higher than that from the masseter muscle. However, because of their usually relatively superficial and easily accessible location, as well as their large volume and strong contractions, masseter muscles may be better target muscles for recording myogenic potentials.展开更多
Endoscopic submucosal dissection(ESD)is a common procedure to treat early and precancerous gastrointestinal lesions.Via submucosal injection,a liquid cushion is created to lift and separate the lesion and malignant pa...Endoscopic submucosal dissection(ESD)is a common procedure to treat early and precancerous gastrointestinal lesions.Via submucosal injection,a liquid cushion is created to lift and separate the lesion and malignant part from the muscular layer where the formed indispensable space is convenient for endoscopic incision.Saline is a most common submucosal injection liquid,but the formed liquid pad lasts only a short time,and thus repeated injections increase the potential risk of adverse events.Hydrogels with high osmotic pressure and high viscosity are used as an alternate;however,with some drawbacks such as tissue damage,excessive injection resistance,and high cost.Here,we reported a nature derived hydrogel of gelatin-oxidized alginate(G-OALG).Based on the rheological analysis and compare to commercial endoscopic mucosal resection(EMR)solution(0.25%hyaluronic acid,HA),a designed G-OALG hydrogel of desired concentration and composition showed higher performances in controllable gelation and injectability,higher viscosity and more stable structures.The G-OALG gel also showed lower propulsion resistance than 0.25%HA in the injection force assessment under standard endoscopic instruments,which eased the surgical operation.In addition,the G-OALG hydrogel showed good in vivo degradability biocompatibility.By comparing the results acquired via ESD to normal saline,the G-OALG shows great histocompatibility and excellent endoscopic injectability,and enables create a longer-lasting submucosal cushion.All the features have been confirmed in the living both pig and rat models.The G-OALG could be a promising submucosal injection agent for esophageal ESD.展开更多
SOX10 is a causative gene of Waardenburg syndrome(WS)that is a rare genetic disorder characterized by hearing loss and pigment disturbance.More than 100 mutations of SOX10 have been found in patients with Type 2 WS(WS...SOX10 is a causative gene of Waardenburg syndrome(WS)that is a rare genetic disorder characterized by hearing loss and pigment disturbance.More than 100 mutations of SOX10 have been found in patients with Type 2 WS(WS2),Type 4 WS(WS4),and more complex syndromes.However,no mutation hotspot has been detected in SOX10,and most cases are sporadic,making it difficult to establish a correlation between the high phenotypic and genetic variability.In this study,a duplication of the 321th cytosine(c.321dupC)was introduced into SOX10 in pigs,which induced premature termination of the translation of SOX10(p.K108QfsX45).The premature stop codon in Exon 3 triggered the degradation of mutant mRNA through nonsense-mediated mRNA decay.However,SOX10^(c.321dupC) induced a highly similar phenotype of WS2 with heterogeneous inner ear malformation compared with its adjacent missense mutation SOX10^(c.325A>T).In addition,a site-saturation mutation analysis of the SOX10 N-terminal nuclear localization signal(n-NLS),where these two mutations located,revealed the correlation between SOX10 haploinsufficiency and WS by an in vitro reporter assay.The analysis combining the in vitro assay with clinical cases may provide a clue to clinical diagnoses.展开更多
Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people worldwide.However,the presence of the blood-labyrinth barrier(BLB)on the surface of the inner ear capillaries great...Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people worldwide.However,the presence of the blood-labyrinth barrier(BLB)on the surface of the inner ear capillaries greatly hinders the effectiveness of systemic drugs for prevention and intervention due to the low permeability,which restricts the entry of most drug compounds from the bloodstream into the inner ear tissue.Here,we report the finding of a novel receptor,low-density lipoprotein receptor-related protein 1(LRP1),that is expressed on the BLB,as a potential target for shuttling therapeutics across this barrier.As a proof-ofconcept,we developed an LRP1-binding peptide,IETP2,and covalently conjugated a series of model small-molecule compounds to it,including potential drugs and imaging agents.All compounds were successfully delivered into the inner ear and inner ear lymph,indicating that targeting the receptor LRP1 is a promising strategy to enhance the permeability of the BLB.The discovery of the receptor LRP1 will illuminate developing strategies for crossing the BLB and for improving systemic drug delivery for inner ear disorders.展开更多
The interaction between the gastric epithelium and immune cells plays key roles in H. pylori-associated pathology. Here, we demonstrate a procolonization and proinflammatory role of tubulointerstitial nephritis antige...The interaction between the gastric epithelium and immune cells plays key roles in H. pylori-associated pathology. Here, we demonstrate a procolonization and proinflammatory role of tubulointerstitial nephritis antigen-like 1 (TINAGL1), a newly discovered matricellular protein, in H. pylori infection. Increased TINAGL1 production by gastric epithelial cells (GECs) in the infected gastric mucosa was synergistically induced by H. pylori and IL-1β via the ERK-SP1 pathway in a cagA-dependent manner. Elevated human gastric TINAGL1 correlated with H. pylori colonization and the severity of gastritis, and mouse TINAGL1 derived from non-bone marrow-derived cells promoted bacterial colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Tinagl1−/− and Tinagl1ΔGEC mice and were increased in mice injected with mouse TINAGL1. Mechanistically, TINAGL1 suppressed CCL21 expression and promoted CCL2 production in GECs by directly binding to integrin α5β1 to inhibit ERK and activate the NF-κB pathway, respectively, which not only led to decreased gastric influx of moDCs via CCL21-CCR7-dependent migration and, as a direct consequence, reduced the bacterial clearance capacity of the H. pylori-specific Th1 response, thereby promoting H. pylori colonization, but also resulted in increased gastric influx of Ly6Chigh monocytes via CCL2-CCR2-dependent migration. In turn, TINAGL1 induced the production of the proinflammatory protein S100A11 by Ly6Chigh monocytes, promoting H. pylori-associated gastritis. In summary, we identified a model in which TINAGL1 collectively ensures H. pylori persistence and promotes gastritis.展开更多
Introduction:With the spread of the epidemic worldwide,an increasing number of doctors abroad have observed the following atypical symptoms of coronavirus disease 2019(COVID-19):olfactory or taste disorders.Therefore,...Introduction:With the spread of the epidemic worldwide,an increasing number of doctors abroad have observed the following atypical symptoms of coronavirus disease 2019(COVID-19):olfactory or taste disorders.Therefore,clarifying the incidence and clinical characteristics of olfactory and taste disorders in Chinese COVID-19 patients is of great significance and urgency.Materials and Methods:A retrospective study was conducted,which included 229 severe acute respiratory syndrome coronavirus 2 confirmed patients,through face-to-face interviews and telephone follow-up.Following the completion of questionnaires,the patients participating in the study,were categorized according to the degree of olfactory and taste disorders experienced,and the proportion of each clinical type of patient with olfactory and taste disorders and the time when symptoms appeared were recorded.Results:Among the 229 patients,31(13.54%)had olfactory dysfunction,and 44(19.21%)had gustatory dysfunction.For the patients with olfactory dysfunction,6(19.35%)developed severe disease and became critically ill.Olfactory dysfunction appeared before the other symptoms in 21.43%of cases.The proportion of females with olfactory and gustatory dysfunction was higher than that of males(P<0.001).Conclusions:The incidence of olfactory and gustatory dysfunction was much lower than that reported abroad;the prognosis of patients with olfactory dysfunction is relatively favorable;olfactory and gustatory dysfunction can be used as a sign for early screening;females are more prone to olfactory and gustatory dysfunction.展开更多
基金supported by the National Key Research and Development Program of China,No.2022YFC2402701(to WC)Key International(Regional)Joint Research Program of the National Natural Science Foundation of China,No.81820108009(to SY)+5 种基金the National Natural Science Foundation of China,Nos.81970890(to WC)and 82371148(to WG)Fujian Provincial Healthcare Young and Middle-aged Backbone Talent Training Project,No.2023GGA035(to XC)Spring City Planthe High-level Talent Promotion and Training Project of Kunming,No.2022SCP001(to SY)the Natural Science Foundation of Hainan Province of China,No.824MS052(to XS)the Sixth Medical Center of Chinese PLA General Hospital Innovation Cultivation,No.CXPY202116(to LX)。
文摘Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Here,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory mechanisms.We established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 hours.We found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with tranylcypromine.The noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with saline.These findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell loss.Additionally,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy pathway.Tranylcypromine treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)production.In conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing function.These findings suggest that inhibiting lysine-specific demethylase 1 is a potential therapeutic strategy for preventing hair cell loss and noise-induced hearing loss.
基金supported by the following:(1)National Natural Science Foundation of China(NSFC#82000976)to Jianan Li(2)National Key Research and Development Program of China(2022YFC2402700)to Wei Chen.
文摘Cochlear implantation(CI)is currently recognized as the most effective treatment for severe to profound sensorineural deafness and is considered one of the most successful neural prostheses.Since its inception in 1961,cochlear implantation has expanded its range of applications to encompass younger newborns,older people,and individuals with unilateral hearing loss.In addition,it has improved its surgical methods to minimize the occurrence of complications.Furthermore,notable advancements have been made in the design of electrodes,techniques for speech processing,and software for programming.Nevertheless,inflammation,fibrosis,and even ossification are observed in the cochlea of nearly all cochlear implant(CI)patients.These tissue responses might have a negative impact on the performance of the implants,residual hearing,and the results of post-operative CI rehabilitation.Animal models are significant translational tools that offer essential preclinical data for possible therapeutics.Thus,this study concentrates on the existing animal models used for cochlear implantation,highlights the advancements made in research,and offers insights into potential future research areas.
基金supported by the National Key Research and Development Project of China(2020YFC20052003 to S.M.Yang)Key International(Regional)Joint Research Program of National Natural Science Foundation of China(NSFC#81820108009 to S.M.Yang)National Natural Science Foundation of China(NSFC#82000976 to J.N.Li).
文摘Purpose: To analyze the effect of right versus left long-term single-sided deafness(SSD) on sound source localization(SSL), discuss the necessity of intervention and treatment for SSD patients, and analyze the therapeutic effect of long-term unilateral cochlear implantation(UCI) from the perspective of SSL.Methods: This study included 25 patients with SSD, 11 patients with UCI, and 30 participants with normal hearing(NH). Their SSL ability was tested by obtaining their average root mean square(RMS) error values of SSL test.Results: The results showed that the RMS error value of SSD, UCI and NH groups were 52.26 ± 20.25°, 69.84 ±12.14° and 4.27 ± 2.66°, respectively. The ability of SSL was better in the SSD-L group than that in the SSD-R group, and no significant difference existed in the SSD-R and the UCI group.Conclusion: When bilateral deafness patients select unilateral treatment, right-side cochlear implantation may be more beneficial in terms of SSL, which means that the central auditory cortex in long-term SSD patients is affected differently based on which side their deafness occurs.
基金This work was supported by the National Natural Science Foundation of China under Grant[81820108009]Beijing Municipal Science and Technology Commission under Grant[Z161100000116038]+3 种基金Beijing Municipal Health Commission under Grant[2016-1-5014]Beijing Nova Program[Z201100006820133]the National Key Research and Development Project[2019YFC0121302]the National Key Research and Development Project[2019YFC0840707].
文摘Subjective tinnitus is the most common type of tinnitus, which is the manifestation of pathologicalactivities in the brain. It happens in a substantial portion of the general population and brings significantburden to the society. Severe subjective tinnitus can lead to depression and insomnia and severely affectspatients’ quality of life. However, due to poor understanding of its etiology and pathogenesis, treatmentof subjective tinnitus remains challenging. In recent decades, a growing number of studies have shownthat subjective tinnitus is related to lesion-induced neural plasticity of auditory and non-auditory centralsystems. This article reviews cellular mechanisms of neural plasticity in subjective tinnitus to providefurther understanding of its pathogenesis.
基金supported by the National Nature Science Foundation of China(81470684,21405130)Postdoctoral Science Foundation of China (2015M571818)+5 种基金Clinical Special Fund of Jiangsu Province (b12014032)Six Major Categories Talent (2014WSN-043,2011-WS-074)Jiangsu Provincial University Fund (16621632)Innovation and Entrepreneurship Training Program for College Students in Jiangsu Province (KYLX14-1455,201610313002Z)Colleges and universities Foundation in Jiangsu Province(16621632,16KJB320016)Nature Science planning Foundation of Xuzhou (KC17087)
文摘Objective: To understand the crucial role of the klotho gene in hearing development in mouse models.Methods: PCR was used to identify CBA mice with different genotypes, i.e. WT, heterozygous(klotho +/-)or homozygous(klotho-/-). Mice phenotype and weight were recorded postnatal 25 days(P-25) and auditory brainstem responses(ABR) were used to determine auditory function at P-60.Results: klotho-/-mice tended to have smaller size, lighter weight and higher ABR thresholds at P-60,showing early onset age-related hearing loss(ARHL).Conclusion: Heterozygous and homozygous klotho deficient mice exhibit different degrees of hearing loss at young age, with homozygous mice(klotho-/-) showing more severe hearing loss. Our results indicate that persisted expression of klotho protein in the inner ear may potentially delay the onset of ARHL and play an important role in the protection of auditory function.
基金supported by grants from the National Basic Research Program of China (973 Program) (#2012CB967900)the Major State Basic Research Development Program of China (973 Program) (#2011CBA01000)+1 种基金the National Nature Science Foundation of China (NSFC#81400472)the National Natural Science Foundation of China (NSFC #81271082)
文摘Cell-cell junctions in the cochlea are highly complex and well organized. The role of these junctions is to maintain structural and functional integrity of the cochlea. In this review, we describe classification of cell junction-associated proteins identified within the cochlea and provide a brief overview of the function of these proteins in adherent junctions, gap junctions and tight junctions. Copyright ? 2016, PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
基金supported by grants from the National Basic Research Program of China(973Program)(2012CB9679002012CB967901)+3 种基金Beijing Natural Science Foundation(5122040)supported by grants from the China Postdoctoral Science Foundation(20100377920100470103)the National Natural Science Foundation of China(NSFC)(31040038)
文摘The development of auditory synapses is a key process for the maturation of heating function. However, it is still on debate regaralng wnemer the development of auditory synapses is dominated by acquired sound stimulations. In this review, we summarize relevant publications in recent decades to address this issue. Most reported data suggest that extrinsic sound stimulations do affect, but not govern the development of periphery auditory synapses. Overall, periphery auditory synapses develop and mature according to its intrinsic mechanism to build up the synaptic connections between sensory neurons and/or interneurons.
基金supported by the national key R&D program(2022YFC2402703).
文摘Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness.The rapid development of nanodrug delivery systems based on hydrogel has provided a new opportunity.Among them,thermo-sensitive hydrogels promote the development of new dosage form for intratympanic injection.This smart biomaterial could transform to semisolid phase when the temperature increased.Thermo-sensitive hydrogel nanodrug delivery system is expected to achieve safe,efficient,and sustained inner ear drug administration.This article introduces the key techniques and the latest progress in this field.
基金supported by grants from the National Basic Research Program of China(973 Program)(2012CB967900. 2012CB967901)the National Nature Science Foundation of China(NSFC81400472)
文摘Mini pig models are large mammals and their ears are more similar with human beings in structure and development than other animals.However,the study on porcine ears is still in the initial stage and there is no description of an ideal operation approach to endocochlear potential and potassium ion concentration measurements.In this article,we describe a pre-auricular surgical approach to access the middle and inner ear for endocochlear potential and potassium ion concentration measures in mini pig models.Ten one-week old normal mini pigs were used in the study.The bulla of the temporal bone was accessed via a pre-auricular approach for endocochlear potential and potassium ion concentration measurements.The condition of the animals during the first post—experiment 24 h was observed.One animal died during surgery.The preauricular approach improved protection and preservation of relevant nervous and vascular elements including the facial nerve and carotid artery.So,the pre-auricular approach can be used for endocochlear potential and potassium ion concentration measurements with improved nerve and artery preservation mini pigs.
基金supported by the Special Funds for National Excellent Doctoral Dissertation of Higher Education from the Ministry of Education (Project Number: 2007B67)the National Major Research Project (2014CB943003)
文摘Objective: The aim of this study was to improve muscle flaps and to evaluate surgical outcomes with the use of a novel specialized retractor, which is a surgical instrument used to locate and shape a bony seat for minimally invasive cochlear implantation.Methods: 50 patients aged 1 e75 years with sensorineural hearing loss who required cochlear implantation were recruited. A small incision(<3 cm) was made, and the novel specialized retractor was used in the study group during cochlear implantation. The incision length, surgical outcomes and operative time were recorded and analyzed.Results: The incision length, total operative time and drilling bony time were shorter in the study group than in the control group(P < 0.05, respectively). All patients recovered well after the surgery without any severe complications.Conclusion: The use of a novel specialized retractor standardized the surgical processes of cochlear implantation. The retractor helped locate and control the size of the bony well during bone drilling. The tool reduced the technical difficulty and improved the efficacy of this minimally invasive operation.
基金supported by grants from the Major State Basic Research Development Program of China(973 Program)(#2011CBA01000)the National Basic Research Program of China(973 Program)(#2012CB967900)the National Natural Science Foundation of China(81400472)
文摘Object： To identify transcript variants and expression patterns of porcine Mitf. Materials and methods： A pairwise BLAST search at NCBI database was performed to deduce the structure of porcine Mitf gene. Subsequently, 5＇ RACE and fluorescent quantitative RT-PCR were used to analyze the expression pattern of porcine Mitf in different tissues. Results： Four transcript variants of porcine Mitf, MITF-A, MITF-H, MITF-M and MITF-SUS were identified, all sharing high homology with those in humans, except Mitf-SUS.Conclusion： The sequence of porcine Mitf appear highly homologous to human MITF. However, only 4 transcript variants of porcine Mitf were identified in these minipigs, less than the 9 transcript variants in human MITF.
基金supported by grants from the National Basic Research Program of China (973 Program) (#2012CB967900)National Natural Science Foundation of China (31300624, 81470684)+3 种基金Postdoctoral Science Foundation of China(2015M571818)Six Major Categories Talent (2014-WSN043, 2011-WS-074)Innovation and Entrepreneurship Training Program for College Students in Jiangsu Province (201510313003Z, 201510313003, KYLX14-1455)Clinic Medical Special Foundation Of Jiangsu Province (b12014032)
文摘Objective:To report detection of vestibular-evoked myogenic potentials (VEMPs) in the miniature pig. Methods:Potentials evoked by 1000 Hz tone bursts were recorded from neck extensor muscles and the masseter muscles in normal adult Bama miniature pigs anesthetized with 3%pentobarbital sodium and Carbachol II. Results:The latency of the first positive wave P from neck extensor muscles was 7.65 ± 0.64 ms, with an amplitude of 1.66 ± 0.34 uv and a rate of successful induction of 75%at 80 dB SPL. The latency of potentials evoked from the masseter muscles was 7.60 ± 0.78 ms, with an amplitude of 1.31 ± 0.28 uv and a rate successful induction of 66%at 80 dB SPL. Conclusion:The latencies and thresholds of VEMPs recorded from the neck extensor muscle and the masseter muscle appear to be comparable in normal adult Bama miniature pigs, although the amplitude recorded from the neck extensor muscle seems to be higher than that from the masseter muscle. However, because of their usually relatively superficial and easily accessible location, as well as their large volume and strong contractions, masseter muscles may be better target muscles for recording myogenic potentials.
基金the the National Science Foundation of China(No.81802982)ChongQing Science&Technology Commission Fund(No.CSTC2018jcyjAX0102).
文摘Endoscopic submucosal dissection(ESD)is a common procedure to treat early and precancerous gastrointestinal lesions.Via submucosal injection,a liquid cushion is created to lift and separate the lesion and malignant part from the muscular layer where the formed indispensable space is convenient for endoscopic incision.Saline is a most common submucosal injection liquid,but the formed liquid pad lasts only a short time,and thus repeated injections increase the potential risk of adverse events.Hydrogels with high osmotic pressure and high viscosity are used as an alternate;however,with some drawbacks such as tissue damage,excessive injection resistance,and high cost.Here,we reported a nature derived hydrogel of gelatin-oxidized alginate(G-OALG).Based on the rheological analysis and compare to commercial endoscopic mucosal resection(EMR)solution(0.25%hyaluronic acid,HA),a designed G-OALG hydrogel of desired concentration and composition showed higher performances in controllable gelation and injectability,higher viscosity and more stable structures.The G-OALG gel also showed lower propulsion resistance than 0.25%HA in the injection force assessment under standard endoscopic instruments,which eased the surgical operation.In addition,the G-OALG hydrogel showed good in vivo degradability biocompatibility.By comparing the results acquired via ESD to normal saline,the G-OALG shows great histocompatibility and excellent endoscopic injectability,and enables create a longer-lasting submucosal cushion.All the features have been confirmed in the living both pig and rat models.The G-OALG could be a promising submucosal injection agent for esophageal ESD.
基金The authors thank Dr.Yi Wu and Na Chen for help with three-dimensional reconstruction.They also thank Dr.Lei Chen for providing plasmids.This study was supported by grants from the National Natural Science Foundation of China,China(81670941 and 81670940)the National Science and Technology Major Project for Transgenic Organisms(2016ZX08009-003 and 2018ZX08010-10B),China.
文摘SOX10 is a causative gene of Waardenburg syndrome(WS)that is a rare genetic disorder characterized by hearing loss and pigment disturbance.More than 100 mutations of SOX10 have been found in patients with Type 2 WS(WS2),Type 4 WS(WS4),and more complex syndromes.However,no mutation hotspot has been detected in SOX10,and most cases are sporadic,making it difficult to establish a correlation between the high phenotypic and genetic variability.In this study,a duplication of the 321th cytosine(c.321dupC)was introduced into SOX10 in pigs,which induced premature termination of the translation of SOX10(p.K108QfsX45).The premature stop codon in Exon 3 triggered the degradation of mutant mRNA through nonsense-mediated mRNA decay.However,SOX10^(c.321dupC) induced a highly similar phenotype of WS2 with heterogeneous inner ear malformation compared with its adjacent missense mutation SOX10^(c.325A>T).In addition,a site-saturation mutation analysis of the SOX10 N-terminal nuclear localization signal(n-NLS),where these two mutations located,revealed the correlation between SOX10 haploinsufficiency and WS by an in vitro reporter assay.The analysis combining the in vitro assay with clinical cases may provide a clue to clinical diagnoses.
基金supported by following funds:National Key Research and Development project of China(2020YFC20052003,to S.Y.)National Science and Technology Major Project for Major New Drugs Innovation and Development under grant(2018ZX09711003,to W.Z.)+3 种基金Key International(Regional)Joint Research Program of National Nature Science Foundation of China(81820108009,to S.Y.)National Nature Science Foundation of China(81800916 to X.S.,31471299 and 81522046 to J.L.)The Nature Science Foundation of Xuzhou(KC20177 to X.S.)Jiangsu Provincial University Fund(19KJA560002 to X.S.).
文摘Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people worldwide.However,the presence of the blood-labyrinth barrier(BLB)on the surface of the inner ear capillaries greatly hinders the effectiveness of systemic drugs for prevention and intervention due to the low permeability,which restricts the entry of most drug compounds from the bloodstream into the inner ear tissue.Here,we report the finding of a novel receptor,low-density lipoprotein receptor-related protein 1(LRP1),that is expressed on the BLB,as a potential target for shuttling therapeutics across this barrier.As a proof-ofconcept,we developed an LRP1-binding peptide,IETP2,and covalently conjugated a series of model small-molecule compounds to it,including potential drugs and imaging agents.All compounds were successfully delivered into the inner ear and inner ear lymph,indicating that targeting the receptor LRP1 is a promising strategy to enhance the permeability of the BLB.The discovery of the receptor LRP1 will illuminate developing strategies for crossing the BLB and for improving systemic drug delivery for inner ear disorders.
基金supported by grants from the National Natural Science Foundation of China(82070578,81870394,82000530 and 81670510)Chongqing Natural Science Fund for Distinguished Young Scholars(cstc2019jcyjjqX0003)+2 种基金Science Innovation Capacity Promotion Project of Army Medical University(2019XQY03)National Key Research and Development Program of China(2016YFC1302200)Collaborative Innovation Center of Chinese Ministry of Education(2020-39).
文摘The interaction between the gastric epithelium and immune cells plays key roles in H. pylori-associated pathology. Here, we demonstrate a procolonization and proinflammatory role of tubulointerstitial nephritis antigen-like 1 (TINAGL1), a newly discovered matricellular protein, in H. pylori infection. Increased TINAGL1 production by gastric epithelial cells (GECs) in the infected gastric mucosa was synergistically induced by H. pylori and IL-1β via the ERK-SP1 pathway in a cagA-dependent manner. Elevated human gastric TINAGL1 correlated with H. pylori colonization and the severity of gastritis, and mouse TINAGL1 derived from non-bone marrow-derived cells promoted bacterial colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Tinagl1−/− and Tinagl1ΔGEC mice and were increased in mice injected with mouse TINAGL1. Mechanistically, TINAGL1 suppressed CCL21 expression and promoted CCL2 production in GECs by directly binding to integrin α5β1 to inhibit ERK and activate the NF-κB pathway, respectively, which not only led to decreased gastric influx of moDCs via CCL21-CCR7-dependent migration and, as a direct consequence, reduced the bacterial clearance capacity of the H. pylori-specific Th1 response, thereby promoting H. pylori colonization, but also resulted in increased gastric influx of Ly6Chigh monocytes via CCL2-CCR2-dependent migration. In turn, TINAGL1 induced the production of the proinflammatory protein S100A11 by Ly6Chigh monocytes, promoting H. pylori-associated gastritis. In summary, we identified a model in which TINAGL1 collectively ensures H. pylori persistence and promotes gastritis.
文摘Introduction:With the spread of the epidemic worldwide,an increasing number of doctors abroad have observed the following atypical symptoms of coronavirus disease 2019(COVID-19):olfactory or taste disorders.Therefore,clarifying the incidence and clinical characteristics of olfactory and taste disorders in Chinese COVID-19 patients is of great significance and urgency.Materials and Methods:A retrospective study was conducted,which included 229 severe acute respiratory syndrome coronavirus 2 confirmed patients,through face-to-face interviews and telephone follow-up.Following the completion of questionnaires,the patients participating in the study,were categorized according to the degree of olfactory and taste disorders experienced,and the proportion of each clinical type of patient with olfactory and taste disorders and the time when symptoms appeared were recorded.Results:Among the 229 patients,31(13.54%)had olfactory dysfunction,and 44(19.21%)had gustatory dysfunction.For the patients with olfactory dysfunction,6(19.35%)developed severe disease and became critically ill.Olfactory dysfunction appeared before the other symptoms in 21.43%of cases.The proportion of females with olfactory and gustatory dysfunction was higher than that of males(P<0.001).Conclusions:The incidence of olfactory and gustatory dysfunction was much lower than that reported abroad;the prognosis of patients with olfactory dysfunction is relatively favorable;olfactory and gustatory dysfunction can be used as a sign for early screening;females are more prone to olfactory and gustatory dysfunction.
