Background:Saccades are often observed on video head impulse tests(vHIT)in patients with Meniere's Disease(MD)and Vestibular Migraine(VM).However,their saccadic features are not fully described.Objective:This stud...Background:Saccades are often observed on video head impulse tests(vHIT)in patients with Meniere's Disease(MD)and Vestibular Migraine(VM).However,their saccadic features are not fully described.Objective:This study aims to identify the saccades characteristics of MD and VM.Methods:75 VM patients and 103 definite unilateral MD patients were enrolled in this study.First raw saccades were exported and analyzed.The VM patients were divided into left and right based on their ears,while the MD patients were separated into affected and unaffected subgroups based on their audiograms and symptoms.Results:The MD patients have more saccades on the affected side(85%vs.69%),and saccade velocity is more consistent than the contralateral side(shown by the coefficient of variation).The saccades occurrence rates on both sides are similar in VM(77%vs.76%),as are other saccadic parameters.The MD patients have more significant inter-aural differences than the VM patients,manifested in higher velocity(p-value 0.000),earlier arriving(p-value 0.010),and more time-domain gathered(p-value 0.003)on the affected side.Conclusions:Bilateral saccades are commonly observed in MD and VM.In contrast to MD,saccades on VM are subtle,scattered,and late-arrived.Furthermore,the MD patients showed inconsistent saccadic distribution with more velocity-uniform saccades on the affected side.展开更多
Background:The National Natural Science Foundation of China(NSFC)is an important part of China’s innovation system.In the last decade,the pig has become more and more widely used in the field of medical science,espec...Background:The National Natural Science Foundation of China(NSFC)is an important part of China’s innovation system.In the last decade,the pig has become more and more widely used in the field of medical science,especially in otology research.Objective:By analyzing and summarizing the funding information over recent years,we intend to identify the characteristics and trends of funding for research using pig models and provide references for future development.Material and methods:This is a comprehensive analysis of features in funding for research projects involving pig models by the NSFC in the past 10 years,with a focus on projects in the field of otolaryngology/head and neck surgery.Results:Both the number and amount of funding provided by the NSFC for research involving pig models are on the rise with each passing year.Researchers at the PLA General Hospital have completed a number of studies using miniature pigs in cochlear morphology,electrophysiology,cochlear implantation,cochlear transcription analysis,gene therapy,inner ear disease modeling and Eustachian tube pathology modeling.Conclusion:Pigs as an ideal large mammal model are well suited in the current national basic research strategy in China,and can help further strengthen China’s leading position in basic research in the world.展开更多
To determine the prevalence and clinical features of olfactory and taste disorders among coronavirus disease 2019(COVID-19)patients in China.A cross-sectional study was performed in Wuhan from April 3,2020 to April 15...To determine the prevalence and clinical features of olfactory and taste disorders among coronavirus disease 2019(COVID-19)patients in China.A cross-sectional study was performed in Wuhan from April 3,2020 to April 15,2020.A total of 187 patients with confirmed severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)completed face-to-face interviews or telephone follow-ups.We found that the prevalence of olfactory and taste disorders was significantly lower in the Chinese cohort than in foreign COVID-19 cohorts.Females were more prone to olfactory and taste disorders.In some patients,olfactory and taste disorders precede other symptoms and can be used as early screening and warning signs.展开更多
The inflammasome is a multiprotein oligomer in the cell cytoplasm and is part of the innate immune system.It plays a crucial role in the pathological process of noise-induced hearing loss(NIHL).However,the mechanisms ...The inflammasome is a multiprotein oligomer in the cell cytoplasm and is part of the innate immune system.It plays a crucial role in the pathological process of noise-induced hearing loss(NIHL).However,the mechanisms of NLR family pyrin domain containing 3(NLRP3)inflammasome activation in NIHL have not been clearly demonstrated.In this study,miniature pigs were exposed to white noise at 120 dB(A)and auditory brainstem response measurements were used to measure their hearing function.Immunofluorescence staining,confocal laser scanning microscopy,western blot assay,and quantitative reverse transcription-polymerase chain reaction were used to analyze inflammasome-related protein distribution and expression.NLRP3,interleukin-1β,interleukin-18,and cleaved-caspase-1 were highly expressed in the cochlea after 120 dB(A)white noise exposure.Our findings suggest that NLRP3-inflammasomes in the cochlea may be activated after acoustic trauma,which may be an important mechanism of noise-induced hearing loss.展开更多
Neural crest(NC)is the primitive neural structure in embryonic stage,which develops from ectodermal neural plate cells and epithelial cells.When the neural fold forms into neural tube,neural crest also forms a cord li...Neural crest(NC)is the primitive neural structure in embryonic stage,which develops from ectodermal neural plate cells and epithelial cells.When the neural fold forms into neural tube,neural crest also forms a cord like structure above the neural tube and below the ectoderm.Neural crest cells(NCC)have strong migration and proliferation abilities.A number of tissue cells differentiate from neural crest cells,such as melanocytes,central and peripheral neurons,glial cells,craniofacial cells,osteoblasts,chondrocytes and smooth muscle cells.The migration and differentiation of neural crest cells are regulated by a gene network where a variety of genes,transcriptional factors,signal pathways and growth factors are involved.展开更多
Objective To investigate the genetic causes of sudden sensorineural hearing loss(SSNHL)patients in China.This study focused on analyzing variations of coding sequence of common genes related to deafness,revealing the ...Objective To investigate the genetic causes of sudden sensorineural hearing loss(SSNHL)patients in China.This study focused on analyzing variations of coding sequence of common genes related to deafness,revealing the molecular pathogenesis of sudden deafness from a genomics perspective,discovering molecular markers associated with the onset of deafness,and then supplying prevention to high-risk populations,classifying disease according to accurate etiology,and choosing a much more precision therapy.Methods We retrospectively analyzed the clinical characteristics of 51 patients diagnosed as SSNHL with vertigo treated in the Chinese PLA General Hospital.In this study,mutation screening of 307 nuclear genes and mitochondrial genome responsible for human or mouse deafness was performed on the 51 cases of unilateral sudden deafness patients with vertigo.Results We identified 51 cases of unilateral sudden deafness,including 2 cases of low-mid frequency hearing impairment,18 cases of mid-high frequency hearing loss,11 cases of flat-type hearing loss,and 20 cases of all frequency hearing loss.Among the 51 cases,8(15.69%)cases of GJB2 heterozygous variations,1(1.96%)case of GJB3 heterozygous variations,5(9.8%)cases of SLC26A4 heterozygous variations,2(3.92%)cases of COCH heterozygous variations,14(27.45%)cases of CDH23 heterozygous variations,14(27.45%)cases of OTOF heterozygous variations,1(1.96%)case of SLC17A8 heterozygous variations and 2(3.92%)cases of KCNE1 heterozygous variations.No mtDNA gene variations were identified.Conclusion SSNHL has some relationship with hereditary in Chinese population,but its complex genetic pathogenic mechanisms need further study.展开更多
Objective This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol(RSV)regulate necroptosis during Vibrio vulnificus(V.vulnificus)-induced sepsis and the potential mechanism.Methods T...Objective This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol(RSV)regulate necroptosis during Vibrio vulnificus(V.vulnificus)-induced sepsis and the potential mechanism.Methods The effect of RSV on V.vulnificus cytolysin(VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays.Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction,western blot,and immunohistochemistry and survival analyses were performed to elucidate the effect and mechanism of RSV on necroptosis in a V.vulnificus-induced sepsis mouse model.Results RSV relieved necroptosis induced by VVC in RAW264.7 and MLE12 cells.RSV also inhibited the inflammatory response,had a protective effect on histopathological changes,and reduced the expression level of the necroptosis indicator pMLKL in peritoneal macrophages,lung,spleen,and liver tissues of V.vulnificus-induced septic mice in vivo.Pretreatment with RSV downregulated the mRNA of the necroptosis indicator and protein expression in peritoneal macrophages and tissues of V.vulnificusinduced septic mice.RSV also improved the survival of V.vulnificus-induced septic mice.Conclusion Our findings collectively demonstrate that RSV prevented V.vulnificus-induced sepsis by attenuating necroptosis,highlighting its potency in the clinical management of V.vulnificus-induced sepsis.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
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
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
基金supported by grants from National Key Research and Development Program of China-part3(2020YFC2005203)Capital's Funds for Health Improvement and Research(No.2022-1-2023).
文摘Background:Saccades are often observed on video head impulse tests(vHIT)in patients with Meniere's Disease(MD)and Vestibular Migraine(VM).However,their saccadic features are not fully described.Objective:This study aims to identify the saccades characteristics of MD and VM.Methods:75 VM patients and 103 definite unilateral MD patients were enrolled in this study.First raw saccades were exported and analyzed.The VM patients were divided into left and right based on their ears,while the MD patients were separated into affected and unaffected subgroups based on their audiograms and symptoms.Results:The MD patients have more saccades on the affected side(85%vs.69%),and saccade velocity is more consistent than the contralateral side(shown by the coefficient of variation).The saccades occurrence rates on both sides are similar in VM(77%vs.76%),as are other saccadic parameters.The MD patients have more significant inter-aural differences than the VM patients,manifested in higher velocity(p-value 0.000),earlier arriving(p-value 0.010),and more time-domain gathered(p-value 0.003)on the affected side.Conclusions:Bilateral saccades are commonly observed in MD and VM.In contrast to MD,saccades on VM are subtle,scattered,and late-arrived.Furthermore,the MD patients showed inconsistent saccadic distribution with more velocity-uniform saccades on the affected side.
基金the key International(Regional)Joint Research Program of National Natural Science Foundation of China(NSFC#81820108009)National Natural Science Foundation of China(NSFC#81970895).
文摘Background:The National Natural Science Foundation of China(NSFC)is an important part of China’s innovation system.In the last decade,the pig has become more and more widely used in the field of medical science,especially in otology research.Objective:By analyzing and summarizing the funding information over recent years,we intend to identify the characteristics and trends of funding for research using pig models and provide references for future development.Material and methods:This is a comprehensive analysis of features in funding for research projects involving pig models by the NSFC in the past 10 years,with a focus on projects in the field of otolaryngology/head and neck surgery.Results:Both the number and amount of funding provided by the NSFC for research involving pig models are on the rise with each passing year.Researchers at the PLA General Hospital have completed a number of studies using miniature pigs in cochlear morphology,electrophysiology,cochlear implantation,cochlear transcription analysis,gene therapy,inner ear disease modeling and Eustachian tube pathology modeling.Conclusion:Pigs as an ideal large mammal model are well suited in the current national basic research strategy in China,and can help further strengthen China’s leading position in basic research in the world.
基金supported in part by the National Natural Science Foundation of China(81830064,81721092,81971841)the National Key Research and Development Plan(2017YFC1103304,2017YFC1104701)。
文摘To determine the prevalence and clinical features of olfactory and taste disorders among coronavirus disease 2019(COVID-19)patients in China.A cross-sectional study was performed in Wuhan from April 3,2020 to April 15,2020.A total of 187 patients with confirmed severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)completed face-to-face interviews or telephone follow-ups.We found that the prevalence of olfactory and taste disorders was significantly lower in the Chinese cohort than in foreign COVID-19 cohorts.Females were more prone to olfactory and taste disorders.In some patients,olfactory and taste disorders precede other symptoms and can be used as early screening and warning signs.
基金supported by the National Key Research and Development Program of China, No.2020YFC2005200(to WWG and WJH)the National Nature Science Foundation of China, Nos.81770992(to NS and WJH), 81970897(to WWG)+1 种基金Health and Family Planning System Research Project of Shenzhen Municipality, No.SZXJ2018079(to YYY)Shenzhen Sanming Project, No.SZSM201612076(to YYY)
文摘The inflammasome is a multiprotein oligomer in the cell cytoplasm and is part of the innate immune system.It plays a crucial role in the pathological process of noise-induced hearing loss(NIHL).However,the mechanisms of NLR family pyrin domain containing 3(NLRP3)inflammasome activation in NIHL have not been clearly demonstrated.In this study,miniature pigs were exposed to white noise at 120 dB(A)and auditory brainstem response measurements were used to measure their hearing function.Immunofluorescence staining,confocal laser scanning microscopy,western blot assay,and quantitative reverse transcription-polymerase chain reaction were used to analyze inflammasome-related protein distribution and expression.NLRP3,interleukin-1β,interleukin-18,and cleaved-caspase-1 were highly expressed in the cochlea after 120 dB(A)white noise exposure.Our findings suggest that NLRP3-inflammasomes in the cochlea may be activated after acoustic trauma,which may be an important mechanism of noise-induced hearing loss.
文摘Neural crest(NC)is the primitive neural structure in embryonic stage,which develops from ectodermal neural plate cells and epithelial cells.When the neural fold forms into neural tube,neural crest also forms a cord like structure above the neural tube and below the ectoderm.Neural crest cells(NCC)have strong migration and proliferation abilities.A number of tissue cells differentiate from neural crest cells,such as melanocytes,central and peripheral neurons,glial cells,craniofacial cells,osteoblasts,chondrocytes and smooth muscle cells.The migration and differentiation of neural crest cells are regulated by a gene network where a variety of genes,transcriptional factors,signal pathways and growth factors are involved.
基金supported by the National Natural Science Foundation of China(No.81830028,No.81900950 and No.81900951).
文摘Objective To investigate the genetic causes of sudden sensorineural hearing loss(SSNHL)patients in China.This study focused on analyzing variations of coding sequence of common genes related to deafness,revealing the molecular pathogenesis of sudden deafness from a genomics perspective,discovering molecular markers associated with the onset of deafness,and then supplying prevention to high-risk populations,classifying disease according to accurate etiology,and choosing a much more precision therapy.Methods We retrospectively analyzed the clinical characteristics of 51 patients diagnosed as SSNHL with vertigo treated in the Chinese PLA General Hospital.In this study,mutation screening of 307 nuclear genes and mitochondrial genome responsible for human or mouse deafness was performed on the 51 cases of unilateral sudden deafness patients with vertigo.Results We identified 51 cases of unilateral sudden deafness,including 2 cases of low-mid frequency hearing impairment,18 cases of mid-high frequency hearing loss,11 cases of flat-type hearing loss,and 20 cases of all frequency hearing loss.Among the 51 cases,8(15.69%)cases of GJB2 heterozygous variations,1(1.96%)case of GJB3 heterozygous variations,5(9.8%)cases of SLC26A4 heterozygous variations,2(3.92%)cases of COCH heterozygous variations,14(27.45%)cases of CDH23 heterozygous variations,14(27.45%)cases of OTOF heterozygous variations,1(1.96%)case of SLC17A8 heterozygous variations and 2(3.92%)cases of KCNE1 heterozygous variations.No mtDNA gene variations were identified.Conclusion SSNHL has some relationship with hereditary in Chinese population,but its complex genetic pathogenic mechanisms need further study.
基金supported by the Beijing Municipal Natural Science Foundation[7204314]the Medical Innovation Project Foundation[CX19027]the Young Researcher Supporting Program[QNF19066]of the Chinese PLA General Hospital.
文摘Objective This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol(RSV)regulate necroptosis during Vibrio vulnificus(V.vulnificus)-induced sepsis and the potential mechanism.Methods The effect of RSV on V.vulnificus cytolysin(VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays.Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction,western blot,and immunohistochemistry and survival analyses were performed to elucidate the effect and mechanism of RSV on necroptosis in a V.vulnificus-induced sepsis mouse model.Results RSV relieved necroptosis induced by VVC in RAW264.7 and MLE12 cells.RSV also inhibited the inflammatory response,had a protective effect on histopathological changes,and reduced the expression level of the necroptosis indicator pMLKL in peritoneal macrophages,lung,spleen,and liver tissues of V.vulnificus-induced septic mice in vivo.Pretreatment with RSV downregulated the mRNA of the necroptosis indicator and protein expression in peritoneal macrophages and tissues of V.vulnificusinduced septic mice.RSV also improved the survival of V.vulnificus-induced septic mice.Conclusion Our findings collectively demonstrate that RSV prevented V.vulnificus-induced sepsis by attenuating necroptosis,highlighting its potency in the clinical management of V.vulnificus-induced sepsis.
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.
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.
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.