Objectives:To quantify the progression of otosclerosis in the unoperated ear between two stapedotomy procedures for patients with bilateral otosclerosis which can help to determine whether a HRCT scan should be re-per...Objectives:To quantify the progression of otosclerosis in the unoperated ear between two stapedotomy procedures for patients with bilateral otosclerosis which can help to determine whether a HRCT scan should be re-performed before the second surgery for patients who already received HRCT imaging before the initial surgery.Methods:35 patients who underwent bilateral stapedotomy were included.Two rounds of HRCT examination and audiometry were performed at the time of the first surgery and second surgery on the ear that was not operated on during the initial surgery.The relationship between the changes in HRCT densitometry and audiometry over time was analyzed.Results:The second round of HRCT did not add significant information about the changes to the otosclerosis lesions in either the imaging diagnosis or the HRCT density values except for small changes in the HRCT densitometry readings at the area anterior to the inner auditory(P=0.01).While the changes in HRCT manifestation are small,changes near the fissula ante fenestram(FAF)were still positively correlated with the air bone gap(ABG)of patients(p=0.031,r=0.388).Conclusions:The progression of lesions in otosclerosis is slow resulting in small and insignificant changes to the HRCT features.Therefore,a repeat HRCT evaluations prior to surgery is not necessary for patients who have had a previous HRCT evaluation within 2 years of the operation.The small changes in HRCT manifestation near the FAF were still correlated with negative effects on the ABG which could cause worsened hearing thresholds over this timeframe。展开更多
Hearing loss is one of the most common sensory disorders worldwide,affecting approximately 466 million people,including 34 million children[1].Genetic mutations accounts for approximately 60%of inherited hearing loss ...Hearing loss is one of the most common sensory disorders worldwide,affecting approximately 466 million people,including 34 million children[1].Genetic mutations accounts for approximately 60%of inherited hearing loss cases[2,3].These genetic changes result in a wide variety of clinical manifestations,ranging from nonsyndromic hearing loss(NSHL)to over 400 syndromes involving hearing loss and from mild adult-onset hearing loss to profound congenital deafness,covering the entire spectrum of Mendelian inheritance.展开更多
Transoral microresection for treatment of vocal cord lesions involving the anterior commissure may result in anterior glottic webs. In this study, we retrospectively reviewed 54 patients who underwent microsurgery for...Transoral microresection for treatment of vocal cord lesions involving the anterior commissure may result in anterior glottic webs. In this study, we retrospectively reviewed 54 patients who underwent microsurgery for bilateral lesions involving the anterior commissure and categorized them into two groups. The keel placement and control groups received endoscopic keel placement and mitomycin C, respectively. During the follow-up of at least 1 year, the laryngeal web formation rate significantly decreased in the keel placement group compared with that in the control group （18.6% versus 54.5%, P 〈 0.05）. Furthermore, the voice handicap index-10 scores for patients without web formation decreased in both the keel placement and control groups （P 〈 0.0001 and P 〈 0.001, respectively）. A pseudomembrane covering the vocal cords was detected in 16.3% （7 of 43） cases after keel removal. A total of 100% （7 of 7） of these cases and 2.8% （1 of 36） of the other cases formed laryngeal webs （P 〈 0.0001）. Endoscopic keel placement could be an effective method for preventing anterior glottic webs after surgery for bilateral vocal cord diseases involving the anterior commissure. The pseudomembrane observed at the time of keel removal may imply a high risk of web formation.展开更多
Because of the unique features of spherical symmetry,angle-independency,good monodispersity,controllable components and morphologies,structural color particles(SCPs)have found great significances in various fields suc...Because of the unique features of spherical symmetry,angle-independency,good monodispersity,controllable components and morphologies,structural color particles(SCPs)have found great significances in various fields such as sensing,monitoring,biological assays,etc.Here,inspired by the melanosome-derived bright structural colors and the self-adhesivity of mussels,we present a kind of bioinspired SCPs assembled from polydopamine(PDA)-adhered multi-layer graphene oxide(GO)encapsulated silica nanoparticles(SNs).It is demonstrated that compared with traditional SCPs,the designed particles possess brighter and more vibrant structural colors,and no complicated modification is required during the functionalization process due to the abundant inherent functional groups of GO.The resultant SCPs are verified to be capable for direct hybridization chain reaction and multiplexed nucleic acid assays.These properties indicate the promising prospects of our designed SCPs.展开更多
CRISPR/RfxCas13d(CasRx)editing system can specifically and precisely cleave single-strand RNAs,which is a promising treatment for various disorders by downregulation of related gene expression.Here,we tested this RNA-...CRISPR/RfxCas13d(CasRx)editing system can specifically and precisely cleave single-strand RNAs,which is a promising treatment for various disorders by downregulation of related gene expression.Here,we tested this RNA-editing approach on Beethoven(Bth)mice,an animal model for human DFNA36 due to a point mutation in Tmc1.We first screened 30 sgRNAs in cell cultures and found that CasRx with sgRNA3 reduced the Tmc1^(Bth)transcript by 90.8%,and the Tmc1 wild type transcript(Tmc1^(+))by 44.3%.We then injected a newly developed AAV vector(AAV-PHP.eB)based CasRx into the inner ears of neonatal Bth mice,and we found that Tmc1^(Bth)was reduced by 70.2%in 2 weeks with few off-target effects in the whole transcriptome.Consistently,we found improved hair cell survival,rescued hair bundle degeneration,and reduced mechanoelectrical transduction current.Importantly,the hearing performance,measured in both ABR and DPOAE thresholds,was improved significantly in all ages over 8 weeks.We,therefore,have validated the CRISPR/CasRx-based RNA editing strategy in treating autosomal-dominant hearing loss,paving way for its further application in many other hereditary diseases in hearing and beyond.展开更多
Conductive hearing loss is the impairment in the mechanical transduction of sound wave through the external ear and the middle ear.Although most cases are sporadic due to acquired causes such as infections(otitis medi...Conductive hearing loss is the impairment in the mechanical transduction of sound wave through the external ear and the middle ear.Although most cases are sporadic due to acquired causes such as infections(otitis media and otitis externa),cerumen obstruction,and injuries,congenital structural defects are uncommon for significant etiologies to recognize.Stapes ankylosis is characterized by conductive hearing loss.It may be difficult to differentiate from otosclerosis,the most common cause of progressive conductive hearing loss,by audiologic evaluation,when the diagnosis is delayed.Skeletal anomalies may be subtle,such that the syndrome may not be recognized(Brown et al.,2002).展开更多
The recent research published in Nature by Bravo and colleagues has deeply carifed the mechanisms of Cas9 recognizing the base-pair mismatches by kinetics-guided Cryo-EM analysis,which provides a perspective for the d...The recent research published in Nature by Bravo and colleagues has deeply carifed the mechanisms of Cas9 recognizing the base-pair mismatches by kinetics-guided Cryo-EM analysis,which provides a perspective for the development of next-generation Cas9 variants with high fidelity.展开更多
To present the clinical characteristics and the misdiagnosis rate of acute coronary syndrome manifested primarily as throat discomfort,we conducted a multicentric and retrospective study in the cardiology and otorhino...To present the clinical characteristics and the misdiagnosis rate of acute coronary syndrome manifested primarily as throat discomfort,we conducted a multicentric and retrospective study in the cardiology and otorhinolaryngology departments.Records of patients with primary complaint of throat discomfort,absence of chest pain at onset,and an ultimate diagnosis of acute coronary syndrome,as well as patients with pharyngitis(as controls)were collected from May 2015 to April 2016.The patients’main manifestations were compared.Logistic regression results showed that chest tightness,dyspnea,perspiring,and exertional throat symptoms were significantly associated with acute coronary syndrome,with odds ratios of 8.3(95%CI 2.2–31.5),10.9(95%CI 1.8–66.9),25.4(95%CI 3.6–179.9),and 81.2(95%CI 13.0–506.7).A total of 25(56.82%)out of 44 acute coronary syndrome patients,who were first admitted to the otorhinolaryngology department,were misdiagnosed,with a 12%(3/25)mortality rate.Throat discomfort can be the principal manifestation of acute coronary syndrome.Such patients exhibit high misdiagnosis and mortality rates.Exertional throat symptoms,chest tightness,perspiring,and dyspnea were important indicators of acute coronary syndrome in patients whose main complaint was throat discomfort.The awareness of this condition will result in prompt diagnosis and reduce morbidity and mortality.展开更多
Adeno-associated virus(AAV)-mediated gene therapy is widely applied to treat numerous hereditary diseases in animal models and humans.The specific expression of AAV-delivered transgenes driven by cell type-specific pr...Adeno-associated virus(AAV)-mediated gene therapy is widely applied to treat numerous hereditary diseases in animal models and humans.The specific expression of AAV-delivered transgenes driven by cell type-specific promoters should further increase the safety of gene therapy.However,current methods for screening cell type-specific promoters are labor-intensive and time-consuming.Herein,we designed a“multiple vectors in one AAV”strategy for promoter construction in vivo.Through this strategy,we truncated a native promoter for Myo15 expression in hair cells(HCs)in the inner ear,from 1,611 bp down to 1,157 bp,and further down to 956 bp.Under the control of these 2 promoters,green fluorescent protein packaged in AAV-PHP.eB was exclusively expressed in the HCs.The transcription initiation ability of the 2 promoters was further verified by intein-mediated otoferlin recombination in a dual-AAV therapeutic system.Driven by these 2 promoters,human otoferlin was selectively expressed in HCs,resulting in the restoration of hearing in treated Otof−/−mice for at least 52 weeks.In summary,we developed an efficient screening strategy for cell type-specific promoter engineering and created 2 truncated Myo15 promoters that not only restored hereditary deafness in animal models but also show great potential for treating human patients in future.展开更多
基金supported by National Natural Science Foundation of China(No.81870726)Clinical Research Plan of SHDC(Grant SHDC2020CR4083).
文摘Objectives:To quantify the progression of otosclerosis in the unoperated ear between two stapedotomy procedures for patients with bilateral otosclerosis which can help to determine whether a HRCT scan should be re-performed before the second surgery for patients who already received HRCT imaging before the initial surgery.Methods:35 patients who underwent bilateral stapedotomy were included.Two rounds of HRCT examination and audiometry were performed at the time of the first surgery and second surgery on the ear that was not operated on during the initial surgery.The relationship between the changes in HRCT densitometry and audiometry over time was analyzed.Results:The second round of HRCT did not add significant information about the changes to the otosclerosis lesions in either the imaging diagnosis or the HRCT density values except for small changes in the HRCT densitometry readings at the area anterior to the inner auditory(P=0.01).While the changes in HRCT manifestation are small,changes near the fissula ante fenestram(FAF)were still positively correlated with the air bone gap(ABG)of patients(p=0.031,r=0.388).Conclusions:The progression of lesions in otosclerosis is slow resulting in small and insignificant changes to the HRCT features.Therefore,a repeat HRCT evaluations prior to surgery is not necessary for patients who have had a previous HRCT evaluation within 2 years of the operation.The small changes in HRCT manifestation near the FAF were still correlated with negative effects on the ABG which could cause worsened hearing thresholds over this timeframe。
基金supported by the STI2030-Major Projects(2022ZD0205400)the National Natural Science Foundation of China(82192861,81922018,82271170,and 82101218)+3 种基金the Foundation from Science and Technology Commission of Shanghai Municipality(22140900800 and 20JC1419500)the Foundation from Shanghai Municipal Health Commission(20234Z0007)the China Postdoctoral Science Foundation(2021M700824 and 2022T150133)the Shanghai Super Postdoctoral Incentive Program.
文摘Hearing loss is one of the most common sensory disorders worldwide,affecting approximately 466 million people,including 34 million children[1].Genetic mutations accounts for approximately 60%of inherited hearing loss cases[2,3].These genetic changes result in a wide variety of clinical manifestations,ranging from nonsyndromic hearing loss(NSHL)to over 400 syndromes involving hearing loss and from mild adult-onset hearing loss to profound congenital deafness,covering the entire spectrum of Mendelian inheritance.
文摘Transoral microresection for treatment of vocal cord lesions involving the anterior commissure may result in anterior glottic webs. In this study, we retrospectively reviewed 54 patients who underwent microsurgery for bilateral lesions involving the anterior commissure and categorized them into two groups. The keel placement and control groups received endoscopic keel placement and mitomycin C, respectively. During the follow-up of at least 1 year, the laryngeal web formation rate significantly decreased in the keel placement group compared with that in the control group （18.6% versus 54.5%, P 〈 0.05）. Furthermore, the voice handicap index-10 scores for patients without web formation decreased in both the keel placement and control groups （P 〈 0.0001 and P 〈 0.001, respectively）. A pseudomembrane covering the vocal cords was detected in 16.3% （7 of 43） cases after keel removal. A total of 100% （7 of 7） of these cases and 2.8% （1 of 36） of the other cases formed laryngeal webs （P 〈 0.0001）. Endoscopic keel placement could be an effective method for preventing anterior glottic webs after surgery for bilateral vocal cord diseases involving the anterior commissure. The pseudomembrane observed at the time of keel removal may imply a high risk of web formation.
基金supported by the National Natural Science Foundation of China(grants 61927805,81822011 , 51773119)the Natural Science Foundation of Jiangsu(Grant no.BE2018707)+1 种基金the Science Foundation of Guangdong Province(2019A1515011750)the Scientific Research Foundation of the Graduate School of Southeast University(Grant No.YBPY1873).
文摘Because of the unique features of spherical symmetry,angle-independency,good monodispersity,controllable components and morphologies,structural color particles(SCPs)have found great significances in various fields such as sensing,monitoring,biological assays,etc.Here,inspired by the melanosome-derived bright structural colors and the self-adhesivity of mussels,we present a kind of bioinspired SCPs assembled from polydopamine(PDA)-adhered multi-layer graphene oxide(GO)encapsulated silica nanoparticles(SNs).It is demonstrated that compared with traditional SCPs,the designed particles possess brighter and more vibrant structural colors,and no complicated modification is required during the functionalization process due to the abundant inherent functional groups of GO.The resultant SCPs are verified to be capable for direct hybridization chain reaction and multiplexed nucleic acid assays.These properties indicate the promising prospects of our designed SCPs.
基金the National Natural Science Foundation of China(82171148,51873107,81770999)National Key Research and Development Program of China(2020YFA0908201)+3 种基金Science and Technology Commission of Shanghai Municipality(21S11905100)National Genetically Modified Organisms Breeding Major Projects of China(2016ZX08009003-006)Clinic Research Plan of SHDC(No.SHDC2020CR4083),“Shuguang Program”supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission(20SG08)National Research Facility for Phenotypic and Genotypic Analysis of Model Animals(Beijing).
文摘CRISPR/RfxCas13d(CasRx)editing system can specifically and precisely cleave single-strand RNAs,which is a promising treatment for various disorders by downregulation of related gene expression.Here,we tested this RNA-editing approach on Beethoven(Bth)mice,an animal model for human DFNA36 due to a point mutation in Tmc1.We first screened 30 sgRNAs in cell cultures and found that CasRx with sgRNA3 reduced the Tmc1^(Bth)transcript by 90.8%,and the Tmc1 wild type transcript(Tmc1^(+))by 44.3%.We then injected a newly developed AAV vector(AAV-PHP.eB)based CasRx into the inner ears of neonatal Bth mice,and we found that Tmc1^(Bth)was reduced by 70.2%in 2 weeks with few off-target effects in the whole transcriptome.Consistently,we found improved hair cell survival,rescued hair bundle degeneration,and reduced mechanoelectrical transduction current.Importantly,the hearing performance,measured in both ABR and DPOAE thresholds,was improved significantly in all ages over 8 weeks.We,therefore,have validated the CRISPR/CasRx-based RNA editing strategy in treating autosomal-dominant hearing loss,paving way for its further application in many other hereditary diseases in hearing and beyond.
基金funded in part by the National Nature Science Foundation of China(81771013,81822011,and 81570914)Science and Technology Commission of Shanghai Municipality(17ZR1448600 and 18410712400)the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health in the United States(R03DC013866 and R01DC015052)
文摘Conductive hearing loss is the impairment in the mechanical transduction of sound wave through the external ear and the middle ear.Although most cases are sporadic due to acquired causes such as infections(otitis media and otitis externa),cerumen obstruction,and injuries,congenital structural defects are uncommon for significant etiologies to recognize.Stapes ankylosis is characterized by conductive hearing loss.It may be difficult to differentiate from otosclerosis,the most common cause of progressive conductive hearing loss,by audiologic evaluation,when the diagnosis is delayed.Skeletal anomalies may be subtle,such that the syndrome may not be recognized(Brown et al.,2002).
基金This work was supported by the National Key Research and Development Program of China grant(2020YF A0908201)National Natural Science Foundation of China grant(82171148),Clinical Research Plan of SHDC(SHDC2020CR4083)+3 种基金the Science and Technology Commission of Shanghai Municipality(21S11905100)Special Project for Clinical Research in Health Industry of Shanghai Municipal Health Commission(20224Z0003)Excellent Doctors-Excellent Clinical Researchers Program of Eye&ENT Hospital of Hehai University(SYB202005)“Shuguang Program”supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission(20SG08).
文摘The recent research published in Nature by Bravo and colleagues has deeply carifed the mechanisms of Cas9 recognizing the base-pair mismatches by kinetics-guided Cryo-EM analysis,which provides a perspective for the development of next-generation Cas9 variants with high fidelity.
基金supported by the National Natural Science Foundation of China(Nos.81822011 and 81771013)Clinical Research Plan of SHDC(No.SHDC2020CR4083).
文摘To present the clinical characteristics and the misdiagnosis rate of acute coronary syndrome manifested primarily as throat discomfort,we conducted a multicentric and retrospective study in the cardiology and otorhinolaryngology departments.Records of patients with primary complaint of throat discomfort,absence of chest pain at onset,and an ultimate diagnosis of acute coronary syndrome,as well as patients with pharyngitis(as controls)were collected from May 2015 to April 2016.The patients’main manifestations were compared.Logistic regression results showed that chest tightness,dyspnea,perspiring,and exertional throat symptoms were significantly associated with acute coronary syndrome,with odds ratios of 8.3(95%CI 2.2–31.5),10.9(95%CI 1.8–66.9),25.4(95%CI 3.6–179.9),and 81.2(95%CI 13.0–506.7).A total of 25(56.82%)out of 44 acute coronary syndrome patients,who were first admitted to the otorhinolaryngology department,were misdiagnosed,with a 12%(3/25)mortality rate.Throat discomfort can be the principal manifestation of acute coronary syndrome.Such patients exhibit high misdiagnosis and mortality rates.Exertional throat symptoms,chest tightness,perspiring,and dyspnea were important indicators of acute coronary syndrome in patients whose main complaint was throat discomfort.The awareness of this condition will result in prompt diagnosis and reduce morbidity and mortality.
基金supported by National Science Fund for Distinguished Young Scholars(82225014)the Science and Technology Commission of Shanghai Municipality(21JC1401000)+8 种基金the Ministry of Science and Technology of China(2021YFA1101302,2020YFA0908201)the National Natural Science Foundation of China(82192860,82171148,82201306)the China Postdoctoral Science Foundation(2022M720780)the Shanghai Municipal Health Commission(20224Z0003)the Science and Technology Commission of Shanghai Municipality(21S11905100 and 23J31900100)the Shanghai Municipal Education Commission(2023ZKZD12)the Shanghai Clinical Medical Research Center for Otolaryngology Diseases(20MC1920200)the science and technology innovation program of Hunan Province(2023RC4005)the Shuguang Program(20SG08)supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation,and Hehai University(yg2022-23).
文摘Adeno-associated virus(AAV)-mediated gene therapy is widely applied to treat numerous hereditary diseases in animal models and humans.The specific expression of AAV-delivered transgenes driven by cell type-specific promoters should further increase the safety of gene therapy.However,current methods for screening cell type-specific promoters are labor-intensive and time-consuming.Herein,we designed a“multiple vectors in one AAV”strategy for promoter construction in vivo.Through this strategy,we truncated a native promoter for Myo15 expression in hair cells(HCs)in the inner ear,from 1,611 bp down to 1,157 bp,and further down to 956 bp.Under the control of these 2 promoters,green fluorescent protein packaged in AAV-PHP.eB was exclusively expressed in the HCs.The transcription initiation ability of the 2 promoters was further verified by intein-mediated otoferlin recombination in a dual-AAV therapeutic system.Driven by these 2 promoters,human otoferlin was selectively expressed in HCs,resulting in the restoration of hearing in treated Otof−/−mice for at least 52 weeks.In summary,we developed an efficient screening strategy for cell type-specific promoter engineering and created 2 truncated Myo15 promoters that not only restored hereditary deafness in animal models but also show great potential for treating human patients in future.
