Sensory hair cells are responsible for detecting and transmitting sound in the inner ear,and damage to HCs leads to hearing loss.HCs do not regenerate spontaneously in adult mammals,which makes the hearing loss perman...Sensory hair cells are responsible for detecting and transmitting sound in the inner ear,and damage to HCs leads to hearing loss.HCs do not regenerate spontaneously in adult mammals,which makes the hearing loss permanent.However,hair cells and supporting cells have the same precursors in the inner ear,and in newborn mice,the adjacent SCs can be activated by gene manipulation to differentiate into newly regenerated hair cells.Here,we demonstrate the role of the Ras association domain family member 2(Rassf2)in supporting cell to hair cell trans-differentiation in the inner ear.Using the AAV vector(AAV-ie)to upregulate Rassf2 expression promoted supporting cell division and hair cell production in cultured cochlear organoids.Also,AAV-Rassf2 enhanced the regenerative ability of Lgr5+SCs in the postnatal cochlea without impairing hearing,and this might due to the modulation of the Wnt,Hedgehog and Notch signaling pathways.Furthermore,AAV-Rassf2 enhances cochlear supporting cell division and hair cell production in the neomycin injury model.In summary,our results suggest that Rassf2 is a key component in HC regenerative repair,and gene modulation mediated by adeno-associated virus may be a promising gene therapy for hearing repair.展开更多
In this retrospective study,we evaluated the preoperative and intraoperative findings and functional results of revision surgery after canal wall down mastoidectomy.We reviewed 34 patients(14 men,20 women;age,17–68 y...In this retrospective study,we evaluated the preoperative and intraoperative findings and functional results of revision surgery after canal wall down mastoidectomy.We reviewed 34 patients(14 men,20 women;age,17–68 years)who underwent revision canal wall down mastoidectomy from March 2006 to March 2017 in the Department of Otology of the First Affiliated Hospital,Wenzhou Medical University,China.This study was approved by the Ethics Committee of the First Affiliated Hospital,Wenzhou Medical University,China(approval No.2008-05-02A11)on May 2,2008.The possible reasons for previous surgical failures were confirmed by the operative findings and included a narrow auditory meatus orifice(100%),recurrent or residual cholesteatoma(82%),high facial ridge(94%),residual air cells(47%),and labyrinthine fistula(12%).The mean time until achievement of dry ear after surgery was 5.8±2.4 weeks.After a mean 6-month follow-up,the mean postoperative air–bone gap decreased from 33.8±4.8 to 17.1±5.1dB in 30 patients who underwent mastoidectomy with simultaneous tympanoplasty.However,no significant postoperative hearing change had occurred in the other 4 patients with eustachian tube occlusion.All patients were followed up for>24 months with a disease-free dry ear and stable hearing results.The main reasons for lack of dry ears after mastoidectomy were a narrow auditory meatus orifice,recurrent or residual cholesteatoma,high facial ridge,and residual air cells.Early dry ear and hearing promotion are obtainable in most patients using revision canal wall down mastoidectomy.展开更多
基金supported by the National Key Research and Development Program of China (2021YFA1101300,2020YFA0112503,2021YFA1101800 and 2020YFA0113600)the National Natural Science Foundation of China (81970882,82030029,92149304,82000984 and 82171146)+6 种基金the China National Postdoctoral Program for Innovative Talents (BX20200082)the China Postdoctoral Science Foundation (2020M681468)the Science and Technology Department of Sichuan Province (2021YFS0371)the Shenzhen Fundamental Research Pro-gram (JCYJ20190814093401920 and JCYJ20210324125608022)the Open Research Fund of State Key Laboratory of Genetic Engineering,Fudan University (SKLGE-2104)2022 Open Project Fund of Guangdong Academy of Medical Sciences to P.N.W. (YKY-KF202201)Key Program of Zhejiang Provincial Natural Science Foundation of China (LZ22H130001).
文摘Sensory hair cells are responsible for detecting and transmitting sound in the inner ear,and damage to HCs leads to hearing loss.HCs do not regenerate spontaneously in adult mammals,which makes the hearing loss permanent.However,hair cells and supporting cells have the same precursors in the inner ear,and in newborn mice,the adjacent SCs can be activated by gene manipulation to differentiate into newly regenerated hair cells.Here,we demonstrate the role of the Ras association domain family member 2(Rassf2)in supporting cell to hair cell trans-differentiation in the inner ear.Using the AAV vector(AAV-ie)to upregulate Rassf2 expression promoted supporting cell division and hair cell production in cultured cochlear organoids.Also,AAV-Rassf2 enhanced the regenerative ability of Lgr5+SCs in the postnatal cochlea without impairing hearing,and this might due to the modulation of the Wnt,Hedgehog and Notch signaling pathways.Furthermore,AAV-Rassf2 enhances cochlear supporting cell division and hair cell production in the neomycin injury model.In summary,our results suggest that Rassf2 is a key component in HC regenerative repair,and gene modulation mediated by adeno-associated virus may be a promising gene therapy for hearing repair.
基金supported by Zhejiang Provincial Natural Science Foundation of China,No.LY19H130003(to YH),LY19H130004(to HL)Wenzhou Basic Scientific Research Project of China,No.Y20180091(to YH).
文摘In this retrospective study,we evaluated the preoperative and intraoperative findings and functional results of revision surgery after canal wall down mastoidectomy.We reviewed 34 patients(14 men,20 women;age,17–68 years)who underwent revision canal wall down mastoidectomy from March 2006 to March 2017 in the Department of Otology of the First Affiliated Hospital,Wenzhou Medical University,China.This study was approved by the Ethics Committee of the First Affiliated Hospital,Wenzhou Medical University,China(approval No.2008-05-02A11)on May 2,2008.The possible reasons for previous surgical failures were confirmed by the operative findings and included a narrow auditory meatus orifice(100%),recurrent or residual cholesteatoma(82%),high facial ridge(94%),residual air cells(47%),and labyrinthine fistula(12%).The mean time until achievement of dry ear after surgery was 5.8±2.4 weeks.After a mean 6-month follow-up,the mean postoperative air–bone gap decreased from 33.8±4.8 to 17.1±5.1dB in 30 patients who underwent mastoidectomy with simultaneous tympanoplasty.However,no significant postoperative hearing change had occurred in the other 4 patients with eustachian tube occlusion.All patients were followed up for>24 months with a disease-free dry ear and stable hearing results.The main reasons for lack of dry ears after mastoidectomy were a narrow auditory meatus orifice,recurrent or residual cholesteatoma,high facial ridge,and residual air cells.Early dry ear and hearing promotion are obtainable in most patients using revision canal wall down mastoidectomy.