The population with tardy deafness accounts for about 10% of my country's total population. It is characterized by its hidden onset and difficult to detect early by hearing screening and routine physical examination; its harm is serious and has a serious impact on speech development; the cause is complex, and the cause and mechanism of the disease are unknown., making it difficult to carry out effective early diagnosis and intervention. Therefore, the prevention and treatment of tardive deafness is a major scientific issue in the field of otolaryngology. In the past 20 years, the project team has focused on the prevention and treatment of tardive deafness, and has achieved a series of innovative results in terms of molecular mechanisms, pathological mechanisms, and early diagnosis and intervention: 1. Revealing the unique genetic mutation map of tardive deafness in China population In response to the bottleneck problem of early diagnosis of tardive deafness, the project team established a large-scale hearing impairment cohort and systematically clarified the pathogenic genes and genotype-phenotype associations of common tardive deafness in China population through high-throughput gene screening research. For the first time in the world, the most important genetic susceptibility factor for tardive hearing impairment in my country has been clarified&.& mdash; GJB2 gene p.V37I mutation. 2. It was discovered that the cause of tardive deafness is complex and difficult to fully explain with a single gene mutation. Based on the concept of functional cloning, the project team is the first in the world to carry out non-coding region mutations and double gene mutations. Research on the molecular mechanism of tardive deafness, cloned four new pathogenic genes for tardive deafness, namely FOXI1, KCNJ10, TBC1D24 and DMXL2, and clarified their molecular pathogenic mechanism. 3. Discovery of a new path of action for hearing protection and treatment of tardive deafness. Based on the research on the molecular etiology of tardive deafness, the pathological mechanism of tardive deafness was further clarified. In response to the challenge of the non-regeneration of hair cells of the auditory system and auditory nerves, the Wnt/beta;-catenin pathway has been discovered on the proliferation and differentiation of cochlear supporting cells, confirming that the regulation of this path can promote the regeneration of inner ear hair cells; It was found that there is obvious autophagy disorder during the degeneration of auditory nerve spiral neurons after the loss of cochlear hair cells, confirming that early intervention can delay or reduce the progress of tardive deafness. 4. The project team to establish an early diagnosis and intervention strategy based on gene-hearing joint screening has proposed for the first time in the world that neonatal genetic screening for children with tardive hearing impairment in China can detect susceptible children in advance and provide early warning., effectively realize early detection and intervention of tardive deafness in children. The independently developed portable childhood hearing impairment screening system and new testing technology containing the susceptibility gene for tardive hearing impairment have been applied and promoted in 10 provinces and cities across the country. It has been found that among the genetically susceptible population detected, children have tardive deafness. The incidence rate is 14%, which significantly improves the efficiency of early screening for tardive deafness. The project team published a total of 75 SCI papers with a total impact factor of 235 points and 3 papers with IF gt;10 points; he cited 312 representative papers, and the highest single paper was cited 58 times. It held 21 national-level study classes, hosted 3 international conferences, and was invited to deliver more than 60 keynote speeches at international conferences in the United States, France, Italy, Japan and other countries. It has been applied and promoted in more than 70 kindergartens in various districts and counties in Shanghai City, and more than 20,000 cases have been screened. Early intervention and screening of children with tardive deafness have received widespread attention. In 2013, it was incorporated into the National Health Commission policy document "Technical Specifications for Children's Ear and Hearing Health Care". It is estimated that about 300,000 people have been screened in the past three years since its implementation. It has trained 53 masters, 51 doctorates, and 7 postdoctoral students, made more than 50 lectures nationwide, and trained more than 2000 professionals in this field. Editor-in-chief of 3 monographs, participated in the formulation of 2 international consensus, and took the lead in the formulation of 1 industry norm, making my country's overall diagnosis and treatment level of tardive deafness reach international advanced and achieving significant social benefits.