? There are 20.04 million deaf people, accounting for 24.16% of the total number of people with disabilities and 1.58% of the national population. Among them, 800,000 are deaf children under the age of 7 and are growing at the rate of 30,000 new deaf children every year …… So many unfortunate people who have to live in a silent world constitute a staggering size of China’s hearing disabled population. Professor Han Dongyi, Director of the Department of Otolaryngology, Head and Neck Surgery at the PLA General Hospital and Deputy Director of the Institute of Otolaryngology, who just led his colleagues to win the second prize of the 2007 Chinese Medical Science and Technology Award, told us that currently, the best way to return severe deafness to the world of sound is to have cochlear implants, however, it would cost at least 3.6 trillion yuan to implant all the existing deaf people in China. This is difficult to achieve with our current national capacity. Currently, the use of genetic diagnosis of deafness to identify the cause of deafness and the use of premarital counseling and prenatal diagnosis to reduce the birth of deaf children is one of the fundamental ways to prevent and treat deafness. Han Dong Yi’s award-winning work is entitled “Basic Research and Clinical Application of Deafness Genetic Resources Collection and Molecular Genetic Mechanism of Deafness”. This is a collective honor,” said Prof. Han Dong Yi, “and it is the result of more than 10 years of unity and collaboration of the whole team. We just took a step forward toward the goal that our teacher, the late academician Jiang Sichang, had not competed for during his lifetime.” Scientific research always gives people the feeling of being rigorous, serious and difficult to get close to. However, when we approached Han Dongyi’s team, we found that the collection and preservation of deafness genetic resources, basic and clinical application research of deafness genes were so vivid and vivid. Breaking the 100-year “spell” Qingtang Village, Lianhua County, Jiangxi Province, has beautiful mountains and clear water. There is a family surnamed Jin in the village that people dare not approach. Because from the end of the Qing Dynasty, almost half of the men in this ancient family were either deaf or mute. One after another, the family gave birth to deaf boys, while the parents of the deaf children were normal. Is this fate or the revenge of evil? Eating the same food and drinking the same water, why is it that only the men in their family suffer from the curse of the deaf ghost in the whole village? The feng shui master told the Jin family in a serious manner that because the old house facing west was facing the Lion Cliff in the distance, it was subject to the revenge of the “Lion God”. If they did not move, the children they would give birth to would either be deaf, blind or lame. In 1999, the Jin family’s niece, Li Shuhua, gave birth to a son named Kuang Xiaopeng. When he was old enough to learn to speak, Xiaopeng could cry and laugh, but he could not say “Dad” or “Mom”. Li Shuhua’s heart lifted, took Xiaopeng to the hospital for a hearing test, diagnosed as “congenital deafness.” …… The Jin family was once again in despair. The only thing Li Shuhua could do was to help her son avoid the tragic fate of becoming deaf and mute. She got a hearing aid for her son. In order to teach Xiaopeng to speak, Li Shuhua quit her job. 8 years, Li Shuhua taught her son to speak every day from morning to night. It usually took weeks for a dog to bark and a siren to blow. The huge effort brought only small results, boring speech training not only made the son resentful, the mother also gradually lost confidence. Li Shuhua even moved to take her son to commit suicide …… once, Li Shuhua will not listen to the son locked at home. The naughty Xiaopeng actually fell out of a 7-meter-high second-story window. When Shuhua rushed to the street, her son, who had a swollen nose and eyes, was crying in her arms, Xiaopeng suddenly spoke: “Mom, don’t cry! Xiaopeng listen to me, Xiaopeng speak well ……” from then on, she never moved to give up the idea of teaching her son to speak. One day in 2003, Li Shuhua happened to see a TV program about deafness, so with a ray of hope, she wrote a letter to the program’s guest, Dr. Yang Weiyan, the director of the Department of Otolaryngology at the PLA General Hospital, and soon the letter went to Dr. Wang Qiuju, who was the first in China to find a typical family line of hereditary deafness. Wang Qiuju led an investigation team to Jiangxi immediately. After the investigation, Qiuju Wang and other people found that among the 40-plus people in the Jin family’s direct line of five generations, there were nine deaf males! What’s even more peculiar is that none of the women in the family had the disease, and those who did were the male offspring of the direct female line, all inherited from one generation to the next. …… The investigation team took blood samples from all members of the family and brought them back to Beijing for genetic testing. There are more than 30,000 genes in the human body, and finding one of them is like looking for a needle in a haystack; once we found the large family line of deafness inheritance, we definitely narrowed down the scope of our search. But with more than 200 genes associated with deafness, only 60 have been found so far, so which gene is the cause of deafness in the Jin family? Dr. Qiuju Wang and her colleagues worked intensely to find the X-chromosome recessive deafness gene carried by females in this family line using the exclusion method, and it was recognized by the International Committee for Human Genome Nomenclature. The 100-year old “curse” was finally broken. The results of the study were heartbreaking for the women in the family, but the family tragedy was ended – with the help of prenatal genetic diagnosis, the family was guaranteed to have normal children. Whoever grasps the valuable genetic resources of deafness has the golden key to unlocking the mystery of deafness. After several years of hard work, experts from the Institute of Otolaryngology of the PLA General Hospital have collected more than 50 genetic deafness families with Chinese characteristics, each of which has its own different genetic rules; behind the different genetic rules, there are different disease-causing genes; and different disease-causing genes, each of which has a different story of attack. Almost at the same time that Qiuju Wang’s family lineage investigation in Jiangxi was making a breakthrough, Huijun Yuan, who had just returned from the United States, also received a good report from Shandong: they discovered the first Chinese family line of DFNA9 hereditary deafness in Texas! Out of 193 members of this family in four generations (113 of them are alive), there are actually 39 deaf patients. The onset of deafness in this family was characterized by equal prevalence in both sexes, age of onset ranging from 7 to 45 years, and symptoms of hearing loss that progressively worsened with age, all with “delayed, progressive hearing loss”. Not every deafness family line collection process is so smooth. In fact, in some large deaf families, members live far away from each other, and some are even out of touch and do not know where they have moved to. In 2004, they traveled to 14 counties in Jiangxi province alone, covering 4,700 kilometers in 3 weeks, investigating more than 20 deaf families and educating tens of thousands of people along the way. The big story behind the “small card” Nowadays, every patient who visits the Molecular Diagnostic Center for Deafness of PLA General Hospital and is found to carry the genetic susceptibility gene for drug-related deafness will receive a business card-sized “medication guide” card, on which The patient and his or her family are asked to present this card to the physician at the time of the visit so that effective early intervention can be made for deafness. This little card tells a big story, including that of Professor Park Dai. He was the first to introduce deafness genetic diagnosis technology to China in 2003. In order to get first-hand information about hereditary deafness, in recent years, Park Dai personally led a team of more than a dozen graduate students to collect clinical data and DNA specimens from more than 5000 deafness cases or family lines in 28 regions of 24 provinces (cities and districts), including Beijing, Shanghai, Shandong, Shanxi, Heilongjiang, Yunnan, Fujian, Guangdong, Jiangxi, Inner Mongolia, Xinjiang, Tibet, and Gansu. All cases had detailed medical history records and audiological examinations. From Mudanjiang in northeast China to Lhasa in Tibet, from Lincang in Yunnan to Korla in Xinjiang, this team, despite of the exhausting journey, has assembled the largest deafness gene bank in China with more than 5000 specimens in a very short time. To date, such a large-scale sample collection is the first of its kind in China. The sweat of Park Dai and others was not in vain. They obtained epidemiological data on deafness genes that fit the genetic characteristics of the Chinese population, and revealed that genetic factors account for about 60% of the etiology of deafness in the Chinese population. We have mapped out the common mutations in Chinese deafness population and established the hot mutations of each gene in Chinese population, which has guided the establishment of deafness screening procedures and the establishment of genes and mutation loci in deafness gene diagnostic microarray in clinical practice. Four years ago, Park Dai, who had just returned from the United States, collaborated with Huijun Yuan to develop a related genetic test kit (granted with a national invention patent in 2006) for the mitochondrial A1555G mutation, a mitochondrial maternal genetic aminoglycoside sensitive deafness locus. We have discovered nearly 200 cases of deafness caused by mitochondrial DNA A1555G mutation among more than 5000 cases of deafness patients attending deaf schools and outpatient clinics in various regions of China, and on average, for every deafness patient with mitochondrial A1555G mutation, 10 maternal members of their families can be prevented from developing deafness due to the application of aminoglycoside antibiotics. Individuals tested positive with the kit and their maternal relatives will be given a “medication guide” card as described earlier, which clearly prohibits aminoglycoside antibiotics and plays an important role in early deafness intervention. In China, drug-induced deafness occurs mostly in poor areas and is a recurring tragedy because it occurs in young children as young as two or three years old, about a month or two after the injection, and many people do not take into account genetic factors,” said Prof. Park. In our research around the country, we were saddened to see that in Kunming, Yunnan, one unfortunate family actually had five children who were all drug deaf! The family members carrying this genetic mutation ranged from one or two to as many as 25 in some families! After the establishment of the Genetic Diagnostic Center for Deafness at the PLA General Hospital, the first couple from Xuzhou rushed to seek help. It was July 2005. The woman was 18 months pregnant and had her 6-year-old deaf son with her at the time of the visit. After examination, the boy was quickly diagnosed as genetically deaf, and both parents were recessive carriers of the deafness gene mutation, ruling out the possibility of environmental factors causing deafness in the first child. Next, Prof. Dai Park performed a prenatal genetic diagnosis of the fetus through amniotic fluid and was pleased to find that the fetus carried only one mutant allele of the father’s gene, meaning it was a normal child. At seven months, the man went to Beijing again with the fetus’ umbilical cord blood, and the test results were still normal …… On the eve of the Chinese New Year in 2006, Professor Dai received a happy call from Xuzhou: the family was smiling and happy that they had indeed given birth to a child with normal hearing! Over the years, the Deafness Genetic Diagnostic Center has used genetic diagnosis in conjunction with prenatal diagnosis to prevent the re-birth of deaf children in 30 families who had a deaf child. A total of 7 fetuses were diagnosed as still having hereditary deafness and both parents voluntarily chose to terminate the pregnancy, using amniocentesis as early as 8 weeks for prenatal diagnosis. The other 17 offspring have been born and have successfully passed the audiological screening or subsequent audiological testing with normal hearing development, with a success rate of 100%. 6 fetuses are still being conceived and are expected to be normal hearing offspring. Seizing the “high ground” of the future: gene-mediated hair cell regeneration Han Dong Yi said that deafness prevention and treatment mainly includes two aspects: conductive deafness and sensorineural deafness prevention and treatment. For more than half a century, conduction deafness has gained mature experience, with a treatment efficiency of more than 90 percent. In contrast, the prevention and treatment of sensorineural deafness is a hot spot and a difficult area of basic deafness research. At present, both prenatal diagnosis and embryonic screening are used to prevent sensorineural deafness; as for treatment, there is still nothing that can be done except for cochlear implants, which are too expensive to be popular. Therefore, the treatment of sensorineural deafness has become an unfulfilled dream of academician Jiang Sichang during his lifetime. Today, in the laboratory of the Ear Nerve Biology Center of the Institute of Otolaryngology, PLA General Hospital, a 42-year-old professor is fulfilling Jiang’s dream among the instruments, test tubes, displays and data piles. He is Dr. Yang Shiming, director of the Ear Nerve Biology Center at the Institute of Otolaryngology, PLA General Hospital. The application of new biological technologies has promoted basic and clinical research on deafness. Shortly after returning from Japan, Shiming Yang obtained an animal model of deafness using gene knockout and found that the gene defect could cause severe hearing impairment in mice and varying degrees of damage to the inner ear auditory organs including hair cells, supporting cells and spiral ganglia. The conventional wisdom is that sensorineural deafness is incurable because hair cells do not regenerate after death. In fact, the most critical technology for the ultimate treatment of sensorineural deafness is the regeneration of hair cells, and the most important thing for clinical application is the development of a product with clinical application prospects – an efficient and safe gene vector. At present, Yang’s group has successfully achieved hair cell regeneration not only in guinea pigs through gene transfer, but also has been verified by repeated experiments. The success of hair cell regeneration provides the possibility of implementing gene therapy for sensorineural deafness,” said Yang optimistically. I hope that the results of this experiment can be applied to the clinic in the near future to save those deaf patients who are declared as ‘incurable’ at an early date.” In this way, Han Dongyi’s team has been divided and united in three aspects, from molecular genetic mechanism of deafness, molecular epidemiology of deafness to clinical application of deafness gene diagnosis and auditory neurobiology research, on the journey of deafness prevention and treatment. In recent years, she has published 47 papers, including 12 SCI-indexed papers, with a cumulative impact factor of 43.4, including the highest impact factor of 12.43. He has applied for 7 patents for deafness-related genetic testing technology. The research results have been promoted and applied in 50 countries.