Amyloid-beta(Aβ)plays a pivotal role in the pathogenesis of Alzheimer's disease(AD)and has been regarded as the main therapeutic target for AD.However,most of the Aβ-targeted clinical trials have not succeeded.T...Amyloid-beta(Aβ)plays a pivotal role in the pathogenesis of Alzheimer's disease(AD)and has been regarded as the main therapeutic target for AD.However,most of the Aβ-targeted clinical trials have not succeeded.Therefore,the Aβ-targeted therapeutic strategy on treating this complex disease needs to be re-evaluated.In this review,we analyzed the challenges and critical points of the current anti-Aβtherapeutic strategies.In addition to Aβ,multiple pathological events such as tau hyperphosphorylation,oxidative stress,and neuroinflammation,which are involved in AD pathogenesis and synergistically drive disease progression,could be important targets for AD treatment.Tertiary prevention strategies are needed for the successful management of AD due to its complex and dynamic pathogenesis.Systemic perspective addressing the disease pathogenesis within and outside the brain,as well as the multidomain intervention targeting risk factors and comorbidities,are important approaches for the therapeutic solutions of AD.展开更多
Background Hearing impairment is one of the most common birth defects in children.Universal newborn hearing screenings have been performed for 19 years in Guangdong province,China.A screening/diagnosis/intervention sy...Background Hearing impairment is one of the most common birth defects in children.Universal newborn hearing screenings have been performed for 19 years in Guangdong province,China.A screening/diagnosis/intervention system has gradually been put in place.Over the past 10 years,a relatively complete data management system had been established.In the present study,an etiological analysis of newborn cases that failed the initial and follow-up screenings was performed.Methods The nature and degree of hearing impairment in newborns were confirmed by a set of procedures performed at the time of initial hearing screening,rescreening and final hearing diagnosis.Then,multiple examinations were performed to explore the associated etiology.Results Over a period of 10 years,720 children were diagnosed with newborn hearing loss.Among these children,445 (61.81%) children had a clearly identified cause,which included genetic factor(s) (30.56%),secretory otitis media (13.30%),maternal rubella virus infection during pregnancy (5.83%),inner ear malformations (4.86%),maternal human cytomegalovirus infection during pregnancy (2.92%),malformation of the middle ear ossicular chain (2.50%) and auditory neuropathy (1.81%).In addition,275 cases of sensorineural hearing loss of unknown etiology accounted for 38.19% of the children surveyed.Conclusions Long-term follow-up is needed to detect delayed hearing impairment and auditory development in children.The need for long-term follow-up should be taken into account when designing an intervention strategy.Furthermore,the use of the deafness gene chip should further elucidate the etiology of neonatal hearing impairment.展开更多
基金supported by the National Natural Science Foundation of China(91749206,81930028,81625007,81870860,31921003)。
文摘Amyloid-beta(Aβ)plays a pivotal role in the pathogenesis of Alzheimer's disease(AD)and has been regarded as the main therapeutic target for AD.However,most of the Aβ-targeted clinical trials have not succeeded.Therefore,the Aβ-targeted therapeutic strategy on treating this complex disease needs to be re-evaluated.In this review,we analyzed the challenges and critical points of the current anti-Aβtherapeutic strategies.In addition to Aβ,multiple pathological events such as tau hyperphosphorylation,oxidative stress,and neuroinflammation,which are involved in AD pathogenesis and synergistically drive disease progression,could be important targets for AD treatment.Tertiary prevention strategies are needed for the successful management of AD due to its complex and dynamic pathogenesis.Systemic perspective addressing the disease pathogenesis within and outside the brain,as well as the multidomain intervention targeting risk factors and comorbidities,are important approaches for the therapeutic solutions of AD.
基金This work was supported by the Guangdong Science and Technology Committee of China(Grant No.2015A020220005)Science and Technology Plan Project of Guangzhou City(Grant No.201704030081).
文摘Background Hearing impairment is one of the most common birth defects in children.Universal newborn hearing screenings have been performed for 19 years in Guangdong province,China.A screening/diagnosis/intervention system has gradually been put in place.Over the past 10 years,a relatively complete data management system had been established.In the present study,an etiological analysis of newborn cases that failed the initial and follow-up screenings was performed.Methods The nature and degree of hearing impairment in newborns were confirmed by a set of procedures performed at the time of initial hearing screening,rescreening and final hearing diagnosis.Then,multiple examinations were performed to explore the associated etiology.Results Over a period of 10 years,720 children were diagnosed with newborn hearing loss.Among these children,445 (61.81%) children had a clearly identified cause,which included genetic factor(s) (30.56%),secretory otitis media (13.30%),maternal rubella virus infection during pregnancy (5.83%),inner ear malformations (4.86%),maternal human cytomegalovirus infection during pregnancy (2.92%),malformation of the middle ear ossicular chain (2.50%) and auditory neuropathy (1.81%).In addition,275 cases of sensorineural hearing loss of unknown etiology accounted for 38.19% of the children surveyed.Conclusions Long-term follow-up is needed to detect delayed hearing impairment and auditory development in children.The need for long-term follow-up should be taken into account when designing an intervention strategy.Furthermore,the use of the deafness gene chip should further elucidate the etiology of neonatal hearing impairment.
