Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Her...Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Here,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory mechanisms.We established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 hours.We found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with tranylcypromine.The noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with saline.These findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell loss.Additionally,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy pathway.Tranylcypromine treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)production.In conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing function.These findings suggest that inhibiting lysine-specific demethylase 1 is a potential therapeutic strategy for preventing hair cell loss and noise-induced hearing loss.展开更多
Background:Research has shown that musicians outperform non-musicians in speech perception in noise(SPiN)tasks.However,it remains unclear whether the advantages of musical training are substantial enough to slow down ...Background:Research has shown that musicians outperform non-musicians in speech perception in noise(SPiN)tasks.However,it remains unclear whether the advantages of musical training are substantial enough to slow down the decline in SPiN performance associated with aging.Objectives:Therefore,we assessed SPiN performances in a continuum of age groups comprising musicians and non-musicians.The goal was to compare how the aging process affected SPiN performances of musicians and non-musicians.Method:A cross-sectional descriptive mixed design was used,involving 150 participants divided into 75 musicians and 75 non-musicians.Each age group(10-19,20-29,30-39,40-49,and 50-59)consisted of15 musicians and 15 non-musicians.Six Kannada sentence lists were combined with four-talker babble.At+5,0,and-5 dB signal-to-noise ratios(SNRs),the percent correct Speech Identification Scores were calculated.Results:The repeated measure ANOVA(RM ANOVA)revealed significant main effects and interaction effects between SNR,musicianship,and age groups(p<0.05).A small to large effect size was noted(ηp2=0.05 to0.17).A significant interaction effect and follow-up post hoc tests showed that SPiN abilities deteriorated more rapidly with increasing age in nonmusicians compared to musicians,especially at difficult SNRs.Conclusions:Musicians had better SPiN abilities than non-musicians across all age groups.Also,age-related deterioration in SPiN abilities was faster in non-musicians compared to musicians.展开更多
The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are...The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start networks.Here we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal cells.In this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)cDNA.To investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were used.Neurite outgrowth is evaluated through the segmentation and measurement of neural processes.These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth.These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22.DDQ-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-tubulin.Additionally,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth.Our findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara cteristics.The key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.展开更多
Objective:Critically appraise the current state of alternate temporal bone training techniques(virtual reality(VR)simulation,3D-printed models,and mental practice(MP))compared to traditional and cadaver methods.Databa...Objective:Critically appraise the current state of alternate temporal bone training techniques(virtual reality(VR)simulation,3D-printed models,and mental practice(MP))compared to traditional and cadaver methods.Databases Reviewed:PubMed,Cochrane,Web of Science.Methods:Search terms utilized“temporal bone training”,“temporal bone surgical modalities”,and“training modalities temporal bone surgery”with“3D”,“rapid prototyp*”,“stereolithography”,“additive manufact*”,“plaster”,“VR”,“virtual reality”,“animal model”,“animal temporal bone”,and“synthetic”with“AND”for all literature.Exclusion criteria:non-ENT,non-English,and did not compare against alternative/traditional methods.Results:10 studies were included with 322 participants(83.9%ENT residents and 16.1%medical students).Costs include the FDM printer($300),materials($5/3D model),and<$5,000 for freeware simulator hardware.The Welling scale was used in 50%of studies.Alternate methods produced comparable or improved assessment scores to traditional and cadaver methods.Injuries were reported in three VR studies,with two reported significantly lower injury scores in the intervention groups.Time to completion was not significantly different in four VR studies,except for one finding that the time to visualize the incus was significantly lower in the intervention group.Performance after MP was not statistically different.Conclusion:More data are needed to assess whether the alternate methods are comparable to cadaveric dissection in temporal bone training.3D models and VR simulation demonstrate promising potential for novel trainees to acquire the basic skills and produce performance comparable to or significantly better than traditional methods of lectures,textbooks,CT images,and operative videos.展开更多
Background: Brainwave entrainment using binaural beats has shown potential in treating tinnitus, but most studies have focused on one-month treatment durations. Objective: This study aimed to evaluate the time-bound e...Background: Brainwave entrainment using binaural beats has shown potential in treating tinnitus, but most studies have focused on one-month treatment durations. Objective: This study aimed to evaluate the time-bound efficacy of brainwave entrainment using binaural beats, comparing it to a standard tinnitus masker over a three-month duration. Method: Sixty-three individuals having tinnitus with normal hearing sensitivity were enrolled in the study. The participants were categorized into groups Ⅰ, Ⅱ, and Ⅲ. They were provided with delta(4 Hz) and alpha(10 Hz) frequency binaural beats and standard tinnitus masker, respectively, for a duration of three months. The tinnitus handicap inventory(THI) scores, Visual analogue scale(VAS) rating for tinnitus distress, and quality of life parameters were measured. The reductions obtained for each measure during the end of the first, second and third month were measured and compared across the groups. Results: All three groups showed considerable reductions in THI and VAS scores and improvements in the quality of life domains, focusing on physical and psychological health. However, groups Ⅰ and Ⅱ, who received binaural beats stimuli, showed higher benefits than those who received standard tinnitus masker. Conclusion: The results of the current study indicated that binaural beats can be an effective treatment technique for individuals with tinnitus having normal hearing sensitivity. Clinicians and otology/audiology practitioners shall adopt this innovative treatment after further validating these findings.展开更多
Purpose It is essential to investigate the audiological profiles of Williams syndrome in a multicultural context.This study aims to examine the characteristics and management of hearing loss in Chinese children with W...Purpose It is essential to investigate the audiological profiles of Williams syndrome in a multicultural context.This study aims to examine the characteristics and management of hearing loss in Chinese children with Williams syndrome and provide references for future clinical management.Method Between January 2007 and March 2022,families with at least 1 WS patient was recruited from the Newborn Cohort Study of Hearing Loss.Audiological tests were performed,and then appropriate medical management was offered.Furthermore,an overview of the hearing loss phenotype in Williams syndrome in different locations was reviewed.Results A total of two families with at least 1 Williams syndrome patient were recruited from the Newborn Cohort Study of Hearing Loss(ChiCTR2100049765).We identified moderately severe sensorineural or conductive hearing loss that emerged as early as the infancy period in Williams syndrome subjects in Chinese children.Our results extended the reported onset ages of hearing loss in WS from late childhood or early adulthood to the infancy period.We also found that with early diagnosis,proper management,and regular monitoring,children with Williams syndrome could return to a normal or near-normal school life.Conclusions Our study demonstrated the distinct hearing profile in Chinese children with Williams syndrome for the first time.This cohort of WS subjects extends the reported onset ages of hearing loss in WS from late childhood or early adulthood to the infancy period,indicating the importance of clinicians screening and monitoring the hearing status of individuals with WS as early as possible.These data provide references for otolaryngologists and paediatricians to inform the clinical understanding and management of hearing loss in Williams syndrome.展开更多
Objective: To study the relationship between cortical auditory evoked potential (CAEP) thresholds and behavioral thresholds in pediatric populations with sensorineural hearing loss (SNHL). Methods: Fifteen children (m...Objective: To study the relationship between cortical auditory evoked potential (CAEP) thresholds and behavioral thresholds in pediatric populations with sensorineural hearing loss (SNHL). Methods: Fifteen children (mean age 6.8 years) with bilateral SNHL underwent behavioral pure-tone audiometry and CAEP testing at 0.5, 1, 2, and 4 kHz. CAEP thresholds were determined using tone bursts, and correlations between CAEP and pure-tone thresholds were analyzed using Pearson correlation and t-tests. Results: A strong positive correlation was observed between P1 thresholds and behavioral thresholds across all test frequencies: 0.5 kHz (r = 0.765, p Conclusion: The strong correlation between P1 and behavioral thresholds demonstrates the reliability of CAEP testing for estimating auditory thresholds in children. These findings support the use of CAEP testing as a reliable objective tool for threshold estimation, particularly in cases where behavioral responses cannot be reliably obtained. When adjusted with frequency-specific correction values, CAEP testing provides a reliable method for assessing hearing thresholds in pediatric populations.展开更多
BackgroundIt's crucial to study the effect of changes in thresholds(T)and most comfortable levels(M)on behavioral measurements in young children using cochlear implants.This would help the clinician with the optim...BackgroundIt's crucial to study the effect of changes in thresholds(T)and most comfortable levels(M)on behavioral measurements in young children using cochlear implants.This would help the clinician with the optimization and validation of programming parameters.ObjectiveThe study has attempted to describe the changes in behavioral responses with modification of T and M levels.MethodsTwenty-five participants in the age range 5 to 12 years using HR90K/HiFocus1J or HR90KAdvantage/HiFocus1J with Harmony speech processors participated in the study.A decrease in T levels,a rise in T levels,or a decrease in M levels in the everyday program were used to create experimental programs.Sound field thresholds and speech perception were measured at 50 dBHL for three experimental and everyday programs.ConclusionThe results indicated that only reductions of M levels resulted in significantly(p<0.01)poor aided thresholds and speech perception.On the other hand,variation in T levels did not have significant changes in either sound field thresholds or speech perception.The results highlight that M levels must be correctly established in order to prevent decreased speech perception and audibility.展开更多
Objective:This study aims to establish an economically viable and easily accessible adult animal model for optogenetic activation of auditory neurons using adeno-associated viruses(AAVs)carrying Ch R2(H134R)to explore...Objective:This study aims to establish an economically viable and easily accessible adult animal model for optogenetic activation of auditory neurons using adeno-associated viruses(AAVs)carrying Ch R2(H134R)to explore the potential of cochlear optogenetics as a hearing restoration technology.Methods:Healthy adult guinea pigs were used in the experiments.The viral vector AAV2/8-Ch R2(H134R)-h Syn-e YFP was administered to the right cochlea via the round window membrane.The confocal microscopy and reverse transcription polymerase chain reaction(RT-PCR)were utilized to analyze the Ch R2(H134R)expression localized to spiral ganglion neurons(SGNs).The auditory pathway activation was assessed by recording the optical compound action potential(oCAP)and acoustic compound action potential(a CAP)at various laser intensities.Results:The Ch R2(H134R)-e YFP expression was confirmed in 90%of the tested animals,localized to the SGNs of the injected ear.Higher m RNA levels of Ch R2(H134R)and e YFP were observed in the injected ear compared to the non-injected ear,while actin(Actb)m RNA levels were not significantly different.The o CAP was successfully elicited by a 470 nm blue light laser stimulus,with similar amplitudes and latency periods to those of a CAPs when the o CAP was evoked by 5.80 m W blue light and the a CAP was evoked by a 40 d B SPL click.The amplitudes of o CAPs increased with increasing laser intensity.Conclusion:This study demonstrates the viability of optogenetic activation of the auditory system in adult guinea pigs through the transduction of AAV-Ch R2(H134R)in SGNs.Cochlear optogenetics demonstrates potential as a hearing restoration technology,providing a basis for further clinical research and opening new avenues for investigation.展开更多
Craniofacial microsomia(CFM)is a congenital malformation with maxillary and/or mandibular hypoplasia,skin tags,and ear malformations(Luo et al.,2023).Microtia,in its mildest form,can occur alone(Quiat et al.,2023).Wit...Craniofacial microsomia(CFM)is a congenital malformation with maxillary and/or mandibular hypoplasia,skin tags,and ear malformations(Luo et al.,2023).Microtia,in its mildest form,can occur alone(Quiat et al.,2023).With a prevalence of 3.8/100,000(Barisic et al.,2014),CFM is the second most common congenital craniofacial abnormality(Li et al.,2022;Luo et al.,2023).Most cases are sporadic,but familial ones suggest autosomal dominant(AD)or autosomal recessive(AR)(Beleza-Meireles et al.,2014).In 2023,Quiat et al.and Mao et al.successively identified FOXI3 variants in 16 pedigrees and 10 sporadic cases,respectively,accounting for 3.1%of CFM cases(Mao et al.,2023;Quiat et al.,2023).FOX/3 has surpassed SF3B2 as the most frequently identified pathogenic gene for CFM to date(Timberlake et al.,2021;Mao et al.,2023;Quiat et al.,2023).In this study,we performed whole-exome sequencing(WES)on 201 CFM pedigrees and detected FOX/3 variants in 8 AD-inherited pedigrees with 24 patients and 28 unaffected individuals(Fig.1A).展开更多
Hearing loss,which currently affects more than 430 million individuals globally and is projected to exceed 700 million by 2050,predominantly manifests as sensorineural hearing loss(SNHL),for which existing technologie...Hearing loss,which currently affects more than 430 million individuals globally and is projected to exceed 700 million by 2050,predominantly manifests as sensorineural hearing loss(SNHL),for which existing technologies such as hearing aids and cochlear implants fail to restore natural auditory function.Research focusing on protecting inner ear hair cells(HCs)from harmful factors through the regulation of epigenetic modifications has gained significant attention in otology for its role in regulating gene expression without altering the DNA sequence,suggesting potential strategies for preventing and treating SNHL.By synthesizing relevant studies on the inner ear,this review summarizes the emerging roles of histone modifications,DNA methylation,and noncoding RNAs in HC damage,with a focus on their therapeutic potential through epigenetic modulation.Moreover,this review examines the therapeutic potential of epigenetic regulation for the prevention and treatment of SNHL,emphasizing the application of small-molecule epigenetic compounds and their efficacy in modulating gene expression to preserve and restore auditory function.展开更多
The cochlea is one of the most complex organs in the human body,exhibiting a complex interplay of characteristics in acoustic,mechanical,electrical,and biological functions.Functional cochlea models are an essential p...The cochlea is one of the most complex organs in the human body,exhibiting a complex interplay of characteristics in acoustic,mechanical,electrical,and biological functions.Functional cochlea models are an essential platform for studying hearing mechanics and are crucial for developing next-generation auditory prostheses and artificial hearing systems for sensorineural hearing restoration.Recent advances in additive manufacturing,organ-on-a-chip models,drug delivery platforms,and artificial intelligence have provided valuable insights into how to manufacture artificial cochlea models that more accurately replicate the complex anatomy and physiology of the inner ear.This paper reviews recent advancements in the applications of advanced manufacturing techniques in reproducing the physical,biological,and intelligent functions of the cochlea.It also outlines the current challenges to developing mechanically,electrically,and anatomically accurate functional models of the inner ear.Finally,this review identifies the major requirements and outlook for impactful research in this field going forward.Through interdisciplinary collaboration and innovation,these functional cochlea models are poised to drive significant advancements in hearing treatments,and ultimately enhance the quality of life for individuals with hearing loss.展开更多
This editorial discusses Alpsoy et al’s significant study of prognosis of pancreatic ductal adenocarcinoma(PDAC),which lacks histopathological markers.This study evaluated the synergistic prognolymphocytes.Peritumora...This editorial discusses Alpsoy et al’s significant study of prognosis of pancreatic ductal adenocarcinoma(PDAC),which lacks histopathological markers.This study evaluated the synergistic prognolymphocytes.Peritumoral budding is significantly correlated with tumor volume,while intratumoral budding is closely related to lymph node metastasis.Peritumoral budding and intratumoral budding are confirmed as independent adverse prognostic factors,and their high levels of expression are associated with immature stromal phenotypes,suggesting the key role of epithelial-mesenchymal transition.These breakthrough findings provide a new multidimensional biomarker system for the prognostic assessment of PDAC,and promote the clinical transformation process of incorporating tumor budding indicators into the pathological reporting process.However,the complexity and spatiotemporal heterogeneity of the tumor microenvironment require us to go beyond traditional morphological analysis and move towards multiomics integration and dynamic monitoring.Through standardized pathological assessment,innovative treatment strategies and interdisciplinary collaboration,it is expected to transform tumor microenvironment-related markers into clinically applicable indicators,ultimately improving the treatment predicament of PDAC.This editorial intended to summarize relevant studies and share some of our views,in order to offer perspectives for future research.展开更多
In this article we commented on an article published recently by Jiao et al.This retrospective study confirmed that the triple therapy of transarterial chemoembolization(TACE)combined with programmed death protein lig...In this article we commented on an article published recently by Jiao et al.This retrospective study confirmed that the triple therapy of transarterial chemoembolization(TACE)combined with programmed death protein ligand 1 inhibitors and molecular targeted therapy can significantly reverse TACE resistance in advanced hepatocellular carcinoma.Compared with TACE alone,the triple therapy reduced the resistance rate from 38.8%to 9.7%and increased the median progression-free survival and median overall survival by 92.3%and 26.8%,respectively.TACE induces tumor antigen release and upregulates programmed death protein ligand 1,activating the effect of immune checkpoint inhibitors while molecular targeted therapy inhibits postembolization vascular regeneration,forming a dynamic synergistic network of embolization-immune activation-vascular inhibition.The maximum tumor diameter,capsule loss,and bilateral distribution were identified as independent predictors.This study provided level I evidence and promoted the transformation of advanced hepatocellular carcinoma treatment from single local intervention to an integrated model of local control-systemic treatment.In the future it will be necessary to analyze the dynamic evolution rules of the tumor microenvironment through crossomics strategies,further explore biomarkers,optimize treatment sequences,and conduct multicenter prospective trials to verify long-term survival benefits and guide the optimization of individualized sequential treatment.展开更多
基金supported by the National Key Research and Development Program of China,No.2022YFC2402701(to WC)Key International(Regional)Joint Research Program of the National Natural Science Foundation of China,No.81820108009(to SY)+5 种基金the National Natural Science Foundation of China,Nos.81970890(to WC)and 82371148(to WG)Fujian Provincial Healthcare Young and Middle-aged Backbone Talent Training Project,No.2023GGA035(to XC)Spring City Planthe High-level Talent Promotion and Training Project of Kunming,No.2022SCP001(to SY)the Natural Science Foundation of Hainan Province of China,No.824MS052(to XS)the Sixth Medical Center of Chinese PLA General Hospital Innovation Cultivation,No.CXPY202116(to LX)。
文摘Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Here,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory mechanisms.We established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 hours.We found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with tranylcypromine.The noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with saline.These findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell loss.Additionally,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy pathway.Tranylcypromine treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)production.In conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing function.These findings suggest that inhibiting lysine-specific demethylase 1 is a potential therapeutic strategy for preventing hair cell loss and noise-induced hearing loss.
文摘Background:Research has shown that musicians outperform non-musicians in speech perception in noise(SPiN)tasks.However,it remains unclear whether the advantages of musical training are substantial enough to slow down the decline in SPiN performance associated with aging.Objectives:Therefore,we assessed SPiN performances in a continuum of age groups comprising musicians and non-musicians.The goal was to compare how the aging process affected SPiN performances of musicians and non-musicians.Method:A cross-sectional descriptive mixed design was used,involving 150 participants divided into 75 musicians and 75 non-musicians.Each age group(10-19,20-29,30-39,40-49,and 50-59)consisted of15 musicians and 15 non-musicians.Six Kannada sentence lists were combined with four-talker babble.At+5,0,and-5 dB signal-to-noise ratios(SNRs),the percent correct Speech Identification Scores were calculated.Results:The repeated measure ANOVA(RM ANOVA)revealed significant main effects and interaction effects between SNR,musicianship,and age groups(p<0.05).A small to large effect size was noted(ηp2=0.05 to0.17).A significant interaction effect and follow-up post hoc tests showed that SPiN abilities deteriorated more rapidly with increasing age in nonmusicians compared to musicians,especially at difficult SNRs.Conclusions:Musicians had better SPiN abilities than non-musicians across all age groups.Also,age-related deterioration in SPiN abilities was faster in non-musicians compared to musicians.
基金supported by NIH grants AG079264(to PHR)and AG071560(to APR)。
文摘The process of neurite outgrowth and branching is a crucial aspect of neuronal development and regeneration.Axons and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start networks.Here we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal cells.In this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)cDNA.To investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were used.Neurite outgrowth is evaluated through the segmentation and measurement of neural processes.These neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite growth.These neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal HT22.DDQ-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-tubulin.Additionally,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic outgrowth.Our findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara cteristics.The key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.
文摘Objective:Critically appraise the current state of alternate temporal bone training techniques(virtual reality(VR)simulation,3D-printed models,and mental practice(MP))compared to traditional and cadaver methods.Databases Reviewed:PubMed,Cochrane,Web of Science.Methods:Search terms utilized“temporal bone training”,“temporal bone surgical modalities”,and“training modalities temporal bone surgery”with“3D”,“rapid prototyp*”,“stereolithography”,“additive manufact*”,“plaster”,“VR”,“virtual reality”,“animal model”,“animal temporal bone”,and“synthetic”with“AND”for all literature.Exclusion criteria:non-ENT,non-English,and did not compare against alternative/traditional methods.Results:10 studies were included with 322 participants(83.9%ENT residents and 16.1%medical students).Costs include the FDM printer($300),materials($5/3D model),and<$5,000 for freeware simulator hardware.The Welling scale was used in 50%of studies.Alternate methods produced comparable or improved assessment scores to traditional and cadaver methods.Injuries were reported in three VR studies,with two reported significantly lower injury scores in the intervention groups.Time to completion was not significantly different in four VR studies,except for one finding that the time to visualize the incus was significantly lower in the intervention group.Performance after MP was not statistically different.Conclusion:More data are needed to assess whether the alternate methods are comparable to cadaveric dissection in temporal bone training.3D models and VR simulation demonstrate promising potential for novel trainees to acquire the basic skills and produce performance comparable to or significantly better than traditional methods of lectures,textbooks,CT images,and operative videos.
文摘Background: Brainwave entrainment using binaural beats has shown potential in treating tinnitus, but most studies have focused on one-month treatment durations. Objective: This study aimed to evaluate the time-bound efficacy of brainwave entrainment using binaural beats, comparing it to a standard tinnitus masker over a three-month duration. Method: Sixty-three individuals having tinnitus with normal hearing sensitivity were enrolled in the study. The participants were categorized into groups Ⅰ, Ⅱ, and Ⅲ. They were provided with delta(4 Hz) and alpha(10 Hz) frequency binaural beats and standard tinnitus masker, respectively, for a duration of three months. The tinnitus handicap inventory(THI) scores, Visual analogue scale(VAS) rating for tinnitus distress, and quality of life parameters were measured. The reductions obtained for each measure during the end of the first, second and third month were measured and compared across the groups. Results: All three groups showed considerable reductions in THI and VAS scores and improvements in the quality of life domains, focusing on physical and psychological health. However, groups Ⅰ and Ⅱ, who received binaural beats stimuli, showed higher benefits than those who received standard tinnitus masker. Conclusion: The results of the current study indicated that binaural beats can be an effective treatment technique for individuals with tinnitus having normal hearing sensitivity. Clinicians and otology/audiology practitioners shall adopt this innovative treatment after further validating these findings.
基金supported by the grants of the National Key Research and Development Program of China(Grant No.2023YFC2508400)the National Natural Science Foundation of China(Grant No.82350005).
文摘Purpose It is essential to investigate the audiological profiles of Williams syndrome in a multicultural context.This study aims to examine the characteristics and management of hearing loss in Chinese children with Williams syndrome and provide references for future clinical management.Method Between January 2007 and March 2022,families with at least 1 WS patient was recruited from the Newborn Cohort Study of Hearing Loss.Audiological tests were performed,and then appropriate medical management was offered.Furthermore,an overview of the hearing loss phenotype in Williams syndrome in different locations was reviewed.Results A total of two families with at least 1 Williams syndrome patient were recruited from the Newborn Cohort Study of Hearing Loss(ChiCTR2100049765).We identified moderately severe sensorineural or conductive hearing loss that emerged as early as the infancy period in Williams syndrome subjects in Chinese children.Our results extended the reported onset ages of hearing loss in WS from late childhood or early adulthood to the infancy period.We also found that with early diagnosis,proper management,and regular monitoring,children with Williams syndrome could return to a normal or near-normal school life.Conclusions Our study demonstrated the distinct hearing profile in Chinese children with Williams syndrome for the first time.This cohort of WS subjects extends the reported onset ages of hearing loss in WS from late childhood or early adulthood to the infancy period,indicating the importance of clinicians screening and monitoring the hearing status of individuals with WS as early as possible.These data provide references for otolaryngologists and paediatricians to inform the clinical understanding and management of hearing loss in Williams syndrome.
文摘Objective: To study the relationship between cortical auditory evoked potential (CAEP) thresholds and behavioral thresholds in pediatric populations with sensorineural hearing loss (SNHL). Methods: Fifteen children (mean age 6.8 years) with bilateral SNHL underwent behavioral pure-tone audiometry and CAEP testing at 0.5, 1, 2, and 4 kHz. CAEP thresholds were determined using tone bursts, and correlations between CAEP and pure-tone thresholds were analyzed using Pearson correlation and t-tests. Results: A strong positive correlation was observed between P1 thresholds and behavioral thresholds across all test frequencies: 0.5 kHz (r = 0.765, p Conclusion: The strong correlation between P1 and behavioral thresholds demonstrates the reliability of CAEP testing for estimating auditory thresholds in children. These findings support the use of CAEP testing as a reliable objective tool for threshold estimation, particularly in cases where behavioral responses cannot be reliably obtained. When adjusted with frequency-specific correction values, CAEP testing provides a reliable method for assessing hearing thresholds in pediatric populations.
文摘BackgroundIt's crucial to study the effect of changes in thresholds(T)and most comfortable levels(M)on behavioral measurements in young children using cochlear implants.This would help the clinician with the optimization and validation of programming parameters.ObjectiveThe study has attempted to describe the changes in behavioral responses with modification of T and M levels.MethodsTwenty-five participants in the age range 5 to 12 years using HR90K/HiFocus1J or HR90KAdvantage/HiFocus1J with Harmony speech processors participated in the study.A decrease in T levels,a rise in T levels,or a decrease in M levels in the everyday program were used to create experimental programs.Sound field thresholds and speech perception were measured at 50 dBHL for three experimental and everyday programs.ConclusionThe results indicated that only reductions of M levels resulted in significantly(p<0.01)poor aided thresholds and speech perception.On the other hand,variation in T levels did not have significant changes in either sound field thresholds or speech perception.The results highlight that M levels must be correctly established in order to prevent decreased speech perception and audibility.
基金supported by the Beijing Natural Science Foundation of China under Grant 7222185。
文摘Objective:This study aims to establish an economically viable and easily accessible adult animal model for optogenetic activation of auditory neurons using adeno-associated viruses(AAVs)carrying Ch R2(H134R)to explore the potential of cochlear optogenetics as a hearing restoration technology.Methods:Healthy adult guinea pigs were used in the experiments.The viral vector AAV2/8-Ch R2(H134R)-h Syn-e YFP was administered to the right cochlea via the round window membrane.The confocal microscopy and reverse transcription polymerase chain reaction(RT-PCR)were utilized to analyze the Ch R2(H134R)expression localized to spiral ganglion neurons(SGNs).The auditory pathway activation was assessed by recording the optical compound action potential(oCAP)and acoustic compound action potential(a CAP)at various laser intensities.Results:The Ch R2(H134R)-e YFP expression was confirmed in 90%of the tested animals,localized to the SGNs of the injected ear.Higher m RNA levels of Ch R2(H134R)and e YFP were observed in the injected ear compared to the non-injected ear,while actin(Actb)m RNA levels were not significantly different.The o CAP was successfully elicited by a 470 nm blue light laser stimulus,with similar amplitudes and latency periods to those of a CAPs when the o CAP was evoked by 5.80 m W blue light and the a CAP was evoked by a 40 d B SPL click.The amplitudes of o CAPs increased with increasing laser intensity.Conclusion:This study demonstrates the viability of optogenetic activation of the auditory system in adult guinea pigs through the transduction of AAV-Ch R2(H134R)in SGNs.Cochlear optogenetics demonstrates potential as a hearing restoration technology,providing a basis for further clinical research and opening new avenues for investigation.
基金support in this study.This work was supported by the National Natural Science Foundation of China(82271889,82172105)the National Key Research and Development Program of China(2021YFC2701000)Shanghai Natural Science Foundation(23ZR1409400,24ZR1409400).
文摘Craniofacial microsomia(CFM)is a congenital malformation with maxillary and/or mandibular hypoplasia,skin tags,and ear malformations(Luo et al.,2023).Microtia,in its mildest form,can occur alone(Quiat et al.,2023).With a prevalence of 3.8/100,000(Barisic et al.,2014),CFM is the second most common congenital craniofacial abnormality(Li et al.,2022;Luo et al.,2023).Most cases are sporadic,but familial ones suggest autosomal dominant(AD)or autosomal recessive(AR)(Beleza-Meireles et al.,2014).In 2023,Quiat et al.and Mao et al.successively identified FOXI3 variants in 16 pedigrees and 10 sporadic cases,respectively,accounting for 3.1%of CFM cases(Mao et al.,2023;Quiat et al.,2023).FOX/3 has surpassed SF3B2 as the most frequently identified pathogenic gene for CFM to date(Timberlake et al.,2021;Mao et al.,2023;Quiat et al.,2023).In this study,we performed whole-exome sequencing(WES)on 201 CFM pedigrees and detected FOX/3 variants in 8 AD-inherited pedigrees with 24 patients and 28 unaffected individuals(Fig.1A).
基金supported by the National Natural Science Foundation of China(Nos.82271158,82301312,82071045,82101219,82071048).
文摘Hearing loss,which currently affects more than 430 million individuals globally and is projected to exceed 700 million by 2050,predominantly manifests as sensorineural hearing loss(SNHL),for which existing technologies such as hearing aids and cochlear implants fail to restore natural auditory function.Research focusing on protecting inner ear hair cells(HCs)from harmful factors through the regulation of epigenetic modifications has gained significant attention in otology for its role in regulating gene expression without altering the DNA sequence,suggesting potential strategies for preventing and treating SNHL.By synthesizing relevant studies on the inner ear,this review summarizes the emerging roles of histone modifications,DNA methylation,and noncoding RNAs in HC damage,with a focus on their therapeutic potential through epigenetic modulation.Moreover,this review examines the therapeutic potential of epigenetic regulation for the prevention and treatment of SNHL,emphasizing the application of small-molecule epigenetic compounds and their efficacy in modulating gene expression to preserve and restore auditory function.
基金support from the UCL GRS/ORS scholarshipUCL Fellowship Incubator Award+9 种基金supported by the NIHR Cambridge Biomedical Research Centre(NIHR203312)funded by the Royal National Institute for Deaf People(RNID,G100138)funded by the Rosetrees Trust Enterprise Fellowship(EF2020100099)RNID Flexigrant(F112)Wellcome Trust Developing Concept Fund(RG93172/BANCE/40181)by the Evelyn Trustfunded by the Woolf Fisher Trust,New Zealandthe Cambridge Commonwealth,European,&International Trustby Trinity CollegeUniversity of Cambridge。
文摘The cochlea is one of the most complex organs in the human body,exhibiting a complex interplay of characteristics in acoustic,mechanical,electrical,and biological functions.Functional cochlea models are an essential platform for studying hearing mechanics and are crucial for developing next-generation auditory prostheses and artificial hearing systems for sensorineural hearing restoration.Recent advances in additive manufacturing,organ-on-a-chip models,drug delivery platforms,and artificial intelligence have provided valuable insights into how to manufacture artificial cochlea models that more accurately replicate the complex anatomy and physiology of the inner ear.This paper reviews recent advancements in the applications of advanced manufacturing techniques in reproducing the physical,biological,and intelligent functions of the cochlea.It also outlines the current challenges to developing mechanically,electrically,and anatomically accurate functional models of the inner ear.Finally,this review identifies the major requirements and outlook for impactful research in this field going forward.Through interdisciplinary collaboration and innovation,these functional cochlea models are poised to drive significant advancements in hearing treatments,and ultimately enhance the quality of life for individuals with hearing loss.
基金Supported by National Natural Science Foundation of China,No.82404058Shanghai Municipal Commission of Health and Family Planning,No.2024ZZ2049Beijing Xisike Clinical Oncology Research Foundation,No.Y-HS202401-0011.
文摘This editorial discusses Alpsoy et al’s significant study of prognosis of pancreatic ductal adenocarcinoma(PDAC),which lacks histopathological markers.This study evaluated the synergistic prognolymphocytes.Peritumoral budding is significantly correlated with tumor volume,while intratumoral budding is closely related to lymph node metastasis.Peritumoral budding and intratumoral budding are confirmed as independent adverse prognostic factors,and their high levels of expression are associated with immature stromal phenotypes,suggesting the key role of epithelial-mesenchymal transition.These breakthrough findings provide a new multidimensional biomarker system for the prognostic assessment of PDAC,and promote the clinical transformation process of incorporating tumor budding indicators into the pathological reporting process.However,the complexity and spatiotemporal heterogeneity of the tumor microenvironment require us to go beyond traditional morphological analysis and move towards multiomics integration and dynamic monitoring.Through standardized pathological assessment,innovative treatment strategies and interdisciplinary collaboration,it is expected to transform tumor microenvironment-related markers into clinically applicable indicators,ultimately improving the treatment predicament of PDAC.This editorial intended to summarize relevant studies and share some of our views,in order to offer perspectives for future research.
基金Supported by the National Natural Science Foundation of China,No.82404058Shanghai Municipal Commission of Health and Family Planning,No.2024ZZ2049Beijing Xisike Clinical Oncology Research Foundation,No.Y-HS202401-0011.
文摘In this article we commented on an article published recently by Jiao et al.This retrospective study confirmed that the triple therapy of transarterial chemoembolization(TACE)combined with programmed death protein ligand 1 inhibitors and molecular targeted therapy can significantly reverse TACE resistance in advanced hepatocellular carcinoma.Compared with TACE alone,the triple therapy reduced the resistance rate from 38.8%to 9.7%and increased the median progression-free survival and median overall survival by 92.3%and 26.8%,respectively.TACE induces tumor antigen release and upregulates programmed death protein ligand 1,activating the effect of immune checkpoint inhibitors while molecular targeted therapy inhibits postembolization vascular regeneration,forming a dynamic synergistic network of embolization-immune activation-vascular inhibition.The maximum tumor diameter,capsule loss,and bilateral distribution were identified as independent predictors.This study provided level I evidence and promoted the transformation of advanced hepatocellular carcinoma treatment from single local intervention to an integrated model of local control-systemic treatment.In the future it will be necessary to analyze the dynamic evolution rules of the tumor microenvironment through crossomics strategies,further explore biomarkers,optimize treatment sequences,and conduct multicenter prospective trials to verify long-term survival benefits and guide the optimization of individualized sequential treatment.
文摘对浙江瑞安、福建宁德、福建东张水库3个地理群体共31例香鱼(Plecoglossus altivelis)的线粒体细胞色素b(Cyt b)基因和线粒体D-loop区序列进行了PCR扩增、序列测定、核苷酸组成和多态性分析。Cytb基因中,A、T、C和G4种核苷酸的比例分别为19.72%、29.71%、32.25%和18.32%,A+T含量为49.43%,G+C含量为50.57%。D-loop区序列中,A、T、C和G4种核苷酸的比例分别为29.99%、29.29%、23.80%和16.92%,A+T含量为59.28%,G+C含量为40.72%。在长度为1141bp的Cytb基因序列中,仅存在1个变异位点,核苷酸多样性指数(π值)为0.00028,31个样本中仅出现两种单倍型;857 bp 长的D-loop区序列中,仅存在5个变异位点,核苷酸多样性指数(π值)为0.00199,仅出现5种单倍型。这表明闽浙地区香鱼的遗传多样性水平很低,应当加大对香鱼的保护力度。
