Objective:The aims of this study were to investigate the clinical applicability of 3D segmentation in measuring cochlear anatomical parameters,explore factors that influence the insertion angle of cochlear implant ele...Objective:The aims of this study were to investigate the clinical applicability of 3D segmentation in measuring cochlear anatomical parameters,explore factors that influence the insertion angle of cochlear implant electrodes in patients with inner ear malformations,and determine the value of 3D segmentation in predicting cochlear implant electrode insertion depth by simulating electrode implantation in a reconstructed 3D model.Methods:Data from 208 temporal bone CT scans of patients with a variety of inner ear malformations(including the CH,IP-Ⅰ,IP-Ⅱ,and IP-Ⅲtypes)who underwent cochlear implantation at our center were retrospectively analyzed.Preoperative temporal bone CT data were subjected to three-dimensional(3D)segmentation of the cochlea with a 3D slicer.Results:Cochlear malformation types,including IP typesⅠ(42 ears),Ⅱ(278ears),Ⅲ(20 ears),and CH(65 ears),were diagnosed and measured in 208 preoperative CT datasets.Cochlear anatomical parameters and electrode length were correlated,which partially explained the variations in electrode insertion angle.The mean angle of implantation among the enrolled patients was 564.33°,and the mean implantation angle prediction error in the 3D segmentation was|23.74|°.Conclusion:Three-dimensional segmentation from temporal bone CT is valuable for surgeons,especially in treating patients with inner ear malformation.Such insights will help surgeons understand overall anatomical variations,predict electrode implantation depth,and complete preoperative imaging assessments for cochlear implant insertion depth in patients with inner ear malformations.展开更多
Background:Sudden sensorineural hearing loss(SSNHL),often associated with tinnitus,significantly impacts individuals'quality of life.Current treatments,such as free drugs via intravenous or intratympanic(IT)admini...Background:Sudden sensorineural hearing loss(SSNHL),often associated with tinnitus,significantly impacts individuals'quality of life.Current treatments,such as free drugs via intravenous or intratympanic(IT)administration of dexamethasone(DEX)and lidocaine,face limitations like low bioavailability and rapid drug clearance.To address these challenges,we developed a local co-delivery system combining DEX microcrystals(DEX MCs)and lidocaine-loaded poly(lactic-co-glycolic acid)(PLGA)non-spherical microparticles(LPNMs)for sustained drug release in the inner ear.Methods:DEX MCs and LPNMs were prepared using the traditional precipitation technique and double emulsion-solvent evaporation,respectively.After characterizing physicochemical properties and drug release kinetics,they were dispersed in sodium hyaluronate solution for IT injection,then in vivo pharmacokinetics and biocompatibility in guinea pigs were studied.Results:DEX MCs exhibited stable dissolution,while LPNMs provided sustained lidocaine release,reducing potential side effects.In vivo studies in guinea pigs demonstrated prolonged drug retention in the perilymph and improved pharmacokinetics.Histological evaluation confirmed the good biocompatibility of this combined delivery system,with no significant inner ear damage observed.Conclusion:This co-delivery system can be used as a depot for delivering both DEX and lidocaine to the inner ear and offers a promising approach for the synergistic treatment of SSNHL associated with tinnitus.展开更多
ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous P...ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous PLGA microspheres(LPMPs)were fabricated using a double emulsion–solvent evaporation method.DEX MCs were physically perfused into LPMPs via negative pressure to form a combined system(DEX MCs+LPMPs).Physicochemical properties,in vitro drug release,pharmacokinetics,and biocompatibility were evaluated.Guinea pigs were used for intratympanic injections of DEX MCs,LPMPs,or DEX MCs+LPMPs.ResultsThe DEX MCs+LPMPs system enabled simultaneous release of both drugs,with DEX exhibiting superior pharmacokinetics(sustained perilymph concentrations up to 7 days)compared to DEX MCs alone.LA release from LPMPs demonstrated prolonged kinetics without burst release.SEM confirmed DEX MCs were localized within/on LPMPs and adhered to the round window membrane(RWM).Histological analysis revealed normal cochlear morphology and no inflammatory response,confirming biocompatibility.ConclusionsThis novel codelivery system combining microcrystals and porous microspheres achieves sustained dual-drug release,enhances therapeutic efficacy,and offers a promising strategy for managing hearing loss via intratympanic administration.展开更多
miRNA-183 family, in normal biology, is expressed in a harmonious and stable manner in the neurosensory organs and cells. Studies have also shown that miRNA-183 family, in different pathways, affects the neurosensory ...miRNA-183 family, in normal biology, is expressed in a harmonious and stable manner in the neurosensory organs and cells. Studies have also shown that miRNA-183 family, in different pathways, affects the neurosensory development, maintenance, survival and function. In addition, it has potential neuroprotective effects in response to neurosensory destructive stimulations. miRNA-96 mutation causes hereditary deafness in humans and mice, and therefore affects the inner ear activity and its maintenance. Certain roles have been identified for mi R-96 in the maintenance and function of the inner ear. The comparison of the target genes of family-183 in transcriptomes of newborn and adult hair cells shows that hundreds of target genes in this family may affect development and maintenance of the ears. Identifying the genes that are regulated by miRNA-183 family provides researchers with important information about the complex development and environmental regulation of the inner ear, and can offer new approaches to the maintenance and regeneration of hair cells and auditory nerve.展开更多
Infants with congenital deafness caused by severe bilateral inner ear malformations frequently suffer from severe hearing loss and poor balance. Unfortunately, the use of hearing aids is usually ineffective in recover...Infants with congenital deafness caused by severe bilateral inner ear malformations frequently suffer from severe hearing loss and poor balance. Unfortunately, the use of hearing aids is usually ineffective in recovering hearing, necessitating cochlear implants. We report a case of a 6-year-old boy with congenital deafness and bilateral inner ear malformations(right side, incomplete partition type I [IP-I]; left side, common cavity deformity). Hearing aids had a remarkable effect in this patient, enabling sufficient and favorable hearing recovery such as to allow the patient to engage in daily conversations. Per-rotatory nystagmus was recorded on an electronystagmogram for both right and left rotations in a damped rotational chair test. It is rare for deaf children with severe bilateral inner ear malformation to demonstrate favorable development in hearing and good equilibrium function. Our findings suggest that auditoryevestibular hair cells in this patient may have been partially preserved despite IP-I in the right ear and common cavity deformity of the left ear.展开更多
Objective:To describe the characteristics of the clinical presentation,diagnosis,surgical methods,and outcomes of patients with otogenic cerebrospinal fluid(CSF)leakage secondary to congenital inner ear dysplasia.Meth...Objective:To describe the characteristics of the clinical presentation,diagnosis,surgical methods,and outcomes of patients with otogenic cerebrospinal fluid(CSF)leakage secondary to congenital inner ear dysplasia.Methods:A retrospective review was performed of 18 patients with otogenic CSF leakage secondary to inner ear dysplasia who underwent surgery in our group from 2007 to 2017 and had a follow-up of at least 4 months.The average length of follow-up was three years.The characteristics of the clinical presentations of all patients,such as self-reported symptoms,radiographic findings,surgical approaches and methods of repair,position of the leakage during surgery,and postoperative course,including the success rate of surgery,are presented.Results:The patients presented mostly with typical symptoms of meningitis,severe hearing impairment,and CSF otorrhea or rhinorrhea.All 18 patients had at least one previous episode of meningitis accompanied by a severe hearing impairment.The preoperative audiograms of 17 patients showed profound sensorineural hearing loss,and one patient had conductive hearing loss.Twelve patients presented with an initial onset of otorrhea,and two had accompanying rhinorrhea.Six patients complained of rhinorrhea,two of whom were misdiagnosed with CSF rhinorrhea and underwent transnasal endoscopy at another hospital.High-resolution computed tomography(HRCT)images can reveal developments in the inner ear,such as expansion of a vestibular cyst,unclear structure of the semicircular canal or cochlea,or signs of effusion in the middle ear or mastoid,which strongly suggest the possibility of CSF otorrhea.The children in the study suffered more severe dysplasia than adults.All 18 patients had CSF leakage identified during surgery.The most common defect sites were in the stapes footplates(55.6%),and 38.9%of patients had a leak around the oval window.One patient had a return of CSF otorrhea during the postoperative period,which did not re-occur following a second repair.Conclusions:CSF otorrhea due to congenital inner ear dysplasia is more severe in children than in adults.The most common symptoms were meningitis,hearing impairment,and CSF otorrhea or rhinorrhea.HRCT has high diagnostic accuracy for this disease.The most common fistula site was around the oval window,including the stapes footplates and the annular ligament.展开更多
In this study,I focused on finding a mean of protecting against hearing loss.By infusing the cochlea with the neurotrophin factor,NT-3 alone or combined treatment with MK 801,a NMDA receptor antagonist I found hearing...In this study,I focused on finding a mean of protecting against hearing loss.By infusing the cochlea with the neurotrophin factor,NT-3 alone or combined treatment with MK 801,a NMDA receptor antagonist I found hearing loss was attenuated and spiral ganglion neuron loss was nearly totally protected indicating that the importance of the combined treatment of NT-3 and NMDA receptor antagonists in the treatment of hearing disorders.展开更多
Bone morphogenetic proteins(BMPs)are the largest subfamily of the transforming growth factor-βsuperfamily,and they play important roles in the development of numerous organs,including the inner ear.The inner ear is a...Bone morphogenetic proteins(BMPs)are the largest subfamily of the transforming growth factor-βsuperfamily,and they play important roles in the development of numerous organs,including the inner ear.The inner ear is a relatively small organ but has a highly complex structure and is involved in both hearing and balance.Here,we discuss BMPs and BMP signaling pathways and then focus on the role of BMP signal pathway regulation in the development of the inner ear and the implications this has for the treatment of human hearing loss and balance dysfunction.展开更多
Seismic P velocity structure is determined for the upper 500 km of the inner core and lowermost 200 km of the outer core from differential travel times and amplitude ratios. Results confirm the existence of a globally...Seismic P velocity structure is determined for the upper 500 km of the inner core and lowermost 200 km of the outer core from differential travel times and amplitude ratios. Results confirm the existence of a globally uniform F region of reduced P velocity gradient in the lowermost outer core, consistent with iron enrichment near the boundary of a solidifying inner core. P velocity of the inner core between the longitudes 45~E and 180~E （quasi-Eastern Hemisphere） is greater than or equal to that of an AK135-F reference model whereas that between 180~W and 45~E （quasi-Western Hemisphere） is less than that of the reference model Observation of this heterogeneity to a depth of 550 km below the inner core and the existence of transitions rather than sharp boundaries between quasi-hemispheres favor either no or very slow inner core super rotation or oscillations with respect to the mantle. Degree- one seismic heterogeneity may be best explained by active inner core freezing beneath the equatorial Indian Ocean dominating structure in the quasi-Eastern Hemisphere and inner core melting beneath equatorial Pacific dominating structure in the quasi-Western Hemisphere. Variations in waveforms also suRgest the existence of smaller-scale （1 to 100 km） heterogeneity.展开更多
Congenital hearing loss is a common disorder worldwide.Heterogeneous gene variation accounts for approximately 20-25%of such patients.We investigated a five-generation Chinese family with autosomaldominant nonsyndromi...Congenital hearing loss is a common disorder worldwide.Heterogeneous gene variation accounts for approximately 20-25%of such patients.We investigated a five-generation Chinese family with autosomaldominant nonsyndromic sensorineural hearing loss(SNHL).No wave was detected in the pure-tone audiometry,and the auditory brainstem response was absent in all patients.Computed tomography of the patients,as well as of two sporadic SNHL cases,showed bilateral inner ear anomaly,cochlear maldevelopment,absence of the osseous spiral lamina,and an enlarged vestibular aqueduct.Such findings were absent in nonaffected persons.We used linkage analysis and exome sequencing and uncovered a heterozygous missense mutation in the PI4 KB gene(p.Gln121 Arg)encoding phosphatidylinositol 4-kinaseβ(PI4 KB)from the patients in this family.In addition,3 missense PI4 KB(p.Val434 Gly,p.Glu667 Lys,and p.Met739 Arg)mutations were identified in five patients with nonsyndromic SNHL from 57 sporadic cases.No such mutations were present within 600 Chinese controls,the 1000 genome project,gnom AD,or similar databases.Depleting pi4 kb m RNA expression in zebrafish caused inner ear abnormalities and audiosensory impairment,mimicking the patient phenotypes.Moreover,overexpression of 4 human missense PI4 KB mutant m RNAs in zebrafish embryos resulted in impaired hearing function,suggesting dominant-negative effects.Taken together,our results reveal that PI4 KB mutations can cause SNHL and inner ear malformation.PI4 KB should be included in neonatal deafness screening.展开更多
K^(+)cycling in the cochlea is critical to maintain hearing.Many sodium-potassium pumps are proved to participate in K^(+)cycling,such as Na/K-ATPase.Theα2-Na/K-ATPase is an important isoform of Na/K-ATPase.The expre...K^(+)cycling in the cochlea is critical to maintain hearing.Many sodium-potassium pumps are proved to participate in K^(+)cycling,such as Na/K-ATPase.Theα2-Na/K-ATPase is an important isoform of Na/K-ATPase.The expression ofα2-Na/K-ATPase in the cochlea is not clear.In this study,we used C57BL/6 mice as a model of presbycusis and implemented immunohistochemistry staining and quantitative real time-PCR,and theα2-Na/K-ATPase expression pattern was confirmed in the inner ear.It was foundα2-Na/K-ATPase was expressed widely in cochlea and its mRNA and protein expression was gradually reduced with aging(4-,14-,26-and 48-weeks old mice).We suspected that,the down-regulation ofα2-Na/K-ATPase expression might be associated with the remodeling of K^(+)cycling,degeneration of morphological structure and decrease of hearing function in aging C57 mice.In conclusion,we speculated that the reduction ofα2-Na/K-ATPase might play an important role in the pathogenesis of age-related hearing loss.展开更多
Shear velocity and density contrast across the inner core boundary are essential for stud- ying deep earth dynamics, geodynamo and geomagnetic evolution. In previous studies, amplitude ratio of PKiKP/PcP at short dist...Shear velocity and density contrast across the inner core boundary are essential for stud- ying deep earth dynamics, geodynamo and geomagnetic evolution. In previous studies, amplitude ratio of PKiKP/PcP at short distances and PKiKP/P at larger distances are used to constrain the shear veloc- ity and density contrast, and shear velocity in the top inner core is found to be substantially smaller than the PREM prediction. Here we present a large dataset of PKiKP/P amplitude ratio measured on 420 seismic records at ILAR array in Alaska for the distance range of 800-90~, where the amplitude ra- tio is sensitive to shear velocity and density contrast. At high frequency （up to 6 Hz）, mantle attenuation is found to have substantial effects on PKiKP/P. After the attenuation effects are taken into account, we find that the density contrast is about 0.2-1.0 g/cm3, and shear velocity of inner core is 3.2-4.0 km/s, close to the PREM （Preliminary Reference Earth Model） prediction （0.6 g/cm3 and 3.5 kin/s, respec- tively）. The relatively high shear velocity in inner core does not require large quantities of defects or melts as proposed in previous studies.展开更多
This study,based on the theory of shifting essence and changing Qi in Inner Canon of Huangdi,deeply explores the theoretical basis,operation method of Conception Vessel Dredging Therapy and its influence on human heal...This study,based on the theory of shifting essence and changing Qi in Inner Canon of Huangdi,deeply explores the theoretical basis,operation method of Conception Vessel Dredging Therapy and its influence on human health.Through case analysis and the statistical analysis of medical records during the pandemic,it reveals the remarkable effects of this method in regulating the endocrine system,improving metabolism,and relieving physical and mental diseases.It provides a theoretical and practical basis for the application of traditional Chinese medicine anti-aging therapy in the modern health field,and helps to explore new ways to delay aging and improve physical and mental health.展开更多
The temperature of bush inner surface temperature is measured by using infrared thermometer and transparent bearing,and temperature rise is measured by using thermocouple. The influence of rotating speed and axial loc...The temperature of bush inner surface temperature is measured by using infrared thermometer and transparent bearing,and temperature rise is measured by using thermocouple. The influence of rotating speed and axial location on the bush inner surface temperature is studied,and the influence of supply pressure and rotating speed on the temperature rise is analyzed. The results show the bush inner surface temperature and temperature rise of spiral oil wedge hydrodynamic bearing increase with the increase of rotation speed. In axial direction,the temperature is higher around the oil return hole. The temperature rise decreases with the increase of supply pressure. The highest temperature of bush inner surface and temperature rise are higher at higher speed,so the temperature rise is the fundamental reason which restricts the increase of rotation speed for high speed sleeve bearing.展开更多
The late Paleozoic tectonic framework of the southeastern Central Asian Orogenic Belt is key to restricting the accretion orogeny between the Siberia Craton and the North China Craton. To clarify the framework, petrog...The late Paleozoic tectonic framework of the southeastern Central Asian Orogenic Belt is key to restricting the accretion orogeny between the Siberia Craton and the North China Craton. To clarify the framework, petrogenesis of early Permian intrusive rocks from southeastern Inner Mongolia was studied. Zircon U-Pb dating for bojite and syenogranite from Ar-Horqin indicate that they were emplaced at 288–285 Ma. Geochemical data reveal that the bojite is highly magnesian and low-K to middle-K calc-alkaline, with E-MORB-type REE and IAB-like trace element patterns. The syenogranite is a middle-K calc-alkaline fractionated A-type granite and shows oceanic-arc-like trace element patterns, with depleted Sr-Nd-Hf isotopes,(~(87)Sr/~(86)Sr)I = 0.7032–0.7042, ε_(Nd)(t) = +4.0 to +6.6 and zircon ε_(Hf)(t) = +11.14 to +14.99. This suggests that the bojite was derived from lithospheric mantle metasomatized by subducted slab melt, while the syenogranite originated from very juvenile arc-related lower crust. Usng data from coeval magmatic rocks from Linxi-Ar-Horqin, the Ar-Horqin intra-oceanic arc was reconstructed, i.e., initial transition in 290–280 Ma and mature after 278 Ma. Combined with regional geological and geophysical materials in southeastern Inner Mongolia, an early Permian tectonic framework as ‘one narrow ocean basin of the PAO', ‘two continental marginal arcs on its northern and southern' and ‘one intra-oceanic arc in its southern' is proposed.展开更多
A human middle ear consists of an eardrum and three ossicles which are linked by each other, and connect with the eardrum and an inner ear. The inner ear consists of a cochlea and a vestibular system. An abnormality o...A human middle ear consists of an eardrum and three ossicles which are linked by each other, and connect with the eardrum and an inner ear. The inner ear consists of a cochlea and a vestibular system. An abnormality of the human middle ear such as ossicular dislocation may cause conductive hearing loss. The conductive hearing loss is generally treated by surgery using artificial ossicles. The treatments of conductive hearing loss require a better understanding of characteristics and dynamic behaviors of the human middle ear when the sounds transmit from outer inner to inner ear. The purpose of this research is to simulate the dynamic behaviors of a human ear system comprising the middle ear and the cochlea in the inner ear using the finite element method (FEM). Firstly, the eigen-value analysis was performed to obtain the natural frequencies and vibration modes of the total ear system. Secondly, the frequency response analysis was carried out. Thirdly, the time history response analyses were performed using human voices as the external forces. In the time history response analyses, the sounds created as input sound pressures were used. Human voices, for example vowels “I”, “u” and “e” as input sound pressures were created by using the sound pressures downloaded from the opening samples of human voices as wav files in a website. Then it was clarified that the high frequency components of sounds are reduced by the middle ear system.展开更多
In the last several years since 2004 an important new finding has been unveiled by combined efforts due to Japanese （Satoru Tanaka）, French （Renaud Deguen, Y Albousierre and Marc Monnereau）, American and Chinese g...In the last several years since 2004 an important new finding has been unveiled by combined efforts due to Japanese （Satoru Tanaka）, French （Renaud Deguen, Y Albousierre and Marc Monnereau）, American and Chinese geophysicists （Xiaodong Song and Vernon F Cormier） who employed from unambi- guous detailed seismological evidence and explained by clear theoretical and sound laboratory arguments drawn from fluid dynamics that there exists a strong East-West hemi-spherical asymmetry on the inner- outer core boundary,展开更多
Autoimmune inner ear disease(AIED) represents a very fertile research field and the advancements in the understanding of this disease have a direct application not only in patients affected with this condition but als...Autoimmune inner ear disease(AIED) represents a very fertile research field and the advancements in the understanding of this disease have a direct application not only in patients affected with this condition but also in other inner ear disorders that share the same injury mechanism, damage to the inner ear hair cells. AIED also presents many challenges that have still to be overcome. Firstly, access to the inner ear is limited, as many interventions such as biopsies can result in great irreversible damage. Secondly, there are no completely specific markers for AIED. Lack of a definitive diagnosis can result in the treatment of patients not affected with the disease and, therefore, no response. Finally, some patients become refractory to glucocorticoids and new therapies are needed. This review offers an overview of the animal models that have contributed to the understanding of AIED pathophysiology, the value of currently available diagnostic tests, and therapeutic options, with a special focus on new therapies for non responders or patients refractory to glucocorticoids. Among these new options for therapy, biological agents have been tested recently, whereas gene and stem celltherapy may have a role in the future. The intratympanic route of administration avoids the systemic side effects associated with currently used drugs, and may become a more frequent approach in the future.展开更多
Gravity core EC2005, located in the mud wedge off the Zhejiang-Fujian coast in the inner shelf of the East China Sea （ECS）, was analyzed for its lithology, grain size, rare earth elements （REE） and AMS14C dating. ...Gravity core EC2005, located in the mud wedge off the Zhejiang-Fujian coast in the inner shelf of the East China Sea （ECS）, was analyzed for its lithology, grain size, rare earth elements （REE） and AMS14C dating. Results revealed high-resolution paleoenvironmental evolution and multiple switches of sediment provenances in the inner shelf of ECS. The lithology, grain size and REE concentrations of sediments varied significantly down the core. Mean grain size ranged from 8 to 121 μm, and the values of ΣREE were 152.8-227.9 μg/g. The chondrite- and shale-normalized REE patterns indicated their similarity to the terrigenous sediments in the study area. Between 17.3-12.3 ka BP the sediments in the inner shelf of ECS were mainly originated from local drainage basins. The source then gradually switched to the Yangtze River between 12.3 and 9.8 ka BP. Since about 10-9.8 ka BP, the sediments in the study area were dominantly derived from the Yangtze River. The continuous rising of sea level and formation of coastal current along the inner shelf played a key role in the switches of sediment provenances.展开更多
基金supported by the National Key Research and Development Program of China(grant no.2022YFC2402705)National Municipal Natural Science Foundation(grant no.82471161)Beijing Municipal Natural Science Foundation(grant no.7244308)。
文摘Objective:The aims of this study were to investigate the clinical applicability of 3D segmentation in measuring cochlear anatomical parameters,explore factors that influence the insertion angle of cochlear implant electrodes in patients with inner ear malformations,and determine the value of 3D segmentation in predicting cochlear implant electrode insertion depth by simulating electrode implantation in a reconstructed 3D model.Methods:Data from 208 temporal bone CT scans of patients with a variety of inner ear malformations(including the CH,IP-Ⅰ,IP-Ⅱ,and IP-Ⅲtypes)who underwent cochlear implantation at our center were retrospectively analyzed.Preoperative temporal bone CT data were subjected to three-dimensional(3D)segmentation of the cochlea with a 3D slicer.Results:Cochlear malformation types,including IP typesⅠ(42 ears),Ⅱ(278ears),Ⅲ(20 ears),and CH(65 ears),were diagnosed and measured in 208 preoperative CT datasets.Cochlear anatomical parameters and electrode length were correlated,which partially explained the variations in electrode insertion angle.The mean angle of implantation among the enrolled patients was 564.33°,and the mean implantation angle prediction error in the 3D segmentation was|23.74|°.Conclusion:Three-dimensional segmentation from temporal bone CT is valuable for surgeons,especially in treating patients with inner ear malformation.Such insights will help surgeons understand overall anatomical variations,predict electrode implantation depth,and complete preoperative imaging assessments for cochlear implant insertion depth in patients with inner ear malformations.
基金Tianjin Natural Science Foundation for Jingjinji Collaboration,Grant/Award Number:23JCZXJC00240Hebei Natural Science Foundation,Grant/Award Number:H2023201903+2 种基金Beijing Natural Science Foundation,Grant/Award Number:J230006Capital's Funds for Health Improvement and Research,Grant/Award Number:CFH:2022-2-5072CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-052。
文摘Background:Sudden sensorineural hearing loss(SSNHL),often associated with tinnitus,significantly impacts individuals'quality of life.Current treatments,such as free drugs via intravenous or intratympanic(IT)administration of dexamethasone(DEX)and lidocaine,face limitations like low bioavailability and rapid drug clearance.To address these challenges,we developed a local co-delivery system combining DEX microcrystals(DEX MCs)and lidocaine-loaded poly(lactic-co-glycolic acid)(PLGA)non-spherical microparticles(LPNMs)for sustained drug release in the inner ear.Methods:DEX MCs and LPNMs were prepared using the traditional precipitation technique and double emulsion-solvent evaporation,respectively.After characterizing physicochemical properties and drug release kinetics,they were dispersed in sodium hyaluronate solution for IT injection,then in vivo pharmacokinetics and biocompatibility in guinea pigs were studied.Results:DEX MCs exhibited stable dissolution,while LPNMs provided sustained lidocaine release,reducing potential side effects.In vivo studies in guinea pigs demonstrated prolonged drug retention in the perilymph and improved pharmacokinetics.Histological evaluation confirmed the good biocompatibility of this combined delivery system,with no significant inner ear damage observed.Conclusion:This co-delivery system can be used as a depot for delivering both DEX and lidocaine to the inner ear and offers a promising approach for the synergistic treatment of SSNHL associated with tinnitus.
基金supported by Capital’s Funds for Health Improvement and Research(CFH:2022-2-5072)the Tianjin Natural Science Foundation for Jingjinji Collaboration(23JCZXJC00240)+1 种基金Beijing Natural Science Foundation(J230006)the CAMS Innovation Fund for Medical Science(2021-I2M-1-052).
文摘ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous PLGA microspheres(LPMPs)were fabricated using a double emulsion–solvent evaporation method.DEX MCs were physically perfused into LPMPs via negative pressure to form a combined system(DEX MCs+LPMPs).Physicochemical properties,in vitro drug release,pharmacokinetics,and biocompatibility were evaluated.Guinea pigs were used for intratympanic injections of DEX MCs,LPMPs,or DEX MCs+LPMPs.ResultsThe DEX MCs+LPMPs system enabled simultaneous release of both drugs,with DEX exhibiting superior pharmacokinetics(sustained perilymph concentrations up to 7 days)compared to DEX MCs alone.LA release from LPMPs demonstrated prolonged kinetics without burst release.SEM confirmed DEX MCs were localized within/on LPMPs and adhered to the round window membrane(RWM).Histological analysis revealed normal cochlear morphology and no inflammatory response,confirming biocompatibility.ConclusionsThis novel codelivery system combining microcrystals and porous microspheres achieves sustained dual-drug release,enhances therapeutic efficacy,and offers a promising strategy for managing hearing loss via intratympanic administration.
文摘miRNA-183 family, in normal biology, is expressed in a harmonious and stable manner in the neurosensory organs and cells. Studies have also shown that miRNA-183 family, in different pathways, affects the neurosensory development, maintenance, survival and function. In addition, it has potential neuroprotective effects in response to neurosensory destructive stimulations. miRNA-96 mutation causes hereditary deafness in humans and mice, and therefore affects the inner ear activity and its maintenance. Certain roles have been identified for mi R-96 in the maintenance and function of the inner ear. The comparison of the target genes of family-183 in transcriptomes of newborn and adult hair cells shows that hundreds of target genes in this family may affect development and maintenance of the ears. Identifying the genes that are regulated by miRNA-183 family provides researchers with important information about the complex development and environmental regulation of the inner ear, and can offer new approaches to the maintenance and regeneration of hair cells and auditory nerve.
文摘Infants with congenital deafness caused by severe bilateral inner ear malformations frequently suffer from severe hearing loss and poor balance. Unfortunately, the use of hearing aids is usually ineffective in recovering hearing, necessitating cochlear implants. We report a case of a 6-year-old boy with congenital deafness and bilateral inner ear malformations(right side, incomplete partition type I [IP-I]; left side, common cavity deformity). Hearing aids had a remarkable effect in this patient, enabling sufficient and favorable hearing recovery such as to allow the patient to engage in daily conversations. Per-rotatory nystagmus was recorded on an electronystagmogram for both right and left rotations in a damped rotational chair test. It is rare for deaf children with severe bilateral inner ear malformation to demonstrate favorable development in hearing and good equilibrium function. Our findings suggest that auditoryevestibular hair cells in this patient may have been partially preserved despite IP-I in the right ear and common cavity deformity of the left ear.
基金Project supported by the National Natural Science Foundation of China(Nos.81570914 and 81700925)
文摘Objective:To describe the characteristics of the clinical presentation,diagnosis,surgical methods,and outcomes of patients with otogenic cerebrospinal fluid(CSF)leakage secondary to congenital inner ear dysplasia.Methods:A retrospective review was performed of 18 patients with otogenic CSF leakage secondary to inner ear dysplasia who underwent surgery in our group from 2007 to 2017 and had a follow-up of at least 4 months.The average length of follow-up was three years.The characteristics of the clinical presentations of all patients,such as self-reported symptoms,radiographic findings,surgical approaches and methods of repair,position of the leakage during surgery,and postoperative course,including the success rate of surgery,are presented.Results:The patients presented mostly with typical symptoms of meningitis,severe hearing impairment,and CSF otorrhea or rhinorrhea.All 18 patients had at least one previous episode of meningitis accompanied by a severe hearing impairment.The preoperative audiograms of 17 patients showed profound sensorineural hearing loss,and one patient had conductive hearing loss.Twelve patients presented with an initial onset of otorrhea,and two had accompanying rhinorrhea.Six patients complained of rhinorrhea,two of whom were misdiagnosed with CSF rhinorrhea and underwent transnasal endoscopy at another hospital.High-resolution computed tomography(HRCT)images can reveal developments in the inner ear,such as expansion of a vestibular cyst,unclear structure of the semicircular canal or cochlea,or signs of effusion in the middle ear or mastoid,which strongly suggest the possibility of CSF otorrhea.The children in the study suffered more severe dysplasia than adults.All 18 patients had CSF leakage identified during surgery.The most common defect sites were in the stapes footplates(55.6%),and 38.9%of patients had a leak around the oval window.One patient had a return of CSF otorrhea during the postoperative period,which did not re-occur following a second repair.Conclusions:CSF otorrhea due to congenital inner ear dysplasia is more severe in children than in adults.The most common symptoms were meningitis,hearing impairment,and CSF otorrhea or rhinorrhea.HRCT has high diagnostic accuracy for this disease.The most common fistula site was around the oval window,including the stapes footplates and the annular ligament.
文摘In this study,I focused on finding a mean of protecting against hearing loss.By infusing the cochlea with the neurotrophin factor,NT-3 alone or combined treatment with MK 801,a NMDA receptor antagonist I found hearing loss was attenuated and spiral ganglion neuron loss was nearly totally protected indicating that the importance of the combined treatment of NT-3 and NMDA receptor antagonists in the treatment of hearing disorders.
基金Project Project supported by the National Key Technologies R&D Program of China(Nos.2017YFA0103900 and 2016YFC0905200)the National Natural Science Foundation of China(Nos.81620108005,8177040802,and 81622013)the Shanghaigng Talents Plan(No.18PJ1401700),China
文摘Bone morphogenetic proteins(BMPs)are the largest subfamily of the transforming growth factor-βsuperfamily,and they play important roles in the development of numerous organs,including the inner ear.The inner ear is a relatively small organ but has a highly complex structure and is involved in both hearing and balance.Here,we discuss BMPs and BMP signaling pathways and then focus on the role of BMP signal pathway regulation in the development of the inner ear and the implications this has for the treatment of human hearing loss and balance dysfunction.
基金supported by the National Science Foundation of USA(Nos.EAR 07-38492 and EAR 11-60917)
文摘Seismic P velocity structure is determined for the upper 500 km of the inner core and lowermost 200 km of the outer core from differential travel times and amplitude ratios. Results confirm the existence of a globally uniform F region of reduced P velocity gradient in the lowermost outer core, consistent with iron enrichment near the boundary of a solidifying inner core. P velocity of the inner core between the longitudes 45~E and 180~E （quasi-Eastern Hemisphere） is greater than or equal to that of an AK135-F reference model whereas that between 180~W and 45~E （quasi-Western Hemisphere） is less than that of the reference model Observation of this heterogeneity to a depth of 550 km below the inner core and the existence of transitions rather than sharp boundaries between quasi-hemispheres favor either no or very slow inner core super rotation or oscillations with respect to the mantle. Degree- one seismic heterogeneity may be best explained by active inner core freezing beneath the equatorial Indian Ocean dominating structure in the quasi-Eastern Hemisphere and inner core melting beneath equatorial Pacific dominating structure in the quasi-Western Hemisphere. Variations in waveforms also suRgest the existence of smaller-scale （1 to 100 km） heterogeneity.
基金supported by the grants from the National Key R&D Program of China(2018YFA0801200)the National Natural Science Foundation of China(31970777,31771628,and 31601165)+1 种基金Guangdong Natural Science Fund for Distinguished Young Scholars(2017A030306024)to J.Z.the Deutsche Forschungsgemeinschaft(DFG:GO 1990/1-1)to M.G
文摘Congenital hearing loss is a common disorder worldwide.Heterogeneous gene variation accounts for approximately 20-25%of such patients.We investigated a five-generation Chinese family with autosomaldominant nonsyndromic sensorineural hearing loss(SNHL).No wave was detected in the pure-tone audiometry,and the auditory brainstem response was absent in all patients.Computed tomography of the patients,as well as of two sporadic SNHL cases,showed bilateral inner ear anomaly,cochlear maldevelopment,absence of the osseous spiral lamina,and an enlarged vestibular aqueduct.Such findings were absent in nonaffected persons.We used linkage analysis and exome sequencing and uncovered a heterozygous missense mutation in the PI4 KB gene(p.Gln121 Arg)encoding phosphatidylinositol 4-kinaseβ(PI4 KB)from the patients in this family.In addition,3 missense PI4 KB(p.Val434 Gly,p.Glu667 Lys,and p.Met739 Arg)mutations were identified in five patients with nonsyndromic SNHL from 57 sporadic cases.No such mutations were present within 600 Chinese controls,the 1000 genome project,gnom AD,or similar databases.Depleting pi4 kb m RNA expression in zebrafish caused inner ear abnormalities and audiosensory impairment,mimicking the patient phenotypes.Moreover,overexpression of 4 human missense PI4 KB mutant m RNAs in zebrafish embryos resulted in impaired hearing function,suggesting dominant-negative effects.Taken together,our results reveal that PI4 KB mutations can cause SNHL and inner ear malformation.PI4 KB should be included in neonatal deafness screening.
基金National Natural Science Foundation of China(Nos.81771004,81271078,81500791,81500794 and 81300827).
文摘K^(+)cycling in the cochlea is critical to maintain hearing.Many sodium-potassium pumps are proved to participate in K^(+)cycling,such as Na/K-ATPase.Theα2-Na/K-ATPase is an important isoform of Na/K-ATPase.The expression ofα2-Na/K-ATPase in the cochlea is not clear.In this study,we used C57BL/6 mice as a model of presbycusis and implemented immunohistochemistry staining and quantitative real time-PCR,and theα2-Na/K-ATPase expression pattern was confirmed in the inner ear.It was foundα2-Na/K-ATPase was expressed widely in cochlea and its mRNA and protein expression was gradually reduced with aging(4-,14-,26-and 48-weeks old mice).We suspected that,the down-regulation ofα2-Na/K-ATPase expression might be associated with the remodeling of K^(+)cycling,degeneration of morphological structure and decrease of hearing function in aging C57 mice.In conclusion,we speculated that the reduction ofα2-Na/K-ATPase might play an important role in the pathogenesis of age-related hearing loss.
基金supported by the National Natural Science Foundation of China(Nos.41204044,40674027)the Fund of Chinese Academy of Sciences(No.KZCX2-EW-121)
文摘Shear velocity and density contrast across the inner core boundary are essential for stud- ying deep earth dynamics, geodynamo and geomagnetic evolution. In previous studies, amplitude ratio of PKiKP/PcP at short distances and PKiKP/P at larger distances are used to constrain the shear veloc- ity and density contrast, and shear velocity in the top inner core is found to be substantially smaller than the PREM prediction. Here we present a large dataset of PKiKP/P amplitude ratio measured on 420 seismic records at ILAR array in Alaska for the distance range of 800-90~, where the amplitude ra- tio is sensitive to shear velocity and density contrast. At high frequency （up to 6 Hz）, mantle attenuation is found to have substantial effects on PKiKP/P. After the attenuation effects are taken into account, we find that the density contrast is about 0.2-1.0 g/cm3, and shear velocity of inner core is 3.2-4.0 km/s, close to the PREM （Preliminary Reference Earth Model） prediction （0.6 g/cm3 and 3.5 kin/s, respec- tively）. The relatively high shear velocity in inner core does not require large quantities of defects or melts as proposed in previous studies.
基金Supported by Natural Science Foundation of China,Taoist Qi Healing the World Project(Project No.:71971359).
文摘This study,based on the theory of shifting essence and changing Qi in Inner Canon of Huangdi,deeply explores the theoretical basis,operation method of Conception Vessel Dredging Therapy and its influence on human health.Through case analysis and the statistical analysis of medical records during the pandemic,it reveals the remarkable effects of this method in regulating the endocrine system,improving metabolism,and relieving physical and mental diseases.It provides a theoretical and practical basis for the application of traditional Chinese medicine anti-aging therapy in the modern health field,and helps to explore new ways to delay aging and improve physical and mental health.
基金Sponsored by the National Natural Science Foundation of China(Grant No.51305242)the Scientific Research Foundation of Shandong University of Science and Technology for Recruited Talents(Grant No.2013RCJJ014)
文摘The temperature of bush inner surface temperature is measured by using infrared thermometer and transparent bearing,and temperature rise is measured by using thermocouple. The influence of rotating speed and axial location on the bush inner surface temperature is studied,and the influence of supply pressure and rotating speed on the temperature rise is analyzed. The results show the bush inner surface temperature and temperature rise of spiral oil wedge hydrodynamic bearing increase with the increase of rotation speed. In axial direction,the temperature is higher around the oil return hole. The temperature rise decreases with the increase of supply pressure. The highest temperature of bush inner surface and temperature rise are higher at higher speed,so the temperature rise is the fundamental reason which restricts the increase of rotation speed for high speed sleeve bearing.
基金funded by project grants from the Chinese Geological Survey (Grants Nos. DD20190039, DD20160048–01, DD20160345–17, DD20190372, DD20190360 and 1212011220435)the Liaoning Education Department (Grant No. LQN201915)。
文摘The late Paleozoic tectonic framework of the southeastern Central Asian Orogenic Belt is key to restricting the accretion orogeny between the Siberia Craton and the North China Craton. To clarify the framework, petrogenesis of early Permian intrusive rocks from southeastern Inner Mongolia was studied. Zircon U-Pb dating for bojite and syenogranite from Ar-Horqin indicate that they were emplaced at 288–285 Ma. Geochemical data reveal that the bojite is highly magnesian and low-K to middle-K calc-alkaline, with E-MORB-type REE and IAB-like trace element patterns. The syenogranite is a middle-K calc-alkaline fractionated A-type granite and shows oceanic-arc-like trace element patterns, with depleted Sr-Nd-Hf isotopes,(~(87)Sr/~(86)Sr)I = 0.7032–0.7042, ε_(Nd)(t) = +4.0 to +6.6 and zircon ε_(Hf)(t) = +11.14 to +14.99. This suggests that the bojite was derived from lithospheric mantle metasomatized by subducted slab melt, while the syenogranite originated from very juvenile arc-related lower crust. Usng data from coeval magmatic rocks from Linxi-Ar-Horqin, the Ar-Horqin intra-oceanic arc was reconstructed, i.e., initial transition in 290–280 Ma and mature after 278 Ma. Combined with regional geological and geophysical materials in southeastern Inner Mongolia, an early Permian tectonic framework as ‘one narrow ocean basin of the PAO', ‘two continental marginal arcs on its northern and southern' and ‘one intra-oceanic arc in its southern' is proposed.
文摘A human middle ear consists of an eardrum and three ossicles which are linked by each other, and connect with the eardrum and an inner ear. The inner ear consists of a cochlea and a vestibular system. An abnormality of the human middle ear such as ossicular dislocation may cause conductive hearing loss. The conductive hearing loss is generally treated by surgery using artificial ossicles. The treatments of conductive hearing loss require a better understanding of characteristics and dynamic behaviors of the human middle ear when the sounds transmit from outer inner to inner ear. The purpose of this research is to simulate the dynamic behaviors of a human ear system comprising the middle ear and the cochlea in the inner ear using the finite element method (FEM). Firstly, the eigen-value analysis was performed to obtain the natural frequencies and vibration modes of the total ear system. Secondly, the frequency response analysis was carried out. Thirdly, the time history response analyses were performed using human voices as the external forces. In the time history response analyses, the sounds created as input sound pressures were used. Human voices, for example vowels “I”, “u” and “e” as input sound pressures were created by using the sound pressures downloaded from the opening samples of human voices as wav files in a website. Then it was clarified that the high frequency components of sounds are reduced by the middle ear system.
基金the Institute of Geodesy and Geophysics, CAS in Wuhanthe National Natural Science Foundation of China
文摘In the last several years since 2004 an important new finding has been unveiled by combined efforts due to Japanese （Satoru Tanaka）, French （Renaud Deguen, Y Albousierre and Marc Monnereau）, American and Chinese geophysicists （Xiaodong Song and Vernon F Cormier） who employed from unambi- guous detailed seismological evidence and explained by clear theoretical and sound laboratory arguments drawn from fluid dynamics that there exists a strong East-West hemi-spherical asymmetry on the inner- outer core boundary,
文摘Autoimmune inner ear disease(AIED) represents a very fertile research field and the advancements in the understanding of this disease have a direct application not only in patients affected with this condition but also in other inner ear disorders that share the same injury mechanism, damage to the inner ear hair cells. AIED also presents many challenges that have still to be overcome. Firstly, access to the inner ear is limited, as many interventions such as biopsies can result in great irreversible damage. Secondly, there are no completely specific markers for AIED. Lack of a definitive diagnosis can result in the treatment of patients not affected with the disease and, therefore, no response. Finally, some patients become refractory to glucocorticoids and new therapies are needed. This review offers an overview of the animal models that have contributed to the understanding of AIED pathophysiology, the value of currently available diagnostic tests, and therapeutic options, with a special focus on new therapies for non responders or patients refractory to glucocorticoids. Among these new options for therapy, biological agents have been tested recently, whereas gene and stem celltherapy may have a role in the future. The intratympanic route of administration avoids the systemic side effects associated with currently used drugs, and may become a more frequent approach in the future.
基金supported by the National Natural Science Foundation of China (40776030)Natural Science Foundation of Shandong Province (ZR2010DL009)+2 种基金Open Fund of the Key Laboratory of Marine Geology and Environment, Chinese Academy of Sciences (MGE2010KG02)Fundamental Research Funds for the Central Universities (10CX04004A)the Doctoral Fund of China University of Petroleum (Y0901036)
文摘Gravity core EC2005, located in the mud wedge off the Zhejiang-Fujian coast in the inner shelf of the East China Sea （ECS）, was analyzed for its lithology, grain size, rare earth elements （REE） and AMS14C dating. Results revealed high-resolution paleoenvironmental evolution and multiple switches of sediment provenances in the inner shelf of ECS. The lithology, grain size and REE concentrations of sediments varied significantly down the core. Mean grain size ranged from 8 to 121 μm, and the values of ΣREE were 152.8-227.9 μg/g. The chondrite- and shale-normalized REE patterns indicated their similarity to the terrigenous sediments in the study area. Between 17.3-12.3 ka BP the sediments in the inner shelf of ECS were mainly originated from local drainage basins. The source then gradually switched to the Yangtze River between 12.3 and 9.8 ka BP. Since about 10-9.8 ka BP, the sediments in the study area were dominantly derived from the Yangtze River. The continuous rising of sea level and formation of coastal current along the inner shelf played a key role in the switches of sediment provenances.
