Vestibular hair cells(HCs)in the inner ear,crucial for balance and spatial orientation,are classified into type I and type II subtypes,but the mechanisms regulating their differentiation remain unclear.In this study,w...Vestibular hair cells(HCs)in the inner ear,crucial for balance and spatial orientation,are classified into type I and type II subtypes,but the mechanisms regulating their differentiation remain unclear.In this study,we examined the role of Pou4f3,an important transcription factor,in vestibular HC differentiation using Pou4f3^(DTR/DTR)(deficient)and Pou4f3CreER/CreER(knockout)mouse models.In Pou4f3-deficient mice,the HC number decreased,and immature HCs failed to develop type I characteristics,indicating a developmental arrest.While type II HCs differentiated normally,Pou4f3 deficiency disrupted HC bundle formation and cell polarity.Findings from knockout models further confirmed the essential role of Pou4f3 in vestibular HC subtype specification.This study underscores the critical role of Pou4f3 in determining vestibular HC subtypes and offers insights into potential strategies for restoring vestibular function through HC regeneration.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
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
Otitis media is an infection of the middle ear mainly caused by bacteria,and current treatments rely heavily on antibiotics.However,the emergence of antibiotic-resistant bacterial strains seriously affects their effic...Otitis media is an infection of the middle ear mainly caused by bacteria,and current treatments rely heavily on antibiotics.However,the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy.In our study,we found that extracellular vesicles(EVs)derived from human natural killer cells(NKs)inhibit the proliferation of both standard and levofloxacin(LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner.Moreover,compared to LVX,EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models.For LVX-sensitive strains,EVs were significantly more effective in terms of curative time but not curative rate.For LVX-resistant strains,EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX.In summary,we found that NK EVs are highly effective in treating otitis media,providing an alternative approach for treating this common disease.展开更多
Objective This study aimed to investigate the effect of Astragalus(AST)on osteoporosis(OP)and the downstream mechanisms.Methods Human bone marrow-derived mesenchymal stem cells(hBMSCs)were induced to differentiate int...Objective This study aimed to investigate the effect of Astragalus(AST)on osteoporosis(OP)and the downstream mechanisms.Methods Human bone marrow-derived mesenchymal stem cells(hBMSCs)were induced to differentiate into osteogenic cells.After transfection with relevant plasmids,cell proliferation,cell cycle progression,and apoptosis were assessed.Alizarin red staining was used to detect calcium nodules in the cells,alkaline phosphatase(ALP)staining was used to detect ALP activity in the cells,and quantitative reverse transcription-polymerase chain reaction and western blotting were used to determine RUNX2 and Osterix expression levels.An OP rat model was established using ovariectomy and micro-computed tomography scanning.Hematoxylin and eosin staining and Masson’s trichrome staining were used to evaluate the pathological conditions of bone tissues,while immunohistochemistry was conducted to detect RUNX2 in bone tissues.Results AST promoted the osteogenic differentiation of BMSCs,reduced miR-181d-5p expression levels,and increased SOX11 expression levels.Restoring miR-181d-5p expression or reducing SOX11 expression levels reversed the effects of AST on the osteogenic differentiation of hBMSCs.miR-181d-5p was found to target SOX11 in hBMSCs.AST improved OP in rats,and miR-181d-5p overexpression or SOX11 inhibition reversed the therapeutic effects of AST on OP in rats.Conclusion AST promoted the osteogenic differentiation of hBMSCs and alleviated OP by targeting SOX11 via miR-181d-5p.展开更多
Cochlear hair cell(HC)damage is a primary cause of sensorineural hearing loss.In this study,we performed metabolomic profiling of cochlear sensory epithelium following neomycin-induced HC injury and identified elevate...Cochlear hair cell(HC)damage is a primary cause of sensorineural hearing loss.In this study,we performed metabolomic profiling of cochlear sensory epithelium following neomycin-induced HC injury and identified elevated arginine metabolism as a key metabolic characteristic of damaged HCs.Using a highly sensitive and specific biosensor,we confirmed that injury induced an increase in arginine levels within cochlear HCs.By manipulating the levels of arginine and its downstream metabolites,we discovered that unmetabolized arginine exerts a strong protective effect on cochlear HCs,independent of its downstream metabolites,such as nitric oxide.Furthermore,integrated metabolomic and transcriptomic analyses revealed that arginine plays a critical role in reprogramming phospholipid metabolism.Arginine supplementation enhanced membrane phospholipid saturation through the Lands cycle and de novo lipogenesis,and protected HCs from phospholipid peroxidation-induced membrane damage and subsequent cell death.Notably,arginine supplementation protected hearing from both noise-and aminoglycoside-induced injury in mice.These findings underscore the role of unmetabolized arginine in modulating phospholipid metabolism and preventing membrane damage in cochlear HCs,highlighting that targeting phospholipid metabolism is an effective hearing protection strategy.展开更多
Craniofacial development relies on the migration of cranial neural crest cells(CNCCs)to the first and second pharyngeal arches,followed by their differentiation into various cell types during embryogenesis.Although th...Craniofacial development relies on the migration of cranial neural crest cells(CNCCs)to the first and second pharyngeal arches,followed by their differentiation into various cell types during embryogenesis.Although the CNCC migration has been well-studied,the role of the niche in relation to CNCC remains unclear.Variants in FOXI3 have been implicated in craniofacial microsomia(CFM),yet the molecular mechanisms remain unexplored.FOXI3 is expressed in the ectoderm and auricle epidermis,but not in CNCCs or cartilage.Deletion of Foxi3 in the mouse CNCCs did not disrupt mandible and auricular development,further confirming that FOXI3 does not directly regulate CNCCs.However,Foxi3 deficiency in the ectoderm reduced the production of chondrogenesis-related cytokines derived from ectodermal cells,such as TGF-β1.This impairment affected CNCC proliferation through cell communication,subsequently altering the development of the mandible and auricle.These results emphasize the critical role of FOXI3 in establishing the microenvironment supporting CNCC function.Furthermore,FOXI3 directly regulates target genes associated with translation,thereby orchestrating cytokine production in epidermal cells.The validation using auricle sample from a CFM patient carrying FOXI3 mutation further supports our findings.These insights highlight the function of FOXI3 in creating the niche necessary for CNCC development and provide a basis for understanding the molecular mechanisms driving CFM pathogenesis.展开更多
Circadian sensitivity significantly influences the severity of noise-induced hearing loss(NIHL),but the underlying mechanisms remain unclear.Here,we applied single-cell RNA sequencing to 97,043 cochlear cells,identify...Circadian sensitivity significantly influences the severity of noise-induced hearing loss(NIHL),but the underlying mechanisms remain unclear.Here,we applied single-cell RNA sequencing to 97,043 cochlear cells,identifying macrophages as the primary immune responders to acoustic trauma,with a notable increase in their proportion in the cochlea.Immunofluorescence confirmed significant recruitment and activation of cochlear macrophages following noise exposure,while in vivo macrophage depletion resulted in the recovery of hearing.Furthermore,analyses of differentially-expressed genes and pathways revealed pronounced activation of NLRP3 inflammasome signaling in macrophages during night-time noise exposure.Measurements of elevated IL-1βand IL-18 expression in cochlear macrophages by multiplex immunohistochemistry correlated with heightened inflammation in the night-time exposure group.These findings were further confirmed by the administration of the selective NLRP3 inhibitor CY-09,which mitigated inflammasome activation,preserved synaptic integrity,and protect against hearing loss.In conclusion,our findings underscore the role of macrophage-driven NLRP3 inflammasome activation in mediating circadian variations in cochlear damage,offering a potential therapeutic target for mitigating NIHL.展开更多
The mammalian cochlea relies on outer and inner hair cells(OHCs/IHCs)for sound amplification and signal transmission.Rab3-interacting molecular binding protein 2(RIMBP2),expressed in receptor cells and neurons at syna...The mammalian cochlea relies on outer and inner hair cells(OHCs/IHCs)for sound amplification and signal transmission.Rab3-interacting molecular binding protein 2(RIMBP2),expressed in receptor cells and neurons at synaptic active zones,remains poorly characterized in hearing.We therefore generated a Rimbp2 knockout(KO)mouse model(Rimbp^(2-/-)),which exhibited severe hearing loss with elevated thresholds,prolonged latencies,and reduced amplitudes in auditory brainstem response Wave I.OHC loss via apoptosis was correlated with threshold elevation.In IHCs,patch-clamp recordings revealed reduced exocytosis,including a diminished readily-releasable pool,impaired sustained release,and blocked fast endocytosis.Immunostaining showed unchanged ribbon synapse numbers but positional shifts in the basal pole of KO IHCs.These findings demonstrated RIMBP2’s essential role in OHC survival and its broader regulatory functions in IHC synaptic transmission than previously recognized.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
Foxtail millet(FM)whole grain has received special attention in recent years.To confirm the hypoglycemic effects of FM,we investigated the effects of FM supplementation on glucose metabolism and gut microbiota in rats...Foxtail millet(FM)whole grain has received special attention in recent years.To confirm the hypoglycemic effects of FM,we investigated the effects of FM supplementation on glucose metabolism and gut microbiota in rats with high-fat diet/streptozotocin(HFD/STZ)-induced diabetes.Specifically,we fully assessed the blood biochemical profiles,pancreatic histopathology,insulin-glucagon immunofluorescence,short-chain fatty acids,and gut microbiota composition of rats with HFD/STZ-induced diabetes before and after FM supplementation.Results showed that both 30% and 48% FM supplementation significantly decreased concentrations of fasting blood glucose,60-min blood glucose,and blood triglycerides(P<0.05);additionally,48% FM supplementation significantly improved blood glucose tolerance and insulin resistance(P<0.05).However,FM supplementation could not effectively repair damage to β-cells over a short period of time.In addition,4 weeks of 48% FM supplementation siginificantly increased the relative abundance of Bifidobacterium and concentration of butyrate,suggesting that the hypoglycemic effects of FM supplementation might be partially mediated by gut microbiota.Collectively,we found a dose-dependent relationship between FM supplementation and improvement of blood glucose metabolism,but did not find a synergistic effect between FM supplementation and metformin(Met)treatment.Our findings provide further support that consuming more whole-grain FM might be beneficial to individuals suffering from type 2 diabetes.展开更多
Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus.Here,we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells(IHCs).We found that ...Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus.Here,we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells(IHCs).We found that IHCs showed significant damage after exposure to a high concentration of salicylate.Whole-cell patch clamp recordings showed that 1–5 mmol/L salicylate did not affect the exocytosis of IHCs,indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input.Instead,salicylate induced a larger peak amplitude,a more negative half-activation voltage,and a steeper slope factor of Ca^(2+)current.Using noise analysis of Ca^(2+)tail currents and qRT-PCR,we further found that salicylate increased the number of Ca^(2+)channels along with CaV1.3 expression.All these changes could act synergistically to enhance the Ca^(2+)influx into IHCs.Inhibition of intracellular Ca^(2+)overload significantly attenuated IHC death after 10 mmol/L salicylate treatment.These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.展开更多
Traditional cochlear implantation surgery has problems such as high surgical accuracy requirement and large trauma,which cause the difficulty of the operation and the high requirements for doctors,so that only a few d...Traditional cochlear implantation surgery has problems such as high surgical accuracy requirement and large trauma,which cause the difficulty of the operation and the high requirements for doctors,so that only a few doctors can complete the operation independently.However,there is no research on robotic cochlear implantation in China.In response to this problem,a robotic cochlear implantation system is proposed.The robot is controlled by robot operating system(ROS).A simulation environment for the overall surgery is established on the ROS based on the real surgery environment.Through the analysis of the kinematics and the motion planning algorithm of the manipulator,an appropriate motion mode is designed to control the motion of the manipulator,and perform the surgery under the simulation environment.A simple and feasible method of navigation is proposed,and through the model experiment,the feasibility of robotic cochlear implantation surgery is verified.展开更多
Objective:To investigate the role of the periotic mesenchyme(POM)in the development of sensory cells of developing auditory epithelium.Methods:Developing auditory epithelium with or without periotic mesenchyme was iso...Objective:To investigate the role of the periotic mesenchyme(POM)in the development of sensory cells of developing auditory epithelium.Methods:Developing auditory epithelium with or without periotic mesenchyme was isolated from mice at embryonic days 11.5(E11.5),E12.5 and E13.5,respectively,and cultured in vitro to an equivalent of E18.5’s epithelium in vivo.Then,the explants were co-stained with antibodies targeting myosin VIIA,Sox2 and BrdU.Results:More hair cells in E11.5 t 7 DIV,E12.5 t 6 DIV and E13.5 t 5 DIV auditory epithelia were found upon culture with POM(225.90±62.44,476.94±100.81,and 1386.60±202.38,respectively)compared with the non-POM group(68.17±23.74,205.00±44.23,and 1266.80±38.84,respectively).Moreover,regardless of developmental stage,the mesenchymal tissue increased the amount of cochlear sensory cells as well as the ratio of differentiated hair cells to total sensory cells.Conclusions:The periotic mesenchyme promotes the development of cochlear sensory cells,and its effect depends on the developmental stage of the auditory epithelium.展开更多
Objectives:To quantify the progression of otosclerosis in the unoperated ear between two stapedotomy procedures for patients with bilateral otosclerosis which can help to determine whether a HRCT scan should be re-per...Objectives:To quantify the progression of otosclerosis in the unoperated ear between two stapedotomy procedures for patients with bilateral otosclerosis which can help to determine whether a HRCT scan should be re-performed before the second surgery for patients who already received HRCT imaging before the initial surgery.Methods:35 patients who underwent bilateral stapedotomy were included.Two rounds of HRCT examination and audiometry were performed at the time of the first surgery and second surgery on the ear that was not operated on during the initial surgery.The relationship between the changes in HRCT densitometry and audiometry over time was analyzed.Results:The second round of HRCT did not add significant information about the changes to the otosclerosis lesions in either the imaging diagnosis or the HRCT density values except for small changes in the HRCT densitometry readings at the area anterior to the inner auditory(P=0.01).While the changes in HRCT manifestation are small,changes near the fissula ante fenestram(FAF)were still positively correlated with the air bone gap(ABG)of patients(p=0.031,r=0.388).Conclusions:The progression of lesions in otosclerosis is slow resulting in small and insignificant changes to the HRCT features.Therefore,a repeat HRCT evaluations prior to surgery is not necessary for patients who have had a previous HRCT evaluation within 2 years of the operation.The small changes in HRCT manifestation near the FAF were still correlated with negative effects on the ABG which could cause worsened hearing thresholds over this timeframe。展开更多
Objective The analgesic effect of acupuncture has been widely accepted.Nevertheless,the mechanism behind its analgesic effect remains elusive,thus impeding the progress of research geared toward enhancing the analgesi...Objective The analgesic effect of acupuncture has been widely accepted.Nevertheless,the mechanism behind its analgesic effect remains elusive,thus impeding the progress of research geared toward enhancing the analgesic effect of acupuncture.This paper investigated the role of acupuncture needle surface textures on acupuncture’s analgesic effect by creating four experimental acupuncture needles with different patterns of surface augmentation.Methods Four types of acupuncture needles with different surface textures(the lined needle,circle needle,sandpaper needle,and threaded needle)were designed.Additionally,the force/torque measurement system used a robot arm and mechanical sensor to measure the force on the needle during insertion and manipulation.To perform acupuncture analgesia experiments,four experimental acupuncture needles and a normal needle were inserted into the Zusanli(ST36)acupoint of rats with inflammatory pain.By comparing the force and torque and the analgesic efficacy of the different acupuncture needles,these experiments tested the role of acupuncture needle body texture on acupuncture analgesia.Results The analgesic effects of different acupuncture needle body textures varied.Specifically,the force required to penetrate the skin with the lined needle was not greater than that for the normal needle;however,the needle with inscribed circles and the sandpaper-roughened needle both required greater force for insertion.Additionally,the torque of the lined needle reached 2×10^(-4)N·m under twisting manipulation,which was four times greater the torque of a normal needle(5×10^(-5)N·m).Furthermore,the lined needle improved pain threshold and mast cell degranulation rate compared to the normal needle.Conclusion Optimizing the texture of acupuncture needles can enhance acupuncture analgesia.The texture of our experimental acupuncture needles had a significant impact on the force needed to penetrate the skin and the torque needed to manipulate the needle;it was also linked to variable analgesic effects.This study provides a theoretical basis for enhancing the analgesic efficacy of acupuncture through the modification of needles and promoting the development of acupuncture therapy.展开更多
Vestibular efferent neurons in the brainstem provide direct cholinergic innervation to peripheral vestibular organs,thereby modulating their sensory responsiveness.In this study,a genetically targeted mouse model with...Vestibular efferent neurons in the brainstem provide direct cholinergic innervation to peripheral vestibular organs,thereby modulating their sensory responsiveness.In this study,a genetically targeted mouse model with choline acetyltransferase-driven fluorescent labeling enabled the precise localization of these neurons to the dorsolateral region of the genu of the facial nerve.Whole-cell patch-clamp recordings in acute brainstem slices revealed that virtually all neurons exhibited spontaneous action potential firing,with marked heterogeneity in discharge patterns and afterhyperpolarization kinetics.Prominent A-type potassium currents were identified and found to be differentially regulated by acetylcholine and calcitonin gene-related peptide.Acute unilateral vestibular deprivation induced a bilateral enhancement of spontaneous firing,indicating sensitivity to altered sensory input.These findings define the intrinsic electrophysiological properties and neuromodulatory mechanisms of vestibular efferent neurons,providing mechanistic insight into their roles in both physiological regulation and adaptive plasticity within the vestibular system.展开更多
This study aimed to evaluate the therapeutic potential of inhibiting protein arginine methyltransferase 5(PRMT5)in cisplatin-induced hearing loss.The effects of PRMT5 inhibition on cisplatin-induced auditory injury we...This study aimed to evaluate the therapeutic potential of inhibiting protein arginine methyltransferase 5(PRMT5)in cisplatin-induced hearing loss.The effects of PRMT5 inhibition on cisplatin-induced auditory injury were determined using immunohistochemistry,apoptosis assays,and auditory brainstem response.The mechanism of PRMT5 inhibition on hair cell survival was assessed using RNA-seq and Cleavage Under Targets and Tagment-quantitative polymerase chain reaction(CUT&Tag-qPCR)analyses in the HEI-OC1 cell line.Pharmacological inhibition of PRMT5 significantly alleviated cisplatin-induced damage to hair cells and spiral ganglion neurons in the cochlea and decreased apoptosis by protecting mitochondrial function and preventing the accumulation of reactive oxygen species.CUT&Tag-qPCR analysis demonstrated that inhibition of PRMT5 in HEI-OC1 cells reduced the accumulation of H4R3me2s/H3R8me2s marks at the promoter region of the Pik3ca gene,thus activating the expression of Pik3ca.These findings suggest that PRMT5 inhibitors have strong potential as agents against cisplatininduced ototoxicity and can lay the foundation for further research on treatment strategies of hearing loss.展开更多
基金supported by the National Natural Science Foundation of China(82271159,82071049,82425018,and 82101219)the STI2030-Major Projects(2022ZD0205400).
文摘Vestibular hair cells(HCs)in the inner ear,crucial for balance and spatial orientation,are classified into type I and type II subtypes,but the mechanisms regulating their differentiation remain unclear.In this study,we examined the role of Pou4f3,an important transcription factor,in vestibular HC differentiation using Pou4f3^(DTR/DTR)(deficient)and Pou4f3CreER/CreER(knockout)mouse models.In Pou4f3-deficient mice,the HC number decreased,and immature HCs failed to develop type I characteristics,indicating a developmental arrest.While type II HCs differentiated normally,Pou4f3 deficiency disrupted HC bundle formation and cell polarity.Findings from knockout models further confirmed the essential role of Pou4f3 in vestibular HC subtype specification.This study underscores the critical role of Pou4f3 in determining vestibular HC subtypes and offers insights into potential strategies for restoring vestibular function through HC regeneration.
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.
基金supported by grants from the Ministry of Science and Technology of China(2021YFA1101302)the National Natural Science Foundation of China(82171141 and 82192862)the Science and Technology Commission of Shanghai Municipality(21 JC401000).
文摘Otitis media is an infection of the middle ear mainly caused by bacteria,and current treatments rely heavily on antibiotics.However,the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy.In our study,we found that extracellular vesicles(EVs)derived from human natural killer cells(NKs)inhibit the proliferation of both standard and levofloxacin(LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner.Moreover,compared to LVX,EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models.For LVX-sensitive strains,EVs were significantly more effective in terms of curative time but not curative rate.For LVX-resistant strains,EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX.In summary,we found that NK EVs are highly effective in treating otitis media,providing an alternative approach for treating this common disease.
基金supported by the National Natural Science Foundation of China(No.81700888).
文摘Objective This study aimed to investigate the effect of Astragalus(AST)on osteoporosis(OP)and the downstream mechanisms.Methods Human bone marrow-derived mesenchymal stem cells(hBMSCs)were induced to differentiate into osteogenic cells.After transfection with relevant plasmids,cell proliferation,cell cycle progression,and apoptosis were assessed.Alizarin red staining was used to detect calcium nodules in the cells,alkaline phosphatase(ALP)staining was used to detect ALP activity in the cells,and quantitative reverse transcription-polymerase chain reaction and western blotting were used to determine RUNX2 and Osterix expression levels.An OP rat model was established using ovariectomy and micro-computed tomography scanning.Hematoxylin and eosin staining and Masson’s trichrome staining were used to evaluate the pathological conditions of bone tissues,while immunohistochemistry was conducted to detect RUNX2 in bone tissues.Results AST promoted the osteogenic differentiation of BMSCs,reduced miR-181d-5p expression levels,and increased SOX11 expression levels.Restoring miR-181d-5p expression or reducing SOX11 expression levels reversed the effects of AST on the osteogenic differentiation of hBMSCs.miR-181d-5p was found to target SOX11 in hBMSCs.AST improved OP in rats,and miR-181d-5p overexpression or SOX11 inhibition reversed the therapeutic effects of AST on OP in rats.Conclusion AST promoted the osteogenic differentiation of hBMSCs and alleviated OP by targeting SOX11 via miR-181d-5p.
基金supported by the National Natural Science Foundation of China(82271159,82425018,82071049,81830029,82192860,81922018,82201283,82101219,and 82192861)Shanghai Clinical Medical Research Center for Otolaryngology Diseases(20MC1920200)the STI2030-Major Projects(2022ZD0205400).
文摘Cochlear hair cell(HC)damage is a primary cause of sensorineural hearing loss.In this study,we performed metabolomic profiling of cochlear sensory epithelium following neomycin-induced HC injury and identified elevated arginine metabolism as a key metabolic characteristic of damaged HCs.Using a highly sensitive and specific biosensor,we confirmed that injury induced an increase in arginine levels within cochlear HCs.By manipulating the levels of arginine and its downstream metabolites,we discovered that unmetabolized arginine exerts a strong protective effect on cochlear HCs,independent of its downstream metabolites,such as nitric oxide.Furthermore,integrated metabolomic and transcriptomic analyses revealed that arginine plays a critical role in reprogramming phospholipid metabolism.Arginine supplementation enhanced membrane phospholipid saturation through the Lands cycle and de novo lipogenesis,and protected HCs from phospholipid peroxidation-induced membrane damage and subsequent cell death.Notably,arginine supplementation protected hearing from both noise-and aminoglycoside-induced injury in mice.These findings underscore the role of unmetabolized arginine in modulating phospholipid metabolism and preventing membrane damage in cochlear HCs,highlighting that targeting phospholipid metabolism is an effective hearing protection strategy.
基金supported by the National Natural Science Foundation of China(No.82271889,82572117,82371173,and 82172105)the National Key Research and Development Program of China(No.2021YFC2701000)Shanghai Natural Science Foundation(23ZR1409400,24ZR1409400)。
文摘Craniofacial development relies on the migration of cranial neural crest cells(CNCCs)to the first and second pharyngeal arches,followed by their differentiation into various cell types during embryogenesis.Although the CNCC migration has been well-studied,the role of the niche in relation to CNCC remains unclear.Variants in FOXI3 have been implicated in craniofacial microsomia(CFM),yet the molecular mechanisms remain unexplored.FOXI3 is expressed in the ectoderm and auricle epidermis,but not in CNCCs or cartilage.Deletion of Foxi3 in the mouse CNCCs did not disrupt mandible and auricular development,further confirming that FOXI3 does not directly regulate CNCCs.However,Foxi3 deficiency in the ectoderm reduced the production of chondrogenesis-related cytokines derived from ectodermal cells,such as TGF-β1.This impairment affected CNCC proliferation through cell communication,subsequently altering the development of the mandible and auricle.These results emphasize the critical role of FOXI3 in establishing the microenvironment supporting CNCC function.Furthermore,FOXI3 directly regulates target genes associated with translation,thereby orchestrating cytokine production in epidermal cells.The validation using auricle sample from a CFM patient carrying FOXI3 mutation further supports our findings.These insights highlight the function of FOXI3 in creating the niche necessary for CNCC development and provide a basis for understanding the molecular mechanisms driving CFM pathogenesis.
基金supported by the Scientific and Innovative Action Plan of Shanghai(CN)(22Y11902000)the National Natural Science Foundation of China(82371144 and 82201273)+2 种基金the Cross-Disciplinary Research Fund of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine(JYJC202231)the Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases(14DZ2260300)We extend our gratitude to Prof.Hao Wu and the Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases for providing essential resources and laboratory facilities,and to Prof.Lei Song and Prof.Zhiyong Liu for valuable insights and guidance.
文摘Circadian sensitivity significantly influences the severity of noise-induced hearing loss(NIHL),but the underlying mechanisms remain unclear.Here,we applied single-cell RNA sequencing to 97,043 cochlear cells,identifying macrophages as the primary immune responders to acoustic trauma,with a notable increase in their proportion in the cochlea.Immunofluorescence confirmed significant recruitment and activation of cochlear macrophages following noise exposure,while in vivo macrophage depletion resulted in the recovery of hearing.Furthermore,analyses of differentially-expressed genes and pathways revealed pronounced activation of NLRP3 inflammasome signaling in macrophages during night-time noise exposure.Measurements of elevated IL-1βand IL-18 expression in cochlear macrophages by multiplex immunohistochemistry correlated with heightened inflammation in the night-time exposure group.These findings were further confirmed by the administration of the selective NLRP3 inhibitor CY-09,which mitigated inflammasome activation,preserved synaptic integrity,and protect against hearing loss.In conclusion,our findings underscore the role of macrophage-driven NLRP3 inflammasome activation in mediating circadian variations in cochlear damage,offering a potential therapeutic target for mitigating NIHL.
基金supported by grants from the National Key R&D Program of China(2021YFA1101300,2021YFA1101800,2020YFA0112503,and 2024YFC2511103)the National Natural Science Foundation of China(82330033,82030029,82401375,81970882,92149304,and 81970883)+7 种基金the Natural Science Foundation of Jiangsu Province(BK20232007)the Science and Technology Department of Sichuan Province(2021YFS0371)Shenzhen Fundamental Research Program(JCYJ20210324125608022)the Open Project Fund of Guangdong Academy of Medical Sciences(YKY-KF202201)Beijing Natural Science Foundation(Z200019)the Jiangsu Provincial Scientific Research Center of Applied Mathematics(BK20233002)the China Postdoctoral Science Foundation(2023TQ0056,2023M730575,and GZC20230435)Jiangsu Funding Program for Excellent Postdoctoral Talent(2023ZB822).
文摘The mammalian cochlea relies on outer and inner hair cells(OHCs/IHCs)for sound amplification and signal transmission.Rab3-interacting molecular binding protein 2(RIMBP2),expressed in receptor cells and neurons at synaptic active zones,remains poorly characterized in hearing.We therefore generated a Rimbp2 knockout(KO)mouse model(Rimbp^(2-/-)),which exhibited severe hearing loss with elevated thresholds,prolonged latencies,and reduced amplitudes in auditory brainstem response Wave I.OHC loss via apoptosis was correlated with threshold elevation.In IHCs,patch-clamp recordings revealed reduced exocytosis,including a diminished readily-releasable pool,impaired sustained release,and blocked fast endocytosis.Immunostaining showed unchanged ribbon synapse numbers but positional shifts in the basal pole of KO IHCs.These findings demonstrated RIMBP2’s essential role in OHC survival and its broader regulatory functions in IHC synaptic transmission than previously recognized.
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.
基金supported by the National Key R&D Program of China(2017YFD0401200)China Agriculture Research System(CARS-07-13.5-A17)+1 种基金General S&T project of Beijing Municipal Commission of Education(KM202010011006)BTBU Youth Fund(PXM2019_014213_000007).
文摘Foxtail millet(FM)whole grain has received special attention in recent years.To confirm the hypoglycemic effects of FM,we investigated the effects of FM supplementation on glucose metabolism and gut microbiota in rats with high-fat diet/streptozotocin(HFD/STZ)-induced diabetes.Specifically,we fully assessed the blood biochemical profiles,pancreatic histopathology,insulin-glucagon immunofluorescence,short-chain fatty acids,and gut microbiota composition of rats with HFD/STZ-induced diabetes before and after FM supplementation.Results showed that both 30% and 48% FM supplementation significantly decreased concentrations of fasting blood glucose,60-min blood glucose,and blood triglycerides(P<0.05);additionally,48% FM supplementation significantly improved blood glucose tolerance and insulin resistance(P<0.05).However,FM supplementation could not effectively repair damage to β-cells over a short period of time.In addition,4 weeks of 48% FM supplementation siginificantly increased the relative abundance of Bifidobacterium and concentration of butyrate,suggesting that the hypoglycemic effects of FM supplementation might be partially mediated by gut microbiota.Collectively,we found a dose-dependent relationship between FM supplementation and improvement of blood glucose metabolism,but did not find a synergistic effect between FM supplementation and metformin(Met)treatment.Our findings provide further support that consuming more whole-grain FM might be beneficial to individuals suffering from type 2 diabetes.
基金This work was supported by the National Natural Science Foundation of China(81770999 and 81670281)the Shanghai Municipal Commission of Science and Technology Research Project(18140900304,and 19140900902)the Big Data and Artificial Intelligence Project(2020DSJ07).
文摘Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus.Here,we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells(IHCs).We found that IHCs showed significant damage after exposure to a high concentration of salicylate.Whole-cell patch clamp recordings showed that 1–5 mmol/L salicylate did not affect the exocytosis of IHCs,indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input.Instead,salicylate induced a larger peak amplitude,a more negative half-activation voltage,and a steeper slope factor of Ca^(2+)current.Using noise analysis of Ca^(2+)tail currents and qRT-PCR,we further found that salicylate increased the number of Ca^(2+)channels along with CaV1.3 expression.All these changes could act synergistically to enhance the Ca^(2+)influx into IHCs.Inhibition of intracellular Ca^(2+)overload significantly attenuated IHC death after 10 mmol/L salicylate treatment.These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.
基金the National Natural Science Foundation of China(Nos.61973211,62133009,51911540479 and M-0221)the Science and Technology Commission of Shanghai Municipality(Nos.21550714200 and 20DZ2220400)+1 种基金the Research Project of Institute of Medical Robotics of Shanghai Jiao Tong Universitythe Interdisciplinary Program of Shanghai Jiao Tong University(Nos.YG2017ZD03 and ZH2018QNB31)。
文摘Traditional cochlear implantation surgery has problems such as high surgical accuracy requirement and large trauma,which cause the difficulty of the operation and the high requirements for doctors,so that only a few doctors can complete the operation independently.However,there is no research on robotic cochlear implantation in China.In response to this problem,a robotic cochlear implantation system is proposed.The robot is controlled by robot operating system(ROS).A simulation environment for the overall surgery is established on the ROS based on the real surgery environment.Through the analysis of the kinematics and the motion planning algorithm of the manipulator,an appropriate motion mode is designed to control the motion of the manipulator,and perform the surgery under the simulation environment.A simple and feasible method of navigation is proposed,and through the model experiment,the feasibility of robotic cochlear implantation surgery is verified.
基金the Chinese National Natural Science Foundation of China(grant number 81371089)。
文摘Objective:To investigate the role of the periotic mesenchyme(POM)in the development of sensory cells of developing auditory epithelium.Methods:Developing auditory epithelium with or without periotic mesenchyme was isolated from mice at embryonic days 11.5(E11.5),E12.5 and E13.5,respectively,and cultured in vitro to an equivalent of E18.5’s epithelium in vivo.Then,the explants were co-stained with antibodies targeting myosin VIIA,Sox2 and BrdU.Results:More hair cells in E11.5 t 7 DIV,E12.5 t 6 DIV and E13.5 t 5 DIV auditory epithelia were found upon culture with POM(225.90±62.44,476.94±100.81,and 1386.60±202.38,respectively)compared with the non-POM group(68.17±23.74,205.00±44.23,and 1266.80±38.84,respectively).Moreover,regardless of developmental stage,the mesenchymal tissue increased the amount of cochlear sensory cells as well as the ratio of differentiated hair cells to total sensory cells.Conclusions:The periotic mesenchyme promotes the development of cochlear sensory cells,and its effect depends on the developmental stage of the auditory epithelium.
基金supported by National Natural Science Foundation of China(No.81870726)Clinical Research Plan of SHDC(Grant SHDC2020CR4083).
文摘Objectives:To quantify the progression of otosclerosis in the unoperated ear between two stapedotomy procedures for patients with bilateral otosclerosis which can help to determine whether a HRCT scan should be re-performed before the second surgery for patients who already received HRCT imaging before the initial surgery.Methods:35 patients who underwent bilateral stapedotomy were included.Two rounds of HRCT examination and audiometry were performed at the time of the first surgery and second surgery on the ear that was not operated on during the initial surgery.The relationship between the changes in HRCT densitometry and audiometry over time was analyzed.Results:The second round of HRCT did not add significant information about the changes to the otosclerosis lesions in either the imaging diagnosis or the HRCT density values except for small changes in the HRCT densitometry readings at the area anterior to the inner auditory(P=0.01).While the changes in HRCT manifestation are small,changes near the fissula ante fenestram(FAF)were still positively correlated with the air bone gap(ABG)of patients(p=0.031,r=0.388).Conclusions:The progression of lesions in otosclerosis is slow resulting in small and insignificant changes to the HRCT features.Therefore,a repeat HRCT evaluations prior to surgery is not necessary for patients who have had a previous HRCT evaluation within 2 years of the operation.The small changes in HRCT manifestation near the FAF were still correlated with negative effects on the ABG which could cause worsened hearing thresholds over this timeframe。
基金funded by National Natural Science Foundation of China(No.12172092,82174488,and 82305416)Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function(No.21DZ2271800)+1 种基金Shanghai Municipal Science and Technology Commission(No.23YF1418300)Scientific Research Project on Traditional Chinese Medicine of Shanghai Municipal Health Commission—Youth Guidance Category(No.2022QN018).
文摘Objective The analgesic effect of acupuncture has been widely accepted.Nevertheless,the mechanism behind its analgesic effect remains elusive,thus impeding the progress of research geared toward enhancing the analgesic effect of acupuncture.This paper investigated the role of acupuncture needle surface textures on acupuncture’s analgesic effect by creating four experimental acupuncture needles with different patterns of surface augmentation.Methods Four types of acupuncture needles with different surface textures(the lined needle,circle needle,sandpaper needle,and threaded needle)were designed.Additionally,the force/torque measurement system used a robot arm and mechanical sensor to measure the force on the needle during insertion and manipulation.To perform acupuncture analgesia experiments,four experimental acupuncture needles and a normal needle were inserted into the Zusanli(ST36)acupoint of rats with inflammatory pain.By comparing the force and torque and the analgesic efficacy of the different acupuncture needles,these experiments tested the role of acupuncture needle body texture on acupuncture analgesia.Results The analgesic effects of different acupuncture needle body textures varied.Specifically,the force required to penetrate the skin with the lined needle was not greater than that for the normal needle;however,the needle with inscribed circles and the sandpaper-roughened needle both required greater force for insertion.Additionally,the torque of the lined needle reached 2×10^(-4)N·m under twisting manipulation,which was four times greater the torque of a normal needle(5×10^(-5)N·m).Furthermore,the lined needle improved pain threshold and mast cell degranulation rate compared to the normal needle.Conclusion Optimizing the texture of acupuncture needles can enhance acupuncture analgesia.The texture of our experimental acupuncture needles had a significant impact on the force needed to penetrate the skin and the torque needed to manipulate the needle;it was also linked to variable analgesic effects.This study provides a theoretical basis for enhancing the analgesic efficacy of acupuncture through the modification of needles and promoting the development of acupuncture therapy.
基金National Natural Science Foundation of China(81870724)National Key Research Program Project(2024YFC2418302)+1 种基金Science and Technology Commission of Shanghai Municipality(23DZ2202900)Shanghai Municipal Health Commission Science and Technology Talent Capacity Enhancement Special Project(JKKPYL-2023-A02)。
文摘Vestibular efferent neurons in the brainstem provide direct cholinergic innervation to peripheral vestibular organs,thereby modulating their sensory responsiveness.In this study,a genetically targeted mouse model with choline acetyltransferase-driven fluorescent labeling enabled the precise localization of these neurons to the dorsolateral region of the genu of the facial nerve.Whole-cell patch-clamp recordings in acute brainstem slices revealed that virtually all neurons exhibited spontaneous action potential firing,with marked heterogeneity in discharge patterns and afterhyperpolarization kinetics.Prominent A-type potassium currents were identified and found to be differentially regulated by acetylcholine and calcitonin gene-related peptide.Acute unilateral vestibular deprivation induced a bilateral enhancement of spontaneous firing,indicating sensitivity to altered sensory input.These findings define the intrinsic electrophysiological properties and neuromodulatory mechanisms of vestibular efferent neurons,providing mechanistic insight into their roles in both physiological regulation and adaptive plasticity within the vestibular system.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.:82271158,82192865,and 82071045)Wenzhou Municipal Science and Technology Research Program(Grant No.:2021Y0681).
文摘This study aimed to evaluate the therapeutic potential of inhibiting protein arginine methyltransferase 5(PRMT5)in cisplatin-induced hearing loss.The effects of PRMT5 inhibition on cisplatin-induced auditory injury were determined using immunohistochemistry,apoptosis assays,and auditory brainstem response.The mechanism of PRMT5 inhibition on hair cell survival was assessed using RNA-seq and Cleavage Under Targets and Tagment-quantitative polymerase chain reaction(CUT&Tag-qPCR)analyses in the HEI-OC1 cell line.Pharmacological inhibition of PRMT5 significantly alleviated cisplatin-induced damage to hair cells and spiral ganglion neurons in the cochlea and decreased apoptosis by protecting mitochondrial function and preventing the accumulation of reactive oxygen species.CUT&Tag-qPCR analysis demonstrated that inhibition of PRMT5 in HEI-OC1 cells reduced the accumulation of H4R3me2s/H3R8me2s marks at the promoter region of the Pik3ca gene,thus activating the expression of Pik3ca.These findings suggest that PRMT5 inhibitors have strong potential as agents against cisplatininduced ototoxicity and can lay the foundation for further research on treatment strategies of hearing loss.
