Objective:Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss,bone destruction,and other severe complications.Despite surgery being the primary treatment,the recurrence rate remai...Objective:Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss,bone destruction,and other severe complications.Despite surgery being the primary treatment,the recurrence rate remains high.Therefore,exploring the molecular mechanisms underlying cholesteatoma is crucial for discovering new therapeutic approaches.This study aims to explore the involvement of N6-methyladenosine(m^(6)A)methylation in long non-coding RNAs(lncRNAs)in the biological functions and related pathways of middle ear cholesteatoma.Methods:The m^(6)A modification patterns of lncRNA in middle ear cholesteatoma tissues(n=5)and normal post-auricular skin tissues(n=5)were analyzed using an lncRNA m^(6)A transcriptome microarray.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to identify potential biological functions and signaling pathways involved in the pathogenesis of middle ear cholesteatoma.Methylated RNA immunoprecipitation(MeRIP)-PCR was used to validate the m^(6)A modifications in cholesteatoma and normal skin tissues.Results:Compared with normal skin tissues,1525 lncRNAs were differentially methylated in middle ear cholesteatoma tissues,with 1048 showing hypermethylation and 477 showing hypomethylation[fold change(FC)≥3 or<1/3,P<0.05].GO enrichment analysis indicated that hypermethylated lncRNAs were involved in protein phosphatase inhibitor activity,neuron-neuron synapse,and regulation ofα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid(AMPA)receptor activity.Hypomethylated lncRNAs were associated with mRNA methyltransferase activity,secretory granule membrane,and mRNA methylation.KEGG analysis revealed that hypermethylated lncRNAs were mainly associated with 5 pathways:the Hedgehog signaling pathway,viral protein interaction with cytokines and cytokine receptors,mitogen-activated protein kinase(MAPK)signaling pathway,cytokine-cytokine receptor interaction,and adrenergic signaling in cardiomyocytes.Hypomethylated lncRNAs were mainly involved in 4 pathways:Renal cell carcinoma,tumor necrosis factor signaling pathway,transcriptional misregulation in cancer,and cytokine-cytokine receptor interaction.Additionally,MeRIP-PCR confirmed the changes in m^(6)A methylation levels in NR_033339,NR_122111,NR_130744,and NR_026800,consistent with microarray analysis.Real-time PCR also confirmed the significant upregulation of MAPK1 and NF-κB,key genes in the MAPK signaling pathway.Conclusion:This study reveals the m^(6)A modification patterns of lncRNAs in middle ear cholesteatoma,suggests a direction for further research into the role of lncRNA m^(6)A modification in the etiology of cholesteatoma.The findings provide potential therapeutic targets for the treatment of middle ear cholesteatoma.展开更多
目的探讨全耳内镜下经外耳道处理上鼓室胆脂瘤的手术方法、术后效果以及临床应用特点。方法回顾性分析我科自2016年1月至2017年1月收治的中耳上鼓室胆脂瘤并行全耳内镜下手术的患者。选取符合标准的病例总数47例,男28例,女19例;年龄15~6...目的探讨全耳内镜下经外耳道处理上鼓室胆脂瘤的手术方法、术后效果以及临床应用特点。方法回顾性分析我科自2016年1月至2017年1月收治的中耳上鼓室胆脂瘤并行全耳内镜下手术的患者。选取符合标准的病例总数47例,男28例,女19例;年龄15~68岁,平均41岁。术中常规取耳屏软骨-软骨膜复合物修补鼓膜、重建上鼓室,于耳内镜下清除胆脂瘤,行鼓室成形术,根据具体情况行上鼓室重建术、听骨链重建术。分别于术后1月、2月、3月和6月复查。结果所有47例患者中,32例(68%)为局限在上鼓室的胆脂瘤,15例(32%)为胆脂瘤同时累及中鼓室、前鼓室;其中21例(45%)听骨链完整,26例(55%)锤骨/砧骨有破坏。其中29例行听骨链重建术。所有患者术后均无面瘫、耳流脓、鼓膜穿孔。术后复查,所有患者的鼓膜形态良好,无内陷、无穿孔,移植物形态良好。术前平均气导听阈为43.45±9.56 d B HL,术后平均气导听阈为27.23±6.89 d B HL,术前术后比较具有统计学差异(P<0.01)。术前平均气骨导差为28.42±6.78 d B HL,术后平均气骨导差为13.62±8.67d B HL,术前术后比较具有统计学差异(P<0.01)。其中29例行听骨链重建术者,术后气骨导差<10d B HL者11例,10~20d B HL者13例,20~30d B HL者3例,>30d B HL者2例。所有患者均未出现病变复发、病变残余,无二次手术者。结论全耳内镜经外耳道手术处理上鼓室胆脂瘤是一种安全有效的手术方法。展开更多
基金supported by the National Natural Science Foundation(82071036,82000973)the Natural Science Foundation of Hunan Province(2022JJ30821,2019JJ50967)the Special Project for the Construction of Innovative Provinces in Hunan Province(2023SK4030),China。
文摘Objective:Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss,bone destruction,and other severe complications.Despite surgery being the primary treatment,the recurrence rate remains high.Therefore,exploring the molecular mechanisms underlying cholesteatoma is crucial for discovering new therapeutic approaches.This study aims to explore the involvement of N6-methyladenosine(m^(6)A)methylation in long non-coding RNAs(lncRNAs)in the biological functions and related pathways of middle ear cholesteatoma.Methods:The m^(6)A modification patterns of lncRNA in middle ear cholesteatoma tissues(n=5)and normal post-auricular skin tissues(n=5)were analyzed using an lncRNA m^(6)A transcriptome microarray.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to identify potential biological functions and signaling pathways involved in the pathogenesis of middle ear cholesteatoma.Methylated RNA immunoprecipitation(MeRIP)-PCR was used to validate the m^(6)A modifications in cholesteatoma and normal skin tissues.Results:Compared with normal skin tissues,1525 lncRNAs were differentially methylated in middle ear cholesteatoma tissues,with 1048 showing hypermethylation and 477 showing hypomethylation[fold change(FC)≥3 or<1/3,P<0.05].GO enrichment analysis indicated that hypermethylated lncRNAs were involved in protein phosphatase inhibitor activity,neuron-neuron synapse,and regulation ofα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid(AMPA)receptor activity.Hypomethylated lncRNAs were associated with mRNA methyltransferase activity,secretory granule membrane,and mRNA methylation.KEGG analysis revealed that hypermethylated lncRNAs were mainly associated with 5 pathways:the Hedgehog signaling pathway,viral protein interaction with cytokines and cytokine receptors,mitogen-activated protein kinase(MAPK)signaling pathway,cytokine-cytokine receptor interaction,and adrenergic signaling in cardiomyocytes.Hypomethylated lncRNAs were mainly involved in 4 pathways:Renal cell carcinoma,tumor necrosis factor signaling pathway,transcriptional misregulation in cancer,and cytokine-cytokine receptor interaction.Additionally,MeRIP-PCR confirmed the changes in m^(6)A methylation levels in NR_033339,NR_122111,NR_130744,and NR_026800,consistent with microarray analysis.Real-time PCR also confirmed the significant upregulation of MAPK1 and NF-κB,key genes in the MAPK signaling pathway.Conclusion:This study reveals the m^(6)A modification patterns of lncRNAs in middle ear cholesteatoma,suggests a direction for further research into the role of lncRNA m^(6)A modification in the etiology of cholesteatoma.The findings provide potential therapeutic targets for the treatment of middle ear cholesteatoma.
文摘目的探讨全耳内镜下经外耳道处理上鼓室胆脂瘤的手术方法、术后效果以及临床应用特点。方法回顾性分析我科自2016年1月至2017年1月收治的中耳上鼓室胆脂瘤并行全耳内镜下手术的患者。选取符合标准的病例总数47例,男28例,女19例;年龄15~68岁,平均41岁。术中常规取耳屏软骨-软骨膜复合物修补鼓膜、重建上鼓室,于耳内镜下清除胆脂瘤,行鼓室成形术,根据具体情况行上鼓室重建术、听骨链重建术。分别于术后1月、2月、3月和6月复查。结果所有47例患者中,32例(68%)为局限在上鼓室的胆脂瘤,15例(32%)为胆脂瘤同时累及中鼓室、前鼓室;其中21例(45%)听骨链完整,26例(55%)锤骨/砧骨有破坏。其中29例行听骨链重建术。所有患者术后均无面瘫、耳流脓、鼓膜穿孔。术后复查,所有患者的鼓膜形态良好,无内陷、无穿孔,移植物形态良好。术前平均气导听阈为43.45±9.56 d B HL,术后平均气导听阈为27.23±6.89 d B HL,术前术后比较具有统计学差异(P<0.01)。术前平均气骨导差为28.42±6.78 d B HL,术后平均气骨导差为13.62±8.67d B HL,术前术后比较具有统计学差异(P<0.01)。其中29例行听骨链重建术者,术后气骨导差<10d B HL者11例,10~20d B HL者13例,20~30d B HL者3例,>30d B HL者2例。所有患者均未出现病变复发、病变残余,无二次手术者。结论全耳内镜经外耳道手术处理上鼓室胆脂瘤是一种安全有效的手术方法。
