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Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps:A pilot study

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World Journal of Otorhinolaryngology-head and neck surgery 2024年第1期10卷 29-36页

作者： Jorge A.Gutierrez III Jeremy L.Barth Rodney J.Schlosser Thomas S.Edwards Timothy L.Smith Zachary M.Soler Department of Otolaryngology-head and neck surgery Medical University of South CarolinaCharlestonSouth CarolinaUSA Department of Regenerative Medicine&Cell Biology Medical University of South CarolinaCharlestonSouth CarolinaUSA Department of Otolaryngology-head and neck surgery Oregon Health&Science UniversityPortlandOregonUSA

Objectives:Prior research on olfactory dysfunction in chronic rhinosinusitis(CRS)has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role.The purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens,comparing normosmic and dysosmic CRS patients without polyps(CRSsNP).Methods:Tissue samples were obtained from the superior turbinates of patients with CRSsNP at the time of endoscopic sinus surgery.Samples subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic(n=7)and normosmic(n=4)patients.Results:Differential gene expression analysis comparing dysosmic and normosmic CRSsNP patients showed upregulation of 563 genes and downregulation of 327 genes.Using stringent criteria for multiple comparisons,one upregulated gene(Immediate Early Response 3[IER3])had an false discovery rate(FDR)correction adjustedP value considered statistically significant(P<0.001,fold change 2.69).Reactome functional analysis revealed eight biological pathways significantly different between dysosmic and normosmic patients(P<0.05,FDR correction)including IL-4 and IL-13 signaling,IL-10 signaling,and rhodopsin-like receptors.Conclusions:RNA sequencing of the superior turbinates in patients with CRSsNP can provide valuable information regarding biological pathways and genes involved in olfactory dysfunction.This study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with CRSsNP.This study also prompts questions regarding the role of IL-10,rhodopsin-like receptors,andIER3 in the pathogenesis of olfactory dysfunction.

关键词： chronic rhinosinusitis without nasal polyps olfactory dysfunction RNA sequencing

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Modified intratympanic steroid therapy for sudden sensorineural hearing loss via tympanic tube and gelfoam as a salvage treatment

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Journal of Otology 2024年第1期19卷 19-23页

作者： Sichao Liang Yunshuo Li Zhenping Guo Manlin Lu Xin Li Jia Xu Wenjing Chen Juanjuan Gao Haijin Yi Department of Otolaryngology Head and Neck SurgeryBeijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijing102218China

Background: Sudden sensorineural hearing loss(SSNHL) is a prevalent emergency in ear, nose, and throat practice. Previous studies have demonstrated that intratympanic steroid therapy(IST) can serve as a salvage treatment for SSNHL after the failure of systemic steroid therapy(SST).Objective: This study aimed to analyze the efficacy of modified IST involving the insertion of a tympanic tube and gelfoam as a salvage treatment for patients with SSNHL, and to explore its associated factors.Methods: Totally, 74 patients who were aged 22–81 years with SSNHL were enrolled and allocated to either the control group(n = 25) or the treatment group(n = 49) based on their treatment modalities. All patients received SST lasting for at least 7 days. Subsequently, patients in the treatment group, after SST failure, underwent IST twice a week for 2–6 weeks, while the control group did not. Efficacy was assessed by the improvement in pure tone average at the affected frequency at the beginning and end of IST.Results: Hearing improvement in all patients after IST in the treatment group was 9.71 ± 14.84 dB, with significant improvement at affected frequencies(250-8000 Hz) compared with the control group(P 0.05).Conclusion: The modified IST was demonstrated to be a safe and effective method as a salvage treatment for SSNHL. This study explored the efficacy of a modified IST approach, incorporating the utilization of tympanic tubes and gelfoam as key components. The findings underscore the advantages of gelfoam as a strategic drug carrier placed in the round window niche. By minimizing drug loss, extending action time, and increasing perilymph concentration, gelfoam enhances the therapeutic impact of IST, contributing to improved hearing outcomes in patients with SSNHL.

关键词： Modified intratympanic steroid therapy Sudden sensorineural hearing loss Gelfoam Tympanic tube

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Clinical studies in COVID-related olfactory disorders:Review of an institutional experience

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World Journal of Otorhinolaryngology-head and neck surgery 2024年第2期10卷 129-136页

作者： Theresa Tharakan Dorina Kallogjeri Jay F.Piccirillo Department of Otolaryngology-head and neck surgery Clinical Outcomes Research OfficeSchool of MedicineWashington University in St LouisSt LouisMissouriUSA

Objective:To share a single institutional experience with clinical research on COVID-related olfactory dysfunction(OD).Data Source/Method:Narrative review of published original data and ongoing clinical trials on COVID-related OD at Washington University from 2020 to 2023.Results:There were three new diagnostic-/patient-reported outcome measures developed and tested.We report five clinical trials of interventions for COVID-related olfactory disorders:combined Visual-Olfactory Training(VOLT)with patient-preferred scents versus standard olfactory training(VOLT trial),oral gabapentin versus placebo(Gabapentin for the Relief of Acquired Chemosensory Experience trial),nasal theophylline irrigations versus placebo(Smell Changes and Efficacy of Nasal Theophylline trial),stellate ganglion block(single-arm),and mindfulness-based stress reduction(MBSR)versus lifestyle intervention(MBSR trial).Conclusions:Initial intervention trials for COVID-related OD have shown potential for improving subjective and objective olfactory outcomes.However,there remains no gold standard treatment that definitively outperforms placebo in controlled trials.Therefore,continued investigation of novel therapeutic strategies for COVID-related OD is necessary to maximize olfactory outcomes for affected patients.

关键词： chemosensory disorders COVID olfactory dysfunction

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Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments

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World Journal of Stem Cells 2024年第5期16卷 604-614页

作者： Edoardo Agosti Marco Zeppieri Mattia Ghidoni Tamara Ius Alessandro Tel Marco Maria Fontanella Pier Paolo Panciani division of Neurosurgery Department of Medical and Surgical SpecialtiesRadiological Sciences and Public HealthUniversity of BresciaBrescia 25123Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Neurosurgery Unit Department of Head-Neck and NeuroScienceUniversity Hospital of UdineUdine 33100Italy Clinic of Maxillofacial surgery Department of Head-Neck and NeuroScienceUniversity Hospital of UdineUdine 33100Italy

BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and plasticity.Recent studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular states.Resistance mechanisms can involve different cellular pathways,most of which have been recently reported in the literature.Despite progress,targeted therapeutic approaches lack consensus due to GSCs’high plasticity.AIM To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying mechanisms.METHODS A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,2023.The search strategy utilized relevant Medical Subject heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text analysis.Among them,201 were deemed eligible after excluding 168 for various reasons.The temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma characteristics.Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance development.Targeted molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette G2(12.1%)as frequent targets underscore their im

关键词： Glioma stem cells Chemoresistance Radioresistance Molecular pathways Targeted therapies Systematic review

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Injury and protection of spiral ganglion neurons

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Chinese Medical Journal 2024年第6期137卷 651-656页

作者： Beilei Duan Kevin A.Peng Line Wang Department of Otorhinolaryngology Head and Neck SurgeryBeijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Neurotology House ClinicLos AngelesCA 90017USA

Cochlear spiral ganglion neurons(SGNs)are bipolar ganglion cells and are the first neurons in the auditory transduction pathway.They transmit complex acoustic information from hair cells to second-order sensory neurons in the cochlear nucleus for sound processing.Injury to SGNs causes largely irreversible hearing impairment because these neurons are highly differentiated cells and cannot regenerate,making treatment of sensorineural hearing loss(SNHL)arising from SGN injury difficult.When exposed to ototoxic drugs or damaging levels of noise or when there is loss of neurotrophic factors(NTFs),aging,and presence of other factors,SGNs can be irreversibly damaged,resulting in SNHL.It has been found that NTFs and stem cells can induce regeneration among dead spiral ganglion cells.In this paper,we summarized the present knowledge regarding injury,protection,and regeneration of SGNs.

关键词： Spiral ganglion Injury Protection Auditory hair cell Ototoxic drugs Aminoglycosides Presbycusis

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Development of Chinese herbal medicine for sensorineural hearing loss

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Acta Pharmaceutica Sinica B 2024年第2期14卷 455-467页

作者： Yunhao Wu Jingwen Zhang Qiuping Liu Zhuang Miao Renjie Chai Wenyong Chen State Key Laboratory of Bioelectronics Department of Otolaryngology Head and Neck SurgeryZhongda HospitalSchool of Life Sciences and TechnologyAdvanced Institute for Life and HealthJiangsu Province HighTech Key Laboratory for Bio-Medical ResearchSoutheast UniversityNanjing 210096China Department of Otolaryngology-head and neck the Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China Department of Otolaryngology-head and neck surgery Affiliated Hospital of Jiangnan UniversityWuxi 214000China Department of Otolaryngology head and neck surgery Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610000China Co-Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China Institute for Stem Cell and Regeneration Chinese Academy of ScienceBeijing 100085China Beijing Key Laboratory of Neural Regeneration and Repair Capital Medical UniversityBeijing 100069China

According to the World Health Organization’s world report on hearing,nearly 2.5 billion people worldwide will suffer from hearing loss by 2050,which may contribute to a severe impact on individual life quality and national economies.Sensorineural hearing loss(SNHL)occurs commonly as a result of noise exposure,aging,and ototoxic drugs,and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear,which is mainly triggered by reactive oxygen species accumulation,inflammation,and mitochondrial dysfunction.Though recent advances have been made in understanding the ability of cochlear repair and regeneration,there are still no effective therapeutic drugs for SNHL.Chinese herbal medicine which is widely distributed and easily accessible in China has demonstrated a unique curative effect against SNHL with higher safety and lower cost compared with Western medicine.Herein we present trends in research for Chinese herbal medicine for the treatment of SNHL,and elucidate their molecular mechanisms of action,to pave the way for further research and development of novel effective drugs in this field.

关键词： Sensorineural hearing loss Chinese herbal medicine Molecular mechanism Active ingredients Prescriptions Ototoxic drugs Noise Hair cells

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Recovery rates of persistent post-COVID-19 olfactory dysfunction using psychophysical assessment:A longitudinal cohort study

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World Journal of Otorhinolaryngology-head and neck surgery 2024年第2期10卷 79-87页

作者： Jeremy P.Tervo Patricia T.Jacobson Brandon J.Vilarello Tiana M.Saak Francesco F.Caruana Liam W.Gallagher Joseph B.Gary David A.Gudis Paule V.Joseph D.P.Devanand Terry E.Goldberg Jonathan B.Overdevest Columbia University Vagelos College of Physicians and Surgeons New YorkNew YorkUSA Department of Otolaryngology-head and neck surgery New York-Presbyterian/Columbia University Irving Medical CenterNew YorkNew YorkUSA Department of Otolaryngology-head and neck surgery University of PittsburghPittsburghPennsylvaniaUSA Department of Otolaryngology-head and neck surgery University of MinnesotaMinneapolisMinnesotaUSA National Institute of Alcohol Abuse and Alcoholism Section of Sensory Science and Metabolism&National Institute of Nursing ResearchBethesdaMarylandUSA New York-Presbyterian/Columbia University Irving Medical Center New YorkNew YorkUSA

Objectives:Persistent olfactory dysfunction(OD)following loss of smell associated with SARS-CoV-2 infection is a major feature of long COVID.Perspectives on the prevalence of persistent OD predominantly rely on self-reported olfactory function.Few studies have tracked longitudinal rates of recovery using psychophysical assessment among patients presenting for evaluation of persistent OD beyond a window of acute recovery.Data anchored in standardized testing methods are needed to counsel patients who fail to acutely regain their sense of smell.This study aims to quantify the degree of persistent OD in post-COVID-19 patients who experience subjective and psychophysical OD.Methods:We grouped participants presenting for OD evaluation into cohorts based on both subjective and psychophysical olfactory status at a baseline assessment and assessed their olfactory abilities with a visual analogue scale and the Sniffin'Sticks extended test at baseline and 1-year time points.Participants had confirmed a history of COVID-19 by lab evaluation or clinical diagnosis if lab evaluation was not available.Results:Baseline olfactory evaluation was completed by 122 participants,53 of whom completed the 1-year follow-up assessment.Among participants presenting with perceived OD,74.5%had confirmed psychophysical OD at baseline,with 55.1%at 1-year follow-up.Participants had reliable trends in self-rated versus psychophysically tested olfactory function at both time points.The total threshold,discrimination,and identification(TDI)score improved by+3.25 points in the cohort with psychophysical OD(p=0.0005),with this improvement largely attributable to an increase in median threshold scores(+2.75 points;p=0.0004).Conclusions:OD persists in a significant number of patients who fail to acutely recovery their sense of smell after COVID-19,with many demonstrating lingering deficits at 1-year.Improvements in threshold,but not discrimination or identification,most significantly mediate improvement of total TDI score at follow-up.

关键词： long COVID olfaction post-COVID condition smell dysfunction

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Comparative utility of vestibular function tests in patients with peripheral and central vestibular dysfunction

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Journal of Otology 2024年第1期19卷 5-9页

作者： Cameron B.Fattahi Christopher Zaro Janice J.Chung Richard F.Lewis Divya A.Chari Department of Otolaryngology-head and neck surgery UMASS Memorial Medical CenterUniversity of Massachusetts Chan Medical SchoolWorcesterMAUSA Jenks Vestibular Physiology Laboratory Massachusetts Eye and EarBostonMAUSA Department of Otolaryngology-head and neck surgery Massachusetts Eye and EarHarvard Medical SchoolBostonMAUSA Department of Neurology Harvard Medical SchoolBostonMAUSA

Background: Bithermal caloric irrigation, video head impulse test(vHIT), and rotational testing are commonly used to assess peripheral vestibular function, but the relative clinical utility of each test in differentiating patients with peripheral vestibulopathy is debated.Objectives: To determine whether(1) the combination of two or more vestibular tests enhances diagnostic utility over a single test;(2) abnormal test results on vestibular tests correlate with one another.Methods: Retrospective analysis of data collected from multidisciplinary vestibular clinics at two academic medical centers from 2016 to 2022.Results: 150 patients(54.10 ± 15.09 years, 88 females) were included. No individual test was significantly better at predicting the presence of peripheral vestibular damage(p > 0.05). vHIT test results improved significantly when combined with either the caloric test(p = 0.007) or rotary chair test(p = 0.039). Caloric and rotational testing had high sensitivity(74.65% and 76.06%, respectively) and specificity(83.54% and 78.48%, respectively). vHIT demonstrated excellent specificity(89.87%) but poor sensitivity(47.89%). Caloric, vHIT, and rotary chair tests results did not correlate with one another(p > 0.05).Conclusions: Vestibular function tests have comparable diagnostic utility, yet each offers unique advantages. Caloric and rotational testing may be best suited for screening peripheral damage and vHIT may function ideally as a confirmatory test.

关键词： vestibular patients specificity

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Stem Cell-Based Hair Cell Regeneration and Therapy in the Inner Ear

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Neuroscience Bulletin 2024年第1期40卷 113-126页

作者： Jieyu Qi Wenjuan Huang Yicheng Lu Xuehan Yang Yinyi Zhou Tian Chen Xiaohan Wang Yafeng Yu Jia-Qiang Sun Renjie Chai State Key Laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck SurgeryZhongda HospitalSchool of Life Sciences and TechnologyAdvanced Institute for Life and HealthJiangsu Province High-Tech Key Laboratory for Bio-Medical ResearchSoutheast UniversityNanjing 210096China Hospital of Southeast University Nanjing 210096China First Affiliated Hospital of Soochow University Suzhou 215006China Department of Otolaryngology-head and neck surgery The First Affliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Otolaryngology head and neck surgery Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072China Co-Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China Institute for Stem Cell and Regeneration Chinese Academy of ScienceBeijing 100101China

Hearing loss has become increasingly prevalent and causes considerable disability,thus gravely burdening the global economy.Irreversible loss of hair cells is a main cause of sensorineural hearing loss,and currently,the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids,but these are of limited benefit in patients.It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies.At present,how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research.Multi-ple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells,and in this article,we first review the principal mechanisms underlying hair cell reproduction.We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration,and we summarize current achievements in hair cell regeneration.Lastly,we discuss potential future approaches,such as small molecule drugs and gene therapy,which might be applied for regenerating functional hair cells in the clinic.

关键词： Hearing loss Cochlea-Stem cell Hair cell regeneration

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Controlled release of dexamethasone from fibrin sealant for intratympanic administration in inner ear therapy

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Journal of Otology 2024年第1期19卷 55-58页

作者： Jing Zou Department of Otolaryngology-head and neck surgery Changhai HospitalSecond Military Medical UniversityShanghai200433China Faculty of Information Technology and Communication Sciences Tampere UniversityTampereFinland

The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere’s disease (MD) and sudden sensorineural hearing loss (SSHL).Gelation occurred shortly after mixing dexamethasone-containing fibrinogen with thrombin.Dexamethasone was constantly released for at least 16 d at a stable level after 7d in protocol 1 (low-dose),while it was robustly released within 4 d and slowed afterward until 10 d in protocol 2(high-dose).There were significant differences among the time points in Protocol 2 (p<0.01,ANOVA),and the exponential model with the formula y=15.299*e~(-0.483*t) fits the association.The estimated concentration of dexamethasone released on 7 d in protocol 2 was slightly lower than that observed in protocol 1.The fibrin sealant is capable of constantly releasing dexamethasone with adjustable dynamics.Targeted and minimally invasive administration of the material can be achieved in the clinic by sequential injections of the fluids using a soft-tipped catheter.

关键词： Intratympanic drug delivery Controlled release Corticosteroids Meniere's disease Sudden sensorineural hearing loss

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