Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of the Association for Research in Otolaryngology

15-04-2024 | Original Article

FDA-Approved Tedizolid Phosphate Prevents Cisplatin-Induced Hearing Loss Without Decreasing Its Anti-tumor Effect

Authors: Zhiwei Yao, Yu Xiao, Wen Li, Shuhui Kong, Hailong Tu, Siwei Guo, Ziyi Liu, Lushun Ma, Ruifeng Qiao, Song Wang, Miao Chang, Xiaoxu Zhao, Yuan Zhang, Lei Xu, Daqing Sun, Xiaolong Fu

Published in: Journal of the Association for Research in Otolaryngology

Login to get access

Abstract

Purpose

Cisplatin is a low-cost clinical anti-tumor drug widely used to treat solid tumors. However, its use could damage cochlear hair cells, leading to irreversible hearing loss. Currently, there appears one drug approved in clinic only used for reducing ototoxicity associated with cisplatin in pediatric patients, which needs to further explore other candidate drugs.

Methods

Here, by screening 1967 FDA-approved drugs to protect cochlear hair cell line (HEI-OC1) from cisplatin damage, we found that Tedizolid Phosphate (Ted), a drug indicated for the treatment of acute infections, had the best protective effect. Further, we evaluated the protective effect of Ted against ototoxicity in mouse cochlear explants, zebrafish, and adult mice. The mechanism of action of Ted was further explored using RNA sequencing analysis and verified. Meanwhile, we also observed the effect of Ted on the anti-tumor effect of cisplatin.

Results

Ted had a strong protective effect on hair cell (HC) loss induced by cisplatin in zebrafish and mouse cochlear explants. In addition, when administered systemically, it protected mice from cisplatin-induced hearing loss. Moreover, antitumor studies showed that Ted had no effect on the antitumor activity of cisplatin both in vitro and in vivo. RNA sequencing analysis showed that the otoprotective effect of Ted was mainly achieved by inhibiting phosphorylation of ERK. Consistently, ERK activator aggravated the damage of cisplatin to HCs.

Conclusion

Collectively, these results showed that FDA-approved Ted protected HCs from cisplatin-induced HC loss by inhibiting ERK phosphorylation, indicating its potential as a candidate for preventing cisplatin ototoxicity in clinical settings.
Appendix
Available only for authorised users
Literature
1.
2.
Small W, Bacon MA, Bajaj A, Chuang LT, Gaffney DK (2017) Cervical cancer: a global health crisis. Obstet Gynecol Surv 72(11):654–655CrossRef
3.
He YZ, Zheng ZW, Liu C, Li W, Zhao LP, Nie GH, Li HW (2022) Inhibiting DNA methylation alleviates cisplatin- induced hearing loss by decreasing oxidative stress-induced mitochondria-dependent apoptosis via the LRP1-PI3K/AKT pathway. Acta Pharmaceutica Sinica B 12(3):1305–1321PubMedCrossRef
4.
5.
Paken J, Govender CD, Pillay M, Sewram V (2022) Cisplatin-associated ototoxicity: perspectives from a single institution cervical cancer cohort and implications for developing a locally responsive monitoring programme in a public healthcare setting. BMC Health Serv Res 22(1):1–14CrossRef
6.
Tang Q, Wang X, Jin H, Mi Y, Zou Z (2021) Cisplatin-induced ototoxicity: updates on molecular mechanisms and otoprotective strategies. Eur J Pharm Biopharm 163(7):60–71PubMedCrossRef
7.
Breglio AM, Rusheen AE, Shide ED, Fernandez KA, Spielbauer KK, McLachlin KM, Hall MD, Amable L, Cunningham LL (2017) Cisplatin is retained in the cochlea indefinitely following chemotherapy. Nat Commun 8(1):1654PubMedPubMedCentralCrossRef
8.
Wang WL, Chen EF, Ding XR, Lu PH, Chen JW, Ma PW, Lu LJ (2022) N-acetylcysteine protect inner hair cells from cisplatin by alleviated celluar oxidative stress and apoptosis. Toxicol In Vitro 81:105354PubMedCrossRef
9.
Gentilin E, Simoni E, Candito M, Cazzador D, Astolfi L (2019) Cisplatin-induced ototoxicity: updates on molecular targets. Trends Mol Med 25(12):1123–1132PubMedCrossRef
10.
Zallocchi M, Hati S, Xu Z, Hausman W, Zuo J (2021) Characterization of quinoxaline derivatives for protection against iatrogenic-induced hearing loss. JCI Insight 6(5):e141561PubMedPubMedCentralCrossRef
11.
Rybak LP (2007) Mechanisms of cisplatin ototoxicity and progress in otoprotection. Curr Opin Otolaryngol Head Neck Surg 15(5):364–369PubMedCrossRef
12.
13.
He FA, Huang XT, Wei GK, Lin XR, Zhang WJ, Zhuang W, He WH, Zhan T, Hu H, Yang HD (2022) Regulation of ACSL4-catalyzed lipid peroxidation process resists cisplatin ototoxicity. Oxid Med Cell Longev 3080263
14.
Mukherjea D, Dhukhwa A, Sapra A, Bhandari P, Rybak L (2020) Strategies to reduce the risk of platinum containing antineoplastic drug-induced ototoxicity. Expert Opin Drug Metab Toxicol 16(10):965–982: PMID:32757852PubMedPubMedCentralCrossRef
15.
Bhatta P, Dhukhwa A, Sheehan K, Al Aameri RFH, Borse V, Ghosh S, Sheth S, Mamillapalli C, Rybak L, Ramkumar V et al (2019) Capsaicin protects against cisplatin ototoxicity by changing the STAT3/STAT1 ratio and activating cannabinoid (CB2) receptors in the cochlea. Sci Rep 9(1):4131PubMedPubMedCentralCrossRef
16.
Kim HJ, Oh GS, Lee JH, Lyu AR, Ji HM, Lee SH, Song J, Park SJ, You YO, Sul JD (2011) Cisplatin ototoxicity involves cytokines and STAT6 signaling network. Cell Res 21(6):13CrossRef
17.
So H, Kim H, Kim Y, Kim E, Pae HO, Chung HT, Kim HJ, Kwon KB, Lee KM, Lee HY et al (2008) Evidence that cisplatin-induced auditory damage is attenuated by downregulation of pro-inflammatory cytokines via Nrf2/HO-1. Jaro-Journal of the Association for Research in Otolaryngology 9(3):290–306PubMedCentralCrossRef
18.
Volker N, Kwang P, Rahul J, Arwa K, Ryan AF (2017) An antioxidant screen identifies candidates for protection of cochlear hair cells from gentamicin toxicity. Front Cell Neurosci 11:242CrossRef
19.
Tian CJ, Kim YJ, Kim SW, Lim HJ, Kim YS, Choung YH (2013) A combination of cilostazol and ginkgo biloba extract protects against cisplatin-induced cochleo-vestibular dysfunction by inhibiting the mitochondrial apoptotic and ERK pathways. J Micro/Nanolithogr MEMS MOEMS 4(2):e509
20.
Tan XD, Zhou YJ, Agarwal A, Lim M, Xu YY, Zhu YM, O’Brien J, Tran E, Zheng J, Gius D et al (2020) Systemic application of honokiol prevents cisplatin ototoxicity without compromising its antitumor effect. Am J Cancer Res 10(12):4416PubMedPubMedCentral
21.
Rolland V, Meyer F, Guitton MJ, Bussières R, Philippon D, Bairati I, Leclerc M, Côté M (2019) A randomized controlled trial to test the efficacy of trans-tympanic injections of a sodium thiosulfate gel to prevent cisplatin-induced ototoxicity in patients with head and neck cancer. J Otolaryngol Head Neck Surg 48(1):4PubMedPubMedCentralCrossRef
22.
Sarafraz Z, Ahmadi A, Daneshi A (2018) Transtympanic injections of N-acetylcysteine and dexamethasone for prevention of cisplatin-induced ototoxicity: double blind randomized clinical trial. International Tinnitus Journal 22(1):40PubMedCrossRef
23.
Freyer DR, Chen L, Krailo MD, Knight K, Villaluna D, Bliss B, Pollock BH, Ramdas J, Lange B, Van Hoff D (2017) Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncology 18(1):63PubMedCrossRef
24.
Brock PR, Maibach R, Childs M, Rajput K, Neuwelt EA (2018) Sodium thiosulfate for protection from cisplatin-induced hearing loss. N Engl J Med 378(25):191CrossRef
25.
Kros CJ, Steyger PS (2019) Aminoglycoside- and cisplatin-induced ototoxicity: mechanisms and otoprotective strategies. Cold Spring Harbor Laboratory Press 9(11):a033548CrossRef
26.
Abada P (2011) SB H: Regulation of cisplatin cytotoxicity by cu influx transporters. Metal Based Drugs 2010:317581PubMedCentral
27.
Kros CJ, Steyger PS (2019) Aminoglycoside- and cisplatin-induced ototoxicity: mechanisms and otoprotective strategies. Cold Spring Harb Perspect Med 9(11):a033548PubMedPubMedCentralCrossRef
28.
Ciarimboli G, Deuster D, Knief A, Sperling M, Holtkamp M, Edemir B, Pavenstädt H, Lanvers-Kaminsky C, Zehnhoff-Dinnesen AA, Schinkel AH et al (2010) Organic cation transporter 2 mediates cisplatin-induced oto- and nephrotoxicity and is a target for protective interventions. Am J Pathol 176(3):1169–1180PubMedPubMedCentralCrossRef
29.
Ingersoll MA, Malloy EA, Caster LE, Holland EM, Teitz T (2020) BRAF inhibition protects against hearing loss in mice. Sci Adv 6(49):eabd0561PubMedPubMedCentral
30.
Kitcher SR, Kirkwood NK, Camci ED, Wu P, Gibson RM, Redila VA, Simon JA, Rubel EW, Raible DW, Richardson GP et al (2019) ORC-13661 protects sensory hair cells from aminoglycoside and cisplatin ototoxicity. Jci Insight 4(15):e126764PubMedPubMedCentralCrossRef
31.
Li M, Liu JW, Liu D, Duan XC, Zhang QC, Wang DW, Zheng QY, Bai XH, Lu ZM (2021) Naringin attenuates cisplatin- and aminoglycoside-induced hair cell injury in the zebrafish lateral line via multiple pathways. J Cell Mol Med 25(2):975–989PubMedCrossRef
32.
Rocha-Sanchez SM, Fuson O, Tarang S, Goodman L, Pyakurel U, Liu HZ, He DZ, Zallocchi M (2019) Quinoxaline protects zebrafish lateral line hair cells from cisplatin and aminoglycosides damage (vol 8, 15119, 2018). Sci Rep 8(1):15119CrossRef
33.
Fernandes VT, Lin VYW (2014) Development of an ototoxicity model in the adult CBA/CaJ mouse and determination of a golden window of corticosteroid intervention for otoprotection. Journal of Otolaryngology-Head & Neck Surgery 43(1):12CrossRef
34.
Garcia-Alcantara F, Murillo-Cuesta S, Pulido S, Bermudez-Munoz JM, Martinez-Vega R, Milo M, Varela-Nieto I, Rivera T (2018) The expression of oxidative stress response genes is modulated by a combination of resveratrol and N-acetylcysteine to ameliorate ototoxicity in the rat cochlea. Hear Res 358:10–21PubMedCrossRef
35.
Teitz T, Fang J, Goktug AN, Bonga JD, Diao SY, Hazlitt RA, Iconaru L, Morfouace M, Currier D, Zhou YM et al (2018) CDK2 inhibitors as candidate therapeutics for cisplatin-and noise-induced hearing loss. J Exp Med 215(4):1187–1203PubMedPubMedCentralCrossRef
36.
Dhillon S (2023) Sodium thiosulfate: pediatric first approval. Pediatr Drugs 25(2):239–244CrossRef
37.
Kisgen JJ, Mansour H, Unger NR, Childs LM (2014) Tedizolid: a new oxazolidinone antimicrobial. Am J Health Syst Pharm 71(8):621–633PubMedCrossRef
38.
Mikamo H, Nagashima M, Kusachi S, Fujimi S, Oshima N, De Anda C, Takase A (2022) Efficacy and safety of tedizolid for the treatment of ventilated gram-positive hospital-acquired or ventilator-associated bacterial pneumonia in Japanese patients: results from a subgroup analysis of a phase 3, randomized, double-blind study comparing tedizolid and linezolid. J Infect Chemother 28(9):1235–1241PubMedCrossRef
39.
Nyberg S, Abbott NJ, Shi X, Steyger PS, Dabdoub A (2019) Delivery of therapeutics to the inner ear: The challenge of the blood-labyrinth barrier. ence Transl Med 11(482):eaao0935
40.
Gu LQ, Ma MN, Zhang Y, Zhang LJ, Zhang S, Huang MC, Zhang MJ, Xin YF, Zheng GL, Chen SH (2019) Comparative pharmacokinetics of tedizolid in rat plasma and cerebrospinal fluid. Regul Toxicol Pharmacol 107:104420PubMedCrossRef
41.
Wenzler E, Adeel A, Wu T, Jurkovic M, Walder J, Ramasra E, Campion M, Cerny J, Theodoropoulos NM (2021) Inadequate cerebrospinal fluid concentrations of available salvage agents further impedes the optimal treatment of multidrug-resistant Enterococcus faecium meningitis and bacteremia. Infectious disease reports 13(3):843–854PubMedPubMedCentralCrossRef
42.
Chen YW, Lear TB, Evankovich JW, Larsen MB, Lin B, Alfaras I, Kennerdell JR, Salminen L, Camarco DP, Lockwood KC et al (2021) A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry. Nat Commun 12(1):3907PubMedPubMedCentralCrossRef
43.
Jin WJ, Yu JM, Su Y, Lin HC, Liu TF, Chen J, Ge C, Zhao FY, Geng Q, Mao L et al (2023) Drug repurposing flubendazole to suppress tumorigenicity via PCSK9-dependent Inhibition and potentiate lenvatinib therapy for hepatocellular carcinoma. Int J Biol Sci 19(7):2270–2288PubMedPubMedCentralCrossRef
44.
Shahab M, Rosati R, Meyers D, Sheilds J, Jamesdaniel S (2021) Cisplatin-induced hair cell loss in zebrafish neuromasts is accompanied by protein nitration and Lmo4 degradation. Toxicol Appl Pharmacol 410(1–2):115342PubMedCrossRef
45.
Drusano GL, Liu W, Kulawy R, Louie A (2011) Impact of granulocytes on the antimicrobial effect of tedizolid in a mouse thigh infection model▿. Antimicrob Agents Chemother 55(11):5300–5305PubMedPubMedCentralCrossRef
46.
He Y, Zheng Z, Liu C, Li W, Zhao L, Nie G, Li H (2022) Inhibiting DNA methylation alleviates cisplatininduced hearing loss by decreasing oxidative stress-induced mitochondria-dependent apoptosis via the LRP1-PI3K/AKT pathway. Acta Pharmaceutica Sinica B 003:012
47.
Yu H, Lin Q, Wang Y, He Y, Fu S, Jiang H, Yu Y, Sun S, Chen Y, Shou J et al (2013) Inhibition of H3K9 methyltransferases G9a/GLP prevents ototoxicity and ongoing hair cell death. Cell Death Dis 4(2):e506PubMedPubMedCentralCrossRef
48.
Drévillon L, Tanguy G, Hinzpeter A, Arous N, de Becdelièvre A, Aissat A, Tarze A, Goossens M, Fanen P (2011) COMMD1-mediated ubiquitination regulates CFTR trafficking. PLoS ONE 6(3):e18334PubMedPubMedCentralCrossRef
49.
Liu JY, Zheng XJ, Li W, Ren LW, Li S, Yang YH, Yang H, Ge BB, Du GH, Shi JY et al (2022) Anti-tumor effects of Skp2 inhibitor AAA-237 on NSCLC by arresting cell cycle at G0/G1 phase and inducing senescence. Pharmacol Res 181:106259PubMedCrossRef
50.
Teitz T, Goktug AN, Chen T, Zuo J (2016) Development of cell-based high-throughput chemical screens for protection against cisplatin-induced ototoxicity. Methods Mol Biol 1427:419–430PubMedCrossRef
51.
Landegger LD, Dilwali S, Stankovic KM (2017) Neonatal murine cochlear explant technique as an in vitro screening tool in hearing research. Jove-Journal of Visualized Experiments 124:55704
52.
Masuda M, Pak K, Chavez E, Ryan AF (2012) TFE2 and GATA3 enhance induction of POU4F3 and myosin VIIa positive cells in nonsensory cochlear epithelium by ATOH1. Dev Biol 372(1):68–80PubMedPubMedCentralCrossRef
53.
Lim HW, Pak K, Ryan AF, Kurabi A (2018) Screening mammalian cochlear hair cells to identify critical processes in aminoglycoside-mediated damage. Front Cell Neurosci 12:179PubMedPubMedCentralCrossRef
54.
Holmgren M, Sheets L (2021) Using the zebrafish lateral line to understand the roles of mitochondria in sensorineural hearing loss. Frontiers in Cell and Developmental Biology 8:628712PubMedPubMedCentralCrossRef
55.
Dehne N, Lautermann J, Petrat F, Rauen U, de Groot H (2001) Cisplatin ototoxicity: involvement of iron and enhanced formation of superoxide anion radicals. Toxicol Appl Pharmacol 174(1):27–34PubMedCrossRef
56.
Mohan S, Smyth BJ, Namin A, Phillips G, Gratton MA (2014) Targeted amelioration of cisplatin-induced ototoxicity in guinea pigs. Otolaryngology-Head and Neck Surgery 151(5):836–839PubMedCrossRef
57.
Langer T, Zehnhoff-Dinnesen AA, Radtke S, Meitert J, Zolk O (2013) Understanding platinum-induced ototoxicity. Trends Pharmacol Sci 34(8):458–469PubMedCrossRef
58.
Kim HJ, Lee JH, Kim SJ, Oh GS, Moon HD, Kwon KB, Park C, Park BH, Lee HK, Chung SY et al (2010) Roles of NADPH oxidases in cisplatin-induced reactive oxygen species generation and ototoxicity. J Neurosci 30(11):3933–3946PubMedPubMedCentralCrossRef
59.
Kim J, Cho HJ, Sagong B, Kim SJ, Lee JT, So HS, Lee IK, Kim UK, Lee KY, Choo YS (2014) Alpha-lipoic acid protects against cisplatin-induced ototoxicity via the regulation of MAPKs and proinflammatory cytokines. Biochem Biophys Res Commun 449(2):183–189PubMedCrossRef
60.
So H, Kim HJ, Lee JH, Park C, Kim Y, Kim E, Kim JK, Yun KJ, Lee LHY, Al E (2007) isplatin cytotoxicity of auditory cells requires secretions of proinflammatory cytokines via activation of ERK and NF- κ B. JARO-J Assoc Res Otolaryngol 8(3):338–55CrossRef
61.
Zheng S, Zheng S, Liu C, Liu C, Tang D, Tang D, Zheng Z, Zheng Z, Yan R, Yan R (2022) The protective effect of rutin against the cisplatin-induced cochlear damage in vitro. Neurotoxicology 90:102–111PubMedCrossRef
62.
Lee JS, Kang SU, Hwang HS, Pyun JH, Choung YH, Kim CH (2010) Epicatechin protects the auditory organ by attenuating cisplatin-induced ototoxicity through inhibition of ERK. Toxicol Lett 199(3):308–316PubMedCrossRef
63.
Wang D, Shi S, Ren T, Zhang Y, Guo P, Wang J, Wang W (2021) U0126 pretreatment inhibits cisplatin-induced apoptosis and autophagy in HEI-OC1 cells and cochlear hair cells. Toxicol Appl Pharmacol 415:115447PubMedCrossRef
64.
Kao C, Chao A, Tsai CL, Chuang WC, Huang WP, Chen GC, Lin CY, Wang TH, Wang HS, Lai CH (2014) Bortezomib enhances cancer cell death by blocking the autophagic flux through stimulating ERK phosphorylation. Cell Death Dis 5(11):e1510PubMedPubMedCentralCrossRef
65.
Hsin MC, Hsiao YH, Chen PN, Lin CW, Wang PH, Yang SF, Lee CY (2022) Dihydromyricetin inhibited migration and invasion by reducing S100A4 expression through ERK1/2/beta-catenin pathway in human cervical cancer cell lines. Int J Mol Sci 23(23):15106PubMedPubMedCentralCrossRef
66.
Astolfi L, Ghiselli S, Guaran V, Chicca M, Simoni E, Olivetto E, Lelli G, Martini A (2013) Correlation of adverse effects of cisplatin administration in patients affected by solid tumours: a retrospective evaluation. Oncol Rep 29(4):1285–1292PubMedPubMedCentralCrossRef
67.
68.
69.
Gu JY, Tong L, Lin X, Chen YM, Wu H, Wang XL, Yu DH (2022) The disruption and hyperpermeability of blood-labyrinth barrier mediates cisplatin-induced ototoxicity. Toxicol Lett 354:56–64PubMedCrossRef
70.
Wang XL, Zhou YY, Wang DL, Wang Y, Zhou ZY, Ma XL, Liu XF, Dong YD (2023) Cisplatin-induced ototoxicity: from signaling network to therapeutic targets. Biomed Pharmacother 157:114045PubMedCrossRef
71.
Fu D, Wu J, Lai J, Liu Y, Zhou L, Chen L, Zhang Q (2020) T cell recruitment triggered by optimal dose platinum compounds contributes to the therapeutic efficacy of sequential PD-1 blockade in a mouse model of colon cancer. Am J Cancer Res 10(2):473–490PubMedPubMedCentral
72.
Kawaguchi Y, Ohshio Y, Watanabe A, Shiratori T, Okamoto K, Ueda K, Kataoka Y, Suzuki T, Hanaoka J (2023) Depletion of tumor-associated macrophages inhibits lung cancer growth and enhances the antitumor effect of cisplatin. Cancer Sci 114(3):750–763PubMedCrossRef
73.
Schacht J, Talaska AE, Rybak LP (2012) Cisplatin and aminoglycoside antibiotics: hearing loss and its prevention. Anatomical Record-advances in Integrative Anatomy & Evolutionary Biology 295(11):1837–1850CrossRef
74.
Liu Y, Wei M, Mao X, Chen TS, Lin P, Wang W (2021) Key signaling pathways regulate the development and survival of auditory hair cells. Neural Plast 5522717
75.
Roux PP, Blenis J (2004) ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev 68(2):320PubMedPubMedCentral
76.
Choi BM, Chen XY, Gao SS, Zhu R, Kim BR (2011) Anti-apoptotic effect of phloretin on cisplatin-induced apoptosis in HEI-OC1 auditory cells. Pharmacological Reports Pr 63(3):708–716PubMedCrossRef
77.
Hall MD, Okabe M, Shen DW, Liang XJ, Gottesman MM (2008) The role of cellular accumulation in determining sensitivity to platinum-based chemotherapy. Annu Rev Pharmacol Toxicol 48(1):495–535PubMedCrossRef
78.
Shen DW, Pouliot LM, Hall MD, Gottesman MM (2012) Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes. Pharmacol Rev 64(3):706–721PubMedPubMedCentralCrossRef
79.
Thomas AJ, Hailey DW, Stawicki TM, Wu P, Coffin AB, Rubel EW, Raible DW, Simon JA, Ou HC (2013) Functional mechanotransduction is required for cisplatin-induced hair cell death in the zebrafish lateral line. J Neurosci 33(10):4405–4414PubMedPubMedCentralCrossRef
Metadata
Title
FDA-Approved Tedizolid Phosphate Prevents Cisplatin-Induced Hearing Loss Without Decreasing Its Anti-tumor Effect
Authors
Zhiwei Yao
Yu Xiao
Wen Li
Shuhui Kong
Hailong Tu
Siwei Guo
Ziyi Liu
Lushun Ma
Ruifeng Qiao
Song Wang
Miao Chang
Xiaoxu Zhao
Yuan Zhang
Lei Xu
Daqing Sun
Xiaolong Fu
Publication date
15-04-2024
Publisher
Springer US
Published in
Journal of the Association for Research in Otolaryngology
Print ISSN: 1525-3961
Electronic ISSN: 1438-7573
DOI
https://doi.org/10.1007/s10162-024-00945-2