Global burden of thyroid cancer from 1990 to 2021: a systematic analysis from the Global Burden of Disease Study 2021.

Thyroid cancer (TC) is a significant global healthcare burden. However, the lack of comprehensive data has impeded our understanding of its global impact. We aimed to examine the burden of TC and its trends at the global, regional, and national levels using data stratified by sociodemographic index (SDI), sex, and age. Data on TC, including incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021, were obtained from the Global Burden of Disease Study 2021. Estimated annual percentage changes (EAPCs) were calculated to assess the incidence rate, mortality, and DALYs trends. The incidence, mortality, and DALYs of TC in 2021 were 249,538 (95% uncertainty interval: 223,290-274,638), 44,799 (39,925-48,541), and 646,741 (599,119-717,357), respectively. The age-standardized incidence rate (ASIR) in 2021 was 2.914 (2.607-3.213), with an EAPC of 1.25 (1.14-1.37) compared to 1990. In 2021, the age-standardized death rate (ASDR) was 0.53 (0.47-0.575) and age-standardized DALYs rate was 14.571 (12.783-16.115). Compared with 1990, the EAPCs of ASDR and age-standardized DALYs rate showed decreasing trends, at - 0.24 (- 0.27 to - 0.21) and - 0.14 (- 0.17 to - 0.11), respectively. Low SDI regions showed the highest ASDR and age-standardized DALYs rate, at 0.642 (0.516-0.799) and 17.976 (14.18-23.06), respectively. Low-middle SDI regions had the highest EAPCs for ASDR and age-standardized DALYs rate, at 0.74 (0.71-0.78) and 0.67 (0.63-0.7), respectively. Females exhibited decreasing trend in ASDR and age-standardized DALYs rate, with EAPCs of - 0.58 (- 0.61 to - 0.55) and - 0.45 (- 0.47 to - 0.42), respectively. In contrast, males showed an increasing trend in ASDR and age-standardized DALYs rate, with EAPCs of 0.41 (0.35-0.46) for both. In high-income regions, most countries with decreased annual changes in deaths experience increasing age-related deaths. Over the past few decades, a notable increase in TC incidence and decreased mortality has been observed globally. Regions characterized by lower SDI, male sex, and an aging population exhibited no improvement in TC mortality. Effective resource allocation, meticulous control of risk factors, and tailored interventions are crucial for addressing these issues.

Single-cell RNA-Seq reveals the heterogeneity of fibroblasts within the tympanojugular paraganglioma microenvironment.

Tympanojugular paragangliomas (TJP) originate from the parasympathetic ganglia in the lateral base of the skull. Although the cellular composition and oncogenic mechanisms of paragangliomas have been evaluated, a comprehensive transcriptomic atlas specific to TJP remains to be established to facilitate further investigations. In this study, single-cell RNA sequencing and whole-exome sequencing were conducted on six surgically excised TJP samples to determine their cellular composition and intratumoral heterogeneity. Fibroblasts were sub-classified into two distinct groups: myofibroblasts and fibroblasts associated with bone remodeling. Additionally, an elaborate regulatory and cell-cell communication network was determined, highlighting the multifaceted role of fibroblasts, which varies depending on expression transitions. The Kit receptor (KIT) signaling pathway mediated interactions between fibroblasts and mast cells, whereas robust connections with endothelial and Schwann cell-like cells were facilitated through the platelet-derived growth factor signaling pathway. These findings establish a foundation for studying the mechanisms underlying protumor angiogenesis and the specific contributions of fibroblasts within the TJP microenvironment. IL6 signaling pathway of fibroblasts interacting with macrophages and endothelial cells may be involved in tumor regrowth. These results enhance our understanding of fibroblast functionality and provide a resource for future therapeutic targeting of TJP.

[Endothelial cells and fibroblasts mediate the microenvironmental regulatory network of carotid body paraganglioma].

Objective:To explore the gene expression characteristics of endothelial cells and fibroblasts in the microenvironment of SDHD-mutated carotid body tumors（SDHD-CBT）, to fine the functional enrichment of each subcluster, and to further explore the network of cell-cell interactions in the microenvironment of SDHD-CBT. Methods:The bioinformatics analysis was used to download and reanalyze the single-nuclear RNA sequencing data of SDHD-CBT, SDHB mutated thoracic and abdominal paraganglioma（SDHB-ATPGL）, SDHB-CBT, and normal adrenal medulla（NAM）, to clarify the information of cell populations of the samples. We focused on exploring the gene expression profiles of endothelial cells and fibroblasts subclusters, and performed functional enrichment analysis based on Gene Ontology（GO） resources. CellChat was used to compare the cell-cell interactions networks of different clinical samples and predict significant signaling pathways in SDHD-CBT. Results:A total of 7 cell populations were profiled. The main subtypes of endothelial cells in SDHD-CBT are arterial and venous endothelial cells, and the main subtypes of fibroblasts are myofibroblasts and pericytes. Compared to NAM, SDHB-CBT and SDHB-ATPGL, cell communication involving endothelial cells and fibroblasts in SDHD-CBT is more abundant, with significant enrichment in pathways such as FGF, PTN, WNT, PROS, PERIOSTIN, and TGFb. Conclusion:Endothelial cells and fibroblasts in SDHD-CBT are heterogeneous and involved in important cellular interactionprocesses, in which the discovery of FGF，PTN，WNT，PROS，PERIOSTIN and TGFb signals may play an important role in the regulation of microenvironment of SDHD-CBT.

[Application of internal carotid artery stent in glomus jugular paraganglioma surgery].

Objective:To summarize the application of internal carotid artery stent in glomus jugular paraganglioma surgery, and to provide an effective strategy for reducing the risk of internal carotid artery injury. Methods:This article reviewed the surgical cases of internal carotid artery stent implanting from 2018.06 to 2022.12, and discussed the stent placement method, treatment protocols, and perioperative management strategies. Results:A total of 5 patients underwent a comprehensive evaluation of the degree of internal carotid artery invasion using imaging techniques such as MRI, carotid CT angiography （CTA）, and digital silhouette angiography （DSA）. All patients were found to have varying degrees of internal carotid artery involvement. Stenting of the internal carotid artery was performed in all patients before surgery, and the stenting process went smoothly without any internal carotid artery injury. Three months after stenting, tumor resection or subtotal resection surgery was performed to avoid internal carotid artery injury during the surgery, and the surgical process was successfully completed. Postoperative follow-up from 4 months to 2 years showed that the internal carotid artery was patent after stent placement, with great endothelialization process and no stent-related complications. Conclusion:In patients with glomus jugular paraganglioma, when preoperative imaging shows internal carotid artery involvement, preoperative stenting is a safe and effective therapeutic strategy to reinforce the arterial wall structure, protect and maintain the integrity of the artery, and reduce the risk of vascular injury during the surgery. This article summarizes the experience of internal carotid artery stent in glomus jugular paraganglioma surgery, which provides an important reference for clinical practice.

[Review and prospect of the diagnosis and treatment of head and neck paragangliomas].

ead and neck paraganglioma（HNPGL） often originates from the parasympathetic ganglia and is a highly invasive benign tumor. The diagnosis and treatment of this disease with strong heterogeneity is still a challenge. In the future, deep exploration is needed in genetic typing, grading diagnosis and treatment decisions, protection of cranial nerves and new drug treatments to better treat this disease.

The role of ATP in sleep-wake regulation: In adenosine-dependent and -independent manner.

ATP plays a crucial role as an energy currency in the body's various physiological functions, including the regulation of the sleep-wake cycle. Evidence from genetics and pharmacology demonstrates a strong association between ATP metabolism and sleep. With the advent of new technologies such as optogenetics, genetically encoded biosensors, and novel ATP detection methods, the dynamic changes in ATP levels between different sleep states have been further uncovered. The classic mechanism for regulating sleep by ATP involves its conversion to adenosine, which increases sleep pressure when accumulated extracellularly. However, emerging evidence suggests that ATP can directly bind to P2 receptors and influence sleep-wake regulation through both adenosine-dependent and independent pathways. The outcome depends on the brain region where ATP acts and the expression type of P2 receptors. This review summarizes the experimental evidence on the relationship between ATP levels and changes in sleep states and outlines the mechanisms by which ATP is involved in regulating the sleep-wake cycle through both adenosine-dependent and independent pathways. Hopefully, this review will provide a comprehensive understanding of the current research basis and progress in this field and promote further investigations into the specific mechanisms of ATP in regulating sleep.

[An analysis of clinical efficacy of microvascular decompression for 21 inpatients suffering from primary hemifacial spasm].

Objective:To assess the effectiveness of microvascular decompression（MVD） in treating inpatients suffering from primary hemifacial spasm（HFS）. Methods:A total of 21 inpatients with HFS underwent MVD. The clinical effect was follow up evaluated according to the clinical symptoms until post operative 6 months. Results:The effective rate of MVD for 1 day, 14 days, 1 month, 3 months and 6 months post-operation was 95.2%, 100%, 100%, 100% and 100%, respectively.one patient had transient tinnitus and the symptom disappeared within 6 days postoperatively.one patient developed postoperative incomplete facial paralysis（HB grade IV facial nerve function, grade Ⅱ） and recovered 6 days after surgery; There was no cerebrospinal fluid leakage, intracranial infection, death or disability occurred during follow-up. Conclusion:Microvascular decompression is a safe and effective method for the treatment of primary hemifacial spasm, which is worthy of clinical promotion.

Global burden of head and neck cancers from 1990 to 2019.

Head and neck cancer (HNC) exerts a significant healthcare burden worldwide. Insufficient data impedes a comprehensive understanding of its global impact. Through analysis of the 2019 Global Burden of Disease (GBD) database, our secondary investigation unveiled a surging global incidence of HNC, yet a decline in associated mortality and disability-adjusted life years (DALYs) owing to enhanced prognosis. Particularly noteworthy is the higher incidence of escalation among females compared to males. Effective resource allocation, meticulous control of risk factors, and tailored interventions are imperative to curtail mortality rates among young individuals afflicted with HNC in underprivileged regions, as well as in elderly individuals grappling with thyroid cancer.

Adenoid lymphocyte heterogeneity in pediatric adenoid hypertrophy and obstructive sleep apnea.

Introduction: Adenoid hypertrophy is the main cause of obstructive sleep apnea in children. Previous studies have suggested that pathogenic infections and local immune system disorders in the adenoids are associated with adenoid hypertrophy. The abnormalities in the number and function of various lymphocyte subsets in the adenoids may play a role in this association. However, changes in the proportion of lymphocyte subsets in hypertrophic adenoids remain unclear. Methods: To identify patterns of lymphocyte subsets in hypertrophic adenoids, we used multicolor flow cytometry to analyze the lymphocyte subset composition in two groups of children: the mild to moderate hypertrophy group (n = 10) and the severe hypertrophy group (n = 5). Results: A significant increase in naïve lymphocytes and a decrease in effector lymphocytes were found in severe hypertrophic adenoids. Discussion: This finding suggests that abnormal lymphocyte differentiation or migration may contribute to the development of adenoid hypertrophy. Our study provides valuable insights and clues into the immunological mechanism underlying adenoid hypertrophy.

Integrative Analysis and Experimental Validation of Competing Endogenous RNAs in Obstructive Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent yet underdiagnosed. This study aimed to develop a predictive signature, as well as investigate competing endogenous RNAs (ceRNAs) and their potential functions in OSA. METHODS: The GSE135917, GSE38792, and GSE75097 datasets were collected from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Weighted gene correlation network analysis (WGCNA) and differential expression analysis were used to identify OSA-specific mRNAs. Machine learning methods were applied to establish a prediction signature for OSA. Furthermore, several online tools were used to establish the lncRNA-mediated ceRNAs in OSA. The hub ceRNAs were screened using the cytoHubba and validated by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Correlations between ceRNAs and the immune microenvironment of OSA were also investigated. RESULTS: Two gene co-expression modules closely related to OSA and 30 OSA-specific mRNAs were obtained. They were significantly enriched in the antigen presentation and lipoprotein metabolic process categories. A signature that consisted of five mRNAs was established, which showed a good diagnostic performance in both independent datasets. A total of twelve lncRNA-mediated ceRNA regulatory pathways in OSA were proposed and validated, including three mRNAs, five miRNAs, and three lncRNAs. Of note, we found that upregulation of lncRNAs in ceRNAs could lead to activation of the nuclear factor kappa B (NF-κB) pathway. In addition, mRNAs in the ceRNAs were closely correlated to the increased infiltration level of effector memory of CD4 T cells and CD56bright natural killer cells in OSA. CONCLUSIONS: In conclusion, our research opens new possibilities for diagnosis of OSA. The newly discovered lncRNA-mediated ceRNA networks and their links to inflammation and immunity may provide potential research spots for future studies.

Anthropometric Determinants of Autonomic Control in Obstructive Sleep Apnea: A Large-Scale Study.

OBJECTIVE: Autonomic dysfunction is an independent risk factor for cardiovascular disease (CVD). Both obesity and obstructive sleep apnea (OSA) are associated with heart rate variability (HRV) (a hall marker of sympathetic arousal) and increased risk of CVD. This study aims to investigate whether anthropometric parameters could predict reduced HRV in adult OSA during wakefulness. STUDY DESIGN: Cross-sectional study. SETTING: Sleep center of Shanghai Jiao Tong University Affiliated Sixth Hospital from 2012 to 2017. METHODS: Total of 2134 subjects (503 non-OSA and 1631 OSA) were included. Anthropometric parameters were recorded. HRV was recorded during a 5-minute wakefulness period and analyzed by using time-domain method and frequency-domain method. Multiple step-wise linear regressions were performed to determine significant predictors of HRV with and without adjustments. Multiplicative interactions between gender, OSA, and obesity on HRV were also determined and evaluated. RESULTS: Waist circumference (WC) was significant negative determinant of root mean square of successive NN intervals (ß = -.116, p < .001) and high-frequency power (ß = -.155, p < .001). Age was the strongest determining factor of HRV. Significant multiplicative interactions between obesity and OSA on HRV, gender, and obesity on cardiovascular parameters were observed. CONCLUSION: Anthropometric parameters could predict reduced HRV during wakefulness in patients with OSA, especially WC was the strongest influenceable factor. Obesity and OSA had significant multiplicative interaction on HRV. Gender and obesity had significant multiplicative interaction on cardiovascular parameters. Early intervention for obesity, especially centripetal obesity, may improve reduction of autonomic function and risk of CVD.

Changes in the oral and nasal microbiota in pediatric obstructive sleep apnea.

Background: Several clinical studies have demonstrated that pediatric obstructive sleep apnea (OSA) is associated with dysbiosis of airway mucosal microbiota. However, how oral and nasal microbial diversity, composition, and structure are altered in pediatric OSA has not been systemically explored. Methods: 30 polysomnography-confirmed OSA patients with adenoid hypertrophy, and 30 controls who did not have adenoid hypertrophy, were enrolled. Swabs from four surface oral tissue sites (tongue base, soft palate, both palatine tonsils, and adenoid) and one nasal swab from both anterior nares were collected. The 16S ribosomal RNA (rRNA) V3-V4 region was sequenced to identify the microbial communities. Results: The beta diversity and microbial profiles were significantly different between pediatric OSA patients and controls at the five upper airway sites. The abundances of Haemophilus, Fusobacterium, and Porphyromonas were higher at adenoid and tonsils sites of pediatric patients with OSA. Functional analysis revealed that the differential pathway between the pediatric OSA patients and controls involved glycerophospholipids and amino acid metabolism. Conclusions: In this study, the oral and nasal microbiome of pediatric OSA patients exhibited certain differences in composition compared with the controls. However, the microbiota data could be useful as a reference for studies on the upper airway microbiome.

TMEM30A is essential for hair cell polarity maintenance in postnatal mouse cochlea.

BACKGROUND: Phosphatidylserine is translocated to the inner leaflet of the phospholipid bilayer membrane by the flippase function of type IV P-tape ATPase (P4-ATPase), which is critical to maintain cellular stability and homeostasis. Transmembrane protein 30A (TMEM30A) is the ß-subunit of P4-ATPase. Loss of P4-ATPase function causes sensorineural hearing loss and visual dysfunction in human. However, the function of TMEM30A in the auditory system is unclear. METHODS: P4-ATPase subtype expression in the cochlea was detected by immunofluorescence staining and quantitative real-time polymerase chain reaction (qRT-PCR) at different developmental stages. Hair cell specific TMEM30A knockout mice and wild-type littermates were used for the following functional and morphological analysis. Auditory function was evaluated by auditory brainstem response. We investigated hair cell and stereocilia morphological changes by immunofluorescence staining. Scanning electron microscopy was applied to observe the stereocilia ultrastructure. Differentially expressed transcriptomes were analyzed based on RNA-sequencing data from knockout and wild-type mouse cochleae. Differentially expressed genes were verified by qRT-PCR. RESULTS: TMEM30A and subtypes of P4-ATPase are expressed in the mouse cochlea in a temporal-dependent pattern. Deletion of TMEM30A in hair cells impaired hearing onset due to progressive hair cell loss. The disrupted kinocilia placement and irregular distribution of spectrin-α in cuticular plate indicated the hair cell planar polarity disruption in TMEM30A deletion hair cells. Hair cell degeneration begins at P7 and finishes around P14. Transcriptional analysis indicates that the focal adhesion pathway and stereocilium tip-related genes changed dramatically. Without the TMEM30A chaperone, excessive ATP8A2 accumulated in the cytoplasm, leading to overwhelming endoplasmic reticulum stress, which eventually contributed to hair cell death. CONCLUSIONS: Deletion of TMEM30A led to disrupted planar polarity and stereocilia bundles, and finally led to hair cell loss and auditory dysfunction. TMEM30A is essential for hair cell polarity maintenance and membrane homeostasis. Our study highlights a pivotal role of TMEM30A in the postnatal development of hair cells and reveals the possible mechanisms underlying P4-ATPase-related genetic hearing loss.

[Retracted] MicroRNA­152 inhibits cell proliferation, migration and invasion by directly targeting MAFB in nasopharyngeal carcinoma.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell migration and invasion assay data shown in Fig. 3A and B were strikingly similar to data appearing in different form in other articles by different authors at different research institutes, some of which have been retracted; moreover, there appeared to be some overlapping data examining the western blots featured in Figs. 5B and 6A. Owing to the fact that the contentious data in the above article had already been published, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 15: 948­956, 2017; DOI: 10.3892/mmr.2016.6059].

HMGB1 accumulation in cytoplasm mediates noise-induced cochlear damage.

Damage-associated molecular pattern molecules (DAMPs) play a critical role in mediating cochlear cell death, which leads to noise-induced hearing loss (NIHL). High-mobility group box 1 (HMGB1), a prototypical DAMP released from cells, has been extensively studied in the context of various diseases. However, whether extracellular HMGB1 contributes to cochlear pathogenesis in NIHL and the potential signals initiating HMGB1 release from cochlear cells are not well understood. Here, through the transfection of the adeno-associated virus with HMGB1-HA-tag, we first investigated early cytoplasmic accumulation of HMGB1 in cochlear hair cells after noise exposure. We found that the cochlear administration of HMGB1-neutralizing antibody immediately after noise exposure significantly alleviated hearing loss and outer hair cells (OHCs) death induced by noise exposure. In addition, activation of signal transducer and activators of transcription 1 (STAT1) and cellular hyperacetylation were verified as potential canonical initiators of HMGB1 cytoplasmic accumulation. These findings reveal the adverse effects of extracellular HMGB1 on the cochlea and the potential signaling events mediating HMGB1 release in hair cells, indicating multiple potential pharmacotherapeutic targets for NIHL.

The Spectrum of Vestibular Disorders Presenting With Acute Continuous Vertigo.

Objective: To explore the composition of vestibular disorders presenting with the acute vestibular syndrome (AVS). Methods: We performed a case analysis of 209 AVS patients between January 2016 and December 2020. These patients were grouped into different disorder categories according to the relevant diagnostic criteria. Results: We classified the 209 patients into 14 disorder categories, including 110 cases of vestibular neuritis, 30 of idiopathic sudden sensorineural hearing loss with vertigo, 17 of the first attack of continuous vertigo with migraine, 15 of Ramsay Hunt syndrome, 11 of acute labyrinthitis secondary to chronic otitis media, 8 of vestibular schwannoma, 6 of posterior circulation infarction and/or ischemia, 3 of cerebellar abscess secondary to chronic otitis media, 3 of AVS caused by trauma or surgery, 2 of AVS with down-beating nystagmus, 1 of multiple sclerosis of the medulla oblongata, 1 of epidermoid cyst of the posterior cranial fossa, 1 of a probable acute otolithic lesion, and 1 of AVS without measurable vestibular dysfunction. Conclusion: When a group of disorders present with AVS, characteristic clinical manifestations and imaging help with an accurate diagnosis.

[Sleep quality and sleep disturbances in Chinese pregnant women: a multicenter cross-sectional study].

Objective: This study aims to investigate the sleep quality of pregnant women in Xuhui District, Shanghai, and the related factors of sleep disturbances during pregnancy. Methods: From February 2019 to February 2021, we used online integrated sleep questionnaire (including PSQI, BQ, ESS, AIS) in Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, The International Peace Maternity and Child Health Hospitals of China Welfare Institution, and Shanghai Eighth People's Hospital, to investigate the sleep quality across pregnancy. We also collected maternal physical examination results, childbearing history, sociodemographic, and other clinical data. The prevalences and related factors of various sleep disturbances in pregnant women were analyzed, including insufficient/excessive nighttime sleep, low sleep efficiency, difficulty falling asleep, poor sleep quality, insomnia, daytime sleepiness, and high risk of sleep-disordered breathing (SDB). Results: This study includes 1 898 cases in the first trimester (T1), 3 099 cases in the second trimester (T2), and 1 539 cases in the third trimester (T3). Poor sleep quality (38.6%), daytime sleepiness (mild 41.9%, moderate 17.7%, severe 2.1%), and suspicious insomnia (32.3%) are most prevalent among women in T1 (P<0.01). In comparison, short sleep time (2.7%), long sleep time (8.6%), difficulty falling asleep (12.2%), poor sleep efficiency (35.4%), very poor sleep quality (6.7%), clinical insomnia (21.8%), and high-risk SDB (6.4%) are most prevalent among women in T3 (P<0.05). During pregnancy, late gestation (OR=1.016, 95%CI: 1.006-1.025) and multiple induced/drug abortions (OR=1.329, 95%CI: 1.043-1.692) are risk factors for poor sleep quality (PSQI>5), while multiple full-term deliveries (OR=0.800, 95%CI: 0.675-0.949) is its protective factor. Advanced maternal age (OR=0.976, 95%CI: 0.956-0.997), multiple full-term deliveries (OR=0.808, 95%CI: 0.680-0.959), late gestation (OR=0.983, 95%CI: 0.974-0.992) and hypertension (OR=0.572, 95%CI: 0.401-0.814) are protective factors for daytime sleepiness (ESS>6). The high-risk pregnancy category (OR=9.312, 95%CI: 1.156-74.978) is a risk factor for insomnia (AIS≥4), while multiple full-term deliveries (OR=0.815, 95%CI: 0.691-0.961) is its protective factor. High BMI (OR=1.334, 95%CI: 1.270-1.402) and hypertension (OR=4.427, 95%CI: 2.539-7.719) are risk factors for high-risk SDB in pregnant women. Conclusions: The prevalences of various sleep disturbances are high throughout pregnancy. Noticeably, symptoms of maternal SDB develop along with pregnancy. Different types of sleep disturbances are associated with different factors. Women of high-risk pregnancy category, in late gestation, with high BMI, hypertension, a history of induced/drug abortion, or without a history of full-term delivery can be at high risk of sleep disturbances during pregnancy.

Changes of Vestibular Symptoms in Menière's Disease After Triple Semicircular Canal Occlusion: A Long-Term Follow-Up Study.

BACKGROUND: The clinical efficacy of triple semicircular canal occlusion (TSCO) and vestibular nerve resection (VNS) for patients with Ménière's disease has been unclear. OBJECTIVE: To explore changes in vestibular symptoms after TSCO and its advantages compared to the classical operation of VNS in patients with Menière's disease. METHODS: In total, 36 patients with Menière's disease performed TSCO or VNS at Shanghai Jiao Tong University Affiliated Sixth People's Hospital, China from May 2005 to July 2021, and all of them were enrolled in our study. Twelve of them underwent TSCO, 23 underwent VNS, and 1 had both treatments. We compared the demographic parameters, clinical symptoms, and selected test results between the two surgical methods. Ten patients each who underwent TSCO and VNS completed the follow-up. We collected and compared data pertaining to changes in vestibular symptoms. RESULTS: No significant difference in demographic parameters, clinical symptoms, or auditory or vestibular test results was detected between the two groups preoperatively. The TSCO group with vertigo as the main complaint experienced less residual paroxysmal dizziness after surgery than the VNS group (P = 0.020). Also, 57% of the patients in the VNS group had unsteadiness after surgery, while no such problems were reported in the TSCO group (P = 0.025). CONCLUSIONS: Our study shows that TSCO controls vertigo in most Menière's disease patients, and also has the advantage of lower rates of postoperative paroxysmal dizziness and unsteadiness than VNS. Thus, TSCO may be an effective surgery for refractory Menière's disease.

Stepwise Induction of Inner Ear Hair Cells From Mouse Embryonic Fibroblasts via Mesenchymal- to-Epithelial Transition and Formation of Otic Epithelial Cells.

Although embryonic stem cells or induced pluripotent stem cells are able to differentiate into inner ear hair cells (HCs), they have drawbacks limiting their clinical application, including a potential risk of tumourigenicity. Direct reprogramming of fibroblasts to inner ear HCs could offer an alternative solution to this problem. Here, we present a stepwise guidance protocol to induce mouse embryonic fibroblasts to differentiate into inner ear HC-like cells (HCLs) via mesenchymal-to-epithelial transition and then acquisition of otic sensory epithelial cell traits by overexpression of three key transcription factors. These induced HCLs express multiple HC-specific proteins, display protrusions reminiscent of ciliary bundle structures, respond to voltage stimulation, form functional mechanotransduction channels, and exhibit a transcriptional profile of HC signature. Together, our work provides a new method to produce functional HCLs in vitro, which may have important implications for studies of HC development, drug discovery, and cell replacement therapy for hearing loss.