GPX4 inhibits apoptosis of thyroid cancer cells through regulating the FKBP8/Bcl-2 axis.

GPX4 has attracted much attention as a key molecule of cell ferroptosis, but its role in cell apoptosis is rarely reported, and its role in apoptosis of thyroid cancer (TC) cell has not been reported. The analysis of TCGA database showed that both GPX4 and FKBP8 were highly expressed in TC tumor tissues; The expression of GPX4 and FKBP8 were positively correlated. The immunohistochemical analysis further confirmed that GPX4 and FKBP8 were highly expressed in TC tumor tissues. In addition, the high expression of GPX4 and FKBP8 were both significantly correlated with the poor prognosis of TC. Silencing GPX4 significantly inhibited the proliferation, induced apoptosis of TC cells, and reduced tumor growth in mice. The co-immunoprecipitation assay revealed a physical interaction between GPX4 and FKBP8 observed in the TC cells. Knockdown of FKBP8 significantly inhibited the proliferation and induced apoptosis of TC cells. Rescue experiments suggested that knockdown of FKBP8 could reverse the strengthens of cell proliferation and apoptosis and the higher expression of FKBP8 and Bcl-2 caused by overexpression of GPX4. Our results suggest that the GPX4/FKBP8/Bcl-2 axis promotes TC development by inhibiting TC cell apoptosis, which provides potential molecular targets for TC therapeutic strategies.

Psychological Distress and Meniere's Disease: A Bidirectional Two-Sample Mendelian Randomization Study.

OBJECTIVE: This study is aim to explore the causal relationship between anxiety, depression, neuroticism, and Meniere's disease (MD). STUDY DESIGN: Two-sample bidirectional Mendelian randomization (MR) analyses. SETTING: IEU, FinnGen, CTG, and UKB databases. METHODS: The genome-wide association studies data for anxiety, depression, neuroticism, and MD involved over 357,957 participants. MR was performed to explore relationships between anxiety, depression, neuroticism, and MD. Sensitivity analyses were performed to assess the robustness of the MR results. Reverse MR was used to exclude the possibility of reverse causality. Finally, multivariate MR was performed to explore the collinear relationships between neuroticism subclusters. RESULTS: MR results showed that anxiety and depression are not causes of MD, nor does MD cause anxiety and depression. Elevated neuroticism sum score is a cause of anxiety, depression, and MD, but MD does not lead to an increase in the level of neuroticism sum score. Further analysis showed that the 5 subclusters of neuroticism often feel lonely, mood often goes up and down, often feel fed-up, feelings easily hurt, and sensitivity to environmental stress and adversity are causes of MD. Multivariate MR analysis results suggested that the 5 neuroticism subclusters have a collinear relationship. CONCLUSION: Anxiety and depression are not causative factors of MD, and vice versa. Elevated neuroticism levels serve as a shared causative factor for anxiety, depression, and MD. Identification and effective management of neuroticism is a potential target for preventing and treating MD.

Reassessment of oxidative stress in idiopathic sudden hearing loss and preliminary exploration of the effect of physiological concentration of melatonin on prognosis.

Background and purpose: The pathogenesis of idiopathic sudden sensorineural hearing loss (ISSNHL) is still unclear, and there is no targeted treatment. This research aimed to verify the role of oxidative stress in ISSNHL and explore whether melatonin has a protective effect on hearing. Materials and methods: A total of 43 patients with ISSNHL and 15 healthy controls were recruited to detect the level of melatonin, reactive oxygen species (ROS), and total antioxidant capacity (TAC) in the blood and compared before and after treatment. Multivariate logistic regression models were performed to assess the factors relevant to the occurrence and improvement of ISSNHL. Results: The patients with ISSNHL showed significantly higher ROS levels than controls (4.42 ± 4.40 vs. 2.30 ± 0.59; p = 0.031). The levels of basal melatonin were higher (1400.83 ± 784.89 vs. 1095.97 ± 689.08; p = 0.046) and ROS levels were lower (3.05 ± 1.81 vs. 5.62 ± 5.56; p = 0.042) in the effective group as compared with the ineffective group. Logistic regression analysis showed that melatonin (OR = 0.999, 95% CI 0.997-1.000, p = 0.049), ROS (OR = 1.154, 95% CI 1.025-2.236, p = 0.037), and vertigo (OR = 3.011, 95% CI 1.339-26.983, p = 0.019) were independent factors associated with hearing improvement. Besides, the level of melatonin (OR = 0.999, 95% CI 0.998-1.000, p = 0.023) and ROS (OR = 3.248, 95% CI 1.109-9.516, p = 0.032) were associated with the occurrence of ISSNHL. Conclusion: Our findings may suggest oxidative stress involvement in ISSNHL etiopathogenesis. The level of melatonin and ROS, and vertigo appear to be predictive of the effectiveness of hearing improvement following ISSNHL treatment.

Obstructive Sleep Apnea and Obesity Are Associated with Hypertension in a Particular Pattern: A Retrospective Study.

Obstructive sleep apnea (OSA) and obesity can increase the risk of hypertension, but the combined effects of these two conditions on hypertension are not yet known. We collected the basic characteristics, sleep parameters, and glucose levels of subjects with a polysomnography test and divided them into four groups, according to whether they had severe OSA and obesity or not. The main effects of severe OSA and obesity and the interactions of the two on systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels were detected using analysis of covariance. The association between obesity and severe OSA and abnormal blood pressure and their combined effects were detected with logistic regression. In total, 686 subjects were included. After adjusting for multiple confounding factors, the strong main effects of obesity and severe OSA were detected in the SBP and DBP levels, with no combined effects from the two conditions on SBP or DBP. Obesity was independently associated with the presence of hyper-systolic blood pressure (hyper-SBP) and hypertension, and severe OSA was independently associated with the presence of hyper diastolic blood pressure (hyper-DBP) and hypertension. No effects of the interaction between severe OSA and obesity on the presence of abnormal blood pressure were observed. Both severe OSA and obesity were associated with hypertension, while obesity was closely associated with hyper-SBP, and severe OSA was associated with hyper-DBP. No effects of the interaction between these two on hypertension were observed.

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.

Prognosis of Idiopathic Sudden Sensorineural Hearing Loss: The Nomogram Perspective.

OBJECTIVE: The aim of this study is to create a nomogram for accurately predicting the prognosis of idiopathic sudden sensorineural hearing loss (ISSNHL) and provide a reference for clinical treatment. METHODS: Three hundred and twenty-three patients with ISSNHL were admitted from September 2014 to November 2020. The clinical data were retrospectively reviewed. Prognostic factors for ISSNHL were assessed based on univariate and multivariate logistic regression analysis and used to create a nomogram. Nomogram performance in terms of predictive and discriminatory ability was evaluated by calculating the concordance index (C-index) and generating calibration plots. RESULTS: The overall hearing improvement rate was 41.4%, comprising complete recovery (13.3%), marked recovery (17.0%), and slight recovery (11.1%). Multivariate logistic regression analysis showed that age, symptoms of vertigo, interval between onset and treatment, low-density lipoprotein, and type of hearing loss were independent predictors of ISSNHL. A nomogram based on these 5 factors had a C index of 0.798 (95% confidence interval 0.750-0.845). CONCLUSIONS: Age, vertigo, interval between onset and treatment, low-density lipoprotein level, and type of hearing loss are closely associated with hearing recovery. The nomogram may enable prediction of the prognosis of ISSNHL and facilitate clinical decision-making.

Genetic and clinical phenotypic analysis of carney complex with external auditory canal myxoma.

Background: Mutations in PRKAR1A gene can lead to Carney complex (CNC), and most CNC patients develop cardiac and cutaneous myxomas. In particular, cardiac myxomas are a common cause of mortality in CNC patients. Cutaneous myxomas of the external ear are extremely rare, and do not have any specific clinical features Methods: In this retrospective study, we analyzed the clinical and genetic data of the proband and his family and fifty whole blood control samples selected from the molecular genetic database of our hospital. Whole exome DNA sequencing analysis was used to detect the mutation in the peripheral blood samples. Results: The results of the clinical analysis showed the presence of spotty skin pigmentation and external auditory canal myxoma in the proband as well as in his sister and mother. Whole-exome DNA sequencing showed a novel heterozygous mutation in the PRKAR1A gene i.e., c.824_825delAG (p.Gln275Leufs*2), in the proband and his sister and mother. Conclusion: In conclusion, the family members had the same autosomal dominant PRKAR1A mutation. DNA sequencing revealed a novel c.824_825delAG in exon 9 of PRKAR1A. This pathogenic mutation has not been reported previously, and may be related to the occurrence of external auditory canal myxomas and spotty pigmentation. This study broadens the genotypic spectrum of PRKAR1A mutations in CNC.

A novel mutation of X-linked recessive deafness gene POU3F4 in a boy with congenital deafness.

Purpose: To report an interstitial deletion of Xq21.1 in chromosome X in a boy with congenital deafness. Methods: The proband underwent a thorough physical examination and a detailed audiological and temporal bone computed tomography (CT) scan. Cochlear implantation was performed on the proband, and follow-up was conducted. High throughput sequencing and copy number analysis was made of peripheral blood samples from the proband, family members, and control subjects. Results: Sensorineural hearing loss was present in the boy and temporal bone CT scan showed a bilateral incomplete partition type III anomaly (IP-III). Q21.1 (79.40-83.32 Mb) of chromosome X in the proband had a copy number deletion with a fragment size of about 3.92 Mb. Categories of auditory performance scores and SIR scores of the cochlea in this child improved after surgery. Conclusion: Through the analysis of POU3F4, a novel mutation site with potentially pathogenic significance was found.Level of Evidence: 5.

Altered Amplitude of Low-Frequency Fluctuations and Degree Centrality in Patients with Acute Subjective Tinnitus: A Resting-State Functional Magnetic Resonance Imaging Study.

BACKGROUND: The difference in spontaneous brain activity between acute subjective tinnitus patients (with or without hearing loss) and control participants was explored using the amplitude of low-frequency fluctuations and degree centrality methods through resting-state functional magnetic resonance imaging. The study aimed to provide an objective basis for clinical diagnosis and pathogenesis of patients with acute subjective tinnitus. METHODS: Fourteen acute subjective tinnitus (AST) patients with hearing loss (AST-HL), 6 AST patients with no hearing loss (AST-NHL), and 14 healthy controls (HCs) with age, sex, and education status matched were recruited for this study. Resting-state functional magnetic resonance imaging (fMRI) examinations were performed in a resting state and the amplitude of low-frequency fluctuations (ALFF) and degree centrality (DC) values of each group were acquired. Statistical analysis was performed to assess the ALFF and DC values of different brain areas of the participants (AST-HL and AST-NHL were compared with HCs, but AST-HL and AST-NHL were not). RESULTS: Patients with acute subjective tinnitus and hearing loss showed a significantly increased amplitude of low-frequency fluctuation values in the left middle temporal gyrus and bilateral frontal gyrus/marginal lobe/cingulate gyrus but a decreased amplitude of low-frequency fluctuations values in the bilateral superior temporal gyrus/anterior cerebellar lobe in comparison with healthy controls. The amplitude of low-frequency fluctuation values of patients with acute subjective tinnitus and hearing loss in the right posterior lobe of the cerebellum, bilateral temporal gyrus, bilateral lenticular nucleus, bilateral frontal gyrus, right inferior occipital gyrus, were higher, but were significantly lower in the bilateral anterior lobe of cerebellum/superior temporal gyrus and left posterior cerebellar lobe as compared with those of healthy controls. Degree centrality values in the healthy controls group were increased in the right superior marginal gyrus and decreased in the right thalamus in patients with acute subjective tinnitus and hearing loss, while patients with acute subjective tinnitus with no hearing loss presented significantly higher degree centrality values in the left frontal lobe and lower degree centrality values in the left center rear return. CONCLUSIONS: Aberrant amplitude of low-frequency fluctuations and values exist in various brain regions, indicating abnormal spontaneous brain activity in both acute subjective tinnitus and hearing loss and acute subjective tinnitus no hearing loss patients. The pathogenesis of acute subjective tinnitus may be related to abnormalities in both the auditory cortex and nonauditory cortex. These findings provide more evidence to help clarify the neuronal symptoms of acute subjective tinnitus patients.

Gender Differences in Pain Subtypes among Patients with Parkinson's Disease.

BACKGROUND: To determine the influence of gender on the different pain subtypes experienced by patients with Parkinson's disease (PD). METHODS: Two hundred patients with PD were recruited for this research. Demographic features for all patients were recorded, as well as clinical data on age, disease duration, levodopa equivalent daily dose (LEDD), and scores for Unified Parkinson's Disease Rating Scale-III (UPDRS III), Hoehn-Yahr Scale (H&Y), King's Parkinson's disease Pain Scale (KPPS), Pittsburgh Sleep Quality Index (PSQI), Mini-mental State Examination (MMSE), activities of daily living scale (ADL), Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Rating Scale (HAMA) scales. RESULTS: Male and female patients showed no significant differences in terms of age, disease duration, LEDD, H&Y stage, and UPDRS III, HAMD, HAMA, PSQI and ADL scores. Women showed significantly lower MMSE than men, but their KPPS scores were higher (both p < 0.05). Female also showed significantly higher scores for chronic, fluctuation-related pain and oro-facial pain and more discoloration;edema/swelling than males (p < 0.05). CONCLUSIONS: Female gender was associated with pain in PD patients, with stronger associations for certain subtypes of PD-related pain.

The Spatiotemporal Expression of Ring1B in the Postnatal Mouse Cochlea.

BACKGROUND: Epigenetic regulation plays significant role in the development of the inner ear. It is known that Ring1B can monoubiquitinate H2AK119 to compact nucleosomes and block gene transcription. Ring1B plays crucial role in embryonic development, heterochromatin function, stem cell maintenance and so on. However, it is still unknown whether Ring1B plays a role in the development of inner ear. METHODS: Here, we used postnatal C56BL/6J mice to examine the expression of Ring1B in the cochlea using real-time quantitative polymerase chain reaction, Western blot, and immunofluorescence staining. RESULTS: Ring1B mRNA expression was observed at postnatal day 0 and postnatal day 14 cochlea. Ring1B protein was expressed in the cochlea on postnatal days 0, 14, and 30. The Ring1B was observed to be expressed in spiral ganglion cells at postnatal days 0, 14, and 30. Additionally, Ring1B was expressed in hair cells at postnatal days 0, 14, and 30. CONCLUSION: Our results provide the basic expression pattern of Ring1B and might be helpful for future investigations of the detailed role of Ring1B in the cochlea.

Evaluation of acoustic changes in and the healing outcomes of rat eardrums with pars tensa and pars flaccida perforations.

Objectives: To systematically explore the differences in acoustic changes and healing outcomes of tympanic membranes (TMs) with pars flaccida perforation (PFP) and pars tensa perforation (PTP). Methods: We created PFPs and PTPs of various sizes in Sprague-Dawley rats, and evaluated TM umbo velocity and hearing function using laser Doppler vibrometry and auditory brainstem response (ABR) measurement before and immediately after perforation. Two weeks later, hearing was reevaluated and TMs were investigated by immunohistochemical staining. Results: Small PFPs and PTPs did not significantly affect umbo velocity and hearing function. Large PFPs increased umbo velocity loss at low frequency (1.5 kHz) and elevated ABR thresholds within 1-2 kHz. Large PTP caused significant velocity loss at low frequencies from 1.5 to 3.5 kHz and threshold elevations at full frequencies (1-2 kHz). Two weeks after the perforation, the hearing function of rats with healed PFPs recovered completely. However, high-frequency hearing loss (16-32 kHz) persisted in rats with healed PTPs. Morphological staining revealed that no increase in the thickness and obvious increase in collagen I level of regenerated par flaccida; regenerated pars tensa exhibited obvious increase in thickness and increased collagen I, while the collagen II regeneration was limited with discontinuous and disordered structure in regenerated pars tensa. Conclusion: The hearing loss caused by large PFP limits at low frequencies while large PTP can lead to hearing loss at wide range frequencies. PFP and PTP have different functional outcomes after spontaneous healing, which is determined by the discrepant structure reconstruction and collagen regeneration.

Prognostic Analysis of Differentially Expressed DNA Damage Repair Genes in Bladder Cancer.

Bladder cancer (BCa) is the tenth most common tumor in humans. DNA damage repair genes (DDRGs) play important roles in many malignant tumors; thus, their functions in BCa should also be explored. We performed a comprehensive analysis of the expression profiles of DDRGs in 410 BCa tumors and 19 normal tissues from The Cancer Genome Atlas database. We identified 123 DDRGs differentially expressed between BCa tumors and normal tissues, including 95 upregulated and 28 downregulated genes. We detected 22 DDRGs associated with overall survival (OS) of patients with BCa by performing univariate Cox regression analysis. To explore the interactions between OS-associated DDRGs, we constructed a PPI network, which showed that the top six DDRGs (CDCA2, FOXM1, PBK, RRM2, ORC1, and HDAC4) with the highest scores in the PPI network might play significant roles in OS of BCa. Moreover, to investigate the latent regulatory mechanism of these OS-associated DDRGs, we analyzed the transcription factors (TFs)-DDRGs regulatory network. The core seven TFs (NCAPG, DNMT1, LMNB1, BRCA1, E2H2, CENPA, and E2F7) were shown to be critical regulators of the OS-related DDRGs. The 22 DDRGs were incorporated into a stepwise multivariable Cox analysis. Then, we built the index of risk score based on the expression of 8 DDRGs (CAD, HDAC10, JDP2, LDLR, PDGFRA, POLA2, SREBF1, and STAT1). The p-value < 0.0001 in the Kaplan-Meier survival plot and an area under the ROC curve (AUC) of 0.771 in TCGA-BLCA training dataset suggested the high specificity and sensitivity of the prognostic index. Furthermore, we validated the risk score in the internal TCGA-BLCA and an independent GSE32894 dataset, with AUC of 0.743 and 0.827, respectively. More importantly, the multivariate Cox regression and stratification analysis demonstrated that the predictor was independent of various clinical parameters, including age, tumor stage, grade, and number of positive tumor lymph nodes. In summary, a panel of 8 DNA damage repair genes associated with overall survival in bladder cancer may be a useful prognostic tool.

Single-Cell RNA-Seq Reveals Heterogeneity of Cell Communications between Schwann Cells and Fibroblasts within Vestibular Schwannoma Microenvironment.

Vestibular schwannomas (VSs), which develop from Schwann cells (SCs) of the vestibular nerve, are the most prevalent benign tumors of the cerebellopontine angle and internal auditory canal. Despite advances in treatment, the cellular components and mechanisms of VS tumor progression remain unclear. Herein, single-cell RNA-sequencing was performed on clinically surgically isolated VS samples and their cellular composition, including the heterogeneous SC subtypes, was determined. Advanced bioinformatics analysis revealed the associated biological functions, pseudotime trajectory, and transcriptional network of the SC subgroups. A tight intercellular communication between SCs and tumor-associated fibroblasts via integrin and growth factor signaling was observed and the gene expression differences in SCs and fibroblasts were shown to determine the heterogeneity of cellular communication in different individuals. These findings suggest a microenvironmental mechanism underlying the development of VS.

The Interaction of Severe Obstructive Sleep Apnea Hypopnea Syndrome and Abdominal Obesity on Cognitive Function.

BACKGROUND: Both obstructive sleep apnea-hypopnea syndrome (OSAHS) and obesity are related to cognitive deficits, but the interaction effects of OSAHS and abdominal obesity on cognitive function are unclear. Thus, we performed this study to investigate this issue. METHODS: We recruited subjects who received polysomnography test, anthropometric measurements and cognitive function assessment and/or blood protein test. Correlations between apnea-hypopnea index (AHI) and cognitive function were assessed. Analysis of covariance was used to compare the differences in cognitive function between groups and detect the interactions of OSAHS and obesity on cognitive function. Multiple linear regression models were used to determine the associations between OSAHS and cognitive function. RESULTS: In total, 196 subjects with Montreal Cognitive Assessment (MoCA), 161 subjects with Symbol Digit Modalities Test (SDMT) and Trail making test, and 44 subjects with blood protein test were enrolled. Significant negative correlations between AHI and visuo-spatial and executive, language, delayed recall and total score of MoCA were observed. After adjusting for multiple confounding factors, subjects with severe OSAHS had significant lower delayed recall score and total score of MoCA, SDMT index, and Aß40 protein level than those with non-severe OSAHS group. Severe OSAHS was independently negatively associated with delayed recall score and total score of MoCA, SDMT index, and Aß40 protein level. An interactive effect of severe OSAHS and abdominal obesity on language score of MoCA was found. CONCLUSIONS: Severe OSAHS increased the risk of cognitive deficits. Interaction effect of severe OSAHS and abdominal obesity on language was seen.

Relationships Between Cardinal Features of Obstructive Sleep Apnea and Blood Pressure: A Retrospective Study.

Background: Obstructive sleep apnea (OSA) is associated with hypertension; however, the associations between cardinal features of OSA, such as intermittent hypoxia (IH) and sleep fragmentation (SF), and blood pressure remain unclear. We performed this study to address this issue. Method: We investigated 335 subjects with the polysomnography (PSG) tests. Data, including basic characteristics, PSG parameters, and blood pressure, were collected. We calculated p-values for linear trends of blood pressure across oxygen-desaturation index (ODI)/microarousal index (MAI) quartiles. Logistic regressions were used to determine the risk factors for abnormal blood pressure and to detect the multiplicative interaction between ODI and MAI with blood pressure. Results: After adjusting for multiple variables, compared with subjects with lower ODI quartiles, those with higher ODI quartiles had significant higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) (p for trend = 0.010 and 0.018, respectively). And compared with subjects with lower ODI quartiles, those with higher ODI quartiles were also more likely to have abnormal DBP and hypertension after adjusting for multiple variables. Similarly, compared with subjects with lower MAI quartiles, those with higher MAI quartiles had significant higher SBP and DBP, and were more likely to have abnormal DBP and hypertension. No significant multiplicative interactions between ODI and MAI with blood pressure were detected. Conclusion: Subjects with more severe IH/SF had significant higher blood pressure and were more likely to have abnormal DBP and hypertension than those with less severe IH/SF. No interaction between IH and SF on the relationship with blood pressure was shown.

Novel Immune-Related Ferroptosis Signature in Esophageal Cancer: An Informatics Exploration of Biological Processes Related to the TMEM161B-AS1/hsa-miR-27a-3p/GCH1 Regulatory Network.

Background: Considering the role of immunity and ferroptosis in the invasion, proliferation and treatment of cancer, it is of interest to construct a model of prognostic-related differential expressed immune-related ferroptosis genes (PR-DE-IRFeGs), and explore the ferroptosis-related biological processes in esophageal cancer (ESCA). Methods: Four ESCA datasets were used to identify three PR-DE-IRFeGs for constructing the prognostic model. Validation of our model was based on analyses of internal and external data sets, and comparisons with past models. With the biological-based enrichment analysis as a guide, exploration for ESCA-related biological processes was undertaken with respect to the immune microenvironment, mutations, competing endogenous RNAs (ceRNA), and copy number variation (CNV). The model's clinical applicability was measured by nomogram and correlation analysis between risk score and gene expression, and also immune-based and chemotherapeutic sensitivity. Results: Three PR-DE-IRFeGs (DDIT3, SLC2A3, and GCH1), risk factors for prognosis of ESCA patients, were the basis for constructing the prognostic model. Validation of our model shows a meaningful capability for prognosis prediction. Furthermore, many biological functions and pathways related to immunity and ferroptosis were enriched in the high-risk group, and the role of the TMEM161B-AS1/hsa-miR-27a-3p/GCH1 network in ESCA is supported. Also, the KMT2D mutation is associated with our risk score and SLC2A3 expression. Overall, the prognostic model was associated with treatment sensitivity and levels of gene expression. Conclusion: A novel, prognostic model was shown to have high predictive value. Biological processes related to immune functions, KMT2D mutation, CNV and the TMEM161B-AS1/hsa-miR-27a-3p/GCH1 network were involved in ESCA progression.

Establishment of an induced pluripotent stem cell line (JTUi003-A) from a patient with otosclerosis.

Otosclerosis is characterized by abnormal bone remodeling in the osseous labyrinth and progressive hearing loss. Although the etiology of otosclerosis is not fully understood, both environmental and genetic factors play important roles in its pathogenesis. Here, we generated an induced pluripotent stem cell line using episomal plasmid vectors from the peripheral blood mononuclear cells of a 48-year-old male with otosclerosis. The morphology and karyotype of the cells were normal. The expression of pluripotency markers was verified by mRNA and protein levels; the pluripotency state of the cell line was verified by successful differentiation into all three germ layers.

Interaction effects between characteristics of obstructive sleep apnea and obesity on dyslipidemia.

OBJECTIVES: Obstructive sleep apnea (OSA) and obesity often coexist, and both can increase the risk of dyslipidemia. However, the interaction effects between the characteristics of OSA and obesity on dyslipidemia are not yet known. This study was performed to investigate this issue. METHODS: Basic characteristics, polysomnography data, and biochemical markers of patients with suspected OSA seen at the First Affiliated Hospital of Nanchang University were collected. Serum lipid levels were compared after adjusting for multiple confounders. We used binary logistic regression models to assess the interaction effects of the oxygen desaturation index (ODI) and obesity, and the apnea-hypopnea index (AHI) and obesity, on dyslipidemia. RESULTS: A total of 343 patients were included in the study. After adjusting for multiple confounders, there were no differences in serum lipid levels between non-obese or obese patients with an AHI ≤ 30 and AHI > 30, and no interaction effect between the AHI and obesity on dyslipidemia. Obese patients, but not non-obese ones, with an ODI > 37.5 had significantly higher total cholesterol (TC) levels, and higher TC/high-density lipoprotein cholesterol (HDL-C) ratios, than patients with an ODI ≤ 37.5. In addition, a significant positive multiplicative interaction effect between obesity and the ODI was found on hyper-TC (odds ratio [OR] = 3.459; 95% confidence interval [CI] = 1.104, 10.838; p = 0.03). CONCLUSION: A positive interaction effect was detected between obesity and intermittent hypoxia on dyslipidemia. Therefore, further attention should be paid to dyslipidemia in obese patients with intermittent hypoxia.

Trehalose protects against cisplatin-induced cochlear hair cell damage by activating TFEB-mediated autophagy.

Cisplatin is a widely used chemotherapeutic agent for the treatment of various tumors, but its side effects limit its application. Ototoxicity, a major adverse effect of cisplatin, causes irreversible sensorineural hearing loss. Unfortunately, there are no effective approaches to protect against this damage. Autophagy has been shown to exert beneficial effects in various diseases models. However, the role of autophagy in cisplatin-induced ototoxicity has been not well elucidated. In this study, we aimed to investigate whether the novel autophagy activator trehalose could prevent cisplatin-induced damage in the auditory cell line HEI-OC1 and mouse cochlear explants and to further explore its mechanisms. Our data demonstrated that trehalose alleviated cisplatin-induced hair cell (HC) damage by inhibiting apoptosis, attenuating oxidative stress and rescuing mitochondrial dysfunction. Additionally, trehalose significantly enhanced autophagy levels in HCs, and inhibiting autophagy with 3-methyladenine (3-MA) abolished these protective effects. Mechanistically, we showed that the effect of trehalose was attributed to increased nuclear translocation of transcription factor EB (TFEB), and this effect could be mimicked by TFEB overexpression and inhibited by TFEB gene silencing or treatment with cyclosporin A (CsA), a calcineurin inhibitor. Taken together, our findings suggest that trehalose and autophagy play a role in protecting against cisplatin-induced ototoxicity and that pharmacological enhancement of TFEB-mediated autophagy is a potential treatment for cisplatin-induced damage in cochlear HCs and HEI-OC1 cells.