Comparison of vestibular aqueduct visualization on computed tomography and magnetic resonance imaging in patients with Ménière's disease.

BACKGROUND: The vestibular aqueduct (VA) serves an essential role in homeostasis of the inner ear and pathogenesis of Ménière's disease (MD). The bony VA can be clearly depicted by high-resolution computed tomography (HRCT), whereas the optimal sequences and parameters for magnetic resonance imaging (MRI) are not yet established. We investigated VA characteristics and potential factors influencing MRI-VA visibility in unilateral MD patients. METHODS: One hundred patients with unilateral MD underwent MRI with three-dimensional sampling perfection with application optimized contrasts using different flip angle evolutions (3D-SPACE) sequence and HRCT evaluation. The imaging variables included MRI-VA and CT-VA visibility, CT-VA morphology and CT-peri-VA pneumatization. RESULTS: The most frequent type of MRI-VA and CT-VA visualization was invisible VA and continuous VA, respectively. The MRI-VA visibility was significantly lower than CT-VA visibility. MRI-VA visibility had a weak positive correlation with ipsilateral CT-VA visualization. For the affected side, the MRI-VA visualization was negatively correlated with the incidence of obliterated-shaped CT-VA and positively with that of tubular-shaped CT-VA. MRI-VA visualization was not affected by CT-peri-VA pneumatization. CONCLUSION: In patients with MD, the VA visualization on 3D-SPACE MRI is poorer than that observed on CT and may be affected by its osseous configuration. These findings may provide a basis for further characterization of VA demonstrated by MRI and its clinical significance.

Comparative Efficacy of Drug Interventions on NAFLD Over 24 Weeks: A Traditional and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD), currently referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), affects approximately 38% of the world's population, yet no pharmacological therapies have been approved for treatment. We conducted a traditional and network meta-analysis to comprehensively assess the effectiveness of drug regimens on NAFLD, and continued to use the old terminology for consistency. METHODS: Randomized, placebo-controlled trials (RCTs) investigating drug therapy in an adult population diagnosed with NAFLD with or without diabetes mellitus were included. We assessed the quality of RCTs via the Risk of Bias 2 (ROB 2) tool. When I2 < 50%, we chose a random-effects model, otherwise a fixed-effects model was selected. A random effects model was applied in the network meta-analysis. The odds ratio (OR), weighted mean difference (WMD) or standard mean difference (SMD) with 95% confidence interval (CI) were used for outcome evaluation. The primary endpoint was the resolution of nonalcoholic steatohepatitis (NASH) without the worsening of liver fibrosis. Other endpoints included histological findings and metabolic changes. The PROSPERO Registration ID was CRD42023404309. RESULTS: Thiazolidinediones (TZDs), vitamin E plus pioglitazone, glucagon-like peptide-1 (GLP-1) receptor agonists and fibroblast growth factor-21 (FGF-21) analogue had a higher surface under the cumulative ranking curve (SUCRA = 76.6, 73.0, 72.0 and 71.6) regarding NASH resolution. Improvement of liver fibrosis stage (≥ 1) was observed with obeticholic acid 25 mg/day (OR 2.01, 95% CI 1.35-2.98), lanifibranor 1200 mg/day (OR 2.39, 95% CI 1.19-4.82) and silymarin (OR 4.54, 95% CI 1.18-17.43) in traditional meta-analysis. CONCLUSIONS: The results of the comprehensive analysis suggested hypoglycemic drug therapy as an effective intervention for NAFLD, with or without diabetes mellitus. A prioritized selection of TZDs, vitamin E plus pioglitazone, GLP-1 receptor agonists and FGF-21 analogue may be considered for NASH resolution. Obeticholic acid, lanifibranor and silymarin could be considered for the improvement of liver fibrosis. Each medication was relatively safe compared with placebo.

Factors impacting the benefits and pathogenicity of Th17 cells in the tumor microenvironment.

Tumor development is closely associated with a complex tumor microenvironment, which is composed of tumor cells, blood vessels, tumor stromal cells, infiltrating immune cells, and associated effector molecules. T helper type 17 (Th17) cells, which are a subset of CD4+ T cells and are renowned for their ability to combat bacterial and fungal infections and mediate inflammatory responses, exhibit context-dependent effector functions. Within the tumor microenvironment, different molecular signals regulate the proliferation, differentiation, metabolic reprogramming, and phenotypic conversion of Th17 cells. Consequently, Th17 cells exert dual effects on tumor progression and can promote or inhibit tumor growth. This review aimed to investigate the impact of various alterations in the tumor microenvironment on the antitumor and protumor effects of Th17 cells to provide valuable clues for the exploration of additional tumor immunotherapy strategies.

Radiomics features from whole thyroid gland tissue for prediction of cervical lymph node metastasis in the patients with papillary thyroid carcinoma.

OBJECTIVE: We aimed to develop a clinical-radiomics nomogram that could predict the cervical lymph node metastasis (CLNM) of patients with papillary thyroid carcinoma (PTC) using clinical characteristics as well as radiomics features of dual energy computed tomography (DECT). METHOD: Patients from our hospital with suspected PTC who underwent DECT for preoperative assessment between January 2021 and February 2022 were retrospectively recruited. Clinical characteristics were obtained from the medical record system. Clinical characteristics and rad-scores were examined by univariate and multivariate logistic regression. All features were incorporated into the LASSO regression model, with penalty parameter tuning performed using tenfold cross-validation, to screen risk factors for CLNM. An easily accessible radiomics nomogram was constructed. Receiver Operating Characteristic (ROC) curve together with Area Under the Curve (AUC) analysis was conducted to evaluate the discrimination performance of the model. Calibration curves were employed to assess the calibration performance of the clinical-radiomics nomogram, followed by goodness-of-fit testing. Decision curve analysis (DCA) was performed to determine the clinical utility of the established models by estimating net benefits at varying threshold probabilities for training and testing groups. RESULTS: A total of 461 patients were retrospectively recruited. The rates of CLNM were 49.3% (70 /142) in the training cohort and 53.3% (32/60) in the testing cohort. Out of the 960 extracted radiomics features, 192 were significantly different in positive and negative groups (p < 0.05). On the basis of the training cohort, 12 stable features with nonzero coefficients were selected using LASSO regression. LASSO regression identified 7 risk factors for CLNM, including male gender, maximum tumor size > 10 mm, multifocality, CT-reported central CLN status, US-reported central CLN status, rad-score, and TGAb. A nomogram was developed using these factors to predict the risk of CLNM. The AUC values in each cohort were 0.850 and 0.797, respectively. The calibration curve together with the Hosmer-Lemeshow test for the nomogram indicated good agreement between predicted and pathological CLN statuses in the training and testing cohorts. Results of DCA proved that the nomogram offers a superior net benefit for predicting CLNM compared to the "treat all or none" strategy across the majority of risk thresholds. CONCLUSION: A nomogram comprising the clinical characteristics as well as radiomics features of DECT and US was constructed for the prediction of CLNM for patients with PTC, which in determining whether lateral compartment neck dissection is warranted.

Discrepancies of video head impulse test results in patients with idiopathic sudden sensorineural hearing loss with vertigo and vestibular neuritis.

Objective: Sudden sensorineural hearing loss with vertigo (SHLV) and vestibular neuritis (VN) remain frequent causes of acute vestibular syndrome (AVS). The aim of study was to compare the results of video head impulse test (vHIT) in patients with SHLV and VN. The characteristics of high-frequency vestibule-ocular reflex (VOR) and the differences of the pathophysiological mechanisms underlying these two AVS were explored. Methods: Fifty-seven SHLV patients and 31 VN patients were enrolled. vHIT was conducted at the initial presentation. The VOR gains and occurrence of corrective saccades (CSs) of anterior, horizontal, and posterior semicircular canals (SCCs) in two groups were analyzed. Pathological vHIT results refer to impaired VOR gains and presence of CSs. Results: In SHLV group, pathological vHIT results was most prevalent in the posterior SCC on the affected side (30/57, 52.63%), followed by horizontal (12/57, 21.05%) and anterior SCC (3/57, 5.26%). In VN group, pathological vHIT preferentially affected horizontal SCC (24/31, 77.42%), followed by anterior (10/31, 32.26%) and posterior SCC (9/31, 29.03%) on the affected side. As for anterior and horizontal SCC on the affected side, the incidences of pathological vHIT results in VN group were significantly higher than those in SHLV group (ß = 2.905, p < 0.01; ß = 2.183, p < 0.001). There were no significant differences in the incidence of pathological vHIT result in posterior SCC between two groups. Conclusion: Comparison of vHIT results in patients with SHLV and VN revealed discrepancies in the pattern of SCCs impairments, which may be explained by different pathophysiological mechanisms underlying these two vestibular disorders presenting as AVS.

Comparison of radiological abnormalities between the jugular bulb and the vestibular aqueduct in patients with Ménière's disease.

Objective: Anatomical variations of the inner ear may contribute to the development of Ménière's disease (MD), which is a complex inner ear disorder histopathologically characterized by idiopathic endolymphatic hydrops (ELH). Abnormalities of the vestibular aqueduct (VA) and the jugular bulb (JB) have been suggested as predisposing factors. Yet, few studies have investigated the correlation between JB abnormalities and VA variations as well as its clinical relevance in these patients. In this retrospective study, we investigated the differences in the incidence of radiological abnormalities of the VA and JB in patients with definite MD. Methods: Anatomical variations of JB and VA were evaluated based on high-resolution CT (HRCT) in a series of 103 patients with MD (93 unilateral cases and 10 bilateral cases). JB-related indices included JB anteroposterior and mediolateral diameter, JB height, JB type regarding to Manjila classification system, and incidences of JB diverticulum (JBD), JB related inner ear dehiscence (JBID), and inner ear adjacent JB (IAJB). VA-related indices included CT-VA visibility, CT-VA morphology (funnel, tubular, filiform, hollow, and obliterated-shaped type), and peri-VA pneumatization. Radiological indices were compared between MD ears and control ears. Results: Radiological JB abnormalities were comparable between MD ears and control ears. As for VA-related indices, the CT-VA visibility was lower in MD ears than in control ears (p = 0.004). The distribution of CT-VA morphology was significantly different between MD and control ears (p = 0.013), with a higher proportion of obliterated-shaped type in MD ears (22.1%) than in control ears (6.6%). Conclusion: Compared with JB abnormalities, the anatomical variations of VA are more likely to be an anatomically predisposing factor for MD.

METTL3 Reduces Oxidative Stress-induced Apoptosis in Presbycusis by Regulating the N6-methyladenosine Level of SIRT1 mRNA.

N6-methyl adenosine (m6A) modification is known to play a crucial role in various aging-related diseases. However, its involvement in presbycusis, a type of age-related hearing loss, is not yet clear. We examined the changes in oxidative stress levels in both plasma of presbycusis patients and mice. To determine the expression of m6A and its functional enzymes, we used liquid chromatography tandem-mass spectrometry (LC-MS/MS), enzyme-linked immunosorbent assay (ELISA), and RT-PCR to analyze the total RNA of presbycusis patients blood cells (n = 8). Additionally, we detected the expression of m6A functional enzymes in the cochlea of presbycusis mice using immunohistochemistry. We assessed the effects of m6A methyltransferase METTL3 on SIRT1 protein expression, reactive oxygen species (ROS) levels, and apoptosis in an oxidative stress model of organ of Corti 1 (OC1) cells. To observe the effect on SIRT1 protein expression, we interfered with the m6A recognition protein IGF2BP3 using siRNA. In both presbycusis patients and mice, there was an increased level of oxidative stress in plasma.There was a decrease in the expression of m6A, METTL3, and IGF2BP3 in presbycusis patients blood cells. The expression of METTL3 and IGF2BP3 was also reduced in the cochlea of presbycusis mice. In OC1 cells, METTL3 positively regulated SIRT1 protein levels, while reversely regulated the level of ROS and apoptosis. IGF2BP3 was found to be involved in the regulation of SIRT1 protein expression. In addition, METTL3 may play a protective role in oxidative stress-induced injury of OC1 cells, while both METTL3 and IGF2BP3 cooperatively regulate the level of m6A and the fate of SIRT1 mRNA in OC1 cells.

Comparison between audio-vestibular findings and contrast-enhanced MRI of inner ear in patients with unilateral Ménière's disease.

Objective: The diagnosis of Ménière's disease (MD), characterized by idiopathic endolymphatic hydrops (ELH), remains a clinical priority. Many ancillary methods, including the auditory and vestibular assessments, have been developed to identify ELH. The newly emerging delayed magnetic resonance imaging (MRI) of the inner ear after intratympanic gadolinium (Gd) has been used for identifying ELH in vivo. We aimed to investigate the concordance of audio-vestibular and radiological findings in patients with unilateral MD. Methods: In this retrospective study, 70 patients with unilateral definite MD underwent three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequences following intratympanic application of Gd. Audio-vestibular evaluations were performed, including pure tone audiometry, electrocochleogram (ECochG), glycerol test, caloric test, cervical and ocular vestibular evoked myogenic potentials (VEMPs), and video head impulse test (vHIT). The relationship between imaging signs of ELH and audio-vestibular results was investigated. Results: The incidence of radiological ELH was higher than that of neurotological results, including the glycerol test, caloric test, VEMPs, and vHIT. Poor or slight agreement was observed between audio-vestibular findings and radiological ELH in cochlear and/or vestibular (kappa values <0.4). However, the pure tone average (PTA) in the affected side significantly correlated with the extent of both cochlear (r = 0.26795, p = 0.0249) and vestibular (r = 0.2728, p = 0.0223) hydrops. Furthermore, the degree of vestibular hydrops was also positively correlated with course duration (r = 0.2592, p = 0.0303) and glycerol test results (r = 0.3944, p = 0.0061) in the affected side. Conclusion: In the diagnosis of MD, contrast-enhanced MRI of the inner ear is advantageous in detecting ELH over the conventional audio-vestibular evaluations, which estimates more than hydropic dilation of endolymphatic space.

Radiological presence of vascular loops in the cerebellopontine angle region in patients with unilateral Ménière's disease.

OBJECTIVE: The relationship between vascular compression of the vestibulocochlear nerve and audio-vestibular symptoms remains controversial. We aimed to examine the radiological features of vascular loops signs in cerebellopontine angle (CPA) and internal auditory canal (IAC) in patients with unilateral Ménière's disease (MD). METHODS: One hundred and thirty-seven patients with unilateral definite MD and 69 control subjects (138 ears) were enrolled. All subjects received magnetic resonance imaging of CPA-IAC. The configuration of vascular loops in CPA-IAC, based on the Kazawa classification system, from MD-affected, non-affected and control ears were compared. The associations between imaging findings and Ménière's stage, electrocochleogram (EcochG) and caloric test were analyzed. RESULTS: (1) Among the MD-affected ears, 6 cases (4.4%) were classified as Kazawa type IA, 27 cases (19.7%) as IB, 60 cases (43.8%) as IIA, and 44 cases (32.1%) as IIB. No significant interaural difference in the distribution of Kazawa's types was found ([Formula: see text] = 4.737, p = 0.578) in unilateral MD patients. (2) The distribution of Kazawa's types were not significantly different between the MD-affected ears and the control subjects ([Formula: see text] = 2.876, p = 0.411). (3) No relationship was found between Kazawa staging of the MD-affected ear and Ménière's stage (H = 2.679, p = 0.444), EcochG ([Formula: see text] = 0.827, p = 0.867) and caloric test ([Formula: see text] = 4.116, p = 0.248). CONCLUSIONS: In patients with unilateral MD, the configuration of vascular loops in CPA-IAC region, measured by Kazawa criteria, did not correlate with the laterality, clinical stage, the results of EcochG and caloric test, suggesting that vascular loops may be natural anatomical variations for patients with MD.

Downregulation of ITIH3 contributes to cisplatin-based chemotherapy resistance in ovarian carcinoma via the Bcl-2 mediated anti-apoptosis signaling pathway.

Platinum resistance of ovarian cancer is one of the primary factors of poor prognosis and inter-α-trypsin inhibitor heavy chain 3 (ITIH3) is a potential DDP resistance-associated gene. The present study assessed protein expression levels of ITIH3 in human ovarian cancer and evaluated the relationship between its expression and platinum-resistance in patients. Furthermore, the effect of ITIH3 on cisplatin (DDP)-resistant ovarian cancer cells and the underlying molecular mechanism were evaluated. Tissue microarrays of ovarian cancer samples were used to assess the association between ITIH3 protein expression levels and drug resistance and the prognosis of ovarian cancer. ITIH3 RNA interference (RNAi) ovarian cancer cell lines were constructed and expression levels of anti- and pro-apoptotic proteins of the Bcl-2 associated pathway, including Bcl-2, Bcl-xL, Mcl-1, Bak, Bim, Bax, caspase 3 and poly ADP-ribose polymerase (PARP), were assessed following DDP treatment. The Bcl-2 inhibitor ABT-737 was used to rescue DDP-resistance induced by loss of ITIH3 in vitro. Finally, a subcutaneous xenograft tumor model was used to evaluate the effect of multiple DDP injections on expression levels of apoptosis-related proteins like Bcl-2, Bcl-xL, Bak, caspase 3 and PARP. The results of tissue microarray immunohistochemistry revealed that decreased ITIH3 protein expression levels were associated with a shorter overall survival for patients with ovarian cancer. The results of Cell Counting Kit-8 assay showed that the half-maximal inhibitory concentration and resistance index of DDP in SKOV3-ITIH3 and OVCAR3-ITIH3 RNAi cells were significantly higher than in control groups. Following DDP treatment, the results of western blotting revealed that expression levels of anti-apoptotic proteins of the Bcl-2 family significantly increased in SKOV3-ITIH3 and OVCAR3-ITIH3 RNAi cells. Pro-apoptotic protein expression was not significantly changed following DDP treatment, whereas cleaved caspase 3, caspase 3 and cleaved (C-PARP) were markedly downregulated. The Bcl-2 inhibitor ABT-737 was demonstrated to reverse increased DDP resistance induced by ITIH3 expression in flow cytometric and western blotting analysis. In the subcutaneous murine xenograft model, an increased number of DDP injections yielded a decrease in phosphorylated Bcl-2, cleaved caspase 3, caspase 3 and C-PARP protein expression levels in the SKOV3-ITIH3 RNAi group tested by western blotting. To the best of our knowledge, this is the first study to demonstrate that ITIH3 could be a vital molecule involved in chemosensitivity via regulation of the Bcl-2 family-mediated apoptotic pathway. Lower protein expression levels of ITIH3 were significantly associated with platinum resistance and poor prognosis in ovarian cancer. ITIH3 may predict cisplatin-resistance in ovarian cancer.

MiR-29a-3p negatively regulates circulating Tfh memory cells in patients with Graves' disease by targeting ICOS.

MicroRNAs (miRNAs) are small endogenous noncoding RNAs that regulate genome expression posttranscriptionally and are involved in autoimmune diseases. Previous studies have indicated that follicular helper T (Tfh) cells play a critical role in the pathogenesis of Graves' disease (GD). However, the molecular mechanisms that contribute to circulating Tfh memory cell response in GD patients remain incompletely understood. This study aimed to investigate the role of miRNAs on circulating Tfh memory cells in GD patients. Herein, our data showed that the proportion of circulating Tfh memory cells, the transcript levels of IL-21, and the plasma concentrations of IL-21 were increased in the peripheral blood from GD patients. We also found that inducible co-stimulator (ICOS) expression, an important molecule expressed on Tfh cells, were significantly augmented in the peripheral blood mononuclear cells (PBMCs) from GD patients and positively correlated with the percentage of circulating Tfh memory cells and the transcript levels of IL-21 in GD. Intriguingly, miRNA sequencing screened miR-29a-3p expression was downregulated and inversely correlated with ICOS expression and the frequency of circulating Tfh memory cells in patients with GD. Luciferase assay demonstrated that ICOS was the direct target gene of miR-29a-3p, and miR-29a-3p could inhibit ICOS at both transcriptional and translational levels. Overexpression of miR-29a-3p reduced the proportion of circulating Tfh memory cells. Moreover, miR-29a-3p expression negatively correlated with serum concentrations of TSH receptor antibody (TRAb) in GD patients. Collectively, our results demonstrate that miR-29a-3p emerges as a post-transcriptional brake to limit circulating Tfh memory cell response in GD patients and may be involved in the pathogenesis of GD.

Vascular loops in cerebellopontine angle in patients with unilateral idiopathic sudden sensorineural hearing loss: Evaluations by three radiological grading systems.

Objective: We aimed to investigate the impact of the position, configuration and neurovascular contact of the anterior inferior cerebellar artery (AICA) in cerebellopontine angle (CPA) and internal auditory canal (IAC) on the clinical features of patients with unilateral idiopathic sudden sensorineural hearing loss (ISSNHL). Methods: One hundred and thirty-six patients with unilateral ISSNHL were enrolled. All patients received detailed history inquiry and standard treatments. Pure tone audiometry and magnetic resonance imaging (MRI) of CPA-IAC were performed. The MRI findings of both ears were evaluated by the Chavda, Gorrie and Kazawa systems. The association between radiological findings and clinical data were analyzed. Results: (1) No significant interaural difference in the position, configuration and neurovascular contact of AICA was observed. (2) There was no significant association between the AICA loop and concomitant vertigo or pre-treatment audiometric configuration in the affected ear. (3) Concomitant tinnitus seemed to be affected by the configuration of AICA categorized by Kazawa system, while the Chavda and Gorrie classification of AICA loop was unassociated with tinnitus. (4) Hearing outcomes were not compromised by the position or configuration of AICA based on the Chavda and Kazawa systems. Patients with Gorrie type B tended to have better hearing recovery than those with type C. Conclusions: In patients with ISSNHL, the position, configuration and neurovascular contact of AICA in the CPA-IAC were unassociated with the side of hearing loss, audiometric configurations, or concomitant vertigo. The neurovascular contact graded by Gorrie system might be associated with hearing outcomes.

Video Head Impulse Test Findings in Patients With Benign Paroxysmal Positional Vertigo Secondary to Idiopathic Sudden Sensorineural Hearing Loss.

Benign paroxysmal positional vertigo (BPPV) is amongst the most common causes of episodic vestibular syndrome. It can be classified as idiopathic and secondary types according to the causative factors, and the underlying mechanism between idiopathic (i-BPPV) and secondary BPPV (s-BPPV) may differ. Idiopathic sudden sensorineural hearing loss (ISSNHL) has been considered as a common inner ear disease that precipitates s-BPPV. Yet, few studies have addressed the functional impairment of the semicircular canal (SCC) system in patients with s-BPPV associated with ISSNHL. Our purpose was to explore the pathophysiological mechanism and investigate the clinical implications of video head impulse test (vHIT) in these patients. Here, the clinical and laboratory data of patients with BPPV secondary to ISSNHL, including the results of vHIT, were retrospectively reviewed, and compared with those of patients with i-BPPV. Pathological vHIT findings (low vestibulo-ocular reflex gain and re-fixation saccade), which mainly affected the posterior SCC, were more common in the s-BPPV group than in the i-BPPV group (41.9 and 0%, respectively). The incidence of horizontal SCC involvement was also higher in the s-BPPV group (45.16 and 16.67%, respectively). Furthermore, patients with s-BPPV showed lower vHIT gains of the posterior and horizontal SCCs in affected ears than in unaffected ears. Compared to i-BPPV, posterior SCC paresis detected by vHIT is more prevalent in BPPV secondary to ISSNHL. This dysfunction may be associated mainly with vestibular impairments caused by ISSNHL, and not with BPPV per se.

Circular RNA circNUP214 Modulates the T Helper 17 Cell Response in Patients With Rheumatoid Arthritis.

Circular RNAs (circRNAs) are important transcriptional regulators of genome expression that participate in the pathogenesis of human diseases. Mechanistically, circRNAs, as competitive endogenous RNAs (ceRNAs), can sponge microRNAs (miRNAs) with miRNA response elements. A previous study identified that hsa_circ_0089172 (circNUP214) is abnormally expressed in Hashimoto's thyroiditis. However, the role of circNUP214 in rheumatoid arthritis (RA) remains unclear. In total, 28 RA patients and 28 healthy controls were enrolled in this study. We found that circNUP214 is an abundant and stable circRNA in RA patients that can potentially differentiate RA patients from healthy subjects. Additionally, the elevated levels of IL-23R positively correlated with circNUP214 expression. The knockdown of circNUP214 resulted in the reduction of IL-23R at both transcriptional and translational levels in human CD4+ T cells. The proportion of circulating Th17 cells and the transcript levels of IL-17A were increased in RA patients and were both positively correlated with IL-23R expression. Moreover, positive correlations between the transcript levels of circNUP214 and the percentage of Th17 cells and the transcript levels of IL-17A were observed in RA patients. The downregulation of circNUP214 decreased the proportion of Th17 cells and the transcript levels of IL-17A in vitro. Furthermore, circNUP214 functioned as a ceRNA for miR-125a-3p in RA patients. Taken together, our results indicate that elevated levels of circNUP214 contribute to the Th17 cell response in RA patients.

Comprehensive Analysis of lncRNA Expression Profile and the Potential Role of ENST00000604491 in Graves' Disease.

Background: Graves' disease (GD) is one of the most common autoimmune diseases worldwide and develops in 20 to 50 cases per 100,000 persons annually. Long noncoding RNAs (lncRNAs) are widely expressed in multiple human diseases and have pivotal functions in gene regulation. This study is aimed at determining the lncRNA profile in peripheral blood mononuclear cells (PBMCs) from GD patients and investigating the role of ENST00000604491 in GD. Methods: A total of 31 GD patients and 32 normal controls were enrolled in the study. Next-generation sequencing was performed to identify the dysregulated lncRNAs in the PBMCs from the 5 GD patients and 5 normal controls, and 26 GD patients and 27 controls were used to verify the selected lncRNAs. The relative expression of verified lncRNAs, forkhead box P1 (FOXP1), and IKAROS family zinc finger 3 (IKZF3) from these samples was detected by quantitative real-time PCR. The potential biomarker value was assessed by using receiver operating characteristic (ROC) curve analysis. Results: A total of 37,683 dysregulated expressed lncRNAs were indicated, of which 5 lncRNAs were significantly upregulated and 83 lncRNAs were remarkably downregulated in the GD patients compared with healthy subjects. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that abnormally expressed lncRNAs were mainly enriched in immune system-related signalling pathways. Among the selected lncRNAs, the relative expression of ENST00000604491 was significantly downregulated and negatively correlated with the serum levels of thyroid-stimulating hormone receptor antibodies (TRAb) in GD patients. Further studies confirmed that decreased FOXP1 expression was inversely correlated with serum TRAb levels in GD patients. Moreover, there was a notably positive correlation between ENST00000604491 expression and FOXP1 transcript levels in GD. The area under the ROC curve of ENST00000604491 was up to 0.74 (95% confidence interval: 0.60-0.87, p < 0.01), and the sensitivity and specificity were 53.85% and 88.89%, respectively. Conclusion: The present study identifies ENST00000604491 as a significantly attenuated lncRNA in GD patients, which may contribute to the pathogenesis of GD by regulating FOXP1 and represent a potential biomarker for GD.

Non-contrast MRI of Inner Ear Detected Differences of Endolymphatic Drainage System Between Vestibular Migraine and Unilateral Ménière's Disease.

Objective: We aimed to evaluate the diagnostic performance of some anatomical variables with regard to endolymphatic sac (ES) and duct (ED), measured by non-contrast three-dimensional sampling perfection with application-optimized contrasts using different flip angle evolutions (3D-SPACE) magnetic resonance imaging (MRI), in differentiating vestibular migraine (VM) from unilateral Ménière's disease (MD). Methods: In this study, 81 patients with VM, 97 patients with unilateral MD, and 50 control subjects were enrolled. The MRI-visualized parameters, such as the distance between the vertical part of the posterior semicircular canal and the posterior fossa (MRI-PP distance) and visibility of vestibular aqueduct (MRI-VA), were measured bilaterally. The diagnostic value of the MRI-PP distance and MRI-VA visibility for differentiating VM from unilateral MD was examined. Results: (1) Compared with the VM patients, patients with unilateral MD exhibited shorter MRI-PP distance and poorer MRI-VA visibility. No differences in the MRI-PP distance and MRI-VA visibility were detected between patients with VM and control subjects. (2) No significant interaural difference in the MRI-PP distance and MRI-VA visibility was observed in patients with VM and those with unilateral MD, respectively. (3) Area under the curve (AUC) showed a low diagnostic value for the MRI-PP distance and MRI-VA visibility, respectively, in differentiating between the VM and unilateral MD. Conclusions: Based on non-enhanced MRI-visualized measurement, anatomical variables with regard to the endolymphatic drainage system differed significantly between the patients with VM and those with unilateral MD. Further investigations are needed to improve the diagnostic value of these indices in differentiating VM from unilateral MD.

The Roles of Exosomes in Immunoregulation and Autoimmune Thyroid Diseases.

Exosomes are extracellular microvesicles (30-150 nm) released from cells that contain proteins, lipids, RNA and DNA. They can deliver bioactive molecules and serve as carriers facilitating cell-cell communication, such as antigen presentation, inflammatory activation, autoimmune diseases (AIDs) and tumor metastasis. Recently, much attention has been attracted to the biology and functions of exosomes in immune regulation and AIDs, including autoimmune thyroid diseases (AITDs). Some studies have shown that exosomes are involved in the occurrence and development of AITDs, but they are still in the preliminary stage of exploration. This review mainly introduces the association of exosomes with immune regulation and emphasizes the potential role of exosomes in AITDs, aiming to provide new research strategies and directions for the pathogenesis and early diagnosis of AITDs.

Elevated Expression of the Long Noncoding RNA MAFTRR in Patients with Hashimoto's Thyroiditis.

BACKGROUND: Long noncoding RNAs (lncRNAs) represent an important novel class of noncoding RNA molecule greater than 200 nucleotides that play a key role in the regulation of autoimmune diseases. Previous studies have demonstrated that MAFTRR (MAF transcriptional regulator RNA) regulated Th1 cells differentiation by inhibiting the expression of MAF in activated CD4+ T cells. However, the effect of MAFTRR on the pathogenesis of Hashimoto's thyroiditis (HT) remains unclear. This research was aimed at investigating the expression of MAFTRR in Hashimoto's thyroiditis (HT) as well as the correlation between MAFTRR and Th1 cells. METHODS: Thirty-eight HT patients and thirty-eight healthy controls were enrolled in the study. The proportion of Th1 cells and CD8+IFN-γ + T cells in peripheral blood mononuclear cells (PBMCs) from these specimens was determined by flow cytometric analysis. The transcript levels of MAFTRR, MAF, and IFNG in PBMCs and thyroid glands were detected by quantitative real-time PCR. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the potential value of MAFTRR in the HT patients. RESULTS: We found that the proportion of circulating Th1 cells and the transcript levels of IFNG were increased in peripheral blood of the HT patients. The transcript levels of MAFTRR were significantly increased in the HT patients and positively correlated with the percentage of Th1 cells and serum levels of antithyroglobulin antibody and antithyroperoxidase antibody. The transcript levels of MAF, a transcription factor that inhibits Th1 cells activity and IFN-γ production, were attenuated in PBMCs from the HT patients. The transcript levels of IFNG had positive and inverse correlations with MAFTRR and MAF expression in PBMCs from the HT patients, respectively. Additionally, a significantly positive correlation between upregulated MAFTRR expression and augmented IFNG expression was revealed in thyroid tissues from the HT patients. ROC curve suggested that MAFTRR could potentially differentiate the HT patients from healthy controls. CONCLUSION: MAFTRR is significantly augmented in the HT patients and may contribute to the pathogenic role of the Th1 cells response in HT.

SLAM/SAP Decreased Follicular Regulatory T Cells in Patients with Graves' Disease.

Signaling lymphocytic activation molecule (SLAM) and SLAM-associated protein (SAP) play important role in inflammatory and autoimmune diseases. Our study is aimed at detecting the expression of SLAM and SAP in patients with Graves' disease (GD) and analyzing the effect of SLAM/SAP on circulating blood CD4+CXCR5+Foxp3+ follicular regulatory T (Tfr) cells. The level of SAP in CD4+CXCR5+ T cells and the level of SLAM on CD19+ B cells were significantly increased in the patients with GD, but no significant difference in the level of SLAM on CD4+CXCR5+ T cells was observed between the patients with GD and the healthy controls. A decrease in the percentage of Foxp3+ cells in CD4+CXCR5+ T cells was observed following anti-SLAM treatment, but the percentages of IFN-γ + cells, IL-4+ cells, and IL-17+ cells showed no obvious differences. The proportion of circulating Tfr cells was decreased in the patients with GD, and the proportion of circulating Tfr cells had a negative correlation with the level of SAP in CD4+CXCR5+ T cells and the levels of autoantibodies in the serum of the patients with GD. Our results suggested that the SLAM/SAP signaling pathway is involved in the decrease of circulating Tfr cells in Graves' disease.

Long non­coding RNA expression profiles identify lncRNA­XLOC_I2_006631 as a potential novel blood biomarker for Hashimoto's thyroiditis.

Long non­coding RNAs (lncRNAs) have been increasingly recognized as important immune checkpoints involved in the pathogenesis of autoimmune diseases. However, the exact role of lncRNAs in Hashimoto's thyroiditis (HT) has been rarely studied. The aim of the present study was to investigate the role of lncRNAs and the potential biomarkers in HT, a total of 33 patients with HT and 32 healthy volunteers were enrolled in the present study, and five patients and five healthy controls were investigated using next generation sequencing. A total of 218 dysregulated lncRNAs, including 94 upregulated and 124 downregulated lncRNAs, were identified and examined in the peripheral blood mononuclear cells (PBMCs) from patients with HT. The majority of the lncRNAs were intergenic and exonic (66.06%). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that abnormally expressed lncRNAs were enriched in the 'NF­kB expression', in the 'TGF­ß signaling pathway' and in the 'JAK­STAT signaling pathway', which are associated with the immunopathogenic mechanisms of HT. In total, three lncRNAs (LOC729737, XLOC_I2_006631 and BC041964) were validated and had a trend identical to that detected by the sequencing results. The expression of lncRNA­XLOC_I2_006631 was upregulated and was positively correlated with the serum concentrations of anti­thyroperoxidase antibody in patients with HT. Methyl­CpG­binding protein 2 (MECP2) was identified as the potential regulatory gene of lncRNA­XLOC_I2_006631 using a prediction program. The expression of MECP2 was increased and was positively correlated with the elevated expression levels of lncRNA­XLOC_I2_006631 and anti­thyroperoxidase antibody in patients with HT. Furthermore, lncRNA­XLOC_I2_006631 was able to regulate MECP2 expression in vitro. Receiver operating characteristic curve analysis suggested that lncRNA­XLOC_I2_006631 has a potential diagnostic value. Collectively, the present results indicated the important role of dysregulated lncRNAs in HT and demonstrated that lncRNA­XLOC_I2_006631 functioned as a positive regulator of MECP2 expression, suggesting a potential mechanism. Thus, lncRNA­XLOC_I2_006631 may be used as a biomarker of HT.