Objective:To investigate the sleep characteristics and clinical features of patients with vestibular migraine（VM）, and to explore the influencing factors of sleep disorder in VM patients. Methods:A cross-sectional study method was adopted to collect VM patients from Otolaryngology department and neurology department of our hospital from June 2022 to June 2024（divided into sleep disorder group and non-sleep disorder group according to whether there is sleep disorder） as the experimental group, and recruit non-VM volunteers with clinical characteristics matching with the experimental group during the same period as the control group. The clinical data of the subjects were collected, and the sleep quality of the subjects was assessed using the Pittsburgh Sleep Quality Index（PSQI）. The influencing factors of sleep disorders in VM patients were analyzed by multivariate Logistic regression, and the correlation between sleep disorders and clinical features such as headache, vertigo and hearing in VM patients was analyzed by Spearman correlation coefficient. Results:A total of 530 individuals with VM were analyzed, including 332 with sleep disturbances（62.64%）, 198 without sleep issues（37.36%）, and 50 in the control group. The overall PSQI score and all its components were significantly higher in the VM group compared with the control group（P<0.05）. A positive correlation was observed between PSQI and VAS, DHI-T, DHI-E, DHI-F and DHI-P（r=0.797, P<0.05; r=0.834, P<0.05; r=0.794, P<0.05; r=0.771, P<0.05; r=0.877, P<0.05）, PSQI had no correlation with pure tone hearing（r=0.324, P=0.167）. Multivariate logistic regression analysis showed that female, age ≥60 years, living alone, duration of disease ≥3 months, motion sickness history, and HADS-A were independent influencing factors for comorbidification of sleep disorder in VM patients（P<0.05）. Conclusion:The prevalence of sleep disorders in patients with vestibular migraine（VM） was significantly higher compared to the control group. Moreover, the severity of sleep disorders was positively correlated with the intensity of headache and vertigo in VM patients. It is recommended that female VM patients aged 60 years or older, living alone, with a disease duration of three months or longer, a history of motion sickness, and anxiety symptoms undergo sleep assessments to determine the presence of sleep disorders. This approach provides a theoretical foundation for precise treatment and prevention strategies for VM.
Humans ; Migraine Disorders/complications* ; Sleep Wake Disorders/complications* ; Cross-Sectional Studies ; Vertigo ; Female ; Male ; Vestibular Diseases/complications* ; Sleep Quality ; Adult ; Middle Aged ; Logistic Models

Objective To explore the role of ocular vestibular evoked myogenic potential (oVEMP) and unilateral centrifugation subjective visual vertical (UC-SVV) tests in evaluating the utricular function of patients with Meniere’s disease (MD) at different clinical stages. Methods A total of 97 unilateral MD patients at Shandong Provincial ENT Hospital from July 2019 to September 2021 were selected. All patients underwent oVEMP, UC-SVV, and pure tone audiometry tests. MD patients were classified into clinical stages 1, 2, 3, and 4, with stages 1 and 2 defined as early stage and stages 3 and 4 as late stage. The results of utricular function tests (abnormal rates of oVEMP, UC-SVV, and oVEMP＋UC-SVV) were compared among patients at different stages. Spearman correlation analysis was used to evaluate the correlation between utricular function and clinical staging. Results Among the 97 MD patients, the abnormal rate of oVEMP was 66.0% (64/97), and the abnormal rate of UC-SVV was 55.7% (54/97). The abnormal rates of oVEMP and oVEMP＋UC-SVV in early-stage patients were significantly lower than those in late-stage patients (P＜0.05), while the difference in UC-SVV abnormal rates between the two groups was not statistically significant. Intra-group comparisons showed that the abnormal rate of oVEMP＋UC-SVV in stage 1 patients was significantly lower than that in stage 2 patients (P＜0.05), without significant difference in the other indices. There were no significant differences among the three indices in stages 3 and 4 patients. Spearman correlation test results indicated that the abnormal rate of oVEMP (r＝0.336, P＝0.001) and the abnormal rate of oVEMP＋UC-SVV (r＝0.301, P＝0.003) were weakly positively correlated with clinical staging, while there was no correlation between the abnormal rate of UC-SVV and clinical staging (r＝0.022, P＝0.832). Conclusions Both oVEMP and UC-SVV tests can assess utricular function in MD patients at different clinical stages. Their combination is helpful of early-stage (stages 1 and 2) MD diagnosis.

Objective:To explore the clinical phenotype and genetic characteristics of a pediatric child with RELA-associated autoinflammatory disease (RAID) caused by a RELA gene variant, and to review the reported cases in the literature. Methods:A pediatric child with RAID who presented with recurrent fever, vomiting, and oral ulcers for over 5 years was selected as the study subject. The child visited the Women and Children′s Hospital of Ningbo University in August 2023. Clinical data were collected, and peripheral blood samples were obtained from the child and his family members for whole exome sequencing (WES) and Sanger sequencing to identify and validate candidate variants. The pathogenicity of the variants was analyzed accordingly. Using the keywords " RELA" " NF-κB" " autoinflammatory disease" " tofacitinib" " sulfasalazine" a literature search was conducted in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed from January 1, 2000 to December 13, 2023. This study was approved by the Medical Ethics Committee of the Women and Children′s Hospital of Ningbo University (Ethics No. EC2020-048).Results:① The child primarily manifested with recurrent fever, vomiting, and oral ulcers. ② WES identified a heterozygous nonsense variant c. 985C>T (p.Arg329Ter) in the RELA gene, which was inherited from the mother. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants and the Clinical Genome Resource (ClinGen) recommendations for PVS1, this variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP4). ③ Despite treatment with adalimumab and tocilizumab, the child′s symptoms persisted. Switching to tofacitinib improved oral ulcers, but fever and vomiting continued. The addition of thalidomide significantly alleviated fever and vomiting, and the patient′s growth and development remained normal. ④ A literature review identified 14 unrelated RAID families, including a total of 35 cases (including the present child). The main clinical features were recurrent oral ulcers, genital ulcers, skin problems, fever, diarrhea, abdominal pain, and vomiting. Conclusion:The nonsense variant c. 985C>T (p.Arg329Ter) in the RELA gene is likely the genetic cause of the child′s recurrent fever, vomiting, and oral ulcers. WES is valuable for timely diagnosis of RAID and provides a basis for clinical treatment strategies.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a pediatric child with RELA-associated autoinflammatory disease (RAID) caused by a RELA gene variant, and to review the reported cases in the literature. METHODS: A pediatric child with RAID who presented with recurrent fever, vomiting, and oral ulcers for over 5 years was selected as the study subject. The child visited the Women and Children's Hospital of Ningbo University in August 2023. Clinical data were collected, and peripheral blood samples were obtained from the child and his family members for whole-exome sequencing (WES) and Sanger sequencing to identify and validate candidate variants. The pathogenicity of the variants was analyzed accordingly. Using the keywords "RELA" "NF-κB" "autoinflammatory disease" "tofacitinib" "sulfasalazine" a literature search was conducted in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed from January 1, 2000 to December 13, 2023. This study was approved by the Medical Ethics Committee of the Women and Children's Hospital of Ningbo University (Ethics No. EC2020-048). RESULTS: The child primarily manifested with recurrent fever, vomiting, and oral ulcers. WES identified a heterozygous nonsense variant c.985C>T (p.Arg329Ter) in the RELA gene, which was inherited from the mother. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants and the Clinical Genome Resource (ClinGen) recommendations for PVS1, this variant was classified as pathogenic (PVS1+PM2_Supporting+PP4). Despite treatment with adalimumab and tocilizumab, the child's symptoms persisted. Switching to tofacitinib improved oral ulcers, but fever and vomiting continued. The addition of thalidomide significantly alleviated fever and vomiting, and the patient's growth and development remained normal. A literature review identified 14 unrelated RAID families, including a total of 35 cases (including the present child). The main clinical features were recurrent oral ulcers, genital ulcers, skin problems, fever, diarrhea, abdominal pain, and vomiting. CONCLUSION The nonsense variant c.985C>T (p.Arg329Ter) in the RELA gene is likely the genetic cause of the child's recurrent fever, vomiting, and oral ulcers. WES is valuable for timely diagnosis of RAID and provides a basis for clinical treatment strategies.
Humans ; Male ; Transcription Factor RelA/genetics* ; Female ; Hereditary Autoinflammatory Diseases/genetics* ; Child ; Pedigree ; Exome Sequencing

Objective To identify the hemodynamic characteristics of frontal polar cortex(FPC)in patients with chronic subjective tinnitus,and to study the short-term efficacy of multielement integration sound(MIS)treatment,and its effects on FPC oxyhemoglobin(HbO).Methods Fifty patients with chronic subjective tinnitus(tinnitus group)and 50 subjects without tinnitus matching their age,sex and education level(control group)were collected from June 2023 to Oc-tober 2023.The tinnitus group and control group received MIS treatment for 15 minutes,respectively.Tinnitus handicap inventory(THI)and visual analogue scale(VAS)scores were collected before and after treatment in tinnitus group.Func-tional near infrared spectroscopy(fNIRS)was used to measure the 8-minute average HbO concentration in the frontal cortex of both groups before and after treatment.The changes of HbO concentration before and after treatment were compared be-tween the two groups.The correlation between clinical features and HbO was analyzed.Results The VAS score of the tin-nitus group decreased after short-term MIS treatment.The HbO concentration of FPC in tinnitus group was higher than that in control group before treatment.The HbO concentration of FPC in tinnitus group was decreased by MIS short-term treatment.The difference of HbO concentration before and after treatment(ΔHbO)was positively correlated with the difference of VAS score before and after treatment(ΔVAS)in the tinnitus group.Conclusion The hemodynamics of the frontal polar cortex in chronic subjective tinnitus patients is different from that of in non-tinnitus control group.MIS can change the hemodynamics of the frontal polar cortex in chronic subjective tinnitus patients.The frontal polar cortex may be the site of MIS.

Objective:To study the feasibility of detecting vertical semicircular canal function and to analyze the three-dimensional(3D)characteristics and normal reference value in healthy young people.Methods:This was a cross-sectional study conducted from January to June 2024. A three-axis rotating chair was used to perform vertical sinusoidal rotation on 52 healthy young adults (26 males and 26 females, aged 18-40 years) in the left anterior-right posterior (LARP) and right anterior-left posterior (RALP) semicircular canal planes. For each plane, nystagmus was induced with six combinations of different angles and velocity front and back rotation angles of ±30°,±60°,±90°, and velocities of 40°/s and 80°/s, the slow phase velocity (SPV) and their symmetry of 3D nystagmus were analyzed. SPSS 20.0 was used to compare the statistical differences in these two parameters across different stimulation protocols.Results:There were no spontaneous nystagmus in the 52 subjects, and all tests were finished. Except the combinations of (±30°-40°/s), three components of nystagmus were induced stably in the rest of the stimulations. The SPVs of vertical components were no statistically insignificant ( P>0.05), and some horizontal or torsion components were statistically significant ( P<0.05). The 95% reference range of the symmetry was≤25% in the vertical and≤30% in the torsional component of the nystagmus except for (±30°-80°/s), the symmetry was 32.2% and 49.2% respectively. The trend changes of the three components were consistent, among which the vertical and torsional components induced by (±60°-80°/s) and (±90°-80°/s) were the best, the SPV value of the vertical components was higher in the latter group than the former apart from the front RALP, while no significant difference was found in the torsional components ( P>0.05). Conclusion:The (±90°-80°/s) combination is the optimal method to detect the function of vertical semicircular canal in 3D chair test. When observing torsional component, the combining scheme of (±60°-80°/s) and (±90°-80°/s) is better. Considering tolerance, the (±60°-80°/s) combination is recommended.

Objective To investigate the influencing factors of auditory hypersensitivity in normal hearing population and build a risk nomogram model according to the results,so as to provide scientific basis for early identi-fication of high risk population and formulation of prevention strategy.Methods A total of 410 volunteers with nor-mal pure tone hearing were recruited from March to July 2024.The hyperacusis questionnaire(HQ)was used to as-sess the audiroty hypersensitivity of the subjects.The participants were divided into a training set(n=287)and a validation set(n=123)according to a ratio of 7∶3.Binary Logistic model was used to construct risk model and no-mogram.Receiver operating characteristic(ROC)curve,Hosmer-Lemeshow calibration curve,clinical decision curve(DCA)and clinical impact curve were used to verify the differentiation,accuracy and clinical applicability of the model,respectively.Results Among 410 participants,54(13.17％)had hyperacusis including 38(13.24％)in the training set amd 16(13.01)in the validation set.LASSO regression and Logistic regression analysis showed that tinnitus(OR=3.784,95％CI=1.627-8.804),HADS-A(OR=3.860,95％CI=1.503-9.913),HADS-D(OR=3.118,95％CI=1.249-7.785),migraine(OR=2.821,95％CI=1.147-6.937)and noise exposure histo-ry(OR=3.799,95％CI=1.715-8.416)were the influential factors for hyperacusis in participants with normal hearing.Conclusion The incidence of hyperacusis in normal hearing population is 13.17％.Tinnitus,HADS-A,HADS-D,migraine and noise exposure history are related to the occurrence of hyperacusis in normal hearing popula-tion.The risk prediction nomogram model based on the above factors has good differentiation and calibration degree.It can effectively predict the risk of hyperacusis in normal hearing people,and has certain clinical practicability.

Objective To identify the hemodynamic characteristics of frontal polar cortex(FPC)in patients with chronic subjective tinnitus,and to study the short-term efficacy of multielement integration sound(MIS)treatment,and its effects on FPC oxyhemoglobin(HbO).Methods Fifty patients with chronic subjective tinnitus(tinnitus group)and 50 subjects without tinnitus matching their age,sex and education level(control group)were collected from June 2023 to Oc-tober 2023.The tinnitus group and control group received MIS treatment for 15 minutes,respectively.Tinnitus handicap inventory(THI)and visual analogue scale(VAS)scores were collected before and after treatment in tinnitus group.Func-tional near infrared spectroscopy(fNIRS)was used to measure the 8-minute average HbO concentration in the frontal cortex of both groups before and after treatment.The changes of HbO concentration before and after treatment were compared be-tween the two groups.The correlation between clinical features and HbO was analyzed.Results The VAS score of the tin-nitus group decreased after short-term MIS treatment.The HbO concentration of FPC in tinnitus group was higher than that in control group before treatment.The HbO concentration of FPC in tinnitus group was decreased by MIS short-term treatment.The difference of HbO concentration before and after treatment(ΔHbO)was positively correlated with the difference of VAS score before and after treatment(ΔVAS)in the tinnitus group.Conclusion The hemodynamics of the frontal polar cortex in chronic subjective tinnitus patients is different from that of in non-tinnitus control group.MIS can change the hemodynamics of the frontal polar cortex in chronic subjective tinnitus patients.The frontal polar cortex may be the site of MIS.

Objective To investigate the influencing factors of auditory hypersensitivity in normal hearing population and build a risk nomogram model according to the results,so as to provide scientific basis for early identi-fication of high risk population and formulation of prevention strategy.Methods A total of 410 volunteers with nor-mal pure tone hearing were recruited from March to July 2024.The hyperacusis questionnaire(HQ)was used to as-sess the audiroty hypersensitivity of the subjects.The participants were divided into a training set(n=287)and a validation set(n=123)according to a ratio of 7∶3.Binary Logistic model was used to construct risk model and no-mogram.Receiver operating characteristic(ROC)curve,Hosmer-Lemeshow calibration curve,clinical decision curve(DCA)and clinical impact curve were used to verify the differentiation,accuracy and clinical applicability of the model,respectively.Results Among 410 participants,54(13.17％)had hyperacusis including 38(13.24％)in the training set amd 16(13.01)in the validation set.LASSO regression and Logistic regression analysis showed that tinnitus(OR=3.784,95％CI=1.627-8.804),HADS-A(OR=3.860,95％CI=1.503-9.913),HADS-D(OR=3.118,95％CI=1.249-7.785),migraine(OR=2.821,95％CI=1.147-6.937)and noise exposure histo-ry(OR=3.799,95％CI=1.715-8.416)were the influential factors for hyperacusis in participants with normal hearing.Conclusion The incidence of hyperacusis in normal hearing population is 13.17％.Tinnitus,HADS-A,HADS-D,migraine and noise exposure history are related to the occurrence of hyperacusis in normal hearing popula-tion.The risk prediction nomogram model based on the above factors has good differentiation and calibration degree.It can effectively predict the risk of hyperacusis in normal hearing people,and has certain clinical practicability.

Objective:To explore the clinical phenotype and genetic characteristics of a pediatric child with RELA-associated autoinflammatory disease (RAID) caused by a RELA gene variant, and to review the reported cases in the literature. Methods:A pediatric child with RAID who presented with recurrent fever, vomiting, and oral ulcers for over 5 years was selected as the study subject. The child visited the Women and Children′s Hospital of Ningbo University in August 2023. Clinical data were collected, and peripheral blood samples were obtained from the child and his family members for whole exome sequencing (WES) and Sanger sequencing to identify and validate candidate variants. The pathogenicity of the variants was analyzed accordingly. Using the keywords " RELA" " NF-κB" " autoinflammatory disease" " tofacitinib" " sulfasalazine" a literature search was conducted in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed from January 1, 2000 to December 13, 2023. This study was approved by the Medical Ethics Committee of the Women and Children′s Hospital of Ningbo University (Ethics No. EC2020-048).Results:① The child primarily manifested with recurrent fever, vomiting, and oral ulcers. ② WES identified a heterozygous nonsense variant c. 985C>T (p.Arg329Ter) in the RELA gene, which was inherited from the mother. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants and the Clinical Genome Resource (ClinGen) recommendations for PVS1, this variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP4). ③ Despite treatment with adalimumab and tocilizumab, the child′s symptoms persisted. Switching to tofacitinib improved oral ulcers, but fever and vomiting continued. The addition of thalidomide significantly alleviated fever and vomiting, and the patient′s growth and development remained normal. ④ A literature review identified 14 unrelated RAID families, including a total of 35 cases (including the present child). The main clinical features were recurrent oral ulcers, genital ulcers, skin problems, fever, diarrhea, abdominal pain, and vomiting. Conclusion:The nonsense variant c. 985C>T (p.Arg329Ter) in the RELA gene is likely the genetic cause of the child′s recurrent fever, vomiting, and oral ulcers. WES is valuable for timely diagnosis of RAID and provides a basis for clinical treatment strategies.