OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

OBJECTIVES: To investigate the effect of in vitro cultured calculus bovis (ICCB) on cerebral ischemia/reperfusion injury (CIRI) and its mechanism. METHODS: A CIRI rat model and a cell model were induced by middle cerebral artery occlusion (MCAO) in Sprague Dawley rats and oxygen glucose deprivation/reperfusion (OGD/R) in BV2 cells, respectively. The CIRI rat model was evaluated using the modified neurological severity score (mNSS), brain water content, and cerebral infarction volume after 1.5 h of ischemia followed by 72 h of reperfusion. Histopathological changes in the cortex and hippocampal CA1 region were observed with hematoxylin and eosin staining. Microglial polarization and NOD-like receptor thermal protein domain associated protein (NLRP) 3 inflammasome expression in the cortex were examined by immunofluorescence. BV2 cell viability was measured via MTT assay after treatment with ICCB and Nigericin. The expressions of NLRP3, ASC, caspase-1 proteins and inflammatory cytokines were detected with Western blotting in OGD/R treated BV2 cells (0.5 h OGD+24 h reperfusion) and in cells pretreated with Nigericin for 24 h. RESULTS: ICCB treatment significantly improved neurological function, reduced cerebral infarct volume and brain water content, and mitigated pathological damage in the cortical and hippocampal CA1 regions of rats subjected to CIRI (all P<0.05). ICCB promoted the transition of cortical microglia from M1 to M2 phenotypes and suppressed NLRP3 activation in microglial cells (all P<0.01). ICCB significantly down-regulated the expression of NLRP3, ASC, and caspase-1 proteins, and reduced the secretion of IL-18 and IL-1β in BV2 cells of OGD/R model (all P<0.01). In addition, Nigericin significantly reversed the salvage effect of ICCB on model cells (both P<0.01) and the modulation of inflammatory cytokines (P<0.05). CONCLUSIONS ICCB exerts a protective effect against CIRI by mitigating neuroinflammation, through the reduction of M1 microglial polarization, promotion of M2 conversion, and suppression of the NLRP3/ASC/caspase-1 signaling pathway.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/prevention & control* ; Microglia/metabolism* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein ; Brain Ischemia/metabolism* ; Male

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 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.

The clinical characteristics, diagnosis and treatment process of a patient with type Ⅰ sialidosis (ST-1) caused by a homozygous mutation in the NEU1 gene who was missed diagnosis for 5 years were retrospectively analyzed to improve the understanding of the disease. A 16-year-old female patient presented with episodic limb shaking for more than 5 years and single generalised tonic-clonic seizure. Electroencephalogram (EEG) tests conducted at external hospital did not show any abnormalities, and head magnetic resonance imaging (MRI) showed general normality. Multiple antiepileptic drugs could not control the attack and the symptoms gradually worsened. After admission, the patient was found to have symptoms of easy wrestling and decreased vision, as well as signs of nystagmus and ataxia. The reexamination of the EEG showed extensive spike-and-slow complexes, and the brain MRI showed cerebellar atrophy. Furthermore, the whole-exome gene testing revealed the c.544A>G homozygous mutation in the NEU1 gene, leading to the diagnosis of ST-1. Levetiracetam tablets and clonazepam were given to improve the patient′s symptoms. During the follow-up, sleep improved compared to before, and myoclonus was significantly reduced. Therefore, patients with recurrent myoclonus, ataxia, and visual impairment without cognitive impairment should be aware of the possibility of sialidosis. Genetic testing plays an important role in the diagnosis of sialidosis.

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.

The clinical characteristics, diagnosis and treatment process of a patient with type Ⅰ sialidosis (ST-1) caused by a homozygous mutation in the NEU1 gene who was missed diagnosis for 5 years were retrospectively analyzed to improve the understanding of the disease. A 16-year-old female patient presented with episodic limb shaking for more than 5 years and single generalised tonic-clonic seizure. Electroencephalogram (EEG) tests conducted at external hospital did not show any abnormalities, and head magnetic resonance imaging (MRI) showed general normality. Multiple antiepileptic drugs could not control the attack and the symptoms gradually worsened. After admission, the patient was found to have symptoms of easy wrestling and decreased vision, as well as signs of nystagmus and ataxia. The reexamination of the EEG showed extensive spike-and-slow complexes, and the brain MRI showed cerebellar atrophy. Furthermore, the whole-exome gene testing revealed the c.544A>G homozygous mutation in the NEU1 gene, leading to the diagnosis of ST-1. Levetiracetam tablets and clonazepam were given to improve the patient′s symptoms. During the follow-up, sleep improved compared to before, and myoclonus was significantly reduced. Therefore, patients with recurrent myoclonus, ataxia, and visual impairment without cognitive impairment should be aware of the possibility of sialidosis. Genetic testing plays an important role in the diagnosis of sialidosis.

With the aging population, the burden of diseases such as atrial fibrillation and venous thrombosis is gradually increasing. Anticoagulant therapy has a positive significance in preventing ischemic stroke, pulmonary embolism, and other related conditions in these patients. However, anticoagulant therapy can have the opposite effect on diseases caused by intracranial hemorrhage, such as falls in the elderly, cerebrovascular accidents, and car accidents. It is still difficult to determine whether and when to restart anticoagulation after cerebral hemorrhage. Although most studies have shown that restarting anticoagulant therapy can reduce stroke risk without significantly increasing bleeding risk, they are mostly based on observational studies, so more high-quality research is needed to guide clinical decision-making. This article reviews the research progress on restart anticoagulation, aiming to provide some assistance for clinical applications.