This study investigates the neuroprotective potential of extracellular vesicles (EVs) delivering quercetin-3-O-β-d-glucuronic acid (QG-EVs) in cerebral ischemia-reperfusion injury (CIRI). Targeted brain delivery of QG-EVs was confirmed, with neuron cells identified as pivotal in modulating CIRI through single-cell RNA sequencing (scRNA-seq). Activating transcription factor 4 (Atf4) was highlighted as a critical regulatory factor, and in vitro studies revealed that silencing Atf4 diminished the neuroprotective effects of QG-EVs, increasing oxidative stress levels and neuronal apoptosis. In a CIRI mouse model, the knockdown of Atf4 attenuated the protective outcomes provided by QG-EVs, further affirming the role of Atf4 in mediating neuroprotection. Behavioral assessments and protein analysis showed that QG-EVs significantly reduced neuronal damage and pro-apoptotic markers, while improving neurological function via Atf4 upregulation. The outcomes hint at the potential of QG-EVs as a beneficial therapeutic modality to mitigate neuronal damage in CIRI by enhancing Atf4 expression, highlighting its potential for improving ischemic stroke outcomes.

Background: and Purpose Essential tremor with a midline distribution (Mid-ET) may represent a distinct subtype of essential tremor (ET) that primarily affects midline structures, often indicating advanced disease stage and increased severity. Recent studies have highlighted the complexity of Mid-ET, but research on neurological soft signs (NSS) in Mid-ET remains insufficient. Methods: The patients with ET included in this cross-sectional study were divided into two subgroups based on whether or not the ET had a midline distribution: Mid-ET and No-MidET. Comparative analyses were performed to assess clinical features and NSS prevalence in these subgroups. Results: Among 1,160 patients, 567 (48.9%) were Mid-ET and 593 (51.1%) were No-Mid-ET.The prevalence rates of head, face (including the jaw), and voice tremors were 31.9%, 23.0%, and 25.8%, respectively. In Mid-ET, tremor often affects multiple midline structures simultaneously. In the entire cohort, 24.7%, 16.6%, and 7.6% of patients exhibited tremors in one, two, and three midline structures, respectively. The prevalence of common NSS, including mild cognitive impairment, impaired tandem gait, and questionable dystonic posturing, was significantly higher in the Mid-ET than the No-Mid-ET subgroup (all p<0.001). Furthermore, we found that female sex (p<0.001), olfactory dysfunction (p=0.003), and questionable dystonic posturing (p=0.004) were associated with Mid-ET. Conclusions Mid-ET and No-Mid-ET presented significant clinical differences. The presence of questionable dystonic posturing may contribute to the distinct characteristics of Mid-ET, suggesting the presence of pathophysiological differences between the subgroups. Further investigations are warranted to determine the potential pathophysiological link between NSS and Mid-ET.

Background: and Purpose Essential tremor with a midline distribution (Mid-ET) may represent a distinct subtype of essential tremor (ET) that primarily affects midline structures, often indicating advanced disease stage and increased severity. Recent studies have highlighted the complexity of Mid-ET, but research on neurological soft signs (NSS) in Mid-ET remains insufficient. Methods: The patients with ET included in this cross-sectional study were divided into two subgroups based on whether or not the ET had a midline distribution: Mid-ET and No-MidET. Comparative analyses were performed to assess clinical features and NSS prevalence in these subgroups. Results: Among 1,160 patients, 567 (48.9%) were Mid-ET and 593 (51.1%) were No-Mid-ET.The prevalence rates of head, face (including the jaw), and voice tremors were 31.9%, 23.0%, and 25.8%, respectively. In Mid-ET, tremor often affects multiple midline structures simultaneously. In the entire cohort, 24.7%, 16.6%, and 7.6% of patients exhibited tremors in one, two, and three midline structures, respectively. The prevalence of common NSS, including mild cognitive impairment, impaired tandem gait, and questionable dystonic posturing, was significantly higher in the Mid-ET than the No-Mid-ET subgroup (all p<0.001). Furthermore, we found that female sex (p<0.001), olfactory dysfunction (p=0.003), and questionable dystonic posturing (p=0.004) were associated with Mid-ET. Conclusions Mid-ET and No-Mid-ET presented significant clinical differences. The presence of questionable dystonic posturing may contribute to the distinct characteristics of Mid-ET, suggesting the presence of pathophysiological differences between the subgroups. Further investigations are warranted to determine the potential pathophysiological link between NSS and Mid-ET.

Objective To explore the association between the relative expression level of SNORD55 in peripheral blood and the outcomes of all-cause mortality and stroke in patients with atrial fibrillation(AF),and to evaluate the predictive value of SNORD55 for prognosis.Methods A total of 133 patients with non-valvular AF admitted in Department of Cardiology of the First Affiliated Hospital of Army Medical University from January 2014 to December 2017 were enrolled in this study.Their baseline information was collected,and the relative expression level of plasma SNORD55 was detected.Cox proportional hazards model was used to explore the association between the relative expression level of SNORD55 in peripheral blood and all-cause mortality as well as stroke in the patients.The predictive performance of CHA2DS2-VASc score for all-cause mortality and stroke was compared with the score combined with the relative expression level of SNORD55 in the AF patients.The area under the receiver operating characteristic curve(AUC)was utilized to evaluate the discrimination,and the net reclassification index(NRI)and comprehensive discriminant improvement index(IDI)were calculated to evaluate the improvement of reclassification ability.Decision curve analysis(DCA)was applied to analyze the change in clinical net benefit.Results The results of multivariate Cox regression showed that high expression of SNORD55 in peripheral blood was an independent risk factor for all-cause mortality and stroke in the AF patients.In predicting the outcomes of all-cause mortality and stroke,the addition of relative expression SNORD55 level with the CHA2DS2-VASc score obtained higher AUC value[0.80(95％CI:0.67～0.93)vs 0.67(95％CI:0.53～0.81),P＜0.05].In predicting the outcome of all-cause death and stroke,combination of the relative expression level of SNORD55 with CHA2DS2-VASc score increased both NRI[54.3(95％CI:10.6～61.9)vs 31.9(95％CI:2.8～47.5),P＜0.05]and IDI[16.1(95％CI:2.4～27.0)vs 7.9(95％CI:0.5～14.8),P＜0.05].The results of DCA showed that our combination of CHA2DS2-VASc score relative expression level of SNORD55 had higher clinical net benefits than the foreign ABC score in the prediction of the outcomes.Conclusion Peripheral blood SNORD55 level is an independent risk factor for all-cause mortality and stroke in AF patients,and has good predictive performance for all-cause mortality and stroke in the patients.

Objectives To explore the association of peripheral blood PIWI-interacting RNA,piR-hsa-2700592,with all-cause mortality and stroke outcomes in patients with atrial fibrillation(AF),and to determine whether piR-hsa-2700592 has the potential to be an AF biomarker.Methods A total of 127 patients with non-valvular AF were enrolled,and the relative expression level of plasma piR-hsa-2700592 was detected.Cox proportional hazard regression was used to analyze the correlation between the expression of piR-hsa-2700592 and all-cause death as well as stroke outcome in the patients.Then the molecule expression level was combined with CHA2DS2-VASc score and ABC stroke(or death)score to establish 2 new prediction models,the improvement of the predictive performance was compared and analyzed.Receiver operating characteristic(ROC)curve analysis(area under the curve,AUC),net reclassification index(NRI),and comprehensive discriminant improvement index(IDI)were used to evaluate the predictive performance,and decision curve analysis(DCA)was employed to assess the clinical benefit.Results Multivariate Cox regression analysis showed that the patients with higher expression level of piR-hsa-2700592 in peripheral blood had a higher risk of stroke(HR:2.203,95%CI:1.120～4.332;P=0.022).In the stroke outcome,combination of plasma piR-hsa-2700592 expression level with CHA2DS2-VASc score and ABC stroke score obtained an AUC of 0.70(95%CI:0.55～0.85,P＜0.001)and 0.84(95%CI:0.73～0.96,P=0.02),respectively.But,no significant association was observed between high plasma piR-hsa-2700592 level and all-cause mortality in the AF patients(HR:1.997;95%CI:0.884～4.509;P=0.096).Combination of plasma piR-hsa-2700592 level improved the discriminative capability than the single CHA2DS2-VASc score and ABC stroke score models,with an NRI and IDI value of 44.20%(95%CI:3.40～59.90,P＜0.001)and 8.20%(95%CI:0.60～15.40,P＜0.001),respectively for the new CHA2DS2-VASc score model,and an NRI and IDI value of 44.20%(95%CI:9.80～58.90,P＜0.001)and 10.40%(95%CI:0.70～21.40,P＜0.001),respectively for the new ABC stroke score model.The DCA curve showed that both new prediction models obtained better net clinical benefits.Conclusion High peripheral blood expression of piR-hsa-2700592 is an independent risk factor for stroke in the AF patients,and the indicator has a good predictive value for prognosis of the patients.piR-hsa-2700592 might be used as a potential biomarker in the diagnosis and prevention of cardiovascular diseases.

Background: and Purpose Essential tremor with a midline distribution (Mid-ET) may represent a distinct subtype of essential tremor (ET) that primarily affects midline structures, often indicating advanced disease stage and increased severity. Recent studies have highlighted the complexity of Mid-ET, but research on neurological soft signs (NSS) in Mid-ET remains insufficient. Methods: The patients with ET included in this cross-sectional study were divided into two subgroups based on whether or not the ET had a midline distribution: Mid-ET and No-MidET. Comparative analyses were performed to assess clinical features and NSS prevalence in these subgroups. Results: Among 1,160 patients, 567 (48.9%) were Mid-ET and 593 (51.1%) were No-Mid-ET.The prevalence rates of head, face (including the jaw), and voice tremors were 31.9%, 23.0%, and 25.8%, respectively. In Mid-ET, tremor often affects multiple midline structures simultaneously. In the entire cohort, 24.7%, 16.6%, and 7.6% of patients exhibited tremors in one, two, and three midline structures, respectively. The prevalence of common NSS, including mild cognitive impairment, impaired tandem gait, and questionable dystonic posturing, was significantly higher in the Mid-ET than the No-Mid-ET subgroup (all p<0.001). Furthermore, we found that female sex (p<0.001), olfactory dysfunction (p=0.003), and questionable dystonic posturing (p=0.004) were associated with Mid-ET. Conclusions Mid-ET and No-Mid-ET presented significant clinical differences. The presence of questionable dystonic posturing may contribute to the distinct characteristics of Mid-ET, suggesting the presence of pathophysiological differences between the subgroups. Further investigations are warranted to determine the potential pathophysiological link between NSS and Mid-ET.

Objective To investigate the relationship between frailty and readmission during vulnerable periods in elderly patients with chronic heart failure.Methods Using convenience sampling method,290 elderly patients with chronic heart failure admitted to Department of Cardiovascular,the People's Hospital of Guangxi Zhuang Autonomous Region from December 2022 to August 2023 were selected as the research subjects.They were followed up for three months and surveyed using general information questionnaire,frailty scale,and Barthel index.Results Spearman correlation analysis showed a positive correlation between readmission during the vulnerable period and frailty(r=0.266,P＜0.05).The readmission rate during the vulnerable period was 28.6％,and the results of multivariate Logistic regression analysis showed that frailty(OR=2.561,95％CI:1.409-4.654),age(OR=1.113,95％CI:1.067-1.161),and renal dysfunction(OR=2.903,95％CI:1.559-5.406)were independent risk factors for unplanned readmission during the vulnerable period in elderly patients with chronic heart failure.Conclusion There is a positive correlation between frailty and readmission during the vulnerable period in elderly patients with chronic heart failure.Frailty,age,and renal dysfunction are independent risk factors for decompensated admission events in vulnerable elderly patients with chronic heart failure.

Essential tremor (ET) is one of the most common movement disorders, and its main clinical feature is action tremor at 4-12 Hz in both upper limbs. With the development and progress of disease, the cognition of ET has changed from benign, single-symptomatic and age-related disease to the disease with heterogeneity in etiology, pathology and clinical manifestation. At present, the etiology and pathogenesis of ET have not been fully defined. With the development of technology, magnetic resonance imaging has been widely used in the research of ET due to its advantages of high temporal and spatial resolution, multi-angle, multi-parameter imaging, and no ionizing radiation, and many new discoveries have been made in the neuropathophysiological mechanism. In this regard, this paper summarizes the latest progress of magnetic resonance imaging in ET, including structural magnetic resonance imaging, functional magnetic resonance imaging, etc., for the purpose of exploring the pathophysiology of ET and looking forward to clinical application prospects of magnetic resonance imaging.

Objective:To report a case of spastic paraplegia type 76 (SPG76) caused by a novel mutation of the CAPN1 gene, and collect the SPG76 cases published in recent years to summarize the clinical phenotype and genetic characteristics and improve the understanding of this disease. Methods:The clinical data of a patient with SPG76 caused by a mutation of the CAPN1 gene were collected, who admitted to Xiangya Hospital of Central South University on April 22, 2024. Relevant literature was searched in PubMed and China National Knowledge Infrastructure databases using the search terms "hereditary spastic paraplegia 76" "spastic paraplegia type 76" "SPG76" and a literature review was performed. Results:The patient was a 44-year-old male with the main symptoms of unsteady walking. Physical examination showed spasticity of both lower limbs, increased muscle tension of the limbs, hyperreflexia of the tendons. Brain and spinal cord magnetic resonance imaging showed no significant abnormalities. Neuroelectrophysiological examination showed no abnormalities in nerve conduction study and needle electromyography, and high amplitude F-waves were observed in the bilateral median nerves. Whole exome sequencing showed that there were compound heterozygous mutations of the CAPN1 gene: c.759+1G>A and c.1341+2T>G, of which c.1341+2T>G had not been reported. A total of 80 SPG76 cases related to CAPN1 gene mutations were reported in the literature, with an average age of onset of 25.68 years, and the clinical manifestations were mainly bilateral lower limb spasticity and tendon hyperreflexia, and about half of the patients were accompanied by upper limb spasticity and tendon hyperreflexia, ataxia, dysarthria, or lower limb weakness. Magnetic resonance imaging of the brain and spinal cord was mostly normal, and 13.8% (11/80) of the patients showed varying degrees of changes in the brain, mainly involving the cerebellum, and 5.0% (4/80) of the patients had cervical and thoracic spinal cord atrophy. The mutation types of CAPN1 gene included missense, nonsense, frameshift, and splice site variation, and the mutation sites were scattered and had no special aggregation tendency, and a total of 14 patients from 9 families carried the c.1176 G>A mutation. Conclusions:SPG76 is a rare subtype of hereditary spastic paraplegia caused by CAPN1 gene mutation, which is more common in young and middle-aged people, and patients have spasticity and tendon hyperreflexia in both lower limbs as the main clinical manifestations, most of which are accompanied by changes in the upper limbs, ataxia, etc., and a small number of patients can show atrophy of the cerebellum and (or) cervical and thoracic spinal cord by magnetic resonance of the head and spinal cord. The CAPN1 gene variants mainly include missense and nonsense variants, and c.1176G>A variant is the most prevalent pathogenic mutation site in the CAPN1 gene.