Cognitive impairment in cerebral small vessel disease induced by hypertension

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

Effects of Progressive Muscle Relaxation Training on Anxiety, Depression, and Quality of Life in Patients with Cerebral Small Vessel Disease

Objective:To explore the effects of progressive muscle relaxation training on anxiety,depression,and quality of life in patients with cerebral small vessel disease(CSVD).Methods:Sixty-one patients with CSVD in the Department of Neurology of a tertiary hospital were divided into an observation group(28 patients)and a control group(33 patients)by lottery method.The control group received conventional nursing care,while the observation group received progressive muscle relaxation training interventions in addition to the conventional care.The Hamilton Anxiety Scale(HAMA),the Hamilton Depression Scale(HAMD),and the Stroke-Specific Quality of Life Scale(SS-QOL)were used to compare the effects before the intervention,7 days after the intervention,and 30 days after the intervention.Results:Over time,at different time points after the intervention,the anxiety and depression scores of patients with CSVD in the observation group were significantly lower than those in the control group(P<0.05).The quality of life scores were significantly higher in the observation group compared to the control group(P<0.05),and these differences were statistically significant.Conclusion:Progressive muscle relaxation training can improve anxiety and depression in patients with cerebral small vessel disease and can effectively enhance their quality of life.

Exosomal miR-320e through wnt2targeted inhibition of the Wnt/β-catenin pathway allevisate cerebral small vessel disease and cognitive impairment

BACKGROUND Exosomal miRNAs play crucial roles in many central nervous system diseases.Cerebral small vessel disease(CVSD)is a small vessel disease that is affected by various factors.This study aimed to investigate the role of exosomal miR-320e in the Wnt/β-catenin pathway stimulated by oxidative stress and assess its clinical correlation with psychiatric symptoms in patients with CVSD.AIM To explore whether exosomal miR-320e could suppress the Wnt/β-catenin pathway and play a protective role in CVSD progression,as well as examine its potential correlation with cognitive impairment and depression in patients with CVSD.METHODS Differentially expressed exosomal miRNAs were filtered by sequencing plasma exosomes from patients with CVSD and healthy controls.Bioinformatics and dual luciferase analyses were used to confirm the binding of miR-320e to Wnt2,and the mRNA and protein levels of downstream components in the Wnt/β-catenin pathway were evaluated when overexpressed or with knockdown of miR-320e under H2O2-induced oxidative stress.In addition,Wnt2-targeting siRNA was used to confirm the role of miR-320e in the Wnt2-mediated inhibition of the Wnt/β-catenin pathway.A retrospective analysis was conducted among patients with CVSD to confirm the correlation between miR-320e expression and the severity of cognitive impairment and depression,which were quantified using the Montreal Cognitive Assessment(MoCA)/Executive Function Assessment(EFA),and the Hamilton Depression Scale(HAMD)/Beck Depression Inventory(BDI),respectively.RESULTS High-throughput sequencing revealed that exosomal miR-320e was downregulated in patients with CVSD.Bioinformatics analysis and dual-luciferase reporter gene experiments showed that exosomal miR-320e inhibited the Wnt/β-catenin pathway in response to oxidative stress by targeting the 3'noncoding region of Wnt2.Uptake of exosomes carrying miR-320e into endothelial cells could also target Wnt2 and inhibit the Wnt2/β-catenin pathway.Elevated miR-320e expression may protect patients with CVSD from relatively severe cognitive impairment and depression,as it was found to have a positive correlation with the MoCA/EFA and HAMD/BDI scores.CONCLUSION Our results suggest that exosomal miR-320e suppresses the Wnt/β-catenin pathway and may play a protective role in CVSD progression.

Association between intercellular adhesion molecule-1 to depression and blood-brain barrier penetration in cerebellar vascular disease

BACKGROUND Cerebral small vessel disease(CSVD)is a prevalent cerebrovascular disease in clinical practice that is often associated with macrovascular disease.A clear understanding of the underlying causes of CSVD remains elusive.AIM To explore the association between intercellular adhesion molecule-1(ICAM-1)and blood-brain barrier(BBB)penetration in CSVD.METHODS This study included patients admitted to Fuyang People’s Hospital and Fuyang Community(Anhui,China)between December 2021 and March 2022.The study population comprised 142 patients,including 80 in the CSVD group and 62 in the control group.Depression was present in 53 out of 80 patients with CSVD.Multisequence magnetic resonance imaging(MRI)and dynamic contrast-enhanced MRI were applied in patients to determine the brain volume,cortical thickness,and cortical area of each brain region.Moreover,neuropsychological tests including the Hamilton depression scale,mini-mental state examination,and Montreal cognitive assessment basic scores were performed.RESULTS The multivariable analysis showed that age[P=0.011;odds ratio(OR)=0.930,95%confidence interval(CI):0.880-0.983]and ICAM-1 levels(P=0.023;OR=1.007,95%CI:1.001-1.013)were associated with CSVD.Two regions of interest(ROIs;ROI3 and ROI4)in the white matter showed significant(both P<0.001;95%CI:0.419-0.837 and 0.366-0.878)differences between the two groups,whereas only ROI1 in the gray matter showed signi-ficant difference(P=0.046;95%CI:0.007-0.680)between the two groups.ICAM-1 was significantly correlated(all P<0.05)with cortical thickness in multiple brain regions in the CSVD group.CONCLUSION This study revealed that ICAM-1 levels were independently associated with CSVD.ICAM-1 may be associated with cortical thickness in the brain,predominantly in the white matter,and a significant increase in BBB permeability,proposing the involvement of ICAM-1 in BBB destruction.

Vitamin D deficiency and increased inflammatory factor intercellular cell adhesion molecule-1 indicate severe leukoaraiosis in northern China

Background and objective:Commonly plaguing in the frigid zone of the world,vitamin D deficiency,as indicated by low levels of 25-hydroxyvitamin D,exacerbated inflammatory responses and impaired endothelial function.Leukoaraiosis(LA)is a prevalent cause of cognitive dysfunction in the elderly and is potentially associated with inflammatory responses.This study aimed to investigate the impact of vitamin D on the severity of LA.Methods:Patients with LA were categorized based on 3.0 T brain MRI findings into mild(N=43),moderate(N=40),or severe groups(N=29)using the Fazekas scale(scoring 1-6).A control group consisting of 41 healthy individuals was included.Serum fibrinogen C,homocysteine,plasma 25-hydroxyvitamin D,and intercellular cell adhesion molecule-1(ICAM-1)levels were measured using ELISA.Results:All LA severity groups exhibited lower plasma 25-hydroxyvitamin D levels compared to the control group,with a more pronounced decrease observed as LA severity increased.Low plasma 25-hydroxyvitamin D was identified as an independent risk factor for LA(P<0.05)according to Multiple logistic regression analysis.Additionally,a negative association was observed between 25-hydroxyvitamin D and vascular inflammatory factor ICAM-1.Conclusions:Disease severity positively correlated with levels of the inflammatory marker ICAM-1,worsening as plasma 25-hydroxyvitamin D concentration decreased.Low 25-hydroxyvitamin D emerged as an independent risk factor for LA,potentially exacerbating the inflammatory response.These findings suggest 25-hydroxyvitamin D supplementation as a potential therapeutic approach for LA.

Neuroprotective effect of penehyclidine hydrochloride on focal cerebral ischemia-reperfusion injury

Penehyclidine hydrochloride can promote microcirculation and reduce vascular permeability. However, the role of penehyclidine hydrochlodde in cerebral ischemia-reperfusion injury remains unclear. In this study, in vivo middle cerebral artery occlusion models were established in experimental rats, and penehyclidine hydrochloride pretreatment was given via intravenous injection prior to model establishment. Tetrazolium chloride, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling and immunohistochemical staining showed that, penehyclidine hydrochloride pretreatment markedly attenuated neuronal histopathological changes in the cortex, hippocampus and striatum, reduced infarction size, increased the expression level of BcI-2, decreased the expression level of caspase-3, and inhibited neuronal apoptosis in rats with cerebral ischemia-reperfusion injury. Xanthine oxidase and thiobarbituric acid chromogenic results showed that penehyclidine hydrochloride upregulated the activity of superoxide dismutase and downregulated the concentration of malondialdehyde in the ischemic cerebral cortex and hippocampus, as well as reduced the concentration of extracellular excitatory amino acids in rats with cerebral ischemia-reperfusion injury. In addition, penehyclidine hydrochloride inhibited the expression level of the NR1 subunit in hippocampal nerve cells in vitro following oxygen-glucose deprivation, as detected by PCR. Experimental findings indicate that penehyclidine hydrochloride attenuates neuronal apoptosis and oxidative stress injury after focal cerebral ischemia-reperfusion, thus exerting a neuroprotective effect.

Diffusion tensor imaging pipeline measures of cerebral white matter integrity: An overview of recent advances and prospects

Cerebral small vessel disease(CSVD)is a leading cause of age-related microvascular cognitive decline,resulting in significant morbidity and decreased quality of life.Despite a progress on its key pathophysiological bases and general acceptance of key terms from neuroimaging findings as observed on the magnetic resonance imaging(MRI),key questions on CSVD remain elusive.Enhanced relationships and reliable lesion studies,such as white matter tractography using diffusion-based MRI(dMRI)are necessary in order to improve the assessment of white matter architecture and connectivity in CSVD.Diffusion tensor imaging(DTI)and tractography is an application of dMRI that provides data that can be used to non-invasively appraise the brain white matter connections via fiber tracking and enable visualization of individual patient-specific white matter fiber tracts to reflect the extent of CSVD-associated white matter damage.However,due to a lack of standardization on various sets of software or image pipeline processing utilized in this technique that driven mostly from research setting,interpreting the findings remain contentious,especially to inform an improved diagnosis and/or prognosis of CSVD for routine clinical use.In this minireview,we highlight the advances in DTI pipeline processing and the prospect of this DTI metrics as potential imaging biomarker for CSVD,even for subclinical CSVD in at-risk individuals.

Buyanghuanwu decoction promotes angiogenesis after cerebral ischemia/reperfusion injury：mechanisms of brain tissue repair

Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury,but the underlying mechanisms remain unclear.In this study,rats were intragastrically given Buyanghuanwu decoction,15 m L/kg,for 3 days.A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion.In rats administered Buyanghuanwu decoction,infarct volume was reduced,serum vascular endothelial growth factor and integrin αvβ3 levels were increased,and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals.These effects of Buyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor（administered through the lateral ventricle for 7 consecutive days）.These data suggest that Buyanghuanwu decoction promotes angiogenesis,improves cerebral circulation,and enhances brain tissue repair after cerebral ischemia/reperfusion injury.

Risk factors and ankle brachial indexes in cerebral infarction combined with peripheral arterial disease

BACKGROUND: Ankle brachial index (ABI) is widely involved in researches and clinical application of peripheral vascular injury of patients with diabetes mellitus (DM); however, the application in cerebral infarction (CI) is rare. OBJECTIVE: To investigate the possible risk factor of cerebral infarction plus peripheral arterial disease (PAD), compare metabolic characteristics of patients who having CI plus PAD or only having CI, and understand the significance of ABI on screening and diagnosing CI plus PAD of lower limb. DESIGN: Contrast observation based on CI patients. SETTING: Department of Neurology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region. PARTICIPANTS: A total of 124 CI patients were selected from Department of Neurology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region from July 2005 to April 2006, including 72 males and 52 females aged from 45 to 88 years. All patients met the diagnostic criteria of cerebrovascular disease established by National Academic Conference of Cerebrovascular Diseases in 1995 and determined as cerebral infarction with MRI or CT examination. All patients provided informed consent. There were 46 cases (37.2%) with CI plus PAD and 78 cases (62.8%) only with CI. METHODS: Blood pressure of bilateral ankles and upper extremities was measured at plain clinostatism with DINAMAP blood pressure monitor (GE Company). The ratio between average systolic pressure of lateral ankle and average systolic pressure of both upper extremities was regarded as ABI. The normal ABI was equal to or more than 0.9. If ABI < 0.9 occurred at one side, patients were diagnosed as PAD. On the second morning after hospitalization, blood was collected to measure fasting blood glucose (FBG), 2-hour postprandial blood glucose (PBG2h), glycosylated hemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Among them, blood glucose, lipid and other biochemical markers were measured with enzyme chemistry assay and HbA1c was measured with HbA1c meter based on high liquid phase. Measurement data and enumeration data were compared with t test and Chi-square test, and multiple factors were dealt with Logistic regression analysis and multivariate linear regression analysis. MAIN OUTCOME MEASURES: Results of correlation between ABI and metabolic markers with multivariate linear regression analysis; risk factors of CI plus PAD with Logistic regression analysis; comparisons of metabolic markers between PAD and non-PAD patients. RESULTS: All 124 patients with acute CI were involved in the final analysis. ① Comparisons of metabolic markers: Levels of serum LDL-C and uric acid (UA) were higher of PAD patients than those of non-PAD patients (t =2.051 9, 3.339 1, P < 0.05); however, there were no significant differences among other metabolic markers (P > 0.05). ② Results of multivariate linear regression analysis: PBG2h, LDL-C and UA were obvious correlation with ABI of posterior tibial artery of lower limb and dorsal pedis artery (partial regression coefficient = -0.231 to -1.010, P < 0.05). ③ Risk factors of CI plus PAD with Logistic regression analysis: Age, smoking history, sum of CI focus (≥3) and LDL-C were independent risk factor of CI plus PAD (OR =1.524-5.422, P < 0.05-0.01). CONCLUSION: ① Levels of serum LDL-C and UA of patients with CI plus PAD are high. ② ABI of lower limbs is correlation with PBG2h, LDL-C and UA. In addition, measuring ABI is beneficial for early diagnosing PAD of lower limbs of patients who have poorly controlled blood glucose, abnormal lipid and poor renal function. ③ Age, LDL-C and sum of CI focus (≥3) are independent risk factors of CI plus PAD. It is of significance for screening non-PAD patients to evaluate risk degrees and prognosis and select therapeutic methods based on ABI measurement.

Concepts and opportunities for repair in cerebral microvascular disease and white matter stroke

Diffuse changes in white matter resulting from cerebral microvascular disease contribute to cognitive impairment （Jokinen et al., 2011）, declines in global functionality （Inzitari et al., 2009）, and even death （Debette and Markus, 2010）. Twenty years ago, estimations of the clinical incidence of ce- rebral microvascular disease approached 11 million per year in the US alone （Leary and Saver, 2003）. More recent estima- tions suggest the prevalence of diffuse white matter disease and silent brain infarction approaches 20% and increases dramatically in the presence of cardiovascular risk factors （Fanning et al., 2014）.

Effect of long-term low dose of aspirin on severity of disease following onset of acute cerebral infarction

BACKGROUND： Aspirin can decrease the incidence risk of high-risk crowdgroup of cerebral infarction, but there are still controversy if it might decrease the degree of disease in degree of patients with acute cerebral infarction. OBJECTIVE： To observe the effect of lower dose of aspirin during taking for a long time on disease degree of disease following onset of acute cerebral infarction. DESIGN： Grouping according to the admission time and 1：1 paired observation.SETTING ： Department of Neurology, Qilu Hospital of Shandong University.PARTICIPANTS ： The participants in present study were 321 patients with acute cerebral infarction who received treatments in the Department of Neurology, Qilu Hospital of Shandong University from January 1999 to June 2000. There were 190 male and 131 female ,with mean （65±11 ）years of age. Inclusive criteria： ① A focal neurological disturbance occurred suddenly and had lasted for more than 24 hours, patients were admitted within 3 days after onset of disease; ② A computed tomography of the brain was performed and excluded hemorrhage in all patients; ③ The patients were proved internal carotid occlusions by clinical features and image findings; ④ The functions of limbs were normal （before the first stroke） or almost normal （before the second stroke）. Exclusive criteria：①The patients who had have cardiogenic cerebral embolism; ②The patients who had taken warfarin orally and other platelet agglutination drugs. METHODS ：①All the patients were divided into 2 groups according to whether they had taken aspirin before： aspirin-treated group （n=110） and blank control group （n=211）. there were 70 male and 40 female in aspirin-treated group, with average（65±10） years of age.All patients had taken 50-100 mg/d aspirin for 6 months to 10 years before onset. There were 120 male and 91 female in blank control group, with average （65±13） years of age. Patients received a clinical scoring within 3 days and similar therapeutic measures （such as anti-platelet agglutination, improving cerebral circulation and metabolism-promoting reagent）. Two groups of patients had the same basic conditions except for taking aspirin or not before. ②The matched pairs were made between 50 cases selected from aspirin-treated group and 50 cases from non-aspirin-treated groups according to age, gender, and other stroke risk factors. ③ Evaluation： Degree of disease after onset was evaluated by means of Acute Cerebral Infarction Clinical Neurologic Impairment Degree Scoring Standard of Carotid Artery System. MAIN OUTCOME MEASURES： Acute Cerebral Infarction Clinical Neurologic Impairment Degree Scoring Standard of Carotid Artery System. RESULTS ： All 321 patients entered the stage of analysis with no loss in the midway. ① The symptom following onset of acute cerebral infarction was evaluated with clinical neurologic impairment scoring criteria, there were no significant differences between aspirin group and blank control group [（17.39±9.90） vs （16.22 ± 9.98） （t=1.025, P〉 0.05）]. ② No significant differences were found in 1：1 matched pairs of 100 cases from aspirin group and blank control group （t=1.74, P 〉 0.05）. CONCLUSION ： Taking a lower dose of aspirin during long time may not decrease the degree of disease following onset of acute cerebral infarction.

The molecular mechanism of meridian qi sensory transmission by heat-sensitive moxibustion in the treatment of cerebral infarction

Background:To explore the potential mechanism of thermal moxibustion in the treatment of i schemic strok e by using the method of network pharmacology and to partially explain the mechanism of acupoint meridian qi sense transmission.Methods:In this project,a training set was formed by researching the intersection of the reported components of M ugwort leaves that entered the blood after combustion and obtained the targets of heat-sensitive moxibustion meridian qi sensing and thermal effect by querying the literature.The Encyclopedia of Tr ad itional Chinese Medicine is used to search and screen the highly active chemical constituents of Artemisia argyi to predict potential targets;search i schemic strok e-related targets through GeneCards,O nline Mendelian Inheritance in Man,Drugbank databases.Gene Oncology functional analysis and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analysis were performed on the potential targets of the blood components of Artemisia argyi and molecular docking simulated the binding activity of key candidate active components and core genes.Results:192 ischemic stroke disease targets with r elevance score greater than 10 were screened out for analysis.Through the database Encyclopedia of Tr ad itional Chinese Medicine query of the action targets(243)of Mugwort leaves and the intersection of heat-sensitive moxibustion effect targets and ischemic stroke-related targets,a Venn diagram was drawn and a total of 17 were obtained.Finally,the effective components of Mugwort leaves into the blood were screened out.Five main volatile components were molecularly docked with 17 targets and 9 targets of acupoint meridian gas sensing/thermal effect.The docking results showed that the main volatile components showed good affinities for binding to key targets,respectively.Conclusion:Using the characteristics of“multi-component-multi-target-multi-pathway”of traditional Chinese medicine,the potential mechanism of action of Artemisia argyi in the treatment of i schemic strok e is explored,which provides a certain basis for the follow-up scientific research and clinical application of Artemisia argyi in the treatment of IS.

A Study on the Correlation Between Cerebral Small Vascular Disease and Constitution Types of Traditional Chinese Medicine

Objective:To study the correlation between cerebral small vascular disease and constitution types of Traditional Chinese Medicine(TCM).Methods:The severity of lacunar infarction and leukoaraiosis were graded in 230 patients with cerebral small vascular disease,and they were divided into TCM constitution types.The survey of TCM constitution types was carried out by using standardized TCM constitution scale,and order multivariate Logistic regression was used to analyze the correlation between TCM constitution types with severity of lacunar infarction and leukoaraiosis.Results:Yang-deficiency(阳虚)constitution,blood-stasis constitution and phlegm-dampness constitution were the most common TCM constitution types in patients with lacunar infarction,accounting for 33.7%,12.5%,11.5%respectively.Yang-deficiency constitution,blood-stasis constitution and Yin-deficiency(阴虚)constitution were the most common TCM constitution types in patients with leukoaraiosis,accounting for 28.8%,18.5%,13.7%respectively.There were significant differences in lacunar infarction of Yang-deficiency constitution and blood stasis constitution(P<0.05),and there were significant differences in leukoaraiosis of phlegmdampness constitution and blood-stasis constitution(P<0.05).Single factor analysis showed that the main risk factors of lacunar infarction were age,smoking,alcohol consumption,Yang-deficiency constitution and blood-stasis constitution,and the main risk factors of leukoaraiosis were age,smoking,hypertensive disease,phlegm-dampness constitution and blood-stasis constitution.The ordered multivariate Logistic regression analysis found that the severity of lacunar infarction was closely related to age,and the severity of leukoplosis was closely related to age,smoking and hypertension disease.Conclusion:TCM constitution types of lacunar infarction in patients with small cerebral vascular disease is mainly Yang-deficiency constitution and blood-stasis constitution,and the risk factors include age,smoking,alcohol consumption,Yang-deficiency constitution and blood-stasis constitution.Age is closely related with lacunar infarction.TCM constitution types with leukoaraiosis are mainly phlegm-dampness constitution and blood-stasis constitution,and the risk factors are age,smoking,hypertension disease,phlegm-dampness constitution and blood-stasis constitution.Age,smoking and hypertension disease are closely related with leukoaraiosis.

Machine Learning for Selecting Important Clinical Markers of Imaging Subgroups of Cerebral Small Vessel DiseaseBased on a Common Data Model

Differences in the imaging subgroups of cerebral small vessel disease(CSVD)need to be further explored.First,we use propensity score matching to obtain balanced datasets.Then random forest(RF)is adopted to classify the subgroups compared with support vector machine(SVM)and extreme gradient boosting(XGBoost),and to select the features.The top 10 important features are included in the stepwise logistic regression,and the odds ratio(OR)and 95%confidence interval(CI)are obtained.There are 41290 adult inpatient records diagnosed with CSVD.Accuracy and area under curve(AUC)of RF are close to 0.7,which performs best in classification compared to SVM and XGBoost.OR and 95%CI of hematocrit for white matter lesions(WMLs),lacunes,microbleeds,atrophy,and enlarged perivascular space(EPVS)are 0.9875(0.9857−0.9893),0.9728(0.9705−0.9752),0.9782(0.9740−0.9824),1.0093(1.0081−1.0106),and 0.9716(0.9597−0.9832).OR and 95%CI of red cell distribution width for WMLs,lacunes,atrophy,and EPVS are 0.9600(0.9538−0.9662),0.9630(0.9559−0.9702),1.0751(1.0686−1.0817),and 0.9304(0.8864−0.9755).OR and 95%CI of platelet distribution width for WMLs,lacunes,and microbleeds are 1.1796(1.1636−1.1958),1.1663(1.1476−1.1853),and 1.0416(1.0152−1.0687).This study proposes a new analytical framework to select important clinical markers for CSVD with machine learning based on a common data model,which has low cost,fast speed,large sample size,and continuous data sources.

Associations among cerebral microbleeds, cerebral large-artery diseases and endothelial function

Background Endothelial dysfunction is not only an early stage of atherosclerosis,but also involved in the pathogenesis of cerebral small-vessel diseases.Patients with cerebral microbleeds （CMBs） may have arteriolosclerosis as well as systemic atherosclerosis.However,little is known about the associations among CMBs,atherosclerosis of cerebral large arteries,and endothelial function.Our study aimed to investigate the relationships among them.Methods This was a cross-sectional study.Ninety patients hospitalized in Peking University First Hospital with acute ischemic stroke were enrolled consecutively between November 1,2007 and January 31,2008.All subjects underwent transcranial Doppler and carotid color duplex ultrasonography to record the intima-media thickness （IMT） of common carotid artery,carotid plaque,and cerebral artery stenosis.Brain magnetic resonance imaging （MRI） routine sequences and gradient recall-echo T2＊-weighted imaging were performed to count CMBs with clinical data blindness.Endothelial function was evaluated using flow-mediated dilation （FMD） and nitroglycerin-mediated dilation （NMD） of the brachial artery.FMD and NMD were examined by an experienced vascular sonographer using a high-resolution ultrasound.Results Thirty cases （33.3%） had CMBs with counts ranging from 1 to 30.Both FMD （（9.9＆#177;4.8）% vs.（15.2＆#177;7.4）%,P=0.001） and NMD （（13.7＆#177;6.1）% vs.（19.0＆#177;7.4）%,P=0.001） were significantly decreased in CMB-positive patients than in CMB-negative patients.No significant relationships were demonstrated between CMBs and intracranial and/or extracranial artery stenosis.The frequencies of CMBs in patients with IMT≥1.0 mm,carotid plaque,and extracranial artery stenosis were 37.5%,39.4%,and 47.6% respectively,with no significant difference,but much higher than in patients with IMT 〈1.0 mm （5%,P 〈0.05）.In Logistic regression analysis,impaired FMD （OR=5.783,95% CI 1.652-6.718,P=0.007） and high pulse pressure （OR=6.228,95% CI 1.594-3.891,P=0.009） were independently associated with the presence of CMBs,as well as previous ischemic stroke.In contrast,NMD was not correlated with CMBs.Conclusions CMBs may coexist with cerebral atherosclerosis in ischemic stroke.Endothelial dysfunction may play a role in the pathogenesis of CMBs,but may not simply reflect functional alterations of large arteries.

Distribution of ApoE Gene Polymorphism and Significance of Auxiliary Diagnosis and Treatment of Cerebrovascular Diseases(Intracerebral Hemorrhage and Cerebral Thrombosis) in the Longyan Area

Objective:To make statistics on the distribution of ApoE gene polymorphism in the Longyan area,provide data for the statistics of regional cerebrovascular diseases,explore the significance of ApoE gene polymorphism distribution for clinical guidance,diagnosis and treatment,and provide more suggestions for clinical diagnosis and treatment of cerebrovascular diseases.Methods:800 patients with cerebrovascular disease in the Longyan area from July 2018 to April 2021 were selected as the research object,and 800 normal healthy patients were selected as the control group.The data were further analyzed according to the collected patient information,and the patients were distinguished according to age and other basic information,the type of cerebrovascular disease,ApoE gene polymorphism and blood lipid test results.The distribution of ApoE gene polymorphism in the cerebrovascular disease population in the Longyan area was given to determine the correlation between the incidence of cerebrovascular disease and the distribution of ApoE gene polymorphism.Results:In the study group,E2/E3 genotyping was the most common 400(50.00%),and E4/E4 genotyping 6(0.75%)was the least common;In the control group,E2/E4 genotyping was the most common 480(60.00%),and E2/E3 genotyping accounted for the second 290(36.25%).In the study group,E3 allele was the most common 383(47.88%),E4 allele 121(15.12%);in the control group,E2 allele was the most common391(48.88%),and E3 allele 142(17.75%).Conclusion:According to the statistics of ApoE gene polymorphism distribution in the Longyan area and the analysis of the correlation of other cerebrovascular diseases,it is found that E2/E3 genotype may be related to cerebrovascular diseases,and E3 allele may be a susceptibility factor.Through the above analysis,the occurrence of diseases can be predicted and prevented.

Progress on Prevention and Treatment of Cerebral Small Vascular Disease Using Integrative Medicine

Cerebral small vessel disease(CSVD)is a senile brain lesion caused by the abnormal structure and function of arterioles,venules and capillaries in the aging brain.The etiology of CsvD is complex,and disease is often asymptomatic in its early stages.However,as CsvD develops,brain disorders may occur,such as stroke,cognitive dysfunction,dyskinesia and mood disorders,and heart,kidney,eye and systemic disorders.As the population continues to age,the burden of CsvD is increasing.Moreover,there is an urgent need for better screening methods and diagnostic markers for CsvD,in addition to preventive and asymptomatic-and mild-stage treatments.Integrative medicine(IM),which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives,has unique advantages for the prevention and treatment of CsvD.In this review,we summarize the biological markers,ultrasound and imaging features,disease-related genes and risk factors relevant to CsvD diagnosis and screening.Furthermore,we discuss IM-based csvD prevention and treatment strategies to stimulate further research in this field.

MRI Features and Site-specific Factors of Ischemic Changes in White Matter： A Retrospective Study

Brain magnetic resonance imaging （MRI） of the elderly often reveals white matter changes （WMCs） with substantial variability across individuals. Our study was designed to explore MRI features and site-specific factors of ischemic WMCs. Clinical data of consecutive patients diagnosed with ischemic cerebral vascular disease who had undergone brain MRI were collected and analyzed. Multi-logistic regression analysis comparing patients with mild versus severe WMCs was performed to detect independent associations. Analyses of variance （ANOVAs） were used to detect regionally specific differences in lesions. We found that lesion distribution differed significantly across five cerebral areas, with lesions being predominant in the frontal lobe and parieto-occipital area. To explore WMCs risk factors, after adjusting for gender, diabetes mellitus, and hypertension, only age （P〈0.01）, creatinine （P=0.01）, alkaline phosphatase （ALP） （P=0.01） and low-density lipoprotein cholesterol （LDL-C） （P=0.03） were found to be independently associated with severe WMCs. Age （P〈0.001） was strongly associated with WMCs in the frontal lobe while hypertension was independently related to lesions in the basal ganglia （P=0.048） or infratentorial area （P=0.016）. In conclusion, MRI of WMCs showed that ischemic WMCs occurred mostly in the frontal lobe and parieto-occipital area. The infratentorial area was least affected by WMCs. Typically, age-related WMCs were observed in the frontal lobes, while hypertension-related WMCs tended to occur in the basal ganglia and infratentorial area.

Paraneoplastic neurological syndrome caused by cystitis glandularis: A case report and literature review

BACKGROUND Paraneoplastic neurological syndrome(PNS)is an unusual event.PNS caused by cystitis glandularis(CG)or a bladder tumor is extremely rare;hence,missed diagnosis or misdiagnosis can easily occur.To date,approximately 21 cases have been reported in PubMed.CASE SUMMARY We report a case of PNS caused by CG and describe the clinical and imaging features.The main clinical feature was advanced cognitive impairment,and early clinical features were memory impairment,decreased computational ability,and abnormal behavior.Later clinical features were dementia,vomiting,inability to eat and walk,urinary incontinence,and hematuria.Imaging features on cranial magnetic resonance imaging were diffuse white matter lesions.Paraneoplastic tumor markers were normal.A total abdominal computed tomography scan showed multiple thickened areas on the bladder wall with local prominence.Cystoscopy revealed a volcanic protuberance on the posterior wall of the bladder with a diameter of 6 cm and no pedicle.The postoperative pathological diagnosis was CG.The patient recovered well following resection of CG.PNS cases caused by previous bladder tumors can be retrieved from PubMed to describe the clinical signs and prognosis of PNS.CONCLUSION The main clinical feature of PNS caused by CG was dementia,and the imaging features were diffuse cerebral white matter lesions.Resection of CG lesions is the fundamental treatment for PNS induced by CG.This case highlights the importance of etiological treatment.

Overview-Research Progress of Leukoaraiosis

In 1987, Hachinski et al. [1] proposed Leukoaraiosis (LA) as an imaging academic term. Since then, LA and other cerebrovascular diseases have become the research focus of scholars at home and abroad. However, the molecular, cellular and pathogenesis of cerebrovascular disease are still unclear. Cerebral small vessel disease is caused by the lesions of perforating arteries, capillaries and veins of the brain. Modern imaging technology makes it possible to classify these diseases that can not be directly distinguished in clinical practice. The imaging features of cerebral infarction include cerebral microvascular atrophy. At present, a large number of studies have been carried out around LA, such as the pathogenesis, risk factors, imaging manifestations and classification, pathophysiological changes, hemodynamics, gene polymorphism and so on. In addition, although LA belongs to the category of cerebral small vessel disease, more scholars believe that there are countless links between large artery atherosclerosis and LA, and to some extent, have the same pathogenesis. This paper reviews the following aspects.