Targeting capabilities of engineered extracellular vesicles for the treatment of neurological diseases

Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases.Owing to their therapeutic properties and ability to cross the blood–brain barrier,extracellular vesicles are recognized as promising drug delivery vehicles for various neurological conditions,including ischemic stroke,traumatic brain injury,neurodegenerative diseases,glioma,and psychosis.However,the clinical application of natural extracellular vesicles is hindered by their limited targeting ability and short clearance from the body.To address these limitations,multiple engineering strategies have been developed to enhance the targeting capabilities of extracellular vesicles,thereby enabling the delivery of therapeutic contents to specific tissues or cells.Therefore,this review aims to highlight the latest advancements in natural and targeting-engineered extracellular vesicles,exploring their applications in treating traumatic brain injury,ischemic stroke,Parkinson's disease,Alzheimer's disease,amyotrophic lateral sclerosis,glioma,and psychosis.Additionally,we summarized recent clinical trials involving extracellular vesicles and discussed the challenges and future prospects of using targeting-engineered extracellular vesicles for drug delivery in treating neurological diseases.This review offers new insights for developing highly targeted therapies in this field.

Contribution of Stress Testing to the Management of Ischemic Heart Disease in Mali

Introduction: Exercise stress testing (on a treadmill or ergometer bicycle) is an important test in cardiology for diagnosing myocardial ischemia. This test in Mali is still in its beginning compared to other countries in the sub-region. The lack of data in Mali prompted this study, which aimed to evaluate the indications of this activity and its diagnostic contribution to cardiology in Mali. Materials and Methods: This was a retrospective, descriptive study. The study was conducted at the “TOUCAM” medical clinic in Kati based on the analysis of stress test reports between January 2016 and August 2022. Result: During the study period, we documented 73 patients who underwent exercise testing on a bicycle ergometer for suspected coronary heart disease. The mean age of our patients was 47.5 ± 13.8 years (14 and 79 years). Males accounted for the majority (78.1%). The sex ratio is 3.5. More than half of our patients were overweight or obese (77.1%). Hypertension and diabetes affected 52.1% and 25.8% of patients, respectively. 20.8% of patients had coronary artery disease. renin-angiotensin-aldosterone system blockers (56.8%) and beta-blockers (51.3%). The main indications were chest pain (63.0%) and ischemia detection (15.1%). A modified STEEP protocol was used. The majority of our patients (71.2%) achieved at least 85% of their maximum theoretical heart rate. The main reason for the termination of the study was fatigue (57.3%). The average duration was 11.3 ± 4.2 minutes. 24.7% thought the stress tests were positive and 17.8% thought they were controversial. Conclusion: This study demonstrates the importance of stress testing in the diagnosis and treatment of ischemic heart disease, especially in settings where we have very limited access to coronary angiography.

Analysis on pulse features of coronary heart disease patients with or without a history of ischemic stroke

Objective To evaluate the capability of wrist pulse analysis in distinguishing three physiolog-ical and pathological conditions:healthy individuals,coronary heart disease(CHD)patients without a history of ischemic stroke,and CHD patients with a history of ischemic stroke.Methods Study participants were recruited from Shuguang East Hospital,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,and Shanghai Municipal Hospital of Traditional Chinese Medicine,affiliated with Shanghai University of Traditional Chinese Medicine,from April 15 to September 15,2021.They were categorized into three groups:healthy controls(Group 1),CHD patients without a history of ischemic stroke(Group 2),and CHD patients with a history of ischemic stroke(Group 3).The wrist pulse signals of the study participants were non-invasively collected using a pulse diagnosis instrument.The linear time-domain features and nonlinear time-series multiscale entropy(MSE)features of the pulse signals were extracted using time-domain analysis and the MSE methods,which were subsequently compared between groups.Based on these extracted features,a recognition model was developed using a random forest(RF)algorithm.The classification performance of the models was evaluated using metrics,including accuracy,precision,recall,and F1-score derived from confusion matrix as well as the area under the receiver operating characteristics(ROC)curve(AUC).Results A total of 189 participants were enrolled,with 63 in Group 1,61 in Group 2,and 65 in Group 3.Compared with Group 1,Group 2 showed significant increases in pulse features H2/H1,H3/H1,W1,W2,and W2/T,and decreased in MSE_(1)-MSE7(P<0.05),while Group 3 showed significant increases in pulse features T5/T4,T,H1/T1,W1,W2,AS,and Ad,and de-creased in MSE_(1)-MSE_(20)(P<0.05).Compared with Group 2,Group 3 demonstrated notable increases in H1/T1 and As(P<0.05).The RF model achieved precision of 80.00%,61.54%,and 61.54%,recall of 74.29%,60.00%,and 68.97%,F1-scores of 70.04%,60.76%,and 65.04%,and AUC values of 0.92,0.74,and 0.81 for Groups 1,2,and 3,respectively.The overall accuracy was 67.69%,with micro-average AUC of 0.83 and macro-average AUC of 0.82.Conclusion Differences in pulse features reflect variations in arterial compliance,peripheral resistance,cardiac afterload,and pulse signal complexity among healthy individuals,CHD patients without a history of ischemic stroke,and those with such a history.The developed pulse-based recognition model holds the potential in distinguishing between these three groups,offering a novel diagnostic reference for clinical practice.

Chinese herbal extract dl-3n-butylphthalide A commonly used drug for the treatment of ischemic stroke as a novel therapeutic approach to treat neurodegenerative diseases

DI-3n-butylphthalide is the active component isolated from the seeds of Apium graveolens Linn. A number of pharmacological and clinical studies have proven that dl-3n-butylphthalide is highly potent and multi-targeted with low toxicity and has a long time-window for the treatment of ischemic cerebrovascular disease. The mechanisms underlying dl-3n-butylphthalide include improving mitochondrial function and microcirculation, inhibiting apoptosis and reducing oxidative stress. Furthermore, dl-3n-butylphthalide may also be promising for the treatment of neurodegenerative diseases, such as Alzheimer＇s disease, vascular dementia and Parkinson＇s disease.

The role of Toll-like receptors in retinal ischemic diseases

Toll-like receptors（TLRs） are commonly referred to a series of evolutionary conserved receptors which recognize and respond to various microbes and endogenous ligands.Growing evidence has demonstrated that the expression of TLRs in the retina is regulated during retinal ischemic diseases,including ischemia-reperfusion injury,glaucoma,diabetic retinopathy（DR） and retinopathy of prematurity（ROP）.TLRs can be expressed in multiple cells in the retina,such as glial cells,retinal pigment epithelium（RPE）,as well as photoreceptor cells and endothelium cells.Activation of TLRs in retina could initiate a complex signal transduction cascade,induce the production of inflammatory cytokines and regulate the level of costimulatory molecules,which play prominent roles in the pathogenesis of retinal ischemic diseases.In this review,we summarized current studies about the relationship between TLRs and ischemic retinopathy.A greater understanding of the effect of TLRs on ischemic injuries may contribute to the development of specific TLR targeted therapeutic strategies in these conditions.

Is Any Correlation between Platelet Indices with Extent of Coronary Artery Involvement in Ischemic Heart Diseases?

Ischemic heart disease (IHD) is the most common cause of death around the world. Nowadays Platelet counts (PC) and volumetric platelet indices are available routinely in most laboratories and reflect the level of mobility and production of platelets. It seems that the excessive flexibility and size of the platelets and their local activation have correlation with extent of ischemic heart disease. So our objective is the study of platelet indices in ischemic heart disease. This non-randomized prospective study was performed on 245 patients with ischemic heart disease, who underwent the coronary angiography. The patients were divided into four groups: stable angina, unstable angina, acute myocardial infarction and control group;and then platelet indices, including the platelet counts (PC), the average platelet volume (MPV), the Platelet Distribution Width (PDW) and plateletcrit (PCT) in each group with the extent of coronary disease were compared based on an Syntax Score system and observational methods. The average ages of the patients were 57 years and 65% of them were male and the rest were female. A significant difference is exists between indices in all three groups compared to the control that this difference was related to gender and the type of the coronary artery involvement. However, only in infarction group, PDW in different disease intensities was significantly different. In this study, unlike many of the previous studies no relationship was found between the MPV with the extent of coronary disease.

Assessment of a portfolio as an effective tool to promote self-management among patients with ischemic heart diseases: A preliminary trial

Portfolio has been used as an approach to promoting self-learning in the field of education and its effectiveness was reported in school education. The purpose of this study was to assess effectiveness of portfolio as a tool for educating patients with ischemic heart diseases as self-management behavior in terms of applicability and efficacy. Subjects of this study were seventeen patients who had myocardial infarction or angina. They were assigned to collect information about their themes chosen from diet, exercise, alcohol intake, smoking cessation, and stress management and gathered in files. Thirty minutes face-to-face educational interviews were conducted by a nurse for once per month over three months. Self-management, self-efficacy, and physiological data were evaluated for baseline and 3 months. Two participants dropped within two months (completion rate is 88.2%). The results showed that portfolio was effective as a self-management education tool on patients who were willing to participate, but did not improve physiological data if they did not continuously implement lifestyle change. Moreover it was dangerous when the patients acquired incorrect information on diseases. For these patients, health education by health professionals is required prior to conducting portfolio. Attributes fit for portfolio were assessed. Effectiveness of portfolio related to high self-efficacy and high self-management, but did not relate to living status, having job, educational background, and health locus of control.

Study on the multi-targets mechanism of YiQiFuMai powder injection on cardio-cerebral ischemic diseases based on network pharmacology

Aim YiQiFuMai Powder Injection is a well-known traditional Chinese medicine formula that has been used extensively in clinical treatment of cardio-cerebral ischemic diseases in China. However, the mechanisms under-lying its clinical efficacy remain unknown. In this study, a network pharmacology approach was employed to identify the YiQiFuMai Powder Injection＇s potential pathways and targets against cardio-cerebral ischemia. The target-path- way interaction network clustered the signaling pathways based on high degree nodes of the drug-target network. The potential protein targets presented in the highly scored clustered pathways were the key network hubs and concentrated on one or limited functional signaling pathways amenable to experimental verification. Twelve main functional annota- tion clusters and main signaling pathways for YiQiFuMai Powder Injection were established by Biocarta analysis, in- eluding the NF-KB signaling pathway, the MAPKinase signaling pathway and the mTOR-signaling pathway and so on. YiQiFuMai Powder Injection is hypothesized to target multiple proteins with a high degree and betweenness of net- work. In addition, the most related pathways were also confirmed in tumor necrosis factor-alpha （TNF-oL） induced human vascular endothelial cell line EA. hy926 by Western blot. This study elucidates the systematic network and pathway analysis of multi-targets in YiQiFuMai Powder Injection. The results provide the possible mechanisms for its mode of action against cardio-cerebral ischemic diseases and may also reveal new clues for its potential application in the inflammatory diseases or tumors.

Significance of ultrasound evaluation of carotid atherosclerotic plaque for diagnosing ischemic cerebrovascular disease

BACKGROUND： Carotid artery is the main source for craniocerebral blood supply. Its intimal plaque formation and arterial stenosis degree both are the risk factors for ischemic cerebrovascular disease.Therefore, the close relationship of carotid atherosclerotic plaque and ischemic cerebrovascular disease, and ultrasound evaluation of carotid atherosclerotic plaque have become the hot spot in studying ischemic cerebrovascular disease.OBJECTIVE： This study was to detect the degree of carotid atherosclerosis of ischemic cerebrovascular disease patients by ultrasonography, and to analyze the situation of carotid atherosclerosis and its relationship with clinic.DESIGN： Clinical randomized concurrent control experiment.SETTING： Lintong Convalescent Hospital of Lanzhou Military Area Command of Chinese PLA.PARTICIPANTS： Totally 60 outpatients and inpatients with ischemic cerebrovascular disease, 42 males and 18 females, admitted to Lintong Convalescent Hospital of Lanzhou Military Area Command of Chinese PLA between January 2006 and December 2006 were involved in the patient group. They met the diagnosis criteria of ischemic cerebrovascular disease constituted by the 4th Cerebrovascular Disease Conference in 1996, and were confirmed to suffer from ischemic cerebrovascular disease by skull CT and MRI. Another 20 subjects who received healthy examination concurrently in the same hospital, 12 males and 8 females, were involved in the control group. Informed consents of detected items were obtained from involved subjects.METHODS： The plaque thickness of mid portion, distal end and crotch of common carotid artery （CCA）,internal carotid artery （ICA）, external carotid artery （ECA） and vertebral artery （VA） of involved subjects,who received health examination was separately detected with color Doppler ultrasonograph （HDI-5000）.Then, total integral of plaque was calculated. The intima-media thickness （IMT） was measured with two-dimensional ultrasonography. The inner diameter stenosis degree of subjects who had plaque was measured. Blood flow parameters were recorded, and stenosis degree and plaque area were calculated. Blood flow volume of bilateral carotid artery and VA was separately measured with ultrasound equipment software,and brain blood flow volume was calculated.MAIN OUTCOME MEASURES： Atherosclerotic degree and blood flow volume of patients of two groups.RESULTS： Sixty patients with ischemic cerebrovascular disease and twenty subjects who received health examination participated in the final analysis. ①The IMT thickness, total plaque score, and total plaque area of patient group was significantly superior to that of control group, respectively（ t=5.216 - 10.158, P 〈 0.05 ）.② There were significant differences in the stenosis degree of CCA, ICA and VA between patient group and control group （t=6.720 - 12.816, P 〈 0.05 ） . ③ The blood flow volume of CCA, ICA, VA and brain of patient group was significantly lower than that of control group, respectively （t=2.872 - 10.860, P 〈 0.05）.CONCLUSION： Ischemic cerebrovascular disease patients have different degrees of changes in atherosclerosis and arterial blood flow.

C-reactive Protein Level,Apolipoprotein B-to-apolipoprotein A-1 Ratio,and Risks of Ischemic Stroke and Coronary Heart Disease among Inner Mongolians in China

Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a Mongolian population in China.Methods From June 2003 to July 2012,2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation.All the participants were divided into four subgroups according to C-reactive protein（CRP） level and ApoB/ApoA-1 ratio.Cox proportional hazard models were used to estimate the hazard ratios（HRs） and 95% confidence intervals（CIs） for the IS and CHD events in all the subgroups.Results The HRs（95% CI） for IS and CHD were 1.33（0.84-2.12）,1.14（0.69-1.88）,and 1.91（1.17-3.11） in the ‘low CRP level with high ApoB/ApoA-1＇,‘high CRP level with low ApoB/ApoA-1＇,and ‘high CRP level with high ApoB/ApoA-1＇ subgroups,respectively,in comparison with the ‘low CRP level with low ApoB/ApoA-1＇ subgroup.The risks of IS and CHD events was highest in the ‘high CRP level with high ApoB/ApoA-1＇ subgroup,with statistical significance.Conclusion High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population.This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.

Use of various CT imaging methods for diagnosis of acute ischemic cerebrovascular disease

Thirty-four patients with cerebral infarction and 18 patients with transient ischemic attack were examined by multi-slice spiral CT scan, CT perfusion imaging, and CT angiography within 6 hours after onset. By CT perfusion imaging, 29 cases in the cerebral infarction group and 10 cases in the transient ischemic attack group presented with abnormal blood flow perfusion, which corresponded to the clinical symptoms. By CT angiography, various degrees of vascular stenosis could be detected in 41 patients, including 33 in the cerebral infarction group and eight in the transient ischemic attack group. The incidence of intracranial artery stenosis was higher than that of extracranial artery stenosis. The intracranial artery stenosis was located predominantly in the middle cerebral artery and carotid artery siphon, while the extracranial artery stenosis occurred mainly in the bifurcation of the common carotid artery and the opening of the vertebral artery. There were 34 cases （83%） with convict vascular stenosis and perfusion abnormalities, and five cases （45%） with perfusion abnormalities but without convict vascular stenosis. The incidence of cerebral infarction in patients with National Institutes of Health Stroke Scale scores 〉 5 points during onset was significantly higher than that in patients with National Institutes of Health Stroke Scale scores 〈 5 points. These experimental findings indicate that the combined application of various CT imaging methods allows early diagnosis of acute ischemic cerebrovascular disease, which can comprehensively analyze the pathogenesis and severity of acute ischemic cerebrovascular disease at the morphological and functional levels.

Associations between nonalcoholic fatty liver disease and ischemic stroke

Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease and affects a considerab-le proportion of the general population. NAFLD is independently associated with increased risk for cardiovascular events, particularly coronary heart disease. Importantly, even though NAFLD is more prevalent in patients with major cardiovascular risk factors(e.g., type 2 diab-etes mellitus, ob-esity and hypertension), the association b-etween NAFLD and cardiovascular disease appears to b-e independent of these risk factors. However, NAFLD also appears to increase the risk for ischemic stroke, a leading cause of mortality and long-term disab-ility worldwide. It also appears that nonalcoholic steatohepatitis is more strongly related to the risk of ischemic stroke than isolated hepatic steatosis. Moreover, emerging data suggest that patients with NAFLD experience more severe ischemic stroke and have more unfavorab-le prognosis after an acute ischemic stroke in terms of functional dependency and short-and long-term mortality. These associations have major pub-lic health implications, since ischemic stroke is the second leading cause of death worldwide and an important cause of long-term disab-ility. The aim of the present review is to summarize the current knowledge regarding the relationship b-etween NAFLD and ischemic stroke incidence, severity and outcome. Given these associations, it might b-e useful to evaluate patients with acute ischemic stroke for the presence of NAFLD and to manage those with NAFLD more aggressively.

Sonographic fatty liver, overweight and ischemic heart disease

AIM: To demonstrate the prevalence of sonographic fatty liver, overweight and ischemic heart disease (IHD) among the male workers in Taiwan, and to investigate the possible association of these three factors.METHODS: From July to September 2003, a total of 2 088 male aircraft-maintenance workers aged from 22to 65 years (mean 40.5) underwent an annual health examination, including anthropometrical evaluation, blood pressure measurement, personal medical history assessment,biochemical blood analysis, abdominal ultrasonographic examination and digital electrocardiography (ECG). The Student's t-test, x2 test and multivariate logistic regression analysis were utilized to evaluate the relationship between IHD and salient risk factors.RESULTS: The all-over prevalence of overweight was 41.4%, and that of fatty liver was 29.5% (mild, moderate and severe fatty liver being 14.5%, 11.3%, and 3.7%,respectively); while the prevalence of ischemic changes on ECG was 17.1% in this study. The abnormal rates for conventional IHD risk factors including hypertension,dyslipidemia, hyperglycemia and overweight increased in accordance with the severity of fatty liver. Overweight and severity of fatty liver were independently associated with increased risks for developing IHD. Overweight subjects had a 1.32-fold (95%CI: 1.01-1.73) increased IHD risk. Participants with mild, moderate, and severe fatty liver had a 1.88-fold (95%CI: 1.37-2.6), 2.37-fold (95%CI: 1.66-3.37) and 2.76-fold (95%CI: 1.62-4.72)increased risk for developing IHD. The prevalence of ischemic ECG for the fatty liver-affected subjects with or without overweight was 30.1% and 19.1%, while that of overweight subjects free from fatty liver was 14.4%.Compared to the subjects without fatty liver nor overweight,IHD risk for the three subgroups above was as follows:OR: 2.95 (95%CI:2.31-4.09), OR: 1.60 (95%CI: 1.07-2.39)and OR: 1.11 (95%CI: 0.78-1.56), respectively.CONCLUSION: The presence of fatty liver and its severity should be carefully considered as independent risk factors for IHD. Results of the study suggest the synergistic effect between fatty liver and overweight for developing IHD.Abdominal sonographic examination may provide valuable information for IHD risk assessment in addition to limited report about liver status, especially for overweight males.

Factors influencing ischemic cerebrovascular disease complicated by hyperhomocysteinemia

BACKGROUND： Hyperhomocysteinemia, as an important risk factor for ischemic cerebrovascular disease is receiving increasing attention. OBJECTIVE： To analyze whether differences of gender, age, cerebrovascular disease typing, and disease conditions exist when ischemic cerebrovascular disease occurs together with hyperhomocysteinemia. DESIGN： A controlled observation. SETTING： Department of Neurology, Tianjin Huanhu Hospital. PARTICIPANTS： A total of 601 acute ischemic cerebrovascular disease inpatients, comprising 386 males and 215 females, aged 33-90 years old, were admitted to the Department of Stroke, Tianjin Huanhu Hospital between August 2005 and April 2007, and were recruited for this study. All included patients consisted of 342 aged patients （≥ 60 years old） and 92 middle-aged and young patients （〈 60 years old）. Among these patients, 48 suffered from transient cerebral ischemic attack, 138 from lacunar cerebral infarction, 273 from atherosclerotic stroke, 38 from cardiogenic cerebral infarction, 44 from agnogenic ischemic stroke, and 6 from other factor-induced ischemic strokes. All included inpatients corresponded to the diagnosis criteria of acute ischemic cerebrovascular disease, formulated in the 4^th National Working Conference of Cerebrovascular Disease, and were confirmed as acute ischemic cerebral infarction by CT and/or MRI examinations. Informed consents of laboratory measurements were obtained from all subjects, and this study was approved by the Hospital＇s Ethics Committee. METHODS： Following admission, 2 mL venous blood was collected from each fasting patient on the third morning. Plasma homocysteine level was measured by an enzymatic cycling assay with a CX5 reader （Beckman, USA）. Plasma homocysteine levels ≥ 16μ mol/L were defined as hyperhomocysteinemia. Clinical neurological function deficit scoring was also performed for each ischemic stroke patient using Chinese stroke scales. Scores ranged from 0 45 （0-15： mild neurological function deficits, 16-30： moderate neurological deficits, and 31-45： severe neurological deficits）. The scores positively correlated with severity of stroke. MAIN OUTCOME MEASURES： Incidence of ischemic cerebrovascular disease patients complicated by hyperhomocysteinemia and the effects of patient age and gender; plasma homocysteine levels of each type of ischemic cerebrovascular disease; and effects of ischemic cerebrovascular disease conditions on plasma homocysteine levels. RESULTS： All 601 inpatients with acute ischemic cerebrovascular disease were included in the final analysis. The detection rate of homocysteine was significantly higher in aged patients than in middle-aged and young patients （ x^2 = 5.353 0, P 〈 0.05）. The incidence of hyperhomocysteinemia was significantly higher in male patients than in female patients （ x^2 = 9.484 4, P 〈 0.05）. There was no significant difference in the incidence of hyperhomocysteinemia among various types of ischemic cerebrovascular diseases （P 〉 0.05）. No significant difference in incidence of hyperhomocysteinemia existed between mild, moderate, and severe cerebrovascular disease patients （P 〉 0.05）. CONCLUSION： There is a greater chance of ischemic cerebrovascular disease complicated by hyperhomocysteinemia in older, male patients.

Stable ischemic heart disease in the older adults

1 Introduction Ischemic heart disease is caused by atherosclerotic and/or thrombotic obstruction of coronary arteries. Clinical spec- trum of ischemic heart disease expands from asymptomatic atherosclerosis of coronary arteries to acute coronary syn- dromes （ACS） including unstable angina, acute myocardial infarction （non-ST elevation myocardial infarction and ST elevation myocardial infarction）. Stable ischemic heart dis- ease （SIHD） refers to patients with known or suspected SIHD who have no recent or acute changes in their symp- tomatic status, suggesting no active thrombotic process is underway.

Meta-analysis of 5, 10-methylenetetrahydrofolate reductase gene polymorphism as a risk factor for ischemic cerebrovascular disease in a Chinese Han population

OBJECTIVE： To assess whether 5, 10-methylenetetrahydrofolate reductase （MTHFR） gene polymorphism （TT genotype or T allele） is a risk factor for ischemic cerebrovascular disease （ICVD）. DATA SOURCES： MEDLINE and PubMed databases from September 1997 to December 2009 were searched for case-control studies that examined MTHFR genotype in human ICVD using ＂MTHFR, gene, polymorphism, and ischemic cerebrovascular disease＂ as search key words. STUDY SELECTION： Eighteen associated studies were identified. The methods used to collect relevant information factors were similar between case and control groups, and diagnosis of ischemic cerebrovascular disease was in accordance with Trial of ORG 10172 in Acute Stroke Treatment criteria classification, with some referring to European Stroke Diagnostic Criteria. Quality of all included studies was evaluated, and meta-analysis was conducted using RevMan4.2 software （Cochrane Collaboration, http：//www.cochrane-handbook.org） following strict screening. MAIN OUTCOME MEASURES： The correlation between MTHFR gene TT genotype or T allele and ICVD was determined. RESULTS： Eighteen studies involving 4 295 patients with ICVD and 6 169 control subjects were included for this meta-analysis. There was a significant difference in MTHFR gene TT genotype or T allele frequency （x^2 = 15.737, 9.186, P 〈 0.01） between ICVD cases and controls. In addition, six Chinese Han population studies were specially reviewed by meta-analysis. Results showed no significant difference between ICVD and control groups with regard to frequency of MTHFR gene TT genotype and T allele （x^2 = 1.076, 2.434, P 〉 0.05） in the Chinese Han population. CONCLUSION： Results from the present meta-analysis suggested that the MTHFR gene TT genotype or T allele is a risk factor for ICVD. However, the TT genotype or T allele is not a risk factor for ICVD in the Chinese Han population.

β-FIBRINOGEN PROMOTER -455 G/A(HaeIII)POLYMORPHISM PREDICTION OF PLASMA FIBRINOGEN BUT NOT OF ISCHEMIC CEREBROVASCULAR DISEASE

Objective The -455 G/A(HaeIII)polymorphism of β-fibrinogen gene influences levels of plasma fibrinogen. We further investigated whether it influences the risk of ischemic cerebrovascular disease. Methods We accumulated 134 acute ischemic cerebrovascular disease(ICVD)cases and compared their -455 G/A status with a control group(n = 166). The β-fibrinogen gene -455 G/A polymorphism was analyzed for all subjects by PCR-RFLP with the restrictive enzyme HaeIII. Results Plasma fibrinogen was higher in AA homozygous participants(341 mg/dL)than in partici-pants carrying the G allele: GA(290 mg/dL), GG(298 mg/dL)in the control group. Plasma fibrinogen was also higher in AA homozygous patients(353 mg/dL)than in cases carrying the G allele: GA(287 mg/dL), GG(302 mg/dL)in the ICVD group. However, there was no significant association between β-fibrinogen gene -455 G/A polymorphism and ICVD group. Conclusions Although a small effect cannot be excluded, β-fibrinogen gene -455 G/A polymor-phism is an independent predictor of plasma fibrinogen, but not of ischemic cerebrovascular disease.

Sleep conditions and quality of life among patients with ischemic heart disease after elective percutaneous coronary intervention

In Japan, percutaneous coronary intervention (PCI) is a major therapeutic intervention for ischemic heart disease (IHD). Previous studies suggested that an association of the risk of IHD caused by sleep duration was related to factors closely associated with daily activities. However, in Japan, there is no study about this relationship objectively measured using the actigraphy in patients with IHD. Moreover, there is little reported data about sleep condition and early outcomes of patient’s Health-Related Quality of Life (QOL) after PCI. This study determines the correlations between sleep conditions and QOL (measured by SF36 version 2) of 25 patients with IHD who underwent elective PCI. Data were collected seven days after PCI using night-sleep condition. Using Spearman’s rank test, the results revealed positive correlation between vitality score and longest sleep duration (ρ = 0.43, p = 0.031): social functioning (SF) score and duration of night-time sleep (ρ = 0.42, p = 0.037);total sleep duration (ρ = 0.45, p = 0.026), and longest sleep duration (ρ = 0.44, p = 0.024);mental health score and longest sleep duration (ρ = 0.54, p = 0.006). However, negative correlation was found between physical functioning score and arousal during sleep (ρ = -0.44, p = 0.027). Sleep condition was significantly correlated with QOL. In particular, SF score was positively related to night-time sleep. This seems to indicate that SF score might be related to night-time sleep condition. Moreover, the longest sleep durations were correlated with the mental component summary. The results of the study suggest that not only the length of whole sleep durations leads to better QOL, but also the increase the amount of uninterrupted sleep.

Moving forward on the pathway of cell-based therapies in ischemic heart disease and heart failure-time for new recommendations?

Although substantial advances have been made in treating ischemic heart disease and subsequent heart failure, the overall morbidity and mortality from these conditions remain high. Stem cell-based therapy has emerged as a promising approach for prompting cardiac rejuvenation. Various cell types have been tested in the clinical arena, proving consistent safety results. As for efficiency outcomes, contradictory findings have been reported, partly due to inconsistency in study protocols but also due to poor survival, engraftment and differentiation of transplanted cells in the hostile milieu of the ischemic host tissue. Studies have varied in terms of route of delivery, type and dose of implanted stem cells, patient selection and randomization, and assessment of therapeutic effect. Founded on the main achievements and challenges within almost 20 years of research, a number of official documents have been published by leading experts in the field. Core recommendations have focused on developing and optimizing effective strategies to enrich cell retention and their regenerative potential. Issued consensus and position papers have stemmed from an unmet need to provide a harmonized framework for future research, resulting in improved therapeutic application of cell-based therapies for cardiac regeneration and repair.