Improved early stroke detection: wavelet-based perception enhancement of computerized tomography exams

Nonenhanced computerized tomography (CT) exams were used to detect acute stroke by notification of hypodense area. Infarction perception improvement by data denoising and local contrast enhancement in multi-scale domain was proposed. The wavelet-based image processing method enhanced the subtlest signs of hypodensity, which were often invisible in standard CT scan review. Thus improved detection efficiency of perceptual ischemic changes was investigated. Data processing became more effective by initial segmentation of brain tissue and extraction of regions susceptible to tissue density changes. The new method was experimentally verified. Sensitivity of stroke diagnosis increased to 56.3% in comparison to 12.5% of standard CT scan preview.     

Can we increase the speed and efficacy of antidepressant treatments? Part II. Glutamatergic and RNA interference strategies

In the second part we focus on two treatment strategies that may overcome the main limitations of current antidepressant drugs. First, we review the experimental and clinical evidence supporting the use of glutamatergic drugs as fast-acting antidepressants. Secondly, we review the involvement of microRNAs (miRNAs) in the pathophysiology of major depressive disorder (MDD) and the use of small RNAs (e.g.., small interfering RNAs or siRNAs) to knockdown genes in monoaminergic and non-monoaminergic neurons and induce antidepressant-like responses in experimental animals.The development of glutamatergic agents is a promising venue for antidepressant drug development, given the antidepressant properties of the non-competitive NMDA receptor antagonist ketamine. Its unique properties appear to result from the activation of AMPA receptors by a metabolite [(2 S,6 S;2 R,6 R)-hydroxynorketamine (HNK)] and mTOR signaling. These effects increase synaptogenesis in prefrontal cortical pyramidal neurons and enhance serotonergic neurotransmission via descending inputs to the raphe nuclei. This view is supported by the cancellation of ketamine's antidepressant-like effects by inhibition of serotonin synthesis.We also review existing evidence supporting the involvement of miRNAs in MDD and the preclinical use of RNA interference (RNAi) strategies to target genes involved in antidepressant response. Many miRNAs have been associated to MDD, some of which e.g., miR-135 targets genes involved in antidepressant actions. Likewise, SSRI-conjugated siRNA evokes faster and/or more effective antidepressant-like responses. Intranasal application of sertraline-conjugated siRNAs directed to 5-HT_1A receptors and SERT evoked much faster changes of pre- and postsynaptic antidepressant markers than those produced by fluoxetine.     

吡拉西坦注射液联合胞磷胆碱注射液治疗缺血性脑卒中的临床研究

目的观察吡拉西坦注射液联合胞磷胆碱注射液治疗缺血性脑卒中的临床疗效与安全性。方法将94例缺血性脑卒中患者随机分为对照组47例和试验组47例。对照组予以吡拉西坦每次20 g,qd,静脉注射;试验组在对照组治疗的基础上,予以胞磷胆碱每次0.5 g,qd,静脉滴注。2组患者均治疗14 d。比较2组患者的临床疗效、血清单核细胞趋化蛋白-1(MCP-1)、同型半胱氨酸(HCY)、高密度脂蛋白胆固醇(HDL-C)水平,以及药物不良反应的发生情况。结果治疗后,试验组和对照组的总有效率分别为87.23%(41例/47例)和63.83%(30例/47例),差异有统计学意义(P<0.05)。治疗后,试验组和对照组的血清MCP-1分别为(90.74±10.33)和(120.71±15.42)pg·mL^-1,HCY分别为(16.68±2.24)和(21.01±3.03)μmol·L^-1,HDL-C分别为(1.31±0.16)和(1.12±0.13)mmol·L^-1,差异均有统计学意义(均P<0.05)。试验组发生的药物不良反应以失眠、食欲缺乏和口干为主,对照组发生的药物不良反应以皮疹、腹泻和低血压为主。试验组和对照组的总药物不良反应发生率分别为10.64%和14.89%,差异无统计学意义(P>0.05)。结论吡拉西坦注射液联合胞磷胆碱注射液治疗缺血性脑卒中的临床疗效确切,其能显著降低患者的血清MCP-1及HCY水平,升高HDL-C水平,且不增加药物不良反应的发生率。     

Non-coding RNAs as therapeutic targets for preventing myocardial ischemia-reperfusion injury

Introduction: New treatments are required to improve clinical outcomes in patients with acute myocardial infarction (AMI), for reduction of myocardial infarct (MI) size and preventing heart failure. Following AMI, acute ischemia/reperfusion injury (IRI) ensues, resulting in cardiomyocyte death and impaired cardiac function. Emerging studies have implicated a fundamental role for non-coding RNAs (microRNAs [miRNA], and more recently long non-coding RNAs [lncRNA]) in the setting of acute myocardial IRI.

Areas covered: In this article, we discuss the roles of miRNAs and lncRNAs as potential biomarkers and therapeutic targets for the detection and treatment of AMI, review their roles as mediators and effectors of cardioprotection, particularly in the settings of interventions such as ischemic pre- and post-conditioning (IPC & IPost) as well as remote ischemic conditioning (RIC), and highlight future strategies for targeting ncRNAs to reduce MI size and prevent heart failure following AMI.

Expert opinion: Investigating the roles of miRNAs and lncRNAs in the setting of AMI has provided new insights into the pathophysiology underlying acute myocardial IRI, and has identified novel biomarkers and therapeutic targets for detecting and treating AMI. Pharmacological and genetic manipulation of these ncRNAs has the therapeutic potential to improve clinical outcomes in AMI patients.     

经颅多普勒超声联合颈动脉超声对缺血性脑血管病的诊断价值

目的分析经颅多普勒超声(TCD)联合颈动脉超声对缺血性脑血管病的诊断价值。方法选取缺血性脑血管病患者93例,均行数字减影血管造影(DSA)、TCD及颈动脉超声检查,并以DSA结果为诊断标准,比较TCD和颈动脉超声单用及两者联合的检查结果,分析三者在缺血性脑血管病中的诊断灵敏度、特异度、阳性预测值及阴性预测值。结果 93例患者颅内外异常血管共763条。单用TCD显示颅内血管异常73例,异常血管294条;单用颈动脉超声显示颅外血管异常64例,异常血管275条;TCD联合颈动脉超声显示颅内外血管异常89例,异常血管569条。TCD联合颈动脉超声在缺血性脑血管病诊断方面的灵敏度、特异度、阳性预测值及阴性预测值均高于单用TCD及单用颈动脉超声。结论 TCD联合颈动脉超声可提高缺血性脑血管病诊断的准确性,可作为颅内外血管病变诊断的有效检查手段。     

急性缺血性卒中患者白细胞计数水平及其与短期预后不良关系

目的了解急性缺血性卒中患者白细胞计数水平及其与短期预后不良的关系,为急性缺血性卒中的预防控制提供参考依据。方法于2015年1月1日—2015年8月31日在中国医科大学附属第一医院鞍山医院、丹东市第一医院、辽阳县医院和大洼县医院采用回顾性队列研究方法收集1 591例急性缺血性卒中患者,分析其白细胞计数水平及其与短期预后不良的关系。结果本次调查的1 591例急性缺血性卒中患者改良Rankin量表(m RS)得分为(1.47±1.79)分;其中,无残疾组患者1 219例(76.6%),残疾组患者284例(17.9%),死亡患者88例(5.5%);共372例患者(23.4%)为短期预后不良。在控制了性别、年龄、缺血性脑卒中病史和胱抑素C水平等混杂因素后,多因素非条件logistic回归分析结果显示,白细胞计数为6.50×10~9/L^8.09×10~9/L和≥8.10×10~9/L急性缺血性卒中患者短期预后不良的发生风险分别为白细胞计数<5.30×10~9/L患者的2.382倍(OR=2.382,95%CI=1.445~3.925)和2.531倍(OR=2.531,95%CI=1.574~4.069)。结论白细胞计数水平是急性缺血性卒中患者短期预后不良的独立危险因素。     

Vascular stiffness in familial hypercholesterolaemia is associated with C-reactive protein and cholesterol burden

BACKGROUND: Familial hypercholesterolaemia (FH) is characterized by very high serum cholesterol and premature coronary atherosclerosis. Arterial stiffness and atherosclerosis are two major underlying pathophysiologies of arterial disease that are predictive of future cardiovascular events. The aims of this study were to quantify atherosclerosis and arterial stiffness and to evaluate their relationship with high sensitive C-reactive protein (hs-CRP) and the level of exposure to high serum cholesterol in FH patients. Materials AND METHODS: We measured traditional risk factors, hs-CRP, intima-media thickness (IMT) of carotid artery, and brachial-ankle pulse wave velocity (baPWV) in 35 heterozygous FH subjects and 17 healthy control subjects. Cholesterol-year score (CYS) was calculated to estimate the lifetime cholesterol burden in FH subjects. RESULTS: FH subjects had significantly elevated total cholesterol, low-density lipoprotein cholesterol, and carotid IMT compared with those without mutations. Among FH patients, the baPWV and carotid IMT were higher in cases with high cholesterol burden than those without. Similarly, the baPWV and carotid IMT were also higher in cases with elevated hs-CRP (> 1 mg L(-1)) than those without. Multiple linear regression analysis demonstrated CYS and hs-CRP were significant independent predictors of baPWV and IMT in FH patients. CONCLUSIONS: Both high cholesterol burden and vascular inflammation are not only associated with atherosclerosis, but also contribute to the development of arterial stiffness in FH patients. Early detection of hypercholesterolaemia in FH patients is warranted to prevent the untoward pathophysiologies.     

Prediction of conversion from paroxysmal to permanent atrial fibrillation

BACKGROUND: Paroxysmal atrial fibrillation (PAF) transits to permanent atrial fibrillation (PEAF). The current study was to determine whether a P wave-triggered P wave signal averaged electrocardiogram (P-SAECG) and chemoreflexsensitivity (CHRS) are useful to predict a conversion to PEAF in patients with PAF. METHODS: The filtered P wave duration (FPD) and the root mean square voltage of the last 20 ms of the P wave (RMS 20) were measured by P-SAECG. The ratio between the difference of RR intervals in the ECG and venous pO2 before and after 5-minutes oxygen inhalation is measured (ms/mmHg) for the determination of CHRS. Results: A total of 180 patients with PAF were enrolled and followed for a mean of 22.5 months. PEAF occurred in 38 patients (21%) and these patients had a significantly larger left atrial size (43.2 +/- 4.9 vs. 41.0 +/- 5.4 mm, P = 0.021), a significantly longer FPD (158.8 +/- 18.2 vs. 136.7 +/- 16.6 ms, P < 0.0001), and a significantly lower CHRS (1.96 +/- 0.99 vs. 2.44 +/- 1.19 ms/mmHg, P = 0.024) than patients with PAF. Patients with PEAF tended to have a lower RMS 20 (2.38 +/- 0.65 vs. 2.75 +/- 1.18 microV, P = 0.067) than patients with PAF. The chi(2) test showed that the combination of FPD > or = 145 ms, RMS 20 < or = 3.0 microV, left atrial size > or = 41 mm, and CHRS < or = 2.0 ms/mmHg had the best predictive power for PEAF. Patients who fulfilled these criteria had a 12-fold increased risk for a conversion from PAF to PEAF. CONCLUSIONS: Our results show that a P-SAECG, an analysis of CHRS, and left atrial enlargement are clinical predictors of a progression from PAF to PEAF.