BACKGROUND & AIMS: :The mechanisms underlying the age-dependent reversal of female cardioprotection are poorly understood and complicated by findings that estrogen replacement is ineffective at reducing cardiovascular mortality in postmenopausal women. Although several protective signals have been identified in young animals, including PKC and Akt, how these signals are affected by age, estrogen deficiency, and ischemia-reperfusion (I/R) remains unknown. To determine the independent and combined effects of age and estrogen deficiency on I/R injury and downstream PKC-Akt signaling, adult and aged female F344 rats (n = 12/age) with ovaries intact or ovariectomy (Ovx) were subjected to I/R using Langendorff perfusion (31-min global-ischemia). Changes in cytosolic (s), nuclear (n), mitochondrial (m) PKC (delta, epsilon) levels, and changes in total Akt and mGSK-3beta phosphorylation after I/R were assessed by Western blot analysis. Senescence increased infarct size 50% in ovary-intact females (P < 0.05), whereas no differences in LV functional recovery or estradiol levels were observed. Ovx reduced functional recovery to a greater extent in aged compared with adult rats (P < 0.05). In aged (vs. adult), levels of m- and nPKC(-delta, -epsilon) were markedly decreased, whereas mGSK3beta levels were increased (P < 0.05). Ovx led to greater levels of sPKC(-delta, -epsilon) independent of age (P < 0.05). I/R reduced p-Akt(Ser473) levels by 57% and increased mGSK-3beta accumulation 1.77-fold (P < 0.05) in aged, ovary-intact females. These data suggest, for the first time, that estrogen alone cannot protect the aged female myocardium from I/R damage and that age- and estrogen-dependent alterations in PKC, Akt, and GSK-3beta signaling may contribute to loss of ischemic tolerance.

背景与目标： ：对雌性心脏保护的年龄依赖性逆转的潜在机制了解甚少，并且因发现雌激素替代不能有效降低绝经后妇女的心血管死亡率而使之复杂化。尽管已在幼小的动物中鉴定出了几种保护性信号，包括PKC和Akt，但这些信号如何受到年龄，雌激素缺乏和缺血再灌注（I / R）的影响仍然未知。为了确定年龄和雌激素缺乏对I / R损伤和下游PKC-Akt信号传导的独立和综合影响，对成年卵巢或卵巢切除术（Ovx）的成年和成年雌性F344大鼠（n = 12 /年龄）进行I / R使用Langendorff灌注（31分钟全球缺血）。通过蛋白质印迹分析评估I / R后细胞质，核仁，线粒体PKC（δ，ε）水平的变化，以及总Akt和mGSK-3beta磷酸化的变化。卵巢完整的女性衰老使梗塞面积增加50％（P <0.05），而在LV功能恢复或雌二醇水平上未观察到差异。与成年大鼠相比，Ovx在老年人中降低的功能恢复程度更大（P <0.05）。在老年人（相对于成年人）中，m-和nPKC（-δ，-ε）水平显着降低，而mGSK3beta水平升高（P <0.05）。 Ovx导致更高水平的sPKC（-delta，-epsilon）与年龄无关（P <0.05）。 I / R在老年卵巢完整女性中将p-Akt（Ser473）水平降低了57％，并使mGSK-3beta积累增加了1.77倍（P <0.05）。这些数据首次表明，单独的雌激素不能保护老年女性心肌免受I / R损伤，PKC，Akt和GSK-3beta信号的年龄和雌激素依赖性改变可能导致缺血耐受性降低。

BACKGROUND & AIMS: UNLABELLED:In this study, protective effects of adenosine and acetylcholine-induced postconditioning were investigated on the contractile function of the ischemic isolated rat ventricular myocytes. A video-based edge-detection system was used to monitor single ventricular myocytes contraction. Adenosine and acetylcholine were administrated for 6 min before ischemia as preconditioning, or 15 min after ischemia as postconditioning. Adenosine and acetylcholine receptor antagonists and mitoKATP inhibitor were used to analyze pathways underlying the effects on postconditioning. RESULTS:(1) The peak shortening of ischemic heart cells was improved by both adenosine and acetylcholine during preconditioning (84.72+/-5.34% and 68.61+/-8.10% vs. control: 8.43+/-5.35% of the pre-ischemia value), as well as postconditioning (76.47+/-7.87% and 57.48+/-6.97% vs. control: 8.43+/-5.35% of the pre-ischemia value) and the effects of preconditioning and postconditioning were comparable. More datum in the normal text. (2) Observed effects of adenosine and acetylcholine postconditioning were missing in the presence of adenosine A1 receptor and muscarinic M2 receptor antagonists, respectively. (3) Adenosine and acetylcholine-induced postconditioning was also blocked by mitoKATP antagonist. These results suggest that both adenosine and acetylcholine protect the contractile function of ischemic heart cells to a similar extent during preconditioning and postconditioning. The postconditioning of adenosine and acetylcholine is relative to the adenosine A1 and muscarinic M2 receptors, respectively. MitoKATP is implicated in the postconditioning of both acetylcholine and adenosine.

背景与目标： 未标记：在本研究中，研究了腺苷和乙酰胆碱诱导的后处理对缺血性离体大鼠心室肌细胞收缩功能的保护作用。基于视频的边缘检测系统用于监测单个心室肌细胞的收缩。缺血前6分钟给予腺苷和乙酰胆碱作为预处理，缺血后15分钟给予腺苷和乙酰胆碱作为后处理。腺苷和乙酰胆碱受体拮抗剂以及mitoKATP抑制剂被用于分析对后处理的影响的潜在途径。
结果：（1）腺苷和乙酰胆碱在预处理过程中均改善了缺血性心脏细胞的峰缩短（与对照组相比分别为84.72 /-5.34%和68.61 /-8.10%：缺血前值的8.43 /-5.35%），以及后处理（相对于对照组，分别为76.47 /-7.87%和57.48 /-6.97%：缺血前值的8.43 /-5.35%），并且预处理和后处理的效果可比。普通文本中的基准面更多。 （2）在腺苷A1受体和毒蕈碱M2受体拮抗剂的存在下，腺苷和乙酰胆碱后处理的观察到的作用分别消失了。 （3）腺苷和乙酰胆碱引起的后处理也被mitoKATP拮抗剂阻断。这些结果表明，腺苷和乙酰胆碱在预处理和后处理过程中均以相似的程度保护缺血性心脏细胞的收缩功能。腺苷和乙酰胆碱的后处理分别相对于腺苷A1和毒蕈碱M2受体。 MitoKATP与乙酰胆碱和腺苷的后处理有关。

BACKGROUND & AIMS: BACKGROUND:Early detection of poststroke depression (PSD) and cognitive impairment (PSCI) remains challenging. It is well documented that the function of autonomic nervous system is associated with depression and cognition. However, their relationship has never been investigated in the early poststroke phase. This pilot study aimed at determining whether resting heart rate (HR) parameters measured in early poststroke phase (1) are associated with early-phase measures of depression and cognition and (2) could be used as new tools for early objective prediction of PSD or PSCI, which could be applicable to patients unable to answer usual questionnaires. METHODS:Fifty-four patients with first-ever ischemic stroke, without cardiac arrhythmia, were assessed for resting HR and heart rate variability (HRV) within the first week after stroke and for depression and cognition during the first week and at 3 months after stroke. RESULTS:Multiple regression analyses controlled for age, gender, and stroke severity revealed that higher HR, lower HRV, and higher sympathovagal balance (low-frequency/high-frequency ratio of HRV) were associated with higher severity of depressive symptoms within the first week after stroke. Furthermore, higher sympathovagal balance in early phase predicted higher severity of depressive symptoms at the 3-month follow-up, whereas higher HR and lower HRV in early phase predicted lower global cognitive functioning at the 3-month follow-up. CONCLUSIONS:Resting HR measurements obtained in early poststroke phase could serve as an objective tool, applicable to patients unable to complete questionnaires, to help in the early prediction of PSD and PSCI.

背景与目标： 背景：早期检测中风后抑郁症（PSD）和认知障碍（PSCI）仍然具有挑战性。有充分的文献证明，自主神经系统的功能与抑郁和认知有关。但是，他们的关系在中风后早期还没有被研究过。这项前瞻性研究旨在确定卒中后早期阶段的静息心率（HR）参数是否与抑郁和认知的早期阶段指标相关；（2）可用作早期客观预测PSD的新工具或PSCI，可能适用于无法回答常规问卷的患者。
方法：对54例首次有缺血性中风的无心律失常的患者进行评估，评估其在卒中后第一周内的静息心率和心率变异性（HRV），以及在卒中后第一周和三个月内的抑郁和认知能力。
结果：对年龄，性别和中风严重程度进行的多项回归分析显示，较高的HR，较低的HRV和较高的交感神经平衡（HRV的低频/高频比率）与第一周内抑郁症状的严重程度较高相关中风后。此外，较高的早期交感神经平衡表示在3个月的随访中抑郁症状的严重程度较高，而较高的HR和较低的HRV则表明在3个月的随访中总体认知功能较低。
结论：在卒中后早期恢复心率测量可作为一种客观工具，适用于无法完成问卷调查的患者，有助于早期预测PSD和PSCI。

BACKGROUND & AIMS: :Neuroinflammation, especially activation of microglia, the key immune cells in the brain, has been proposed to contribute to the pathogenesis of ischemic stroke. However, the dynamics and the potential mediators of microglial activation following ischemic neuronal injury are not well understood. In this study, using oxygen/glucose deprivation and reoxygenation with neuronal and microglial cell cultures as an in vitro model of ischemic neuronal injury, we set out to identify neuronal factors released from injured neurons that are capable of inducing microglial activation. Conditioned media (CM) from hippocampal and cortical neurons exposed to oxygen/glucose deprivation and reoxygenation induced significant activation of microglial cells as well as primary microglia, evidenced by up-regulation of inducible nitric oxide synthase, increased production of nitrite and reactive oxygen species, and increased expression of microglial markers. Mechanistically, neuronal ischemia-responsive protein 94 (Irp94) was a key contributor to microglial activation since significant increase in Irp94 was detected in the neuronal CM following ischemic insult and immunodepletion of Irp94 rendered ischemic neuronal CM ineffective in inducing microglial activation. Ischemic insult-augmented oxidative stress was a major facilitator of neuronal Irp94 release, and pharmacological inhibition of NADPH oxidase significantly reduced the ischemic injury-induced neuronal reactive oxygen species production and Irp94 release. Taken together, these results indicate that neuronal Irp94 may play a pivotal role in the propagation of ischemic neuronal damage. Continued studies may help identify Irp94 and/or related proteins as potential therapeutic targets and/or diagnostic/prognostic biomarkers for managing ischemia-associated brain disorders.

背景与目标： 已经提出：神经炎症，特别是小胶质细胞的激活，小胶质细胞是大脑中的关键免疫细胞，有助于缺血性中风的发病。然而，尚不清楚缺血性神经元损伤后小胶质细胞激活的动力学和潜在的介质。在这项研究中，将缺氧/葡萄糖剥夺和再充氧与神经元和小胶质细胞培养物一起用作缺血性神经元损伤的体外模型，我们着手确定从受伤的神经元释放的能够诱导小胶质细胞活化的神经元因子。来自暴露于氧气/葡萄糖剥夺和再充氧的海马和皮质神经元的条件培养基（CM）诱导了小胶质细胞以及原代小胶质细胞的显着活化，这可通过诱导型一氧化氮合酶的上调，亚硝酸盐和活性氧的产生增加来证明并增加小胶质细胞标志物的表达。从机理上讲，神经元缺血响应蛋白94（Irp94）是小胶质细胞激活的关键因素，因为在缺血性损伤后神经元CM中检测到Irp94的显着增加，并且Irp94的免疫耗竭使得缺血性神经元CM不能诱导小胶质细胞激活。缺血性损伤加剧的氧化应激是神经元Irp94释放的主要促进因素，并且NADPH氧化酶的药理抑制作用显着降低了缺血性损伤诱导的神经元活性氧的产生和Irp94的释放。综上，这些结果表明神经元Irp94可能在缺血性神经元损伤的传播中起关键作用。继续进行的研究可能有助于将Irp94和/或相关蛋白识别为潜在的治疗靶标和/或诊断/预后生物标记物，以治疗与缺血相关的脑部疾病。

BACKGROUND & AIMS: :D-dimer is a product of cross linked fibrin degradation and is a measure of the amount of fibrin turnover. As such, D-dimer might be of utility in the prediction of both thrombotic and hemorrhagic events. Therefore, the aim of the present study was to evaluate whether elevated D-dimer levels on admission and at discharge could predict subsequent ischemic and hemorrhagic events in patients with acute myocardial infarction (AMI). D-dimer was measured on admission and at discharge in 461 out of a total of 3,602 patients in the HORIZONS-AMI trial, as part of the formal prespecified biomarker substudy. The predictive value for major adverse cardiovascular events (MACE) and non-CABG major bleeding after 3 year follow up was investigated by stratifying patients in groups of D-dimer level and comparing event rates using Kaplan-Meier and calculating hazard ratios using Cox proportional hazards models. D-dimer levels ≥ 0.71 μg/mL on admission were associated with an adjusted hazard ratio of 2.58 for MACE (p = 0.0014) and 4.61 for major bleeding (p = 0.0018). A discharge D-dimer level ≥ 1.26 μg/mL was associated with a higher risk for MACE by univariate analysis (HR 1.88, p = 0.037), but lost its significance after multivariate adjustment (HR 1.77, p = 0.070). High D-dimer levels on admission were associated with a higher risk of MACE and non-CABG major bleeding in STEMI patients undergoing pPCI.

背景与目标： ：D-二聚体是交联的纤维蛋白降解的产物，是纤维蛋白周转量的量度。这样，D-二聚体可能在血栓形成和出血事件的预测中都有用。因此，本研究的目的是评估急性心肌梗死（AMI）患者入院时和出院时D-二聚体水平升高是否可以预测随后的缺血和出血事件。作为正式的预先指定生物标志物子研究的一部分，在HORIZONS-AMI试验中，总共3,602名患者中的461名入院时和出院时测量了D-二聚体。通过对D-二聚体水平组中的患者进行分层并使用Kaplan-Meier比较事件发生率并使用Cox比例风险计算风险比来研究3年随访后重大不良心血管事件（MACE）和非CABG重大出血的预测价值楷模。入院时D-二聚体水平≥0.71μg/ mL与调整后的MACE危险比（p = 0.0014）为2.58（p = 0.0018）和4.61重大出血（p = 0.0018）相关。单变量分析显示，排出D-二聚体水平≥1.26μg/ mL与发生MACE的风险较高相关（HR 1.88，p = 0.037），但在进行多变量调整后（HR 1.77，p = 0.070）失去了意义。接受pPCI的STEMI患者入院时高D-二聚体水平与发生MACE和非CABG大出血的风险较高相关。

BACKGROUND & AIMS: :Previous studies have shown associations of fetuin-A (alpha2-Heremans-Schmid glycoprotein, AHSG) with various disorders, including insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and atherosclerosis. In this study, genotype and allele frequencies of the rs4918 SNP in the AHSG gene were examined in 380 patients with ischemic stroke and 350 healthy controls from a Northern Han Chinese population via the PCR-RFLP technique. Frequencies of the GG genotype and the G allele in AHSG (rs4918) were significantly higher in patients with ischemic stroke or atherosclerotic cerebral infarction than those in the control group (P < 0.05). Logistic regression analysis demonstrated the significance of rs4918 in these patients, after adjustment for confounding factors (P < 0.05). These findings suggest that rs4918 SNPs of the AHSG gene are associated with a risk for ischemic stroke in a Northern Han Chinese population.

背景与目标： ：先前的研究表明胎球蛋白A（α2-Heremans-Schmid糖蛋白，AHSG）与多种疾病相关，包括胰岛素抵抗，2型糖尿病，代谢综合征和动脉粥样硬化。在这项研究中，通过PCR-RFLP技术检测了380名来自中国北方汉族人群的缺血性卒中患者和350名健康对照的AHSS基因中rs4918 SNP的基因型和等位基因频率。在缺血性中风或动脉粥样硬化性脑梗死患者中，AHSSG中GG基因型和G等位基因的频率显着高于对照组（P <0.05）。校正混杂因素后，Logistic回归分析证明了rs4918在这些患者中的意义（P <0.05）。这些发现表明，在北方汉族人群中，AHSS基因的rs4918 SNP与缺血性中风的风险有关。

BACKGROUND & AIMS: :Antisera directed against the 48 kDa and 50 kDa cytoskeletal antigens were used to examine changes in the astroglial fabric of the goldfish visual pathways following optic nerve crush. Several major observations are described. First, an optic nerve crush lesion in these animals appears to be devoid of glial cells for at least the first month after surgery. As a corollary, regenerating axons that grow across the lesion may do so over an aglial substrate. Once the axons cross the lesion, their growth is confined to the astroglial domains of the proximal nerve stump. In the optic nerve, gliosis comprises hypertrophy of astrocytic processes such that the open framework characterizing the normal nerve is obscured. In addition, during regeneration, optic nerve glia express large amounts of the 50 kDa cytoskeletal protein, which they ordinarily express at only minimal levels. In the optic tract, gliosis is reflected in a markedly increased expression of the 50 kDa protein as well as an apparent increase in the number and complexity of glial processes. In addition, optic tract glia begin to express the 48 kDa antigen during regeneration. This protein is ordinarily confined for the most part to the optic nerve and is not seen in the tract glia. Finally, no obvious changes were seen in the glia of the optic tectum. These results demonstrate many points of similarity between gliosis in the goldfish and in mammals. However, in some particulars the two responses differ, and it is possible that these differences are related to the differing ability of central axons to regenerate in the two groups of organisms.

背景与目标： ：针对48 kDa和50 kDa细胞骨架抗原的抗血清用于检查视神经挤压后金鱼视觉通路的星形胶质纤维的变化。描述了几个主要的观察结果。首先，这些动物的视神经挤压病变至少在术后第一个月似乎没有神经胶质细胞。必然的结果是，在病变处生长的再生轴突可以在胶质基质上生长。一旦轴突穿过病变，它们的生长就被限制在近端神经残端的星形胶质结构域。在视神经中，神经胶质增生包括星形细胞过程的肥大，使得表征正常神经的开放框架被遮盖。另外，在再生期间，视神经胶质表达大量的50kDa细胞骨架蛋白，它们通常仅以最小的水平表达。在视道中，神经胶质增生反映为50 kDa蛋白的表达显着增加以及神经胶质过程的数量和复杂性明显增加。此外，视神经胶质细胞在再生过程中开始表达48 kDa抗原。该蛋白通常大部分局限于视神经，在胶质细胞胶质细胞中看不到。最后，在视神经胶质的胶质细胞中未见明显变化。这些结果证明了金鱼和哺乳动物的神经胶质增生之间有许多相似点。但是，在某些情况下，这两种反应是不同的，并且这些差异可能与中央轴突在两组生物体中再生的能力不同有关。

BACKGROUND & AIMS: :Warfarin decreases risk of stroke for patients with atrial fibrillation (AF) dependent on percent time in the therapeutic range (TTR) with an international normalized ratio (INR) of 2 to 3. We hypothesized that gender differences in ischemic stroke risk are related to TTR. From the AFFIRM database of 4,060 patients with AF, we determined the incidence of ischemic stroke by gender. We evaluated the INR at time of ischemic stroke and calculated TTR. We determined the relation between gender and ischemic stroke by TTR. Women had CHADS(2) Scores (3.7 ± 1.3 vs 2.5 ± 1.3, p <0.0001) and more ischemic strokes than men (5% vs 3%, odds ratio 1.6, 95% confidence interval 1.19 to 2.26, p = 0.002). Mean INR near time of ischemic stroke was 2 for women and men; median values were subtherapeutic (1.7 and 1.8, respectively). Women spent more time outside the therapeutic range (40 ± 0.7% vs 37 ± 0.5%, p = 0.0001), with more time below the therapeutic range (29 ± 0.7% vs 26 ± 0.5%, p = 0.0002). A higher TTR protected against ischemic stroke for women but not for men. Women who had a comparably high TTR (≥66%) still had more ischemic strokes (p = 0.009). A fitted Cox proportional hazard regression model showed that gender, TTR <46% versus >80%, age, and previous stroke were significantly related to stroke incidence. In conclusion, women in AFFIRM were at greater risk of ischemic stroke than men, in part related to differences in TTR. Women with AF may benefit from more aggressive or novel anticoagulation to decrease their risk of stroke.

背景与目标： ：华法林降低心房纤颤（AF）患者的中风风险，这取决于治疗范围（TTR）中的百分比时间，国际标准化比率（INR）为2至3。我们假设缺血性中风风险的性别差异与TTR。从AFFIRM数据库中的4,060例AF患者中，我们按性别确定了缺血性中风的发生率。我们评估了缺血性卒中时的INR，并计算了TTR。我们通过TTR确定了性别与缺血性中风之间的关系。女性的CHADS（2）得分（3.7±1.3 vs 2.5±1.3，p <0.0001）和缺血性中风的比例高于男性（5％vs 3％，优势比1.6，95％置信区间1.19至2.26，p = 0.002）。男性和女性在缺血性卒中附近的平均INR为2；中位数是亚治疗的（分别为1.7和1.8）。女性在治疗范围之外花费的时间更多（40±0.7％vs 37±0.5％，p = 0.0001），而在治疗范围以下的时间更多（29±0.7％vs 26±0.5％，p = 0.0002）。较高的TTR可以保护女性免受缺血性中风的侵害，而男性则不能。 TTR相对较高（≥66％）的女性仍有更多的缺血性中风（p = 0.009）。拟合的Cox比例风险回归模型显示，性别，TTR <46％对> 80％，年龄和以前的中风与中风发生率显着相关。总之，AFFIRM中的女性患缺血性中风的风险比男性高，部分原因是TTR的差异。患有AF的女性可能会从更具侵略性或新颖性的抗凝治疗中受益，以减少中风的风险。

BACKGROUND & AIMS: :Purpose: Using a new analysis program for scanning laser-Doppler flowmetry (SLDF) by a Heidelberg retina flowmeter (HRF), we studied the relation between flow and visual field or disc morphology.Subjects and Methods: In 42 eyes of 21 patients with normal tension glaucoma (NTG) the mean-flow of the HRF blood flow parameters at the disc rim was measured and analyzed by a new analysis program for perfusion maps (the SLDF analysis tool), to minimize the influence of large vessels or/and artifacts caused by small eye movements. We investigated whether difference of the mean-flow between a pair of eyes had any relation to differences between a pair of eyes in visual field indices and those in disc morphological measurements of the Heidelberg retina tomograph.Results: We found statistically significant correlations between the mean-flow and optic disc parameters (Disk Area, Cup Area, Height Variation Contour, Cup Volume, Rim Volume, Mean RNFL Thickness). We found no statistically significant correlations between the mean-flow and visual field parameters (mean deviation, corrected pattern standard deviation).Conclusion: The results suggested that eyes with less flow in the optic disc rim have more advanced glaucomatous morphological changes.

背景与目标： 目的：使用海德堡视网膜流量计（HRF）的新型分析程序扫描激光多普勒血流仪（SLDF），研究血流与视野或椎间盘形态之间的关系。对象与方法：在21例患有眼疾的患者的42眼中正常张力性青光眼（NTG）通过新的灌注图分析程序（SLDF分析工具）测量并分析了椎间盘边缘HRF血流参数的平均流量，以最大程度地减少大血管或/和伪影的影响眼睛的小动作引起的。我们调查了两只眼睛的平均流量差异与两只眼睛在视野指数和海德堡视网膜断层扫描仪的椎间盘形态测量中的差异是否有任何关系。结果：我们发现平均值之间存在统计学上的显着相关性流量和光盘参数（磁盘面积，杯面积，高度变化轮廓，杯体积，轮辋体积，平均RNFL厚度）。我们发现，平均流量与视野参数（均值偏差，校正后的模式标准偏差）之间无统计学意义的相关性。结论：结果表明，视盘边缘流动较少的眼睛的青光眼形态学改变更为明显。

BACKGROUND & AIMS: :Abstract An accumulating number of studies are revealing that platelet reactivity above specific cut-off scores leads to exponentially increased rates of post-percutaneous coronary intervention (PCI) ischemic events. To evaluate the optimal predictive values for three different platelet function measurement assays of platelet reactivity on early clinical outcomes in Korean patients undergoing PCI, we enrolled 228 patients receiving clopidogrel prior to PCI. Platelet reactivity was measured by light transmittance aggregometry (LTA), VerifyNow P2Y12 assay, and multiple electrode platelet aggregometry (MEA). The primary endpoint was the 30-day occurrence of ischemic events after PCI. MACE occurred in 36 patients (15.8%), including 35 patients (15.4%) with periprocedural MI and the death of one patient (0.4%). ADP-induced LTA and VerifyNow values (pre- and post-PCI) were significantly higher in patients with the subsequent occurrence of periprocedural MI, but the MEA assay data (PCI and post-PCI) displayed no significant differences (pre-PCI p=0.25 and post-PCI p=0.33). ROC curve analysis demonstrated HPR values for LTA (pre-PCI, >66% and post-PCI, >53 %, all p<0.001), VerifyNow (pre-PCI, >347 PRU and post-PCI >272 PRU, all p<0.001) and MEA (pre-PCI, >50 U and post-PCI >39 U, all p>0.05). The platelet reactivity measurements by LTA and the VerifyNow assay can discriminate the risk of 30-day ischemic events after PCI. The predictive cut-off values for adverse events are dependent on sampling time.

背景与目标： 摘要：越来越多的研究表明，超过特定临界值的血小板反应性会导致经皮冠状动脉介入治疗（PCI）缺血事件的发生率呈指数增加。为了评估在接受PCI手术的韩国患者中进行血小板反应性对早期临床结局的三种不同血小板功能测量测定的最佳预测值，我们招募了228名在接受PCI前接受氯吡格雷的患者。血小板反应性通过透光率聚集法（LTA），VerifyNow P2Y12测定和多电极血小板聚集法（MEA）进行测量。主要终点是PCI后30天发生的缺血性事件。 MACE发生在36例（15.8％）患者中，其中35例（15.4％）患有围手术期心肌梗死且1例患者死亡（0.4％）。在随后发生围手术期MI的患者中，ADP诱导的LTA和VerifyNow值（PCI之前和之后）明显更高，但是MEA分析数据（PCI和PCI之后）没有显着差异（PCI之前p = 0.25，PCI后p = 0.33）。 ROC曲线分析显示了LTA的HPR值（PCI前> 66％，PCI后> 53％，所有p <0.001），VerifyNow（PCI前> 347 PRU和PCI后> 272 PRU，所有p <0.001）和MEA（PCI前> 50 U，PCI后> 39 U，所有p> 0.05）。通过LTA和VerifyNow测定进行的血小板反应性测量可以区分PCI后30天缺血事件的风险。不良事件的预测临界值取决于采样时间。

BACKGROUND & AIMS: :Nitric oxide (NO) plays an important role in acute ischemic preconditioning (IPC). In addition to activating soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signaling pathways, NO-mediated protein S-nitros(yl)ation (SNO) has been recently shown to play an essential role in cardioprotection against ischemia-reperfusion (I/R) injury. In our previous studies, we have shown that IPC-induced cardioprotection could be blocked by treatment with either N-nitro-L-arginine methyl ester (L-NAME, a constitutive NO synthase inhibitor) or ascorbate (a reducing agent to decompose SNO). To clarify NO-mediated sGC/cGMP/PKG-dependent or -independent (i.e., SNO) signaling involved in IPC-induced cardioprotection, mouse hearts were Langendorff-perfused in the dark to prevent SNO decomposition by light exposure. Treatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, a highly selective inhibitor of sGC) or KT5823 (a potent and selective inhibitor of PKG) did not abolish IPC-induced acute protection, suggesting that the sGC/cGMP/PKG signaling pathway does not play an important role in NO-mediated cardioprotective signaling during acute IPC. In addition, treatment with ODQ in IPC hearts provided an additional protective effect on functional recovery, in parallel with a higher SNO level in these ODQ+IPC hearts. In conclusion, these results suggest that the protective effect of NO is not related primarily to activation of the sGC/cGMP/PKG signaling pathway, but rather through SNO signaling in IPC-induced acute cardioprotection.

背景与目标： 一氧化氮（NO）在急性缺血预处理（IPC）中起重要作用。除了激活可溶性鸟苷基环化酶（sGC）/环鸟苷单磷酸（cGMP）/蛋白激酶G（PKG）信号传导途径外，最近还证明了NO介导的蛋白S-亚硝酰基（SNO）发挥着重要作用。对缺血再灌注（I / R）损伤的心脏保护作用。在我们以前的研究中，我们表明通过用N-硝基-L-精氨酸甲酯（L-NAME，组成型NO合酶抑制剂）或抗坏血酸（一种分解SNO的还原剂）治疗可以阻断IPC诱导的心脏保护。 。为了阐明与IPC诱导的心脏保护有关的NO介导的sGC / cGMP / PKG依赖性或非依赖性（即SN​​O）信号传导，在黑暗中对小鼠心脏进行Langendorff灌注，以防止SNO通过光照分解。用1H- [1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ，一种高度选择性的sGC抑制剂）或KT5823（一种有效且选择性的PKG抑制剂）治疗，不会废除IPC-诱导的急性保护，提示sGC / cGMP / PKG信号通路在急性IPC期间在NO介导的心脏保护信号中不发挥重要作用。此外，在这些ODQ IPC心脏中，用ODQ对IPC心脏进行治疗可对功能恢复提供额外的保护作用，同时具有更高的SNO水平。总之，这些结果表明，NO的保护作用主要与sGC / cGMP / PKG信号通路的激活无关，而是通过IPC诱导的急性心脏保护中的SNO信号传导。

BACKGROUND & AIMS: :An elderly man experienced recurrent transient episodes of right arm weakness and expressive aphasia. He was initially treated with aspirin and then with coumadin. Thirteen days after initial presentation, he became febrile and had signs of meningitis. The illness progressed relentlessly to death 9 weeks after admission to the hospital. Necropsy showed prominent meningitis with vasculitis extending into the left frontal lobe. Polymerase chain reaction identified the organism as Listeria monocytogenes.

背景与目标： ：一位老人经历了右臂无力和表现性失语的反复短暂发作。他最初接受阿司匹林治疗，然后接受香豆素治疗。初次就诊后13天，他发热并出现脑膜炎迹象。入院9周后，该病无情地发展到死亡。尸检显示明显的脑膜炎，血管炎延伸至左额叶。聚合酶链反应鉴定该生物为单核细胞增生性李斯特菌。

BACKGROUND & AIMS: INTRODUCTION:Neurological complications secondary to the uremic state, contribute largely to the morbidity and mortality in patients with renal failure. The prevalence of peripheral neuropathy remains high in advanced renal dysfunction. MATERIALS AND METHODS:The present cross-sectional study was conducted on 100 adult patients of chronic kidney disease between 18 and 75 years of age with serum creatinine greater than 2 mg/dL. Apart from routine examination and baseline investigations, detailed history was elicited pertaining to patients' neurological symptoms, and scored according to the Neurological Symptom Score. Motor nerve conduction velocity was measured from right median, ulnar, peroneal, and tibial nerves. RESULTS:It was observed that neurological symptoms increased steadily with raise in serum creatinine. The mean nerve conduction velocities (NCVs) of right median nerve, ulnar nerve, peroneal nerve, and tibial nerve were 51.34 ± 6.07, 53.04 ± 5.91, 44.72 ± 6.14, and 44.20 ± 5.17, respectively. The NCVs of all the tested nerves decreased significantly with increase in serum creatinine levels (p < 0.01): 70% of the patients had uremic polyneuropathy; 6% had asymptomatic neuropathy, 51% had symptomatic non-disabling neuropathy, while disabling neuropathy was seen in 13% of the patients. CONCLUSION:Our data suggests that NCV testing when complimented with meticulous neurological assessment can provide invaluable input. These tests apart from helping us detect neuropathy in advanced renal dysfunction; can also detect the disease in largely asymptomatic patients which avoids the necessity to order for detailed neurophysiological investigation.

背景与目标： 简介：继发于尿毒症状态的神经系统并发症在很大程度上影响了肾衰竭患者的发病率和死亡率。在晚期肾功能不全中，周围神经病变的患病率仍然很高。
材料与方法：本横断面研究是针对100名年龄在18至75岁之间，血清肌酐大于2mg / dL的慢性肾脏病成年患者进行的。除了常规检查和基线检查外，还可以得出有关患者神经系统症状的详细病史，并根据神经系统症状评分进行评分。从右正中，尺骨，腓骨和胫神经测量运动神经传导速度。
结果：观察到神经症状随着血清肌酐水平的升高而稳定增加。右正中神经，尺神经，腓神经和胫神经的平均神经传导速度（NCVs）分别为51.34±6.07、53.04±5.91、44.72±6.14和44.20±5.17。随着血清肌酐水平的升高，所有受测神经的NCV均显着下降（p <0.01）：70％的患者患有尿毒症性多发性神经病。 6％有无症状神经病，51％有症状非致残性神经病，而13％的患者可见致残性神经病。
结论：我们的数据表明，NCV测试与细致的神经系统评估相辅相成，可以提供宝贵的信息。这些测试除了可以帮助我们检测晚期肾功能不全的神经病变以外，还可以帮助我们更好地检测神经病变。也可以在很大程度上无症状的患者中发现这种疾病，从而避免了进行详细的神经生理学检查的必要性。

BACKGROUND & AIMS: BACKGROUND:Although beta blockers (BBs) are established therapy in heart failure, some patients whose left ventricular ejection fraction (LVEF) initially increases on BB therapy experience a subsequent LVEF decline. This study aimed to evaluate the proportion of patients with non-ischemic cardiomyopathy (NICM) whose LVEF declines while on BB therapy and determine important predictors of LVEF decline. METHODS:A retrospective analysis of 238 patients receiving a BB (carvedilol, metoprolol succinate, or tartrate), with an ejection fraction of ≤40% and NICM, whose LVEF initially rose ≥5% after 1 year of BB therapy, was conducted. Post-response LVEF decline ≥5% to a final LVEF of ≤35% was evaluated within 4 years of BB initiation. RESULTS:In our study, we had 52 Caucasians (22%), 78 Hispanics (33%), and 108 African Americans (45%). Overall, 32 patients (13.44 %) had post-response LVEF decline. The nadir LVEF of patients with post-response LVEF decline was 25% (interquartile range 20-27). Compared with others, Hispanics had lower nadir LVEF (22%, p < 0.001). Important predictors of LVEF decline were Hispanic race (odds ratio (OR) 6.094, p < 0.001), New York Heart Association (NYHA) class (OR 2.287, p < 0.05), baseline LVEF (OR 1.075, p < 0.05), and age (OR 0.933, p < 0.001). CONCLUSION:A significant proportion (13.44%) of NICM patients with LVEF increase over 1 year of BB therapy experienced subsequent LVEF decline. Race, NYHA class, baseline LVEF, and age are important predictors of this decline.

背景与目标： 背景：尽管β受体阻滞剂（BBs）已被确立为心力衰竭的治疗方法，但一些在BB治疗中最初增加左心室射血分数（LVEF）的患者却经历了随后的LVEF下降。这项研究旨在评估BB治疗时LVEF下降的非缺血性心肌病（NICM）患者的比例，并确定LVEF下降的重要预测指标。
方法：回顾性分析238例接受BB（卡维地洛，美托洛尔琥珀酸盐或酒石酸盐），射血分数≤40％的BB和NICM的患者，这些患者在接受BB治疗1年后LVEF最初升高≥5％。 BB启动后4年内评估反应后LVEF下降≥5％至最终LVEF≤35％。
结果：在我们的研究中，我们有52名高加索人（22％），78名西班牙裔人（33％）和108名非裔美国人（45％）。总体而言，有32例患者（13.44％）的反应后LVEF下降。反应后LVEF下降的患者的最低LVEF为25％（四分位数范围为20-27）。与其他人相比，西班牙裔患者的最低点LVEF较低（22％，p <0.001）。 LVEF下降的重要预测指标是西班牙裔种族（比值比（OR）6.094，p <0.001），纽约心脏协会（NYHA）级别（OR 2.287，p <0.05），基线LVEF（OR 1.075，p <0.05）和年龄（OR 0.933，p <0.001）。
结论：在BB治疗1年以上的NICEF升高的NICM患者中，有相当比例（13.44％）随之而来的是LVEF下降。种族，NYHA等级，基线LVEF和年龄是这一下降的重要预测因素。

BACKGROUND & AIMS: :Objectives. The aim of this study was to investigate endothelium dependent relaxation (EDR) in coronary artery and the myocardial contractility after 24 h of non-ischemic heart preservation (NIHP). Design. Explanted cardioplegic hearts from six pigs were preserved by NIHP for 24 h. The perfusion medium consisted of an albumin containing hyperoncotic cardioplegic nutrition-hormone solution with erythrocytes to a hematocrit of 10%. Coronary artery ring segments were then studied in organ baths. Thromboxane A2 was used for vasocontraction and Substance P to elicit endothelium dependent relaxation. A heart trabecula from the right ventricle was mounted in an organ bath and a special stimulation protocol was used to characterize myocardial contractility. Fresh cardioplegic hearts from 11 pigs were used as controls. The water content of the hearts was calculated. Results. There was no significant difference between NIHP and fresh controls regarding EDR (91.2 ± 1.2% vs 93.1 ± 1.8%). The contraction force, potentiation and calcium recirculation fraction did not differ between the groups. The water content of the myocardium was 79.3 ± 0.2% for NIHP and 79.5 ± 0.2% for controls. Conclusions. NIHP for 24 h keeps coronary artery EDR and myocardial contractility intact and causes no edema.

背景与目标： ：目标。这项研究的目的是研究非缺血性心脏保存（NIHP）24小时后冠状动脉的内皮依赖性舒张（EDR）和心肌收缩性。设计。 NIHP将六只猪的心脏停搏后心脏保存24小时。灌注培养基由含白蛋白的高渗性心脏停搏营养激素溶液和红细胞组成，血细胞比容为10％。然后在器官浴中研究冠状动脉环节段。血栓烷A2用于血管收缩，P物质引起内皮依赖性舒张。将来自右心室的小梁安装在器官浴中，并使用特殊的刺激方案来表征心肌的收缩性。使用来自11只猪的新鲜心脏停搏心脏作为对照。计算心脏的水含量。结果。 NIHP与新鲜对照组在EDR方面无显着差异（91.2％±1.2％和93.1％±1.8％）。两组之间的收缩力，增强作用和钙循环分数无差异。对于NIHP，心肌的水含量为79.3±0.2％，而对于对照，为79.5±0.2％。结论NIHP 24小时保持冠状动脉EDR和心肌收缩力完整，不引起水肿。