BACKGROUND & AIMS: INTRODUCTION:Management of traumatic brain injury (TBI) is focused on minimizing or preventing secondary brain injury. Remote ischemic conditioning (RIC) is an established treatment modality that has been shown to improve patient outcomes in different clinical settings by influencing inflammatory insults. In a clinical trial, RIC showed amelioration of SB100 and neuron-specific enolase. The aim of our study was to further elucidate the mechanisms and outcome when applying RIC in a mouse model of traumatic brain injury. METHODS:We subjected 100 male C57BL mice to a closed-skull cortical-controlled impact injury. Two hours after the TBI, the animals were allocated to either the RIC group (n = 50) or the sham group (n = 50). By clamping the exposed femoral artery, we induced RIC by six 4-minute cycles of ischemia and reperfusion. Circulating levels of S100-B, neuron-specific enolase, and glial fibrillary acidic protein were measured at multiple time points. Animals were additionally observed daily for cognition and motor coordination via novel object recognition and rotarod. Brain sections were stained and evaluated for neuronal injury at post-TBI Day 5. RESULTS:The RIC animals had a significantly higher recognition index than did sham at 24, 48, and 72 hours after intervention. Rotarod latency was higher in the RIC animals compared to the sham animals at all-time points, and statistically significant at 120 hours after intervention. The RIC group demonstrated preserved cognitive function and motor coordination compared to the sham. On hematoxylin and eosin and immunohistochemical staining of brain sections, there was less area of neuronal degeneration and astrocytosis, respectively, in the RIC group compared to the sham group. There was no significant difference in systemic neuronal markers between the RIC and sham animals. CONCLUSION:Remote ischemic conditioning 2 hours after injury preserved cognitive functions and motor coordination in a mouse model of TBI. Remote ischemic conditioning can preserve viability of neurons and astrocytes after TBI and has potential as a clinically noninvasive and relatively easy method to improve outcome after TBI. LEVEL OF EVIDENCE:Therapeutic studies, randomized controlled trial, level I.

背景与目标： 简介：创伤性脑损伤（TBI）的管理重点在于最大程度地减少或预防继发性脑损伤。远程缺血调节（RIC）是一种既定的治疗方式，已显示可通过影响炎症损伤改善不同临床环境下的患者预后。在一项临床试验中，RIC显示SB100和神经元特异性烯醇化酶得到改善。我们研究的目的是进一步阐明将RIC应用于创伤性脑损伤小鼠模型的机制和结果。
方法：我们对100只雄性C57BL小鼠进行了闭合颅骨皮质控制的撞击损伤。 TBI后两小时，将动物分为RIC组（n = 50）或假组（n = 50）。通过夹紧暴露的股动脉，我们通过六个4分钟的缺血和再灌注周期诱导RIC。在多个时间点测量了S100-B，神经元特异性烯醇化酶和神经胶质原纤维酸性蛋白的循环水平。每天还通过新颖的物体识别和旋转仪观察动物的认知和运动协调。在TBI后第5天对脑切片进行染色并评估其神经元损伤。
结果：在干预后24、48和72小时，RIC动物的识别指数明显高于假手术。与假手术动物相比，RIC动物的Rotarod潜伏期在所有时间点都更高，并且在干预后120小时具有统计学意义。与假手术相比，RIC组显示出保留的认知功能和运动协调能力。关于苏木精和曙红以及脑切片的免疫组织化学染色，与假手术组相比，RIC组的神经元变性和星形胶质细胞减少的区域分别较少。 RIC动物和假动物之间的系统神经元标记没有显着差异。
结论：TBI小鼠模型在损伤后2小时可进行远程缺血调节，以保持认知功能和运动协调性。远端缺血性调理可以保留TBI后神经元和星形胶质细胞的活力，并具有作为临床无创且相对容易的方法来改善TBI后预后的潜力。
证据级别：治疗研究，随机对照试验，I级。

BACKGROUND & AIMS: BACKGROUND AND PURPOSE:The prognostic significance of interictal epileptiform discharges (IED) and periodic patterns (PP) after ischemic stroke has not been assessed. We sought to test whether IED and PP, detected on standard Electroencephalography (EEG) performed during the acute phase of ischemic stroke are associated with a worse functional outcome. METHODS:One-hundred-fifty-seven patients 18 years or older with a diagnosis of acute ischemic stroke presenting within 72 h from stroke onset were prospectively enrolled and followed. Patients with a pre-stroke history of seizures or epilepsy, previous debilitating neurological disease or conditions that precluded the performance of EEG were excluded. Interpretation was performed by a blinded board certified neurophysiologist. IED and PP (grouped as epileptiform activity [EA]) were defined according to proposed guidelines. Univariable and multivariable analyses were used to identify predictors of outcome (modified Rankin Scale dichotomized ≤2 vs. ≥3) at 3 months. RESULTS:In the univariable analysis, admission NIHSS (OR 1.20, 95% CI 1.12-1.28, p = 0.001), age (OR 1.03, 95% CI 1.01-1.05, p = 0.02), and presence of EA (OR 2.94, 95% CI 1.51-5.88, p = 0.001) were significantly associated with the outcome at 3 months. In the multivariable analysis, only admission NIHSS (OR 1.19, 95% CI 1.11-1.28, p < 0.001) and the presence of EA (OR 2.27, 95% CI 1.04-5.00, p = 0.04) were independently associated with the prognosis. SIGNIFICANCE:The importance of EEG in the prognosis of acute ischemic stroke warrants additional research, examining the role of medication therapy on the outcome and the occurrence of seizures for those patients with specific EEG patterns.

背景与目标： 背景与目的：尚未评估缺血性中风后发作性癫痫样放电（IED）和周期性模式（PP）的预后意义。我们试图测试在缺血性中风急性期通过标准脑电图（EEG）检测到的IED和PP是否与较差的功能预后相关。
方法：前瞻性纳入并随访了18岁或以上的157例诊断为中风发作后72小时内出现急性缺血性中风的患者。中风前有癫痫发作或癫痫病史，先前使人衰弱的神经系统疾病或无法进行脑电图检查的患者被排除在外。解释由一位盲目合格的神经生理学家进行。根据提出的指南定义了IED和PP（分组为癫痫样活性[EA]）。在3个月时使用单变量和多变量分析来确定结果的预测因子（修正的Rankin量表分为≤2vs.≥3）。
结果：在单变量分析中，入院NIHSS（OR 1.20，95％CI 1.12-1.28，p = 0.001），年龄（OR 1.03，95％CI 1.01-1.05，p = 0.02）和EA（OR 2.94， 95％CI 1.51-5.88，p = 0.001）与3个月时的结局显着相关。在多变量分析中，仅入院NIHSS（OR 1.19，95％CI 1.11-1.28，p <0.001）和EA的存在（OR 2.27，95％CI 1.04-5.00，p = 0.04）与预后独立相关。
意义：脑电图在急性缺血性中风的预后中的重要性值得进一步研究，研究对于特定脑电图模式的患者，药物治疗对预后和癫痫发作的作用。

BACKGROUND & AIMS: BACKGROUND:Outcome in stroke trials is often based on a 3-month modified Rankin scale (mRS). How 3-month mRS relates to longer-term outcomes will depend on late recovery, delayed stroke-related deaths, recurrent strokes, and nonstroke deaths. We evaluated 3-month mRS and death/disability at 1 and 5 years in a population-based cohort study. METHODS AND RESULTS:In 3-month survivors of ischemic stroke (Oxford Vascular Study; 2002-2014), we related 3-month mRS to disability (defined as mRS >2) at 1 and 5 years and/or death rates (age/sex adjusted). Accrual of disability and index-stroke-related and nonstroke deaths in each poststroke year was categorized according to 3-month mRS. Among 1606 patients with acute ischemic stroke, 181 died within 3 months, but 126 index-stroke-related deaths and 320 other deaths occurred during the subsequent 4866 patient-years of follow-up up to 5 years. Although 69/126 (54.8%) post-3-month index-stroke-related deaths occurred after 1 year, mRS>2 at 1 year strongly predicted these deaths (adjusted hazard ratio=21.94, 95%CI 7.88-61.09, P<0.0001). Consequently, a 3-month mRS >2 was a strong independent predictor of death at both 1 year (adjusted hazard ratio=6.67, 95%CI 4.16-10.69, P<0.0001) and 5 years (adjusted hazard ratio=2.93, 95%CI 2.38-3.60, P<0.0001). Although mRS improved by ≥1 point from 3 months to 1 year in 317/1266 (25.0%) patients with 3-month mRS ≥1, improvement in mRS after 1 year was limited (improvement by ≥1 point: 91/858 [10.6%]; improvement to mRS ≤2: 13/353 [3.7%]). CONCLUSIONS:Our results reaffirm use of the 3-month mRS outcome in stroke trials. Although later recovery does occur, extending follow-up to 1 year would capture most long-term stroke-related disability. However, administrative mortality follow-up beyond 1 year has the potential to demonstrate translation of early disability gains into additional reductions in long-term mortality without much erosion by non-stroke-related deaths.

背景与目标： 背景：中风试验的结果通常基于3个月的改良兰金量表（mRS）。 3个月的mRS与长期预后的关系将取决于晚期康复，中风相关的延迟死亡，中风复发和非中风死亡。在一项基于人群的队列研究中，我们评估了3个月的mRS和1年和5年时的死亡/残疾。
方法和结果：在3个月的缺血性中风幸存者中（牛津血管研究; 2002-2014年），我们将3个月的mRS与1岁和5岁时的残疾（定义为mRS> 2）和/或死亡率（年龄/性别调整）。根据每个月的3个月mRS对残疾的累积以及与卒中相关的卒中和非卒中死亡进行分类。在1606例急性缺血性中风患者中，有3个月内有181例死亡，但在随后的4866个患者年的随访中（长达5年）发生了126例与中风相关的死亡和320例其他死亡。尽管1年后发生69/126（54.8％）的3个月后与指数卒中相关的死亡，但1年时的mRS> 2强烈预测了这些死亡（调整后的危险比= 21.94，95％CI 7.88-61.09，P < 0.0001）。因此，在1年（调整后的危险比= 6.67，95％CI 4.16-10.69，P <0.0001）和5年（调整后的危险比= 2.93，95％）下，三个月的mRS> 2是死亡的强有力的独立预测因子。 CI 2.38-3.60，P <0.0001）。尽管317/1266（35.0％）3个月mRS≥1的患者在3个月至1年间mRS改善了≥1点，但1年后mRS的改善是有限的（≥1点的改善：91/858 [10.6 ％]； mRS≤2的改善：13/353 [3.7％]）。
结论：我们的研究结果重申了在卒中试验中使用3个月的mRS结果。尽管确实会出现稍后的康复，但将随访延长至1年将捕获大多数与中风相关的长期残疾。但是，对1年以上的行政死亡率进行随访，有可能证明将早期残疾的增加转化为长期死亡率的进一步降低，而不会因非中风相关的死亡而受到很大的侵蚀。

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。