BACKGROUND & AIMS: :The cardioprotective drugs used for treatment against ischemia/reperfusion (MI/R) injury have been well evaluated and are considered inadequate. The Chinese herbal medicine formula, Xinji pill (XJP) has been used traditionally for the prevention and treatment of ischemic heart diseases for decades. In the present study, the cardioprotective effects of XJP against MI/R injury were assessed in vivo and its possible mechanism was examined. Male Sprague‑Dawley rats were selected for establishing an MI/R model, which was induced by ischemia for 30 min followed by 24 h reperfusion. Drugs and saline were administered intragastrically from day 14 prior to MI/R. Blood samples were collected for biochemical detection. The rats were then sacrificed and cardiac muscle tissues were harvested. The mRNA expression levels of antioxidant genes were measured by reverse transcription‑quantitative polymerase chain reaction and the protein levels were measured by western blotting. Pretreatment with XJP for 14 days protected the heart against I/R‑induced myocardial function disorder, protected against heart injury, as demonstrated by normalized serum levels of lactate dehydrogenase and creatine kinase, and suppressed oxidative stress. XJP markedly upregulated the expression of antioxidant genes, including superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase, and promoted the protein expression of heme oxygenase‑1 and NFE2‑related factor 2 (Nrf2) in the heart tissues. Furthermore, Akt kinase was confirmed to be upstream of Nrf2 in the XJP treatment. LY294002, a specific inhibitor of Akt, significantly eliminated the cardioprotective effects of XJP. In conclusion, these results demonstrated that XJP exhibited notable cardioprotective properties, in which the Akt/Nrf2 signaling pathway may be involved.

背景与目标： ：用于抵抗缺血/再灌注（MI / R）损伤的心脏保护药物已得到很好的评估，被认为是不足的。几十年来，传统的中草药配方辛集丸（XJP）被用于预防和治疗缺血性心脏病。在本研究中，体内评估了XJP对MI / R损伤的心脏保护作用，并研究了其可能的机制。选择雄性Sprague-Dawley大鼠建立MI / R模型，该模型由局部缺血30分钟然后再灌注24 h诱导。从MI / R之前第14天开始，在胃内施用药物和盐水。收集血样用于生化检测。然后处死大鼠并收获心肌组织。通过逆转录定量聚合酶链反应测量抗氧化剂基因的mRNA表达水平，并通过蛋白质印迹法测量蛋白质水平。 XJP预处理14天可以保护心脏免受I / R诱导的心肌功能障碍的侵害，防止心脏受伤，如血清乳酸脱氢酶和肌酸激酶水平的正常化以及抑制氧化应激所证明的。 XJP明显上调了抗氧化基因的表达，包括超氧化物歧化酶，过氧化氢酶，谷胱甘肽还原酶和谷胱甘肽过氧化物酶，并促进了心脏组织中血红素加氧酶-1和NFE2相关因子2（Nrf2）的蛋白表达。此外，在XJP处理中，证实Akt激酶位于Nrf2的上游。 LY294002是Akt的特异性抑制剂，可显着消除XJP的心脏保护作用。总之，这些结果表明，XJP具有明显的心脏保护特性，其中可能涉及Akt / Nrf2信号传导途径。

BACKGROUND & AIMS: :Mitochondrial dysfunction is the most prominent source of oxidative stress in acute and chronic kidney disease. NLRX1 is a receptor of the innate immune system that is ubiquitously expressed and localized in mitochondria. We investigated whether NLRX1 may act at the interface of metabolism and innate immunity in a model of oxidative stress. Using a chimeric mouse model for renal ischemia-reperfusion injury, we found that NLRX1 protects against mortality, mitochondrial damage, and epithelial cell apoptosis in an oxidative stress-dependent fashion. We found that NLRX1 regulates oxidative phosphorylation and cell integrity, whereas loss of NLRX1 results in increased oxygen consumption, oxidative stress, and subsequently apoptosis in epithelial cells during ischemia-reperfusion injury. In line, we found that NLRX1 expression in human kidneys decreased during acute renal ischemic injury and acute cellular rejection. Although first implicated in immune regulation, we propose that NLRX1 function extends to the control of mitochondrial activity and prevention of oxidative stress and apoptosis in tissue injury.

背景与目标： 线粒体功能障碍是急性和慢性肾脏疾病中最主要的氧化应激源。 NLRX1是先天免疫系统的受体，在线粒体中普遍表达和定位。我们调查了NLRX1是否可能在氧化应激模型中的新陈代谢和先天免疫的界面上起作用。使用针对肾缺血-再灌注损伤的嵌合小鼠模型，我们发现NLRX1以氧化应激依赖性的方式防止死亡，线粒体损伤和上皮细胞凋亡。我们发现NLRX1调节氧化磷酸化和细胞完整性，而NLRX1的缺失导致缺血再灌注损伤期间上皮细胞的耗氧量增加，氧化应激和随后的细胞凋亡。一致地，我们发现在急性肾缺血性损伤和急性细胞排斥期间，人肾脏中的NLRX1表达降低。尽管首先涉及免疫调节，但我们认为NLRX1功能扩展到线粒体活性的控制以及组织损伤中氧化应激和细胞凋亡的预防。

BACKGROUND & AIMS: :Repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, has shown experimental and clinical efficacy in a range of neuromodulatory models, even when delivered at low intensity (i.e. subthreshold for action potential generation). After central nervous system (CNS) injury, studies suggest that reactive astrocytes and microglia can have detrimental but also beneficial effects; thus modulating glial activity, for example through application of rTMS, could potentially be a useful therapeutic tool following neurotrauma. Immunohistochemistry was used to measure the effect of low intensity rTMS (LI-rTMS) on GFAP (astrocyte), IBA1 (microglial), and CS56 (proteoglycan) expression in a unilateral penetrating cortical stab injury model of glial scarring in young adult and aged male and female C57BL6/J mice. Mice received contralateral low frequency, ipsilateral low frequency, ipsilateral high frequency or sham LI-rTMS (4-5mT intensity), for two weeks following injury. There was no significant difference in the overall volume of tissue containing GFAP positive (+) astrocytes, IBA1+ microglia, or proteoglycan expression, between sham and LI-rTMS-treated mice of all ages and sex. Importantly however, the density of GFAP+ astrocytes and IBA1+ microglia immediately adjacent to the injury was significantly reduced following ipsilateral low and high frequency stimulation in adult and aged females (p≤0.05), but was significantly increased in adult and aged males (p≤0.05). LI-rTMS effects were generally of greater magnitude in aged mice compared to young adult mice. These results suggest that sex differences need to be factored into therapeutic rTMS protocols. In particular, more work analyzing frequency and intensity specific effects, especially in relation to age and sex, is required to determine how rTMS can best be used to modify glial reactivity and phenotype following neurotrauma.

背景与目标： ：反复经颅磁刺激（rTMS）是一种非侵入性的脑刺激形式，即使在低强度下（即产生动作电位的阈值下），也已在一系列神经调节模型中显示出实验和临床功效。中枢神经系统（CNS）损伤后，研究表明反应性星形胶质细胞和小胶质细胞可能具有有害作用，但也有有益作用。因此，例如通过应用rTMS调节神经胶质活动可能是神经创伤后的一种有用的治疗工具。免疫组织化学方法用于测定低强度rTMS（LI-rTMS）对单侧穿透性胶质瘢痕形成的成年男性和老年男性的单侧穿透性皮层刺伤模型中GFAP（星形胶质细胞），IBA1（微胶质细胞）和CS56（蛋白聚糖）表达的影响。和雌性C57BL6 / J小鼠。小鼠在受伤后两周接受对侧低频，同侧低频，同侧高频或假LI-rTMS（4-5mT强度）。在假手术和LI-rTMS处理的所有年龄和性别的小鼠之间，含有GFAP阳性（）星形胶质细胞，IBA1小胶质细胞或蛋白聚糖表达的组织总体积均无显着差异。然而重要的是，成年和老年女性在同侧低频和高频刺激后，紧邻损伤的GFAP星形胶质细胞和IBA1小胶质细胞的密度显着降低（p≤0.05），而成年和老年男性显着增加（p≤0.05） ）。与成年小鼠相比，老年小鼠的LI-rTMS效应通常更大。这些结果表明，性别差异需要纳入治疗性rTMS方案中。特别是，需要做更多的工作来分析频率和强度的具体影响，尤其是与年龄和性别相关的影响，以确定rTMS如何最好地用于改变神经外伤后的神经胶质反应性和表型。

BACKGROUND & AIMS: OBJECTIVE:To investigate: (1) the course of coronary heart disease risk factors (lipid profiles and body mass index (BMI)) in the first five years after discharge from inpatient spinal cord injury (SCI) rehabilitation and (2) the association between lifestyle (physical activity, self-care related to fitness, smoking, alcohol, body mass and low-fat diet) and coronary heart disease risk factors during that period. DESIGN:Prospective cohort study. PARTICIPANTS/METHODS:Individuals with SCI (N=130). Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG) and BMI were determined at discharge from inpatient rehabilitation and 1 and 5 years after discharge. Using multilevel regression models, the effects of lifestyle (drinking alcohol, smoking, active lifestyle and self-care) on the lipid profiles and BMI were determined. RESULTS:After correction for lesion and personal characteristics, no changes in lipid profiles in the five years after discharge were seen, whereas the BMI increased significantly with 1.8 kg m(-2). A high percentage was at risk of cardiovascular disease due to high BMI (63-75%) or HDL (66-95%). The individuals who indicated to maintain their fitness level as good as possible and the individuals with a low BMI showed better lipid profiles. Individuals with a more active lifestyle showed higher HDL levels. Individuals who avoid smoking showed a 1.5 kg m(-2) higher BMI. CONCLUSION:Lipid profiles seem to stabilize in the years after discharge from inpatient SCI rehabilitation, whereas the BMI increased. Lifestyle factors associated with a favorable lipid profile and BMI could be identified.

背景与目标： 目的：调查：（1）住院脊髓损伤（SCI）康复出院后的最初五年中，冠心病危险因素（血脂和体重指数（BMI））的病程，以及（2）在此期间的生活方式（体育锻炼，与健身，吸烟，饮酒，体重和低脂饮食有关的自我保健）和冠心病的危险因素。
设计：前瞻性队列研究。
参与者/方法：具有SCI的个人（N = 130）。在住院康复出院时以及出院后1和5年测定总胆固醇（TC），高密度脂蛋白（HDL），低密度脂蛋白（LDL），甘油三酸酯（TG）和BMI。使用多级回归模型，确定了生活方式（饮酒，吸烟，积极的生活方式和自我保健）对血脂和BMI的影响。
结果：校正病灶和个人特征后，出院后五年内血脂没有变化，而BMI显着增加，为1.8 kg m（-2）。高百分比的BMI（63-75％）或HDL（66-95％）导致罹患心血管疾病的风险较高。表示要尽可能保持健康水平的个体和BMI较低的个体表现出更好的血脂状况。生活方式更加活跃的人表现出较高的HDL水平。避免吸烟的人的BMI升高1.5 kg m（-2）。
结论：住院SCI康复出院后的几年中，脂质分布似乎稳定，而BMI升高。可以确定与良好的脂质状况和BMI相关的生活方式因素。

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。远程缺血性调节（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伤害。 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。在所有时间点，RIC动物的罗塔洛德潜伏期均高于假动物，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: PURPOSE:The purpose of this study was to test whether low-grade Lachman test (i.e. Grade 0-1+) and a negative pivot shift at 6-12 weeks post-ACL rupture in recreational alpine skiers can be used to predict good function and normal knee laxity in nonoperated patients at minimum 2 years after the injury. METHODS:Office registry was used to identify 63 recreational alpine skiers treated by the senior author within 6 weeks of a first-time ACL injury between 2003 and 2008. Of these, 34 had early ACL reconstruction but 29 patients were observed and re-evaluated. Office charts and MRI were reviewed. Inclusion criteria for this study were as follows: ACL rupture documented on MRI after the injury, and minimum 2-year follow-up. Exclusion criterion was contralateral knee ligament injury. Of the 29 patients treated nonoperatively, 17 had low-grade Lachman and negative pivot shift tests within 6-12 weeks after the injury and were recommended to continue follow-up without surgery. Of these 17 patients, 6 were lost to follow up, but 11 patients were recalled and evaluated at more than 2 years after the injury. They completed Marx and Tegner activity level and IKDC subjective scores, physical examination of the knee and KT-1000 anterior laxity assessment. RESULTS:Median age at injury was 43 years (range 29-58). Median follow-up was 42 months (range 30-68). Mean IKDC subjective score at latest follow-up was 91.6 ± 6.7. Median Tegner score was 6 (range 6-9) before the injury and 6 (range 4-6) at latest follow-up (p = n.s). Median Marx score was 6 (range 0-16) before the injury and 4 (range 0-12) at latest follow-up (p = 0.03). Ten patients had Lachman Grade 0-1+, and one had Lachman Grade 2+ at latest follow-up. KT-1000 showed mean side-to-side difference of 0.8 ± 1.6 mm, and less than 3 mm difference in the 10 patients with Lachman Grade 0-1+. CONCLUSION:Recreational alpine skiers who sustain ACL injury should be re-evaluated at 6-12 weeks after the injury rather than being operated acutely. If they have negative Lachman and pivot shift tests at that point, they can be treated without surgery since good outcome and normal knee anterior laxity at more than 2 years after the injury is expected. LEVEL OF EVIDENCE:Case series, Level IV.

背景与目标： 目的：本研究的目的是测试休闲性高山滑雪者在ACL破裂后6-12周进行低度Lachman测试（即0-1级）和负枢轴位移是否可以用来预测良好的功能和正常状态受伤后至少2年内，非手术患者的膝盖松弛。
方法：使用Office注册表确定2003年至2008年首次ACL损伤6周内由资深作者治疗的63名休闲高山滑雪者。其中34例早期ACL重建，但观察并重新评估了29例患者。审查了办公室图表和MRI。这项研究的纳入标准如下：受伤后MRI记录ACL破裂，至少进行2年随访。排除标准为对侧膝关节韧带损伤。在非手术治疗的29例患者中，有17例在受伤后6-12周内进行了低度Lachman和枢轴移位测试阴性，建议继续随访而不进行手术。在这17例患者中，有6例失去随访，但有11例患者在受伤后2年以上被召回并进行了评估。他们完成了Marx和Tegner的活动水平和IKDC主观评分，膝盖的身体检查以及KT-1000前松弛度评估。
结果：受伤时的中位年龄为43岁（范围29-58）。中位随访时间为42个月（范围30-68）。最近一次随访的IKDC主观平均得分为91.6±6.7。伤前Tegner评分中位数为6（范围6-9），而最近一次随访（p = n.s）为6（范围6-6）。受伤前的马克思得分中位数为6（范围0-16），最近一次随访中得分为4（范围0-12）（p = 0.03）。在最近的随访中，有10例Lachman为0-1级，而1例为Lachman为2级。在10例Lachman 0-1级患者中，KT-1000的平均左右差异为0.8±1.6 mm，并且差异小于3 mm。
结论：遭受ACL损伤的休闲高山滑雪者应在受伤后6-12周重新评估，而不要进行急性手术。如果他们当时的Lachman和枢轴移位测试阴性，则可以在不超过手术的情况下进行治疗，因为预期在受伤后2年以上可获得良好的预后和正常的膝前松弛。
证据级别：案例系列，IV级。

BACKGROUND & AIMS: :The purpose of this study is to compare the effects of spinal and epidural anesthesia on a rat transverse rectus abdominus myocutaneous flap ischemia-reperfusion injury model.Forty Sprague-Dawley rats were divided into 4 experimental groups: group I (n = 10), sham group; group II (n = 10), control group; group III (n = 10), epidural group; and group IV (n = 10), spinal group. After the elevation of the transverse rectus abdominus myocutaneous flaps, all groups except for the sham group were subjected to normothermic no-flow ischemia for 4 hours, followed by a reperfusion period of 2 hours. At the end of the reperfusion period, biochemical and histopathological evaluations were performed on tissue samples.Although there was no significant difference concerning the malonyldialdehyde, nitric oxide, and paraoxonase levels in the spinal and epidural groups, the total antioxidant state levels were significantly increased, and the total oxidative stress levels were significantly decreased in the epidural group in comparison to the spinal group. The pathological evaluation showed that findings related to inflammation, nuclear change rates and hyalinization were significantly higher in the spinal group compared with the epidural group.Epidural anesthesia can be considered as a more suitable method that enables a decrease in ischemia-reperfusion injuries in the muscle flaps.

背景与目标： ：本研究的目的是比较脊髓麻醉和硬膜外麻醉对大鼠横直肌腹肌皮瓣缺血再灌注损伤模型的影响。40只Sprague-Dawley大鼠分为4个实验组：I组（n = 10），假小组第二组（n = 10），对照组；第三组（n = 10），硬膜外组；第四组（n = 10），脊柱组。腹直肌横肌皮瓣抬高后，除假手术组外，其余各组均进行常温无血流缺血4小时，然后再灌注2小时。在再灌注期结束时，对组织样本进行了生化和组织病理学评估。尽管在脊髓和硬膜外组中丙二酰二醛，一氧化氮和对氧磷酶水平没有显着差异，但总抗氧化剂状态水平却明显升高，与硬膜外组相比，硬膜外组的总氧化应激水平显着降低。病理评估显示，与硬膜外组相比，脊髓组炎症，核变化率和透明质化相关的发现显着更高。硬膜外麻醉被认为是一种更合适的方法，可以减少肌肉的缺血再灌注损伤襟翼。

BACKGROUND & AIMS: :Traumatic brain injury (TBI) remains the leading cause of injury-related death and disability. Brain edema, one of the most major complications of TBI, contributes to elevated intracranial pressure, and poor prognosis following TBI. Nerve growth factor (NGF) appears to be a viable strategy to treat brain edema and TBI. Unfortunately, due to its poor blood-brain barrier (BBB) permeability, the clinical application of NGF has been greatly limited. We previously demonstrated that intranasal NGF could bypass the BBB and distribute throughout the brain. Here we further studied whether intranasal NGF could attenuate TBI-induced brain edema and its putative mechanisms. TBI was produced by a modified weight-drop model. We found that intranasal administration of NGF (5μg/d) attenuated the brain edema, as assayed by hemisphere water content, at 12h, 24h and 72h after TBI induction. This attenuation was associated with a prominent decrease of the content of aquaporin-4, which plays a pivotal role in the formation of brain edema. By the use of RT-PCR and ELISA, we showed that intranasal NGF markedly inhibited the transcription and expression of pro-inflammatory cytokines including IL-1β and TNF-α. An electrophoretic mobility shift assay (EMSA) displayed a significant activation of nuclear factor-κB following TBI, which was, however, much lowered in the NGF-treated rats. Furthermore, upon intranasal NGF supplementation, mitochondria-mediated apoptosis following TBI was minimized, as indicated by upregulation of Bcl-2 and downregulation of caspase-3. Collectively, our findings suggested that intranasal NGF may be a promising strategy to treat brain edema and TBI.

背景与目标： ：脑外伤（TBI）仍然是与伤害相关的死亡和残疾的主要原因。脑水肿是TBI最主要的并发症之一，导致颅内压升高，TBI后预后较差。神经生长因子（NGF）似乎是治疗脑水肿和TBI的可行策略。不幸的是，由于其不良的血脑屏障（BBB）通透性，NGF的临床应用受到了极大的限制。我们先前证明了鼻内NGF可以绕过BBB并分布在整个大脑中。在这里，我们进一步研究了鼻内NGF是否可以减轻TBI诱导的脑水肿及其可能的机制。 TBI是通过修改后的体重减轻模型产生的。我们发现鼻内施用NGF（5μg/ d）可以减轻脑水肿，通过​​TBI诱导后12h，24h和72h的半球水含量进行分析。这种衰减与aquaporin-4含量的显着下降有关，aquaporin-4的含量在脑水肿的形成中起着关键作用。通过使用RT-PCR和ELISA，我们显示鼻内NGF明显抑制促炎细胞因子包括IL-1β和TNF-α的转录和表达。电泳迁移率迁移分析（EMSA）显示TBI后核因子-κB的显着激活，但是在NGF治疗的大鼠中其活性大大降低。此外，鼻内补充NGF后，TBI后线粒体介导的凋亡得以最小化，如Bcl-2的上调和caspase-3的下调所示。总体而言，我们的研究结果表明，鼻内NGF可能是治疗脑水肿和TBI的一种有前途的策略。

BACKGROUND & AIMS: :In the present account it is proposed that in smokers the transition from peripheral airway disease to COPD is characterized by three sequential stages: Stage I, during which the closing volume eventually exceeds the functional residual capacity; Stage II, during which tidal expiratory flow limitation (EFL) is eventually exhibited; and Stage III, during which dynamic hyperinflation progressively increases leading to dyspnea and exercise limitation, which may be considered as markers of overt disease. Presence of airway closure (Stage I) and EFL (Stage II) in the tidal volume range may promote peripheral airway injury and accelerate the abnormalities of lung function. It is such injury that may determine which smoker is destined to develop COPD.

背景与目标： ：在目前的研究中，建议吸烟者从周围呼吸道疾病到COPD的转变以三个连续阶段为特征：第一阶段，其关闭量最终超过功能性剩余容量；第二阶段，最终表现为潮气呼气流量限制（EFL）；第三阶段，在此期间，动态过度充气会逐渐增加，导致呼吸困难和运动受限，这可能被认为是明显疾病的标志。潮气量范围内存在气道闭合（I期）和EFL（II期）可能会促进周围气道损伤并加速肺功能异常。正是这种伤害可能决定了哪个吸烟者注定会发展为COPD。

BACKGROUND & AIMS: :Cortical cavity lesions and lateral ventricular injections of quinolinic acid, a NMDA receptor agonist, induce Fos and Fos-related antigens (FRAs) throughout ipsilateral adult rat brain cortex in similar patterns. c-fos mRNA, assessed using in situ hybridization, was induced by 1 h and disappeared between 3 and 8 h following cortical lesions. Fos proteins, detected using a specific monoclonal antibody, were induced by 1 h and disappeared by 4 h after cortical lesions. FRA proteins, detected using polyclonal antibodies, were induced between 1 and 4 h and persisted for at least 72 h following focal cortical injury. Intraventricular injections of CPP, a competitive NMDA receptor antagonist, completely blocked the induction of these nuclear proteins in cortex ipsilateral to the focal cortical lesions--except around the injury site itself. Intraventricular injections of quisqualate, a non-NMDA glutamate analogue, induced Fos in hippocampus but not in cortex. These data show that NMDA receptors mediate the induction of Fos and FRAs following cortical injury. It is proposed that local cortical injury releases excitatory amino acids that act at NMDA receptors to initiate spreading depression and that the resultant depolarization induces Fos in neurons throughout the cortex. Since Fos and FRAs are proteins that regulate the expression of target genes, they could mediate long-term biochemical adaptations in neurons following cortical injury.

背景与目标： ：NMDA受体激动剂喹啉酸的皮层腔病变和侧脑室注射以相似的方式在整个同侧成年大鼠大脑皮层中诱导Fos和Fos相关抗原（FRA）。使用原位杂交评估的c-fos mRNA诱导1 h，并在皮层病变后3至8 h消失。使用特异性单克隆抗体检测到的Fos蛋白在皮层损伤后1小时被诱导并在4小时后消失。使用多克隆抗体检测到的FRA蛋白在局灶性皮层损伤后1至4小时内被诱导并持续至少72 h。心室注射CPP是一种竞争性NMDA受体拮抗剂，完全阻断了局灶皮层病变同侧皮层中这些核蛋白的诱导-损伤部位周围除外。脑室内注射非NMDA谷氨酸类似物quisqualate在海马中诱导Fos，但在皮层中诱导Fos。这些数据表明，NMDA受体在皮层损伤后介导Fos和FRA的诱导。有人提出，局部皮层损伤释放出兴奋性氨基酸，该氨基酸作用于NMDA受体，从而开始扩散性抑郁，并且最终的去极化作用会在整个皮质的神经元中诱导Fos。由于Fos和FRAs是调节靶基因表达的蛋白质，因此它们可以介导皮层损伤后神经元的长期生化适应。

BACKGROUND & AIMS: :Mesenchymal stem cells (MSCs) have been exploited as cellular vectors to treat a wide array of diseases but the mechanisms responsible for their therapeutic effect remain indeterminate. Previously, we reported that MSCs inhibit bleomycin (BLM)-induced inflammation and fibrosis within the lungs of mice. Interrogation of the MSC transcriptome identified interleukin 1 receptor antagonist (IL1RN) as a potential mediator of this effect. Fractionation studies indicated that MSCs are the principal source of IL1RN in murine bone marrow and that its expression is restricted to a unique subpopulation of cells. Moreover, MSC-conditioned media was shown to block proliferation of an IL-1alpha-dependent T cell line and inhibit production of TNF-alpha by activated macrophages in vitro. Studies conducted in mice revealed that MSC administration was more effective than recombinant IL1RN delivered via adenoviral infection or osmotic pumps in inhibiting BLM-induced increases in TNF-alpha, IL-1alpha, and IL1RN mRNA in lung, IL1RN protein in bronchoalveolar lavage (BAL) fluid, and trafficking of lymphocytes and neutrophils into the lung. Therefore, MSCs protect lung tissue from BLM-induced injury by blocking TNF-alpha and IL-1, two fundamental proinflammatory cytokines in lung. Identification of IL1RN-expressing human MSC subpopulations may provide a novel cellular vector for treating chronic inflammatory diseases in humans.

背景与目标： 间充质干细胞（MSCs）已被用作治疗多种疾病的细胞载体，但其治疗效果的机制仍不确定。以前，我们报道了MSC抑制博来霉素（BLM）诱导的小鼠肺内炎症和纤维化。对MSC转录组的询问确定白介素1受体拮抗剂（IL1RN）是这种作用的潜在介体。分级研究表明，MSC是鼠骨髓中IL1RN的主要来源，其表达仅限于细胞的独特亚群。此外，MSC条件培养基显示在体外可阻断IL-1alpha依赖性T细胞系的增殖并抑制巨噬细胞活化TNF-α的产生。在小鼠中进行的研究表明，与通过腺病毒感染或渗透泵输送的重组IL1RN相比，MSC抑制BLM诱导的肺中TNF-α，IL-1alpha和IL1RN mRNA的增加，支气管肺泡灌洗（BAL）中的IL1RN蛋白的抑制作用更有效。液体，以及淋巴细胞和中性粒细胞向肺的运输。因此，MSC通过阻断TNF-α和IL-1（肺中两种基本的促炎细胞因子）来保护肺组织免受BLM诱导的损伤。鉴定表达IL1RN的人MSC亚群可以提供用于治疗人的慢性炎性疾病的新型细胞载体。

BACKGROUND & AIMS: :Acute kidney injury (AKI) represents a significant clinical concern that is associated with high mortality rates and also represents a significant risk factor for the development of chronic kidney disease (CKD). This article will consider alterations in renal endothelial function in the setting of AKI that may underlie impairment in renal perfusion and how inefficient vascular repair may manifest post-AKI and contribute to the potential transition to CKD. We provide updated terminology for cells previously classified as 'endothelial progenitor' that may mediate vascular repair such as pro-angiogenic cells and endothelial colony-forming cells. We consider how endothelial repair may be mediated by these different cell types following vascular injury, particularly in models of AKI. We further summarize the potential ability of these different cells to mitigate the severity of AKI, improve perfusion and maintain vascular structure in pre-clinical studies.

背景与目标： ：急性肾损伤（AKI）代表了与高死亡率相关的重大临床问题，并且还代表了慢性肾脏疾病（CKD）发生的重要危险因素。本文将考虑在AKI的背景下肾内皮功能的改变，这可能是肾脏灌注受损的基础，以及AKI后的低效血管修复可能如何表现出来，并可能导致向CKD的转变。我们为以前被归类为“内皮祖细胞”的细胞提供了更新的术语，这些细胞可能介导血管修复，例如促血管生成细胞和内皮集落形成细胞。我们考虑血管损伤后这些不同细胞类型可能如何介导内皮修复，尤其是在AKI模型中。在临床前研究中，我们进一步总结了这些不同细胞减轻AKI严重性，改善灌注和维持血管结构的潜在能力。

BACKGROUND & AIMS: INTRODUCTION:The antiplatelet effects of low-dose aspirin (LDA) vary between individuals. Here, we investigated the relationship between the incidence of LDA-induced mucosal injury, antiplatelet effects of LDA, and intragastric pH. METHODS:We evaluated gastric injury severity and platelet function using the VerifyNow® System before and after administration of 100 mg aspirin for 7 days to 18 young healthy subjects (study 1). We investigated whether injury was correlated with platelet function and gastric juice pH in 45 patients with cardiovascular disease administered LDA daily (study 2). RESULTS:In study 1, platelet aggregation was attenuated by LDA to different degrees. Although 55.6% of subjects (10/18) developed gastric injury of modified Lanza score (MLS) ≥ 3, no significant difference in platelet function was detected between the mild (n = 8, MLS: 0-2) and severe injury groups (n = 10, MLS: 3-5). In study 2, the severity of LDA-induced injury was associated with gastric juice pH, but not with antiplatelet effects of LDA. DISCUSSION:In contrast to gastric juice pH, the antiplatelet effect had no correlation with the severity of gastric mucosal injury. Monitoring gastric acidity, rather than platelet function, may be useful for predicting the risk of gastric injury during LDA treatment.

背景与目标： 简介：低剂量阿司匹林（LDA）的抗血小板作用因人而异。在这里，我们调查了LDA引起的粘膜损伤的发生率，LDA的抗血小板作用和胃内pH值之间的关系。
方法：我们对18名年轻健康受试者在服用100 mg阿司匹林7天之前和之后，使用VerifyNow®系统评估了胃损伤的严重程度和血小板功能（研究1）。我们调查了每天服用LDA的45例心血管疾病患者的损伤与血小板功能和胃液pH是否相关（研究2）。
结果：在研究1中，血小板聚集被LDA减弱到不同程度。尽管55.6％（10/18）的受试者发展为改良Lanza评分（MLS）≥3的胃损伤，但轻度（n = 8，MLS：0-2）与重度损伤组之间，血小板功能没有发现显着差异（ n = 10，MLS：3-5）。在研究2中，LDA诱导的损伤的严重程度与胃液pH值相关，但与LDA的抗血小板作用无关。
讨论：与胃液pH值相比，抗血小板作用与胃粘膜损伤的严重程度无关。监测胃酸度而不是血小板功能可能有助于预测LDA治疗期间胃部损伤的风险。

BACKGROUND & AIMS: STUDY DESIGN:Retrospective study. OBJECTIVES:To analyze the neurogenic bladder characteristics and treatment approaches in patients with upper and lower cervical spinal cord injury (SCI) in order to make proper and reasonable decisions to the relevant patients. SETTING:Rehabilitation center in Ankara, Turkey. METHOD:Ninety patients with cervical SCI were included. The urodynamic analyses of the patients were conducted retrospectively by using the urodynamic laboratory records. The patients were divided into two groups as the upper cervical SCI (UCSCI) group (C1-C5) and lower cervical SCI (LCSCI) group (C6-C8). RESULTS:In this study, 82 male (91.1%) and 8 (8.9%) female patients were included. There were 51 UCSCI patients with the mean age of 34.2 ± 16.1 years and 39 LCSCI patients with the mean age of 30.4 ± 12.5 years. Detrusor overactivity and preservation of the bladder-filling sensation were significantly more frequent in the UCSCI group than in the LCSCI group (P=0.048, P=0.000 respectively). Moreover, there were statistically significant differences between the groups regarding the bladder-emptying methods, residual volume and the frequency of anticholinergic and alpha blocker use (all P<0.05). No significant difference was found between the groups regarding the frequency of autonomic dysreflexia, detrusor hypocompliancy and the bladder-storage and -emptying disorders (all P>0.05). CONCLUSION:Our results demonstrate that there are differences in the upper and lower SCI cases in terms of neurogenic bladder characteristics and treatment approaches.

背景与目标： 研究设计：回顾性研究。
目的：分析上下颈脊髓损伤（SCI）患者的神经源性膀胱特征和治疗方法，以便对相关患者做出正确合理的决定。
地点：土耳其安卡拉的康复中心。
方法：纳入90例宫颈SCI患者。使用尿流动力学实验室记录对患者进行尿流动力学分析。将患者分为上颈SCI（UCSCI）组（C1-C5）和下颈SCI（LCSCI）组（C6-C8）两组。
结果：本研究纳入了82例男性患者（91.1％）和8例患者（8.9％）。 UCSCI患者51例，平均年龄34.2±16.1岁，LCSCI患者39例，平均年龄30.4±12.5岁。与LCSCI组相比，UCSCI组的逼尿肌过度活动和膀胱充盈感的保持明显更为频繁（分别为P = 0.048，P = 0.000）。此外，各组之间在膀胱排空方法，残留量以及抗胆碱能药和α-受体阻滞剂的使用频率上有统计学差异（均P <0.05）。两组之间在自主神经反射不良，逼尿肌功能不全以及膀胱存储和排空障碍的发生率上无显着差异（所有P> 0.05）。
结论：我们的结果表明，就神经源性膀胱特征和治疗方法而言，上下SCI病例存在差异。

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/或相关蛋白鉴定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。