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Christopher D Hue Frances S Cho Siqi Cao Cameron R ”Dale” Bass David F Meaney Barclay Morrison III 《Journal of cerebral blood flow and metabolism》2015,35(7):1191-1198
Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in recent military conflicts, there is an urgent need to develop effective therapies for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been reported to occur after primary blast exposure, making restoration of BBB function and integrity a promising therapeutic target. We tested the hypothesis that treatment with dexamethasone (DEX) after primary blast injury potentiates recovery of an in vitro BBB model consisting of mouse brain endothelial cells (bEnd.3). DEX treatment resulted in complete recovery of transendothelial electrical resistance and hydraulic conductivity 1 day after injury, compared with 3 days for vehicle-treated injured cultures. Administration of RU486 (mifepristone) inhibited effects of DEX, confirming that barrier restoration was mediated by glucocorticoid receptor signaling. Potentiated recovery with DEX treatment was accompanied by stronger zonula occludens (ZO)-1 tight junction immunostaining and expression, suggesting that increased ZO-1 expression was a structural correlate to BBB recovery after blast. Interestingly, augmented ZO-1 protein expression was associated with specific upregulation of the α+ isoform but not the α− isoform. This is the first study to provide a mechanistic basis for potentiated functional recovery of an in vitro BBB model because of glucocorticoid treatment after primary blast injury. 相似文献
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目的 利用MRI技术连续采集头颈部肿瘤患者吞咽时图像,观察并测量软腭、舌、喉的运动规律及最大活动度。方法 随机选取2018年7月-10月在中国医学科学院肿瘤医院接受调强放疗的原发头颈部恶性肿瘤20例患者,其中男17例、女3例,中位年龄58.5岁(28~78岁)。20例患者中鼻咽癌7例,口腔癌3例,口咽癌5例,下咽癌3例,鼻腔鼻旁窦2例。根据AJCC第八版分期Ⅰ-Ⅱ期患者2例,Ⅲ期8例,Ⅳ期10例。结果 吞咽时软腭向上移动移动距离为(1.06±0.31) cm且服从正态分布,向后移动距离为(0.83±0.24) cm且近似正态分布。舌体向后移动距离为(0.77±0.22) cm,且服从正态分布。含压舌板行图像采集患者舌上移位移为0,无压舌板患者舌体中位上移距离为1.23 cm (0.59~1.41 cm)。喉向上移动距离为(1.14±0.22) cm且服从正态分布,向前移动的中位距离为0.4 cm (0.27~0.90 cm)。结论 吞咽运动有可能发生于头颈部肿瘤患者放疗过程中,并引起大体肿瘤体积(GTV)及周围正常组织移动;因此在制定放疗计划时应注意GTV至PGTV的个体化外放距离,以保证肿瘤处方剂量。 相似文献
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Richard Kim Elaine Tan Emily Wang Amit Mahipal Dung-Tsa Chen Biwei Cao Fadzai Masawi Cindy Machado James Yu Dae Won Kim 《The oncologist》2020,25(12):e1893-e1899
Lessons Learned
- The combination of trametinib and sorafenib has an acceptable safety profile, albeit at doses lower than approved for monotherapy.
- Maximum tolerated dose is trametinib 1.5 mg daily and sorafenib 200 mg twice daily.
- The limited anticancer activity observed in this unselected patient population does not support further exploration of trametinib plus sorafenib in patients with hepatocellular carcinoma.
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Shengxuan Cao Chen Wang Xin Ma Xu Wang Jiazhang Huang Chao Zhang Li Chen Xiang Geng Kan Wang 《Journal of orthopaedic research》2019,37(8):1860-1867
Patients with mechanic ankle instability experience increased tibiotalar and subtalar joint laxity. However, in vivo joint kinematics in functional ankle instability (FAI) patients and lateral ankle sprain (LAS) copers, especially during dynamic activities, are poorly understood. Ten FAI patients, 10 LAS copers, and 10 healthy controls were included in this study. A dual fluoroscopic imaging system was used to analyze the tibiotalar and subtalar joint kinematics during stair descent. Five key poses of stair descent were analyzed. Kinematic data from six degrees of freedom were calculated utilizing a solid modeling software. The range of motion and joint positions in each degree of freedom were compared among the three groups. The tibiotalar joints of FAI patients and LAS copers were significantly more inverted than those of healthy controls during the foot strike (p = 0.016, = 0.264). The subtalar joints of FAI patients were significantly more anteriorly translated (pose 2, p = 0.003, = 0.352; pose 3, p < 0.001, = 0.454; pose 4, p = 0.004, = 0.334), inverted (pose 4, p = 0.027, = 0.234; pose 5,p = 0.034, = 0.221), and externally rotated (pose 4, p = 0.037, = 0.217; pose 5; p = 0.004, = 0.331) than those of healthy controls during the mid‐stance and the heel off. The FAI patients showed excessive tibiotalar inversion and subtalar joint hypermobility during stair descent. Meanwhile, the LAS copers maintained subtalar joint stability, and only showed excessive tibiotalar inversion in foot strike. These data provide insight into the mechanisms behind the development of FAI after initial LAS. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1860–1867, 2019 相似文献
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By means of the ultrasonic surface impact (amplitude of 30 μm, strike number of 48,000 times/mm2), nanograins have been achieved in the surfaces of both Ti6Al4V(TC4) and Ti3Zr2Sn3Mo25Nb(TLM) titanium alloys, mainly because of the dislocation motion. Many mechanical properties are improved, such as hardness, residual stress, and roughness. The rotating–bending fatigue limits of TC4 and TLM subjected to ultrasonic impact are improved by 13.1% and 23.7%, separately. Because of the bending fatigue behavior, which is sensitive to the surface condition, cracks usually initiate from the surface defects under high stress amplitude. By means of an ultrasonic impact tip with the size of 8 mm, most of the inner cracks present at the zone with a depth range of 100~250 μm in the high life region. The inner crack core to TC4 usually appears as a deformed long and narrow α-phase, while the cracks in TLM specimens prefer to initiate at the triple grain boundary junctions. This zone crosses the grain refined layer and the deformed coarse grain layer. With the gradient change of elastic parameters, the model shows an increase of normal stress at this zone. Combined with the loss of plasticity and toughness, it is easy to understand these fatigue behaviors. 相似文献
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