In Vivo Kinematics of Functional Ankle Instability Patients and Lateral Ankle Sprain Copers During Stair Descent

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     

基于剂量组学预测肺癌患者放射性肺炎发生的研究

目的 探讨剂量组学在预测肺癌根治性放疗患者放射性肺炎发生中的应用潜能。方法 回顾性收集行根治性放疗的314例肺癌患者的临床资料、放疗剂量文件、定位及随访CT图像,根据临床资料及影像学随访资料对放射性肺炎进行分级,提取全肺的剂量组学特征,构建机器学习模型。应用1000次自助抽样法（bootstrap）的最小绝对值收敛和选择算子嵌套逻辑回归（LASSO‐LR）及1000次bootstrap的赤池信息量准则（AIC）向后法筛选与放射性肺炎相关的剂量组学特征,随机按照7∶3划分为训练集及验证集,应用逻辑回归建立预测模型,并应用ROC曲线及校正曲线评价模型的性能。结果 共提取120个剂量组学特征,经LASSO‐LR降维筛选得到12个特征进入“特征池”,再经过AIC向后法筛选,最终筛选出6个剂量组学特征进行模型构建,训练集AUC为0.77（95%CI为0.65~0.87）,独立验证集AUC为0.72（95%CI为0.64~0.81）。结论 利用剂量组学建立的预测模型具有预测放射性肺炎发生的潜力,但仍需继续纳入多中心数据及前瞻性数据进一步挖掘剂量组学的应用潜能。     

妇科腹腔镜围手术期碳水化合物口服疗法对术后胰岛素抵抗影响的研究

目的观察妇科腹腔镜手术围术期碳水化合物口服疗法和传统禁饮食方案两种不同的临床处理措施对于术后胰岛素抵抗（IR）的影响。 方法选取2018年2月至8月入住徐州医科大学附属医院妇科，行腹腔镜下全子宫切除手术的非糖尿病患者共98例，将采用围术期碳水化合物口服疗法者作为观察组（50例），采用传统禁饮食方案者作为对照组（48例）。检测所有病例的术前、术后第1天及第3天的空腹血糖（FPG）及空腹胰岛素（FINS），并利用稳态模式评估法计算稳态模型胰岛素抵抗指数（HOME-IR）。对于观察组与对照组患者术前、术后第1天和术后第3天的FPG、FINS和HOME-IR等指标，组间比较采用独立样本t检验。两组患者术后腹胀、术后24 h通气、术后发热的发生情况的比较采用确切概率法检验。 结果观察组与对照组比较，术前和术后第1天FPG差异无统计学意义（P均>0.05），术后第3天FPG明显降低［（4.34±0.59）mmol/L vs （4.96±0.64）mmol/L］，差异有统计学意义（t=-4.96，P=0.002）。观察组与对照组比较，术前和术后第1天FINS差异无统计学意义（P均>0.05），术后第3天FINS明显降低［（45.39±13.55）mIU/L vs （51.18±9.34） mIU/L］，差异有统计学意义（t=-2.46，P=0.033）。观察组与对照组比较，术前HOME-IR差异无统计学意义（P>0.05），术后第1天和术后第3天HOME-IR明显降低［（13.08±4.80）vs （15.03±4.11）；（9.37±3.65）vs （11.30±2.55）］，差异有统计学意义（t=-0.69，P=0.042；t=-3.99，P=0.033）。两组患者术后其他观察指标比较，观察组术后24 h通气率与对照组比较明显增高（76.0% vs 64.6%），差异有统计学意义（P=0.045）。两组患者在术后腹胀、术后发热的发生率方面差异无统计学意义（P均>0.05）。两组患者均未发生术中误吸。 结论妇科腹腔镜手术围术期应用碳水化合物口服疗法较传统禁饮食方案，能有效减轻术后IR程度，促进术后康复进程，且不增加围术期并发症的发生率。     

Pharmacological doses of melatonin impede cognitive decline in tau‐related Alzheimer models,once tauopathy is initiated,by restoring the autophagic flux

Alterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV‐hTau^P301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau‐related models. Melatonin (10 μmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV‐hTau^P301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase‐3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD.