Poly(ortho ester) nanoparticles targeted for chronic intraocular diseases: ocular safety and localization after intravitreal injection

Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5?mg/ml and 10?mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases.     

高压氧治疗对慢性脑缺血大鼠认知功能的影响及其作用机制

目的 探讨高压氧（hyperbaric oxygen，HBO）治疗对慢性脑缺血（chronic cerebral ischemia，CCI）大鼠 学习记忆能力的影响及其作用机制。 方法 选取240只雄性SD大鼠随机分为假手术组、CCI组和HBO组，每组80只。采用双侧颈总动脉阻 断法建立CCI模型，HBO组建模12 h后开始进行HBO治疗28 d，压力0.2 MPa，每日1次，每次60 mi n。采用 Morri s水迷宫实验评估7、14、21、28 d大鼠的学习记忆能力，每个时间点20只，检测前均进行3 d训练， 记录各组大鼠的逃避潜伏时间、穿越平台次数。28 d后处死大鼠取海马组织进行HE染色评估神经元 损伤病理变化，RT-PCR法检测Nogo-A mRNA，Western blot法检测Nogo-A蛋白的表达水平。 结果 ①与假手术组比较，CCI 组7、14、21、28 d逃避潜伏时间均延长（均P＜0.05），28 d跨越平台次 数减少（P＜0.05）；与CCI 组比较，HBO组7、14、21、28 d逃避潜伏时间均缩短（均P＜0.05），28 d跨越 平台次数增加（P＜0.05）。②HE染色显示HBO组神经元损伤程度较CCI组减轻；③CCI组Nogo-A mRNA 和Nogo-A蛋白表达水平均较假手术组升高（均P＜0.05），HBO组表达水平均较CCI组下降（P＜0.05）。 结论 HBO治疗可改善慢性脑缺血大鼠认知功能，其机制可能与下调海马组织中Nogo-A的表达水平 有关。     

Is dose modification or discontinuation of nilotinib necessary in nilotinib-induced hyperbilirubinemia?

Nilotinib is a specific breakpoint cluster region-Abelson leukemia virus-tyrosine kinase inhibitor that is used as an effective first- or second-line treatment in imatinib-resistant chronic myelogenous leukemia (CML) patients. Hepatotoxicity due to nilotinib is a commonly reported side effect; however, abnormal liver function test (LFT) results have been reported in asymptomatic cases. When alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are more than five-fold the upper limit of the normal (ULN) or when the serum total bilirubin level is more than three-fold the ULN, dose modification or discontinuation of nilotinib is recommended, resulting in decreased levels of hematological indicators in certain patients with CML. Nilotinib-induced hyperbilirubinemia typically manifests as indirect bilirubinemia without elevated ALT or AST levels. Such abnormal liver functioning is thus not attributed to the presence of a true histologic lesion of the liver. The underlying mechanism may be related to the inhibition of uridine diphosphate glucuronosyltransferase activity. Therefore, nilotinib dose adjustment is not recommended for this type of hyperbilirubinemia, and in the absence of elevated liver enzyme levels or presence of abnormal LFT findings, physicians should consider maintaining nilotinib dose intensity without modifications.     

Predicting Renal Function Outcomes After Partial and Radical Nephrectomy

Background

Partial nephrectomy (PN) is generally favored for cT1 tumors over radical nephrectomy (RN) when technically feasible. However, it can be unclear whether the additional risks of PN are worth the magnitude of renal function benefit.

Evaluation of the anterolateral ligament of the knee by magnetic resonance imaging in patients with chronic anterior cruciate ligament rupture

ObjectiveThe purpose of this study was to evaluate the visibility of the anterolateral ligament (ALL) by magnetic resonance imaging (MRI) in patients with chronic anterior cruciate ligament (ACL) rupture.Materials and methodsThis retrospective case – control study compared 1.5 - T MRI scans for 50 patients with a chronic ACL rupture with those of a control group of 50 patients with an intact ACL. The ALL was evaluated in three portions: femoral, meniscal, and tibial. The status of each portion was classified as visualized or non-visualized. Two radiologists separately reviewed all the MRI scans to evaluate interobserver reliability.ResultsAt least one portion of the ALL was visualized in 100% of the control group and 72% of the chronic ACL rupture group. All three portions of the ALL were identified in 72% of the control group but only 10% of the chronic ACL rupture group. In both groups, the most commonly visualized portion was the meniscal portion and the least visualized was the tibial portion. In 18% of the chronic ACL rupture group, no portion of the ALL was visualized.ConclusionsThe visibility of the ALL of the knee was significantly lower in patients with a chronic ACL rupture than in those with an intact one.     

Voluntary ambulation using voluntary upper limb muscle activity and Hybrid Assistive Limb® (HAL®) in a patient with complete paraplegia due to chronic spinal cord injury: A case report

Context: We sought to describe our experience with the Hybrid Assistive Limb® (HAL®) for active knee extension and voluntary ambulation with remaining muscle activity in a patient with complete paraplegia after spinal cord injury.

Findings: A 30-year-old man with complete paraplegia used the HAL® for 1 month (10 sessions) using his remaining muscle activity, including hip flexor and upper limb activity. Electromyography was used to evaluate muscle activity of the gluteus maximus, tensor fascia lata, quadriceps femoris, and hamstring muscles in synchronization with the Vicon motion capture system. A HAL® session included a knee extension session with the hip flexor and voluntary gait with upper limb activity. After using the HAL® for one month, the patient’s manual muscle hip flexor scores improved from 1/5 to 2/5 for the right and from 2/5 to 3/5 for the left knee, and from 0/5 to 1/5 for the extension of both knees.

Conclusion/clinical relevance: Knee extension sessions with HAL®, and hip flexor and upper-limb-triggered HAL® ambulation seem a safe and feasible option in a patient with complete paraplegia due to spinal cord injury.     

多层螺旋CT定量评估慢性阻塞性肺疾病病情的价值

目的探讨多层螺旋CT(MSCT)定量评估慢性阻塞性肺疾病病情的价值。方法选取2017年8月～2018年7月在湖州市第一人民医院就诊的73例慢性阻塞性肺疾病(COPD)患者作为研究对象,按照病情轻重分为Ⅰ组(轻度患者17例)、Ⅱ组(中度患者32例)、Ⅲ组(重度患者24例),并选取同期于该院体检的健康者20例为对照组。所有研究对象均行MSCT低剂量扫描,观察比较各组管腔面积(Ai)、支气管壁面积百分比(WA%)、管壁厚度与体表面积比值(T/BSA)、壁厚度与直径比值(TDR),同时予以肺功能检查,采用定量CT气道分析软件分别测量气道相关参数,并用Siemens Pulmo软件Pearson定量分析其相关性。结果对照组、Ⅰ组、Ⅱ组、Ⅲ组的FEV1均呈逐渐下降趋势,FEV1/FVC呈逐渐上升趋势,差异均有统计学意义(P0.05)。对照组、Ⅰ组、Ⅱ组、Ⅲ组的WA%、T/BSA、TDR比较,均呈逐渐上升趋势,Ai呈下降趋势,差异均有统计学意义(P0.05)。FEV1与WA%、TDR之间呈负相关(r=-0.291,P=0.000;r=-0.473,P=0.000),FEV1/FVC与WA%、TDR之间呈正相关(r=0.285,P=0.000;r=0.472,P=0.000)。结论 MSCT扫描及定量分析可为COPD患者气道病变情况提供可靠的评估信息。