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.     

The impact of dusk phenomenon on total glucose exposure in Chinese people with type 2 diabetes

This study was aimed at assessing the impact of the dusk phenomenon on the total glucose exposure in Chinese people with type 2 diabetes.A total of 380 type 2 diabetes who received a retrospective continuous glucose monitoring system (CGMs) for 72 hours were enrolled in our study, 32 of them failed in CGMs. The patients were first divided into 2 groups: dusk phenomenon (n = 95) and non dusk phenomenon group (n = 253). The magnitude of the dusk phenomenon (δDusk) was quantified by pre-dinner glucose minus post-lunch 2 hours glucose. A persistent δDusk ≥ 0 or a once only δDusk < 0 can be diagnosed with the dusk phenomenon. The participants were secondarily matched for the post-lunch 2 hours glucose to assess the impact of the dusk phenomenon on the overall glucose exposure. The impact of the dusk phenomenon was assessed on high-performance liquid chromatography assay (HbA1c) and 24-hour mean glucose.There were 95 of 348 (27.3%) participants with the dusk phenomenon in the overall population, and the median of δDusk level was –0.8 (–1.8, 0.2) mmol/L. The median of glucose differences between the 2 paired groups were 0.4 (–0.4, 1.0)% for HbA_1c, 0.9 (0.2, 1.4) mmol/L for 24 hours mean glucose. The correlation analysis showed no relationship between the magnitude of dawn phenomenon and the dusk phenomenon (r = 0.052, P = .472).The incidence of dusk phenomenon is about 27.3% in people with type 2 diabetes. The impacts of dusk phenomenon on HbA1c and 24-hour mean glucose were about 0.4% and 0.9 mmol/L and the dusk phenomenon was not related with the dawn phenomenon.     

小儿推拿特定操作——分手阴阳考析

分手阴阳是小儿推拿特色操作之一,临床被应用于各类疾病,具有平衡阴阳,调和脏腑的作用.该文通过对此穴古今文献的研究整理,详细地从该穴的定位、操作、应用配伍等各个方面进行分析,以期更全面深入地认识手阴阳穴位及分手阴阳操作,为临床应用提供文献支持.     

我国高等医学院校医学人才培养体制现状调查与分析

目的  为了遵循医学人才培养规律，规范医学人才培养体制，提高医学人才培养质量，探索符合我国实际需求的医学人才培养模式。方法  采用问卷调查法对全国140所高等医学院校进行调查，并对相关调查结果进行分析。结果  ①86.96%的高校对统一规范为“5+3”一体化为主体，同时参加住院医师规范化培训，毕业合格者授予医学博士（MD）学位表示赞成。②76.80%的高校对将“5+3”一体化作为培养全科医生主要渠道的医学博士培养体系表示赞成。③90.40%的高校对通过“5+3+X”一贯制培养授予MD+PhD项目，培养复合型高水平临床医学人才表示赞成。④84.80%的高校对医学学位授予与专科医师规范化培训相脱离，后者应纳入职业培训范畴表示赞成。结论  全面推进落实“5+3”为主体的高素质临床医学相关人才培养模式，将培养目标定位为以满足社会需求的高水平全科医生为主体，加快高层次复合型医学人才的培养体系建设。     

PEDF对氧诱导视网膜病变小鼠视网膜MCP-1表达的影响

目的：观察色素上皮衍生因子(pigment epithelium-derived factor，PEDF)在氧诱导视网膜病变(oxygen-induced retinopathy，OIR)中对小鼠视网膜新生血管(retinal neovascularization，RNV)和单核细胞趋化因子-1(monocyte chemoattractant protein-1，MCP-1)表达的影响，探讨PEDF对缺血缺氧性视网膜病变的保护作用和机制。

方法：取7日龄C57BL/6J新生小鼠160只，将120只7日龄小鼠与哺乳母鼠共同置于氧浓度为(75±2)%的氧环境内饲养5d，然后返回正常氧环境中饲养5d，建立OIR模型； 40只小鼠始终置于正常氧环境饲养。分别于12日龄和14日龄给予PEDF药物治疗组小鼠右眼玻璃体腔注射PEDF(2μg/μL)各1μL，给予PBS治疗对照组和正常对照组小鼠右眼玻璃体腔注射等量的磷酸盐缓冲液(phosphate buffered saline，PBS)。所有小鼠于17日龄麻醉处死后取视网膜，采用视网膜铺片和Lectin染色法观察各组小鼠病理性新生血管的生成情况； Western-blot检测PEDF和MCP-1蛋白在各组小鼠视网膜的表达； 实时荧光定量逆转录多聚酶链反应(RT-PCR)检测各组小鼠视网膜PEDF和MCP-1 mRNA的表达。

结果：视网膜铺片和Lectin染色结果显示OIR模型组RNV面积较正常组显著增大，差异有统计意义(P<0.01)，PEDF药物治疗组RNV面积较PBS治疗对照组明显减小，差异有统计意义(P<0.01)。Western-blot和RT-PCR结果显示，OIR模型组MCP-1蛋白和mRNA的表达水平均明显高于正常组，差异有统计意义(均P<0.05)； OIR模型组PEDF蛋白和mRNA的表达水平均明显低于正常组，差异有统计意义(均P<0.01)； PEDF药物治疗组MCP-1蛋白和mRNA的表达量较PBS治疗对照组均显著减少，差异有统计意义(均P<0.05)； PEDF药物治疗组MCP-1蛋白和mRNA的表达量较正常对照组升高，但差异均无统计学意义(均P>0.05)。

结论：PEDF能够抑制OIR小鼠视网膜新生血管形成，同时下调MCP-1在OIR小鼠视网膜的表达，后者可能是其抑制新生血管形成从而发挥视网膜保护作用的机制之一。     

Ki-67表达与原发性肝癌根治性切除术后行预防性肝动脉化疗栓塞患者预后的关系

目的:探讨Ki-67表达与原发性肝癌根治性切除术后行预防性TACE患者预后的关系。方法:采用回顾性队列研究,收集2014年12月—2016年1月福建医科大学孟超肝胆医院150例行原发性肝癌根治性切除术并在术后2个月内行预防性TACE患者的临床病理资料,根据术后肝癌组织病理Ki-67评分分为为低表达组(Ki-67评分≤20%,44例)和高表达组(Ki-67评分20%,106例);分析Ki-67表达量与患者临床病理因素及复发与生存的关系。结果:高表达组肿瘤多发、肿瘤包膜不完整及合并微血管癌栓患者比例明显高于低表达组(均P0.05)。Ki-67高表达与肿瘤多发、肿瘤直径大为影响无瘤生存期的独立危险因素(均P0.05);Ki-67高表达与肿瘤多发、肿瘤直径大、肿瘤包膜不完整、合并微血管癌栓为影响总生存期的独立危险因素(均P0.05);高表达组患者复发率明显高于低表达组(57.9%vs. 37.7%,χ~2=6.777,P0.05),总生存率明显低于低表达组(45.6%vs. 75.9%,χ~2=8.447,P0.05)。结论:Ki-67的表达量对肝癌根治性切除术后行预防性TACE患者的预后有显著影响,高表达者预后不良。