Prognostic impact of FLT3-ITD mutation on NPM1+ acute myeloid leukaemia patients and related molecular mechanisms

The prognosis of acute myeloid leukaemia (AML) patients carrying NPM1 mutations is significantly worse when accompanied by FLT3-ITD mutations. However, accurate quantitative detection of FLT3-ITD mutations remains challenging. To identify a novel biomarker in NPM1⁺FLT3-ITD⁺ AML patients for more accurate stratification, we analysed the differential gene expression between the NPM1⁺FLT3-ITD⁺ and NPM1⁺FLT3-ITD⁻ groups in five public AML datasets and identified a biomarker by taking the intersection of differentially expressed genes. We validated this biomarker in bone marrow samples from NPM1⁺ AML patients at the Peking University Institute of Haematology and analysed its prognostic significance. BCAT1 expression was higher in the NPM1⁺FLT3-ITD⁺ group than in the NPM1⁺FLT3-ITD⁻ group in all seven cohorts. BCAT1 was able to predict the prognosis of NPM1⁺FLT3-ITD⁺ AML patients, and its predictive ability was superior to that of the FLT3-ITD allelic ratio (AR). FLT3-targeted inhibitor quizartinib reduced BCAT1 expression. BCAT1 knockdown using lentiviral vectors led to the downregulation of MYC expression. Thus, we identified BCAT1 as a novel biomarker for NPM1⁺FLT3-ITD⁺ AML patients. The FLT3-ITD/BCAT1/MYC signalling pathway may play a biological role in promoting the occurrence and development of AML in FLT3-ITD⁺ cell lines.     

Pharmacokinetics,pharmacodynamics and safety of LPM3480392 in two phase I clinical trials in healthy Chinese male subjects

Drugs for acute postoperative pain and breakthrough cancer pain are still urgent in clinical. LPM3480392 is a G-protein-biased ligand at the μ-opioid receptor and showed potent analgesia in nonclinical studies. Two phase I studies of LPM3480392 were conducted in healthy Chinese male volunteers to explore its tolerability, pharmacokinetics and pharmacodynamics under single ascending doses (Study I 0.1–3.0 mg, 30 min) and different infusion times (Study II, 0.6–1.0 mg, 2–15 min). There was one serious adverse event (AE) observed in Study II, and the rest AEs were mild or moderate in severity and resolved by the end of the study. Plasma LPM3480392 maximum concentration (C_max) (under lower infusion rate) and area under the plasma concentration-time curve (AUCs) were generally increased with dose. Moreover, LPM3480392 at a dose of 0.6 mg under a 2 min infusion rate elicited effective analgesia as the peak effect within 10–30 min, which was measured by cold pain test and pupillometry. These findings suggest that LPM3480392 could be a potential treatment for acute pain management.     

超微针刀结合肌内效贴治疗急性踝关节损伤60例

目的:研究超微针刀结合肌内效贴治疗急性踝关节损伤的临床疗效,并与扶他林治疗组对照,为临床寻求一种不良反应少、安全性高、见效更快、疗效更佳的治疗急性踝关节损伤的方法。方法:按统一的诊断、纳入和排除标准,将60例符合本研究的患者按随机分组方法分为治疗组和对照组各30例。在基础治疗上,治疗组用超微针刀和肌内效贴治疗,对照组用扶他林软膏损伤处局部外用治疗。治疗组隔1天治疗1次,对照组每天治疗三次,分别于治疗前、治疗第4天及治疗第10天记录患者的疼痛程度、肿胀度、Kofoed踝关节功能恢复情况,并结合踝关节急性损伤的中医病症诊断疗效标准评价其疗效。结果:治疗组总有效率为90.00%(27/30),对照组为73.33%(22/30);治疗后的治疗组在踝关节疼痛程度、肿胀度方面都明显轻于对照组,在Kofoed踝关节功能恢复方面明显优于对照组。结论:超微针刀结合肌内效贴能尽快消除因踝关节急性损伤所导致的疼痛、肿胀、功能障碍及伴随症状,疗效明显优于扶他林软膏外用治疗。     

Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription

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影响分化型甲状腺癌肺转移患者预后的临床因素

目的:探讨影响分化型甲状腺癌（DTC）肺转移患者预后的临床因素。方法:回顾性分析西安交通大学第一附属医院2011年至2017年间接受放射性碘治疗的DTC肺转移患者。根据随访患者影像学检查结果、无进展生存率（PFS）和癌症特异性生存率评估其肺转移病灶碘摄取能力和血清甲状腺球蛋白（Tg）水平对预后的影响。结果:最终63例患者被纳入分析。在中位随访35个月（5~91个月）后，多变量分析结果提示肺转移灶摄碘阴性，但Tg分泌阳性是DTC肺转移的独立预后因素，其是导致较短PFS的独立危险因素（P=0.032）。结论:肺转移灶摄碘阴性，但Tg分泌阳性是预测DTC肺转移不良结局最重要的预后因素。     

伴微浸润的乳腺导管原位癌中肿瘤浸润淋巴细胞分布状态分析

目的 回顾性分析乳腺导管原位癌（DCIS）患者的临床病理资料,探讨伴微浸润的DCIS中肿瘤浸润淋巴细胞（TILs）的分布情况。方法 74例乳腺DCIS患者作为研究对象,不伴微浸润的DCIS（pure-DCIS）共42例作为对照组,伴微浸润的DCIS（mi-DCIS）32例作为实验组,分析其临床病理资料及TILs分布的差异,并进一步对mi-DCIS组原位癌及微浸润区域的TILs密度进行对比。结果 400倍高倍镜下,mi-DCIS组热点区域及平均值区域TILs百分比分别为57.50（18.75,80.00）%,8.00（5.00,15.00）%,pure-DCIS组分别为5.00（1.00,16.25）%,1.00（1.00,5.00）%,无论是热点区域还是平均值,mi-DCIS组TILs百分比均高于pure-DCIS组（P均< 0.001）。mi-DCIS组中微浸润灶处平均TILs比例为15.00 （5.00, 50.00）%,高于原位癌区域8.00（5.00,15.00）%,差异有统计学意义（P = 0.004）。结论 相较于pure-DCIS,mi-DCIS中TILs的分布密度明显增高;mi-DCIS中,微浸润灶处TILs的分布情况较整体有上升的趋势。