Ponatinib may overcome resistance of FLT3-ITD harbouring additional point mutations, notably the previously refractory F691I mutation

Fms-like tyrosine kinase (FLT3) mutations are the most frequent mutations in patients with acute myeloid leukaemia (AML) that confer a poor prognosis. Constitutively active FLT3-ITD (internal tandem duplications) mutations define a promising target for therapeutic approaches using small molecule inhibitors. However, several point mutations of the FLT3 tyrosine kinase domain (FLT3-TKD) have been identified to mediate resistance towards FLT3 tyrosine kinase inhibitors (FLT3-TKI), including secondary mutations of FLT3. We investigated the cellular effects of the recently characterised FLT3-TKI ponatinib (AP24534) on murine myeloid cells transfected with FLT3-ITD with or without additional point mutations of the FLT3-TKD including the (so far) multi-resistant F691I mutation. Ponatinib effectively induced apoptosis not only in the parental FLT3-ITD cell line but also in all stably transfected subclones harbouring additional FLT3-TKD point mutations (N676D, F691I or G697R). These observations correlated with a strong inhibition of FLT3-ITD and its downstream targets STAT5, AKT and ERK1/2 upon ponatinib incubation, as determined by Western blotting. We conclude that ponatinib represents a promising FLT3-TKI that should be further investigated in clinical trials. The targeted therapy of FLT3-ITD-positive AML with ponatinib might be associated with a lower frequency of secondary resistance caused by acquired FLT3-TKD mutations.     

耳穴压豆法减轻正畸治疗疼痛的临床效果观察

目的:观察耳穴压豆法减轻正畸治疗牙周疼痛的临床效果.方法:选择初次正畸治疗患者40人,初次戴入矫治弓丝后随机分为实验组和对照组,每组20人.实验组上弓丝后即加用耳穴磁疗法;对照组复诊时用耳穴磁疗法,观察记录患者牙周疼痛的发生率、疼痛的持续时间,并对其进行统计学分析.结果:应用耳穴压豆法的正畸患者疼痛发生率明显降低,持续时间也明显减少(P＜0.05).结论:耳穴压豆法能有效减轻正畸治疗时的牙周疼痛.     

心理语言、穴位刺激和胃电起搏协同改善功能性消化不良的胃感觉功能

目的研究心理语言、穴位刺激、胃电起搏协同治疗方法(Coordinated Treatment of Psychological language,Acupuncture pointstimulation and Gastric pacing,CTPAG)治疗难治性功能性消化不良的临床疗效及可能机制。方法根据罗马Ⅲ标准选取80例难治性功能性消化不良患者,随机分为两组:口服药物组(n=38)和CTPAG组(n=42),比较两组受试者在症状评分、临床疗效、胃感觉功能中的差异。结果与口服药物组比较,CTPAG组中临床症状评分明显下降,疗效显著率明显升高;胃的初次饱足阈值和最大耐受阈值均明显增加,差异具有统计学意义(P<0.05)。结论心理语言、穴位刺激和胃电起搏协同治疗(CTPAG)可能通过增加胃的可耐受容积,降低内脏敏感性,达到改善早饱、腹胀、进食少等疗效;并且CTPAG组优于常规口服药物组,是难治性FD非药物治疗的一种新选择。     

Detecting viruses by using salivary diagnostics

BackgroundDiagnostics that involve the use of oral fluids have become increasingly available commercially in recent years and are of particular interest because of their relative ease of use, low cost and noninvasive collection of oral fluid for testing.Types of Studies ReviewedThe authors discuss the use of salivary diagnostics for virus detection with an emphasis on rapid detection of infection by using point-of-care devices. In particular, they review salivary diagnostics for human immunodeficiency virus, hepatitis C virus and human papillomavirus. Oral mucosal transudate contains secretory immunoglobulin (Ig) A, as well as IgM and IgG, which makes it a good source for immunodiagnostic-based devices.Clinical ImplicationsBecause patients often visit a dentist more regularly than they do a physician, there is increased discussion in the dental community regarding the need for practitioners to be aware of salivary diagnostics and to be willing and able to administer these tests to their patients.     

Sensory outcomes of the anterior tongue after lingual nerve repair in oropharyngeal cancer

Primary treatment of oropharyngeal cancer often involves surgical resection and reconstruction of the affected area. However, during base of tongue reconstruction the lingual nerve is often severed on one or both sides, affecting sensation in the preserved tissue of the anterior tongue. The loss of specific tongue sensations could negatively affect a person's oral function and quality of life. The aim of this study was to explore the effects of different types of lingual nerve intervention on sensory function for patients with base of tongue cancer as compared to healthy, age-matched adults. Subjects included 30 patients who had undergone primary oropharyngeal reconstruction with a radial forearm free-flap and 30 matched controls. Sensations tested were temperature, two-point discrimination, light touch, taste, oral stereognosis and texture on the anterior two-thirds of the tongue. Results indicated that type of surgical nerve repair may not have a significant impact on overall sensory outcomes, providing mixed results for either nerve repair technique. Sensations for the nonoperated tongue side and operated side with lingual nerve intact were comparable to matched controls, with mixed outcomes for nerve repair. The poorest sensory outcomes were observed in patients with the lingual nerve severed, while all patients with lingual nerve intervention exhibited deteriorated taste sensation on the affected tongue side. Overall, patients in this study who had undergone oropharyngeal reconstruction with lingual nerve intervention exhibited decreased levels of sensation on the operated tongue side, with minimal differences between types of lingual nerve repair.