Inhibition of autophagy enhances apoptosis induced by bortezomib in AML cells

Bortezomib is a novel proteasome inhibitor, which has been successfully used to treat mantle cell lymphoma and multiple myeloma. However, the direct effects of bortezomib on acute promyelocytic leukaemia (APL) have not been fully investigated. In the present study, the WST-8 assay, western blotting, flow cytometry, monodansylcadaverine staining and transmission electron microscopy were performed. It was demonstrated that bortezomib treatment induced a time- and dose-dependent decrease in the viability of NB4 cells. Bortezomib treatment induced cell apoptosis in NB4 cells, as assessed by Annexin V/propidium iodide analysis, and the detection of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, Bax and Bcl-2 expression. Furthermore, bortezomib treatment induced autophagy in NB4 cells, as indicated by autophagosome formation, p62 degradation, LC3-I to LC3-II conversion and formation of acidic autophagic vacuoles. Notably, autophagy induced by bortezomib was initiated prior to apoptosis. Inhibition of autophagy by knocking down Beclin-1 expression increased bortezomib-induced apoptosis in NB4 cells. Therefore, the present study revealed that the combination of bortezomib and autophagy inhibition may be a potential treatment strategy for APL.     

Silencing KLF16 inhibits oral squamous cell carcinoma cell proliferation by arresting the cell cycle and inducing apoptosis

Krüppel-like factor 16 (KLF16), a member of the Krüppel-like factor (KLF) family, has been extensively investigated in multiple cancer types. However, the role of KLF16 in oral squamous cell carcinoma (OSCC) remains unknown. Thus, we conducted this study to investigate its related mechanism. KLF16 expression in OSCC cell lines was quantified by western blotting. Then, OECM1 and OC3 cells were divided into Blank, siCtrl, siKLF16#1 and siKLF16#2 groups. Subsequently, cell proliferation was detected using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays, cell migration and invasion were detected with wound healing and Transwell assays, and cell cycle distribution and cell apoptosis were detected via flow cytometry. KLF16, p21, CDK4, Cyclin D1 and p-Rb expression was detected by western blotting. Finally, xenograft models were established in nude mice to observe the in vivo effects of KLF16 on OSCC. KLF16 protein expression was upregulated in OSCC cells. Compared to the cells in the Blank group, the OECM1 and OC3 cells in the siKLF16#1 group and siKLF16#2 group exhibited a sharp decrease in proliferation but a remarkable increase in apoptosis. Moreover, the proportion of cells in the G0/G1 phase notably increased and that in the S phase decreased, with evident decreases in cell invasion and migration. Moreover, KLF16, cyclin-dependent kinase 4 (CDK4), Cyclin D1 and p-Rb protein expression was upregulated, but p21 expression was downregulated. The mice in the siKLF16#1 and siKLF16#2 xenograft model groups exhibited slower tumour growth and smaller tumours with evident downregulation of Ki67 expression compared to the mice in the Blank group. KLF16 expression was upregulated in OSCC cells, and interfering with KLF16 led to cell cycle arrest, inhibited OSCC cell growth and promoted cell apoptosis.     

国内外安宁疗护准入标准的研究进展

安宁疗护可提高患者在生命终末阶段的生活质量，减轻患者和家属的身心痛苦。科学合理的安宁疗护准入标准可帮助医护人员识别出需要安宁疗护服务的患者，使其及时获得安宁疗护服务，因此明确安宁疗护的准入标准是推进安宁疗护发展的基础。本文就国内外安宁疗护准入标准的制定方法、具体内容及优缺点进行综述，以期为我国安宁疗护准入标准的构建提供参考。     

妊娠早期阴道微环境变化及与阴道炎症的关系分析

目的分析妊娠早期阴道微环境变化及与阴道炎症的关系。方法回顾性分析2017年3月-2018年12月韶关市曲江区妇幼保健计划生育服务中心104例妊娠早期孕产妇临床资料。记录其非妊娠期及妊娠早期阴道微环境变化情况,包括酸碱度(pH)、菌群密集度、菌群多样性、阴道微生物功能正常率、乳杆菌阳性率、阴道微生态正常率,并比较妊娠早期阴道炎症发生情况及其阴道微环境。结果孕产妇非妊娠期pH、阴道微生物功能正常率、乳杆菌阳性率及阴道微生态正常率明显高于妊娠早期,菌群密集度、菌群多样性则低于妊娠早期,差异均有统计学意义(P<0.05)。孕产妇妊娠早期阴道炎症组pH、菌群密集度、菌群多样性明显高于无阴道炎症组,阴道微生物功能正常率及乳杆菌阳性率则低于无阴道炎症组,差异均有统计学意义(P<0.05)。结论妊娠早期阴道微环境出现一系列变化,造成阴道炎症发生率升高,对此临床应给予重视。     

新生儿肺炎PCT和炎性因子水平表达及其意义

目的研究新生儿肺炎(NP)患儿血清高敏C反应蛋白(hs-CRP)、降钙素原(PCT)、白细胞介素-6(IL-6)水平表达及其意义。方法选取2017年1月-2018年2月韶关市曲江区妇幼保健计划生育服务中心诊治的NP患儿80例,按细菌感染情况分为观察1组和观察2组,各40例。选择同期40例健康新生儿作为对照组。测定并比较三组的hs-CRP、PCT和IL-6水平。结果观察1组血清PCT、hs-CRP和IL-6水平明显高于观察2组和对照组,差异均有统计学意义(P<0.05)。观察1组血清PCT、hs-CRP和1L-6检测阳性率明显高于观察2组和对照组,差异均有统计学意义(P<0.05),且观察1组血清PCT、hs-CRP和1L-6诊断NP的敏感度均明显高于观察2组,差异均有统计学意义(P<0.05);观察组各指标特异度与观察2组比较差异无统计学意义(P>0.05)。结论血清hs-CRP、PCT、IL-6水平可作为NP患儿的辅助鉴别指标,为抗生素的合理使用和疗效提供依据。     

肿瘤免疫检查点抑制剂相关的肝毒性

肿瘤免疫检查点抑制剂治疗为肿瘤患者带来生存获益的同时,也面临了许多挑战,例如免疫介导的肝毒性的发生。深入了解免疫检查点抑制剂治疗肿瘤过程中导致肝损伤的发生情况、可能机制、危险因素等,有助于更好地临床管理。