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.     

肝门部胆管癌的分型分期系统及其临床应用价值

肝门部胆管癌（hilar cholangiocarcinoma，HC）分型和分期系统较为庞杂，包括改良Bismuth-Corlette分型，Gazzaniga T分期，Blumgart T分期，美国纪念Sloan-Kattering癌症中心（Memorial Sloan Katering Cancer Center，MSKCC）T分期，Mayo分期系统，美国癌症联合委员会（American Joint Committee on Cancer，AJCC）和国际抗癌联盟（International Union Against Cancer，UICC）联合发布的TNM分期，欧洲肝胆胰协会分期（Consensus classification from the European Hepato-Pancreato-Biliary Association，EHPBA），以及日本肝胆胰外科学会（Japanese Society of Hepato-Biliary-Pancreatic Surgery，JSHBPS）分期，各分期系统所包含的内容差异较大，各具特色和优缺点，本文就HC常见的分型和分期系统及其在临床中的应用价值做一综述。     

Correlates of Mental Illness and Health Categories among Older Adults in China: An Empirical Study Based on the Two Continua Model

Objective: Keyes’ two continua model is a useful concept in which mental health and mental illness exist on two separate axes. Based on this model, this study examined the prevalence and correlates of three mental health categories among older adults in China.

Methods: Cross-sectional data were derived from Wave 1 of the Study on Global AGEing and Adult Health. Participants were categorized into complete mental health (CMH), complete mental illness (CMI), and moderate mental health (MMH) groups. Multinomial logistic regressions were used.

Results: The prevalence of CMH, CMI, and MMH in China was 18%, 16%, and 66%, respectively. Being female, unmarried, younger, and feeling unhealthy were more likely to result in placement in the CMI category. Employment, education, and cognitive function were identified as important protective factors of CMH. Age, income, urban or rural residence, and physical function difficulty were associated with all three categories.

Discussion: We demonstrated the utility of the two continua model in identifying mental health needs in Chinese contexts. The findings suggest that future policy reforms and clinical interventions should establish a more comprehensive mental health category as a screening tool nationwide. The promotion of social engagement could play an important role in treating mental illness and improving positive mental health.     

25-羟维生素D_3治疗2型糖尿病患者早期肾损害的临床观察

目的观察25-羟维生素D3(Vit D3)对2型糖尿病(T2DM)患者早期肾损害的临床疗效。方法纳入T2DM早期肾损伤患者80例,采用随机数字表法等分为治疗组与对照组,对照组继续原有降糖方案,治疗组在既往用药基础上,肌肉注射Vit D3注射液,疗程均为10个月,治疗结束后进行疗效评价。结果 1与治疗前相比,治疗组糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平上调,微量白蛋白(MA)、β2-微球蛋白(β2-M)及肾脏损伤分子-1(KIM-1)水平下调,治疗组低于对照组差异有统计学意义(P<0.05)。2与治疗前相比,治疗组治疗后Vit D3水平上调,治疗组高于对照组差异有统计学意义(P<0.01)。3T2DM患者Vit D3水平与MA(r=-0.432),β2-M(r=-0.615),及KIM-1(r=-0.763)水平均呈负相关(P<0.05)。结论 Vit D3可有效减轻T2DM患者的早期肾损害,对肾脏具有保护作用。