Diabetic nephropathy (DN), the principal pathogeny of end-stage renal disease (ESRD), is related to metabolic disorders, chronic inflammation, and oxidative stress. It was reported that high expression of interleukin-17A (IL-17A) was intimately related to the progression of DN, and targeting IL-17A exhibited regulating effects on inflammation and autoimmunity but had only limited impact on the oxidative stress damage in DN. Recent studies showed that interleukin-22 (IL-22) could inhibit mitochondrial damage and inflammatory response. Thus, the cytokine IL-22 was first fused to anti-IL-17A antibody for endowing the antibody with the anti-hyperglycemia and anti-inflammation activity. Our study demonstrated that the fusion molecule, anti-IL17A/IL22 fusion protein, could not only lead to the increase of M1 macrophages and the decrease of M2 macrophages, further improving the immune microenvironment, but also prevent the loss of mitochondrial membrane potential by reducing the production of ROS in murine DN model. In addition, the fusion protein could block TRAF6/NF-κB and AKT/ROS/TXNIP signaling pathways, further synergistically restraining the production of NLRP3, thus suppressing the inflammatory response and playing beneficial effect on slowing down the progression of DN. In conclusion, our findings demonstrated that the bifunctional IL-17A antibody and IL-22 fusion protein were of great benefit to DN, which highlighted a potential therapeutic strategy. KEY POINTS: • Anti-IL17A/IL22 fusion protein could improve the immune microenvironment and reduce the production of ROS. • Anti-IL17A/IL22 fusion protein could block TRAF6/NF-κB and AKT/ROS/TXNIP signaling pathways and then restrain the activation of NLRP3.

公立医院党支部"双带头人"建设对加强医院党建有重要意义."双带头人"建设能进一步加强党支部战斗堡垒作用,为公立医院高质量发展提供坚强的组织保障.本文结合上海市某区公立医院工作实践,对公立医院党支部"双带头人"推进中存在的问题进行分析,提出党支部"双带头人"建设策略与建议,推动公立医院党建和业务工作双融合、双促进.

当前,公立医院整体进入转型发展时期,需要更高素质、具有更高专业化水平的医院管理人才.在医院职业化管理队伍的数量和专业化水平仍不尽如人意的现实情况下,如何建设高素质职业化医院管理人才队伍,值得探索和总结.