摘要：Immune evasion behavior and immunosuppressive characteristics of tumor extensively impedethe immune initiation effect of therapy triggered immunogeniccell death (Icd). In this work, a carrier-adjuvantedimmunostimulator (designated as CoCeC) is developed toboost photodynamic immunotherapy by downregulatingprogrammed death ligand 1 (PD-L1) and impairing adenosinetriphosphate (ATP) hydrolysis. Among these, the crosslinkedchitosan oligosaccharide is applied as the drug carrier fordelivery of Ce6 and Ceritinib, which also serves as an immuneadjuvant to downregulate PD-L1. Meanwhile, the robustphotodynamic therapy (PDT) of CoCeC exhibits lethal toxicityagainst tumor cells to induce Icd and release damage-associated molecular patterns (DAMPs), which can also impairATP hydrolysis by blocking cd39. In vitro and in vivo resultsdemonstrate the robust therapeutic efficacy of CoCeC tosuppress primary tumor growth and activate a superior immune elimination against lung metastasis by amplifying theimmune initiation of Icd with the assistance of immune *** work provides a self-adjuvanted strategy to enhance the immune response of therapy induced Icd, which ispromising to activate systemic antitumor immunity in consideration of the complicated immunosuppressive factors.

摘要：目的建立糖尿病动物模型,研究cd59基因点突变与大鼠2型糖尿病的相关性。方法将Wistar大鼠随机分为正常组、双高饮食组和模型组。采用链尿佐菌素(STZ)制备糖尿病模型,设计MRcd59寡核苷酸探针(MRcd59X38 C39 W40 K41 H42 X43 X44 C45 X46),与大鼠肝、肾、胰组织进行原位杂交,以检测大鼠cd59基因点突变。同时采用免疫组化(SABC)法检测正常cd59在大鼠组织中表达情况。结果成功建立2型糖尿病大鼠模型。寡核苷酸探针及SABC证实双高饮食组及模型组大鼠组织正常cd59表达降低,而突变的Rcd59增高,与正常组比较(P<0.01)有显著差异。结论Rcd59基因突变与糖尿病密切相关。