AbstractAndrogen deprivation therapy (ADT) is a crucial and effective strategy for prostate cancer, while systemic administration may cause profound side effects on normal tissues. More importantly, the ADT can easily lead to resistance by involving the activation of NF-κB signaling pathway and high infiltration of M2 macrophages in tumor microenvironment (TME). Herein, we developed a biomimetic nanotherapeutic platform by deriving cell membrane nanovesicles from cancer cells and probiotics to yield the hybrid cellular nanovesicles (hNVs), loading flutamide (Flu) into the resulting hNVs, and finally modifying the hNVs@Flu with Epigallocatechin-3-gallate (EGCG). In this nanotherapeutic platform, the hNVs significantly improved the accumulation of hNVs@Flu-EGCG in tumor sites and reprogramed immunosuppressive M2 macrophages into antitumorigenic M1 macrophages, the Flu acted on androgen receptors and inhibited tumor proliferation, and the EGCG promoted apoptosis of prostate cancer cells by inhibiting the NF-κB pathway, thus synergistically stimulating the antitumor immunity and reducing the side effects and resistance of ADT. In a prostate cancer mouse model, the hNVs@Flu-EGCG significantly extended the lifespan of mice with tumors and led to an 81.78% reduction in tumor growth compared with the untreated group. Overall, the hNVs@Flu-EGCG are safe, modifiable, and effective, thus offering a promising platform for effective therapeutics of prostate cancer. Graphical Abstract

Background: Inducing immunogenic cell death (ICD) is a promising strategy to enhance immune responses for immune checkpoint blockade (ICB) therapy, but the lack of a simple and effective platform to integrate ICD and ICB therapy limits their clinical application. Methods: Here, we developed programmed cell death protein 1 (PD1)-overexpressing genetically engineered nanovesicles (NVs)-coated curcumin (Cur)-loaded poly (lactic-co-poly-polyglycolic acid) nanoparticles (PD1@Cur-PLGA) to integrate ICD and ICB therapy for enhancing tumor immunotherapy. Results: Genetically engineered NVs greatly enhanced the tumor targeting of nanoparticles, and the PD1 on NVs dramatically blocked the PD1/PDL1 signaling pathway and stimulated antitumor immune responses. Meanwhile, the delivered Cur successfully induced tumor cell apoptosis and activated ICD by inhibiting NF-kappa B phosphorylation and Bcl-2 protein expression and activating caspase and Bax apoptotic signaling. By synergizing the ICD effect of Cur and the PD1/PDL1 axis blocking function of genetically engineered NVs, the PD1@Cur-PLGA enhanced the intratumoral infiltration rate of mature dendritic cells and CD8+T cells in tumor tissues, resulting in significantly inhibiting tumor growth in breast and prostate tumor-bearing mouse models. Conclusion: This synergistic ICD and ICB therapy based on genetically engineered NVs provides a low-cost, safe, and effective strategy to enhance cancer immunotherapy.

目的 总结并分析延胡索酸水合酶缺陷型肾细胞癌(FH-RCC)的临床资料,提高对其诊断、治疗及预后的认知.方法 回顾性分析郑州大学第一附属医院2019年3月—2021年12月收治的12例FH-RCC患者的一般临床资料,总结分析患者的影像学、病理学、基因检测、手术治疗和辅助治疗、随访结果等信息.结果 12例FH-RCC均经病理或基因检测确诊,1例并发子宫肌瘤,3例并发肾囊肿.4例子宫肌瘤家族史,2例肾癌家族史.4例影像学呈囊实性不规则密度影,增强幅度为25.8 Hu.7例行基因检测,2例发生胚系和体系突变、1例胚系突变、1例体系突变、3例未判断胚系或体系突变.9例接受肾根治手术治疗,平均手术时间3.8 h,平均出血量625 mL.10例患者行免疫治疗以及靶向药物等全身治疗,7例为手术联合术后辅助治疗,1例酪氨酸激酶抑制剂联合免疫检查点抑制剂治疗(TKI/ICI)具有良好效果.12例均获得随访资料,3例因肿瘤复发死亡、1例未见复发、8例见肿瘤影像学进展.结论 FH-RCC是一种罕见且高度恶性的肾细胞癌分型,易发生转移.影像学可表现为囊实性占位,存在特征性FH免疫组化染色阴性,需基因检测确诊.TKI/ICI联合治疗方案有良好生存获益.

目的:探讨雄性小鼠体内TSC21 基因的生物功能.方法:C57BL/6J TSC21 基因敲除杂合子雄性小鼠12只(实验组)和野生型雄性小鼠12 只(对照组),比较交配后雌性小鼠产仔数目,泌尿生殖系统发育情况,睾丸质量和组织形态,以及精子密度和精子活率.结果:两组交配后雌性小鼠产仔数目、雄性小鼠睾丸质量、精子密度和精子活率比较差异均无统计学意义(P>0.05).两组雄性小鼠泌尿生殖系统发育情况,睾丸组织和精子形态均正常.结论:TSC21 基因部分缺失对雄性小鼠生育功能未造成明显影响.

目的 探讨中性粒细胞淋巴细胞比率(NLR)、血小板淋巴细胞比率(PLR)对肾上腺皮质癌(ACC)患者预后的影响.方法 回顾性分析2011-11—2022-01于郑州大学第一附属医院诊治的57例ACC患者的临床资料.男27例,女30例;年龄(48.21±15.85)岁(范围:4～72岁).采用单因素分析及多因素分析评价NLR、PLR对ACC患者预后的影响.结果 ACC患者的NLR、PLR均显著高于肾上腺皮质腺瘤患者(P<0.001、P=0.080).NLR、PLR的最佳截断值分别为5.06和208.68.单因素分析显示,ACC患者预后效果和NLR、PLR水平,临床分期、肿瘤大小、是否进行手术有关(均P<0.05).多因素分析显示,NLR水平、肿瘤大小是ACC患者的肿瘤预后的独立影响因素(P<0.05).结论 较高水平的NLR、PLR提示ACC可能性大,NLR可能是影响ACC患者预后的独立因素,可作为一种新的预测ACC患者预后的指标.

目的 总结分析98例嗜铬细胞瘤和副神经节瘤(pheochromocytoma and paraganglioma,PPGL)患者的临床特点,以期提高PPGL的诊治水平.方法 回顾性分析2018-01—2020-12在郑州大学第一附属医院手术治疗且经术后病理结果诊断为PPGL的患者的临床资料.采用单因素及多因素Logistics分析患者的症状、激素水平、肿瘤部位和大小等与术中血压波动的相关因素.结果 98例患者中,男42例(42.9％),女56例(57.1％);年龄(47.16±15.4)岁,最高年龄段为≥51岁(P<0.05).82例首诊于泌尿外科(83.7％),最常见的原因是在影像学检查中发现肾上腺或其他部位占位病变(72例,73.5％).74例(75.5％)PPGL位于肾上腺,24例(24.5％)位于肾上腺外.术前有高血压49例(50％).67例(68.4％)患者术中血压出现波动,31例(31.6％)无血压波动.术中血压波动与肿瘤大小(P=0.039)、年龄(P=0.016)有相关性.结论 大部分PPGL患者初发症状不明显,最常见的就诊原因是在影像学检查中发现肾上腺或其他部位占位病变.对年龄较大及肿瘤较大的患者,应警惕术中出现血压波动,做好预备应对措施,以减少手术和并发症发生风险.