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

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:探索T279基因在雄性小鼠精子发生中的作用.方法:C57BL/6J品系成年雄性T279基因敲除纯合子小鼠(T279-/-)12只为实验组,成年雄性野生型小鼠(T279+/+)12只为对照组,每只成年雄性小鼠与两只成年野生型雌性小鼠合笼(交配生育实验),1个月后记录雌性小鼠产仔数目,观察两组小鼠泌尿生殖系统的发育情况,HE染色观察睾丸组织形态,采用精子形态学分析技术观察两组小鼠的精子形态.结果:两组小鼠体重和睾丸质量的差异无统计学意义(P>0.05);肾脏、输尿管、膀胱、睾丸、附睾整体形态和大小无明显差异;睾丸精曲小管内均为正常的精子发生状态,各级精子细胞排列有序,可见正常睾丸支持细胞、间质细胞、管周肌样细胞.两组小鼠精子密度和精子活率比较,差异无统计学意义(P>0.05).实验组小鼠精子畸形率(20.3％)高于对照组(7.4％),差异有统计学意义(P<0.001).实验组小鼠精子头部畸形.结论:T279基因敲除可导致雄性小鼠精子畸形率明显升高.

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.

Background Eukaryotic translation initiation factors (eIFs) are the key factors to synthesize translation initiation complexes during the synthesis of eukaryotic proteins. Besides, eIFs are especially important in regulating the immune function of tumor cells. However, the effect mechanism of eIFs in prostate cancer remains to be studied, which is precisely the purpose of this study. Methods In this study, three groups of prostate cancer cells were investigated. One group had its eIF5B gene knocked down; another group had its Programmed death 1 (PD-L1) overexpressed; the final group had its Wild-type p53-induced gene 1 (Wig1) overexpressed. Genetic alterations of the cancer cells were performed by plasmid transfection. The expression of PD-L1 mRNA was detected by quantitative real-time PCR ( qRT-PCR), and the expressions of PD-L1 and eIF5B proteins were observed by western blot assays. Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell and Transwell martrigel were used to investigated cell proliferation, apoptosis, migration and invasion, respectively. The effect of peripheral blood mononuclear cells (PBMCs) on tumor cells was observed, and the interaction between eIF5B and Wig1 was revealed by co-immunoprecipitation (CoIP) assay. Finally, the effects of interference with eIF5B expression on the growth, morphology, and immunity of the tumor, as well as PD-L1 expression in the tumor, were verified by tumor xenograft assays in vivo. Results Compared with normal prostate epithelial cells, prostate cancer cells revealed higher expressions of eIF5B and PD-L1 interference with eIF-5B expression can inhibit the proliferation, migration, invasion and PD-L1 expression of prostate cancer cells. Meanwhile, the cancer cell group with interference with eIF5B expression also demonstrated greater, apoptosis and higher vulnerability to PBMCs. CoIP assays showed that Wig1 could bind to eIF5B in prostate cancer cells, and its overexpression can inhibit the proliferation, migration, invasion and PD-L1 expression of cancer cells while promoting apoptosis. Moreover, interference with eIF5B expression can inhibit tumor growth, destroy tumor morphology, and suppress the proliferation of tumor cells. Conclusion eIF5B can promote the expression of PD-L1 by interacting with Wig1. Besides, interference with eIF5B expression can inhibit the proliferation, migration, invasion and immunosuppressive response of prostate cancer cells. This study proposes a new target, eIF5B, for immunotherapy of prostate cancer.

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.

目的 探讨前列腺癌(PCa)根治术后尿控功能恢复的相关因素.方法 回顾性分析2016-10—2019-10在郑州大学第一附属医院行PCa根治术的390例PCa患者的临床资料.根据术后第1、3个月的尿控功能恢复情况分为尿控组和尿失禁组.比较2组患者的年龄、体质量指数(BMI)、吸烟、饮酒、手术方式;是否保留膀胱颈、神经血管束(NVB)和后方筋膜重建;经尿道前列腺电切术(TURP)史,以及术后提肛训练等因素的差异.结果 患者术后第1个月、3个月的尿控率分别为25.64％和53.59％.分析结果显示,TURP史是术后尿控功能恢复的不利因素(P<0.05).机器人辅助腹腔镜手术(RALP),术后保留膀胱颈、保留NVB和后方筋膜重建,以及术后提肛训练,对患者术后尿控功能恢复有积极影响(P<0.05).结论 RALP、术中保留膀胱颈、NVB和后方筋膜重建,以及术后提肛训练,有利于术后尿控的恢复;TU RP史是术后尿控功能恢复的不利因素.对临床医师术中及术后患者尿控功能恢复具有指导意义.

Exosomes mediate the interaction between cancer cells and their microenvironment, and play a key role in tumor development. Although exosomes can package lncRNAs to mediate extracellular communication, the role of exosomal lncRNA AY927529 in prostate cancer (PCa) remains unclear. Exosomes were extracted from normal human prostatic epithelial cell lines (BPH-1 and RWPE-1) and PCa cell lines (VCaP and LNCaP, DU145, PC3) by ultrahigh speed centrifugation. Results of Western blot indicated that Alix, HSC70 and TSGl01 protein levels were upregulated in exosomes derived from PCa cells. LncAY927529 level was upregulated in PCa cells and exosomes derived from PCa patient serum and human PCa cells. CCK-8, Transwell and Flow cytometry assays demonstrated that bone marrow stromal cell line (ST2) conditioned medium (ST2-CM), treated with exosomes derived from PCa cells with high lncAY927529 level, promoted proliferation and invasion of PC3 and DU145 cells, and inhibited cell apoptosis. RT-qPCR assay indicated that lncAY927529 level was downregulated in PC3 and DU145 cells, exosomes derived from PCa cells (PCa-Exo) and ST2-CM treated with PCa-Exo with low expression of lncAY927529, and overexpression of lncAY927529 had the opposite results. In addition, Western blot assay showed that the autophagy related protein LC3II level was increased in ST2 cells treated with exosomes derived from DU145 cells with high expression of lncAY927529, and LC3I protein level was decreased. CXCL14 acted as a RNA-binding protein of lncAY927529, and exosome-mediated lncAY927529 positively regulated CXCL14 levels in ST2 cells. In general, exosome-mediated lncAY927529 could promote PCa cell proliferation and invasion by regulating bone microenvironment, suggesting that exosomal lncAY927529 may be a potential molecular diagnostic marker of PCa.