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关键词： 纳米膜过滤   抗人T细胞猪免疫球蛋白   病毒去除   猪细小病毒   脑心肌炎病毒  

摘要： 目的评价纳米膜(DV20 nm)过滤法在抗人T细胞猪免疫球蛋白生产过程中对病毒的去除效果。方法在三批抗人T细胞猪免疫球蛋白中分别加入猪细小病毒(PPV)和脑心肌炎病毒(EMCV)作为指示病毒,滴度分别为7.00 lgTCID50/0.1 ml和7.80 lgTCID50/0.1ml,采用两个品牌的纳米膜(DV20nm)进行除病毒过滤。根据不同过滤时间点和过滤体积取样,检测样品中残余病毒滴度,以评价不同品牌纳米膜的病毒去除效果。结果Virosart^(TM)HC纳米膜对PPV的去除效果为病毒滴度降低4.56~5.00 lgTCID50/0.1ml,对EMCV的去除效果为病毒滴度降低4.18~4.50 lgTCID50/0.1 ml;Planova^(TM)20N纳米膜对PPV的去除效果为病毒滴度降低4.32~4.62 lgTCID50/0.1 ml,对EMCV的去除效果为病毒滴度降低4.19~4.32 lgTCID50/0.1 ml。结论经Virosart^(TM)HC和Planova^(TM)20N纳米膜过滤后,样品中PPV病毒和EMCV病毒的残留均低于最低检测限度,病毒滴度下降值均大于4.0 lgTCID50/0.1 ml,均符合现行《血液制品去除/灭活病毒技术方法及验证指导原则》的要求,两个品牌纳米膜均能用于免疫球蛋白类制品中病毒的病毒去除。

关键词： 雷公藤甲素   肝毒性   自然杀伤细胞   T细胞亚群   细胞因子   免疫表型分析   小鼠  

摘要： 目的 探讨NK细胞在雷公藤甲素(TP)肝损伤过程中的动态变化及作用。方法 C57BL/6雌性小鼠分为对照组,TP给药(600μg·kg^(-1))1、3、5、7 d组,抗NK1.1抗体与TP合用1、3、5、7 d组。在不同时间点收集小鼠血液,分离肝脏非实质细胞,通过流式细胞术检测NK细胞、CD4^(+)/CD8^(+)T细胞亚群及细胞因子(IFN-γ、IL-4)的时空变化。结果 TP处理后,肝脏NK细胞比例在1 d显著升高(P<0.05),3~7 d时CD69^(+)NK细胞持续增加(P<0.05)。细胞因子分泌呈现时间依赖性:5 d时IFN-γ^(+)NK细胞比例升高(P<0.05),而1和7 d以IL4^(+)NK细胞为主(P<0.05)。NK细胞耗竭显著降低血清丙氨酸氨基转移酶(Alanie Transaminase, ALT)水平(P<0.05),减少IFN-γ分泌(P<0.05),使肝脏NK细胞分泌的细胞因子向Th2偏倚(IFN-γ/IL-4比值降低,P<0.05)。此外,TP诱导外周血中CD4^(+)T细胞持续增加(1~7 d均P<0.05)与CD8^(+)T细胞选择性减少(3~5 d, P<0.05),导致CD4^(+)/CD8^(+)比率失衡。结论 肝脏NK细胞在TP肝损伤中发挥作用。

关键词： 乳腺肿瘤   同位素标记   镓放射性同位素   抗原   CD44   干细胞   肿瘤细胞   培养的  

摘要： 目的进行CD44^(+)CD24^(-)三阴性乳腺癌(TNBC)干细胞样细胞富集及生物学行为研究, 并构建^(68)Ga标记的CD44多肽[^(68)Ga-1, 4, 7-三氮杂环壬烷-1, 4, 7-三乙酸(NOTA)-CD44p], 评价其对TNBC干细胞样细胞表面标志物CD44的靶向能力。方法采用悬浮球培养法, 进行TNBC细胞株MDA-MB-231与非TNBC细胞株MCF-7中的CD44^(+)CD24^(-)细胞亚群的富集培养。采用流式细胞仪检测不同组干细胞标志物的表达情况, 用细胞划痕实验检测CD44^(+)CD24^(-)细胞亚群迁移能力, 通过Transwell侵袭实验评价CD44^(+)CD24^(-)细胞亚群的侵袭能力。制备^(68)Ga-NOTA-CD44p, 并用高效液相色谱(HPLC)法对其进行纯化和鉴定。通过细胞摄取和阻断实验评价^(68)Ga-NOTA-CD44p对CD44^(+) TNBC细胞的靶向能力。采用两独立样本t检验和单因素方差分析(最小显著差异t检验)进行数据分析。结果悬浮球培养法成功富集CD44^(+)CD24^(-) TNBC干细胞样细胞球。与非TNBC细胞MCF-7细胞相比, TNBC细胞MDA-MB-231细胞表现出更好的成球能力[(18.50±3.73)与(31.83±4.92)个;t=5.29, P<0.001]以及更高的CD44^(+)CD24^(-)细胞亚群占比[(24.97±8.12)%与(90.93±4.46)%;F=170.10, t=14.93, 均P<0.001]。CD44^(+)CD24^(-) MDA-MB-231组较CD44^(+)CD24^(-) MCF-7组细胞的伤口愈合率[(71.00±11.00)%与(28.33±4.16)%;F=42.91, t=8.02, 均P<0.001]、侵袭率[(60.60±16.87)%与(24.16±8.15)%;F=11.83, t=4.40, 均P<0.01]明显升高。MDA-MB-231对^(68)Ga-NOTA-CD44p具有较强的摄取能力, CD44p阻断后摄取能力下降。结论与CD44^(+)CD24^(-) MCF-7相比, CD44^(+)CD24^(-) MDA-MB-231表现出更高的恶性生物学行为;^(68)Ga-NOTA-CD44p可靶向TNBC干细胞样细胞表面标志物CD44, 研究为以肿瘤干细胞为靶点的TNBC靶向治疗手段的建立奠定了基础。

关键词： IL22   Th17   enteroid models   infant   neonate   RNAseq   intestinal development   organoid  

摘要： Introduction The intestinal epithelium of human infants is developmentally immature compared to that of adults. Exactly how this immaturity affects key epithelial functions and their interactions with nearby immune cells remains an understudied area of research, partly due to limited access to non-diseased infant gut tissues. Human intestinal organoids, or "mini guts" generated from tissue stem cells, are promising models for investigating intestinal biology and disease mechanisms. These three-dimensional structures closely mimic their tissue of origin, including cellular physiology and genetics. We have also previously shown that neonatal Th17 cells represent a distinct cell population with a cytokine profile skewed toward IL-22 production rather than IL-17A, as seen in adult Th17 cells. Methods In this study, we sought to model the impact of neonatal-derived Th17 cytokine, namely IL-22 and the intestinal epithelium using infant-derived ileal enteroids. We generated enteroids from ileal biopsies from infants (< 6 months old) and cultured them for seven days with standard organoid growth media, organoid media supplemented with conditioned media from cord-blood-derived Th17 cells, or media supplemented with recombinant IL-22. We assessed morphological changes and conducted transcriptomics profiling via RNAseq. Results Exposing enteroids to neonatal Th17-cells-derived conditioned media led to enhanced growth, maturation, and differentiation as compared to control media. These effects were ablated when an IL-22 neutralizing antibody was used, while conversely, supplementing with recombinant IL-22 mimicked the Th17 effects, increasing intestinal epithelial cell proliferation and inducing marked differentiation of secretory cells. Our transcriptomic profiling similarly demonstrated significant changes in response to IL-22 with downregulation of Wnt and Notch signaling and upregulation of immune pathways, particularly interferon signaling. The transcriptomic data also sug

关键词： Pancreatic Cancer   Irreversible Electroporation   Immune Therapy   Type-2 Conventional Dendritic Cells   CD4+T Cells  

摘要： Pancreatic ductal adenocarcinoma (PDAC) is a "cold" solid tumor with frequent Major Histocompatibility Complex I (MHC-I) deficiency, thereby making it resistant to type-1-conventional dendritic cell (cDC1)-CD8+T cell mediated anti-tumor immunity. Current studies have demonstrated the emerging compensatory role of MHCII-mediated antigen presentation and CD4+T cell activation in anti-tumor immunity against MHC-I-deficient tumors. However, the underlying mechanism of the compensatory immune response by CD4+T cells in cancer ablation therapy remains to be elucidate. In clinical samples and murine models, we observed that irreversible electroporation (IRE) ablation therapy promoted immune infiltration and the conversion of CD4+T cells into anti-tumor IFN-gamma+Th1 cells and Th17 cells in MHC-I low-expressed PDAC using scRNA-seq and flow-cytometry analyses. Furthermore, we found that PD-L1 blockade predominantly enhanced the activation of CD11b+CD103-type-2 conventional dendritic cells (cDC2s) and their antigen presentation to CD4+T cells after ablation, stimulating the anti-tumor immune response through the tumor antigen-specific IFN-gamma+Th1-NK cell axis. Elevated plasma levels of IL-6 in pancreatic cancer patients receiving ablation therapy are significant indicators for impaired prognosis. IL-6 and PD-L1 dual blockade could significantly augment the ratio of IFN-gamma+Th1 in CD4+T cells to boost the anti-tumor immunity of NK cells, leading to prolonged survival of mouse bearing pancreatic cancer. Collectively, we have elucidated that PD-L1 blockade activates the cDC2-CD4+T cell axis after IRE therapy, thereby playing a pivotal compensatory anti-tumor role in MHC-I low-expressed pancreatic cancer. Moreover, a combination strategy involving dual-target blockade of PD-L1/IL-6 along with ablation therapy could emerge as a novel therapeutic approach for MHC-I deficient tumors.

关键词： 支气管肺发育不良   肺动脉高压   白细胞介素33   肺部感染   预后  

摘要： 目的探讨支气管肺发育不良(bronchopulmonary dysplasia,BPD)早产儿血清白细胞介素(interleukin,IL)-33表达水平与肺动脉高压的相关性。方法纳入2022年8月-2024年8月新乡医学院第一附属医院新生儿科和焦作市妇幼保健院新生儿科收治住院的BPD早产儿130例,根据是否合并肺动脉高压,分为BPD组(n=74)和BPD合并肺动脉高压组(n=56)。另外,纳入新乡医学院第一附属医院新生儿科和焦作市妇幼保健院新生儿科非BPD早产儿为对照组(n=50)。收集所有患儿临床资料,并对130例BPD早产儿随访3个月,以IL-33中位表达水平为界限,分为IL-33高表达组(n=66)和低表达组(n=64)。采用logistic分析对BPD早产儿合并肺动脉高压的危险因素进行分析,采用受试者工作特征曲线分析IL-33预测BPD早产儿合并肺动脉高压的临床效能。结果3组血清IL-33表达水平差异有统计学意义(P<0.001);对照组、BPD组和BPD合并肺动脉高压组血清IL-33表达水平依次升高,差异均有统计学意义(P<0.05)。两组BPD分级差异有统计学意义(P<0.05)。与BPD组相比,BPD合并肺动脉高压组羊水污染、绒毛膜羊膜炎、呼吸衰竭、机械通气和呼吸机相关性肺炎占比均较大,而5 min Apgar评分降低,差异均有统计学意义(P<0.05)。多因素logistic回归分析结果显示,BPD分级、呼吸机相关性肺炎和IL-33表达水平均是BPD早产儿合并肺动脉高压的独立危险因素(P<0.05)。绘制受试者工作特征曲线,结果显示血清IL-33表达水平预测BPD早产儿合并肺动脉高压的曲线下面积为0.931,当IL-33为433.82 pg/ml时,敏感度和特异度分别为95.45%和93.21%。对所有BPD患儿随访3个月,与IL-33低表达组相比,IL-33高表达组发生肺部感染占比较高,差异有统计学意义(P=0.026)。结论BPD早产儿血清IL-33升高,IL-33高表达可能参与了肺动脉高压的发生机制且与患儿短期预后不良显著相关。

关键词： Reduced graphene oxide   [BMIM]HSO 4   Hierarchical material   MoS2  

摘要： To address the issues of low electrical conductivity and poor structural stability of MoS2, this study proposed a [BMIM]HSO4 induced layer-by-layer self-assembly method for the fabrication of MoS2/reduced graphene oxide (rGO) composite. Additionally, MoS2 nanocrystals were embedded in the amorphous carbon on the surface of rGO, ultimately resulting in the formation of three-dimensional IL-MoS2@C/rGO hierarchical material. The ILMoS2@C/rGO electrode exhibited excellent rate capability (145 mA h g-1 at 2 C) and cycle stability (712.85 mA h g-1 at 0.2 C after 200 cycles). The redox peak potential difference (Delta V) was 0.68 Vat 0.5 mV s-1, with b values of 0.78 and 1.07, indicating excellent charge storage performance. The electrode exhibited a pseudocapacitance contribution of 78.4 % at 0.1 mV s-1, highlighting its high capacitance and favorable reaction kinetics. The MoS2@C composite model within the IL-MoS2@C/rGO hierarchical material represented the optimal lithium storage structure. The nearly bilayer graphene coating structure shortened the electron transfer path at the MoS2 interface and provided excellent electrical conductivity, resulting in the highest charge density at the MoS2 interface and the smallest bandgap of the system, thereby promoting efficient Li+ storage and transfer during charge-discharge cycles. The three-dimensional IL-MoSS@C/rGO hierarchical material is recognized as a highly promising candidate for anode materials in LIBs.

关键词： 卵巢肿瘤   T淋巴细胞   预后   病理特征   预测价值  

摘要： 目的探讨上皮性卵巢癌(OC)患者外周血T淋巴细胞水平变化并分析其与病理参数的关联性和对患者预后的预测价值。方法选取上皮性OC患者60例为病例组,另选卵巢良性肿瘤患者85例作为良性组;病例组患者均接受腹腔镜手术治疗,术后均随访3年,根据预后情况分为预后良好组(32例)和预后不良组(28例)。检测受试者外周血CD3^(+)、CD4^(+)、CD8^(+)水平,并计算CD4^(+)/CD8^(+)比值;对比不同临床病理特征上皮性OC患者外周血T淋巴细胞水平;绘制受试者工作特征(ROC)曲线分析外周血T淋巴细胞对上皮性OC患者预后的预测价值。结果与良性组比较,病例组外周血CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平降低,CD8^(+)水平升高(P<0.05)。与Ⅰ—Ⅱ期、高分化、无腹腔积液、无淋巴结转移的上皮性OC患者比较,Ⅲ—Ⅳ期、中低分化、有腹腔积液、有淋巴结转移的上皮性OC患者外周血CD3^(+)、CD4^(+)水平更低,而CD8^(+)更高(P<0.05)。与预后良好组比较,预后不良组外周血CD3^(+)、CD4^(+)水平更低,而CD8^(+)更高(P<0.05)。ROC分析显示,CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)联合检测预测上皮性OC患者预后的曲线下面积(AUC)为0.952,高于各指标单独检测的AUC(P<0.05)。结论外周血T淋巴细胞水平与上皮性OC患者临床病理特征和预后有关,各指标联合检测预测上皮性OC患者预后更具优势。