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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： 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： 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： 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： 高尿酸血症   白细胞介素-41   生长分化因子15   病情程度  

摘要： 目的研究高尿酸血症患者血清白细胞介素-41(IL-41)、生长分化因子15(GDF-15)与病情程度的关系。方法选取2023年1月至2024年12月来院就诊的126例高尿酸血症患者为病例组,另取同期100例健康体检者纳入对照组,对比两组血清IL-41、GDF-15水平。按照《中国高尿酸血症相关疾病诊疗多学科专家共识》标准,将病例组分为轻度组(41例)、中度组(52例)、重度组(33例),检测病例组和对照组血清IL-41、GDF-15水平,采用Pearson相关系数分析血清IL-41、GDF-15表达与血清尿酸的相关性,采用Logistic回归分析患者病情程度的影响因素,绘制受试者工作特征曲线(ROC)分析血清IL-41、GDF-15水平及二者联合检测对病情程度的预测价值。结果病例组血清IL-41、GDF-15水平高于对照组(P<0.05);重度组血清尿酸、IL-41、GDF-15水平高于中度组、轻度组(P<0.05),中度组血清尿酸、IL-41、GDF-15水平高于轻度组(P<0.05);Pearson相关性分析显示,血清IL-41、GDF-15水平与血清尿酸水平呈正相关(r>0,P<0.05);经Logistic回归分析,结果显示,高血清IL-41(OR=1.062,95%CI:1.035~1.090)、GDF-15(OR=1.151,95%CI:1.085~1.221)、尿酸(OR=1.021,95%CI:1.011~1.033)水平是高尿酸血症患者病情加重的危险因素(P<0.05);绘制ROC曲线,血清IL-41、GDF-15单独及两项联合、尿酸预测高尿酸血症患者病情发展为中重度的AUC分别为0.851(95%CI:0.785~0.916)、0.818(95%CI:0.744~0.892)、0.898(95%CI:0.844~0.951)、0.767(95%CI:0.683~0.851),其中IL-41联合GDF-15的AUC均显著大于IL-41、GDF-15、尿酸的AUC,差异有统计学意义(Z=2.222、2.554、2.770,P=0.026、0.011、0.006)。结论高尿酸血症患者血清IL-41、GDF-15水平升高,与病情程度呈正相关,临床可通过检测血清IL-41、GDF-15水平预测患者病情变化。

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。

关键词： 益肾通痹汤   督灸   强直性脊柱炎   Th17偏移   炎症   骨代谢   脊柱骨结构损伤  

摘要： 目的:观察益肾通痹汤联合督灸对强直性脊柱炎患者脊柱骨结构损伤、骨代谢失衡、激素水平及血清白细胞介素23(IL-23)、辅助性T细胞17(Th17)的影响。方法:选取符合纳入标准98例强直性脊柱炎患者,依据随机数字表随机分为对照组和治疗组,每组各49例。对照组给予常规西医治疗,治疗组在对照组治疗基础上给予益肾通痹汤联合督灸治疗,均连续治疗4周。治疗结束后评估两组临床疗效,分别于治疗前后通过改良Stoke强直性脊柱炎脊柱评分(mSASSS)评价脊柱骨结构损伤情况,强直性脊柱炎功能指数(BASFI)评价脊柱功能,同时比较两组患者中医症状评分变化情况,检测血清核因子-κB、软骨寡聚基质蛋白(COMP)、IL-23、前列腺素E2、缓激肽、人可溶性CD14、多巴胺、骨钙素水平、睾酮、Th17水平。结果:治疗组总有效率为97.96%(48/49),对照组总有效率为81.63%(40/49),两组比较差异有统计学意义(P<0.05)。治疗后,两组患者中医症状评分、mSASSS评分、BASFI评分、核因子-κB、IL-23、人可溶性CD14、Th17细胞含量、COMP、睾酮、前列腺素E2、缓激肽、多巴胺水平均降低(P<0.05),骨钙素水平升高(P<0.05),且治疗组上述指标改善情况优于对照组(P<0.01)。结论:益肾通痹汤联合督灸可明显改善强直性脊柱炎患者Th17偏移,减少炎症,调节骨代谢平衡、睾酮水平,减少疼痛介质含量,减轻脊柱骨结构损伤,缓解病情,提升临床疗效及生活质量。