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关键词： 西妥昔单抗   结直肠癌   CD8+肿瘤浸润性淋巴细胞   肿瘤标志物  

摘要： 目的对比分析西妥昔单抗靶向药物治疗结直肠癌对CD8+肿瘤浸润性淋巴细胞(TILs)密度及血清肿瘤标志物表达量影响。方法选取河北省衡水市人民医院2021年1月至2023年12月就诊的80例结直肠癌患者进行研究,根据治疗方法的不同将其分为两组,每组各40例,对照组给予Xelox化疗方案(奥沙利铂和卡培他滨联合)治疗,观察组在对照组基础上给予西妥昔单抗靶向药物治疗,比较两组患者的临床疗效、CD8+TILs密度、血清肿瘤标志物。对两组患者进行为期1年的随访,采用Kaplan-Meire法进行生存分析,以Graph Pad Prism8.0绘制生存曲线。结果观察组患者的临床总有效率(70.00%)高于对照组(42.50%),差异有统计学意义(P<0.05)。观察组患者治疗后的CD8+TILs密度高于对照组(P<0.05);血清糖类抗原19-9(CA19-9)、癌胚抗原(CEA)、糖类抗原242(CA242)、糖类抗原72-4(CA72-4)水平均低于对照组(P<0.05)。观察组患者的1年生存率(92.50%)高于对照组(75.00%),差异有统计学意义(P<0.05)。结论西妥昔单抗靶向治疗联合Xelox化疗,可有效提高结直肠癌患者CD8+TILs密度,抑制肿瘤标志物过度表达,提高生存率。

关键词： mTOR信号通路   凡纳滨对虾   亮氨酸   雷帕霉素   生长   抗氧化   非特异性免疫  

摘要： 为探究mTOR信号通路对凡纳滨对虾(Litopenaeus vannamei)生长、抗氧化及非特异性免疫力的影响,设计了3组等氮等能的配合饲料,分别命名为对照组(Con组)、亮氨酸组(Leu组)和雷帕霉素组(Rap组),在Con组中添加了1%的丙氨酸(Ala),在Leu组中添加了1%的亮氨酸,在Rap组中添加了0.003%的雷帕霉素。选取初始体质量(0.70±0.01)g的凡纳滨对虾,在室内循环水系统中进行养殖实验,每个处理组3个重复,每个重复60尾虾,养殖周期为56 d。养殖结束后,对生长、抗氧化及非特异性免疫力相关指标进行分析。研究显示,Leu组的特定生长率极显著高于Con组(P<0.01),Rap组的特定生长率极显著低于Con组(P<0.01)。对虾肌肉S6蛋白的磷酸化水平在摄食后1 h激活程度最强,然后逐渐减弱。与Con组相比,Leu组摄食后1 h肌肉S6蛋白的磷酸化水平显著上升,Rap组摄食后1 h肌肉S6蛋白的磷酸化水平显著下降(P<0.05)。在对虾血淋巴中,Leu组的碱性磷酸酶、酚氧化酶活力显著高于Con组(P<0.05),Rap组的酸性磷酸酶活力显著低于Con组(P<0.05)。在对虾肝胰腺中,Leu组的过氧化氢酶、总抗氧化酶和酚氧化酶活力显著高于Con组(P<0.05),Leu组的丙二醛含量显著低于Rap组(P<0.05)。Leu组的Lysozyme、C-MnSOD、Lectin相对表达量显著高于Con组(P<0.05),Rap组的Relish、Hsp70相对表达量显著低于Con组(P<0.05)。研究结果表明,饲料中添加亮氨酸可有效激活mTOR信号通路,从而提升凡纳滨对虾的生长性能、抗氧化及非特异性免疫能力;而添加雷帕霉素可有效抑制mTOR信号通路,对凡纳滨对虾生长性能、抗氧化及免疫功能起到抑制作用。

关键词： 特异性免疫治疗   玉屏风散   支气管哮喘   肺脾气虚证   中西医结合疗法  

摘要： 目的:观察特异性免疫疗法(SIT)联合玉屏风散治疗肺脾气虚型支气管哮喘(BA)慢性持续期临床疗效。方法:选取2021年5月—2024年5月内蒙古鄂尔多斯市中医医院收治的肺脾气虚型慢性持续性BA患者60例,根据统计学软件产生的随机号,按1∶1对照原则分为对照组和观察组各30例。对照组给予SIT治疗,观察组在对照组基础上给予玉屏风散治疗。经治12周后,比较两组患者临床疗效、中医证候积分、肺功能指标[第1秒用力呼气容积(FEV1)、最大呼气流量(PEF)]、嗜酸性粒细胞计数及比率、生活质量(AQLQ)评分及安全性评价。结果:治疗后,观察组总有效率为93.33%(28/30),高于对照组的76.67%(23/30)(P<0.05);治疗6周及12周后,两组患者中医证候评分较治疗前均降低(P<0.05),且观察组优于对照组(P<0.05);两组患者FEV1和PEF较治疗前均改善(P<0.05),且观察组优于对照组(P<0.05);两组患者嗜酸性粒细胞计数及比率较治疗前均降低(P<0.05),且观察组优于对照组(P<0.05);两组AQLQ评分较治疗前均提高(P<0.05),且观察组优于对照组(P<0.05)。治疗期间,两组均未出现严重不良反应和肝肾功能损伤。结论:SIT联合玉屏风散治疗肺脾气虚型慢性持续期BA,能够有效缓解临床症状,可通过改善肺功能,降低过敏反应,从而提高患者生活质量,且安全性良好。

关键词： antibodies   glioblastoma   IL13Rα2   immuno-PET   melanoma  

摘要： Interleukin-13 receptor a-2 (IL13Rα2) is a cell surface receptor frequently expressed in solid malignancies, such as glioblastoma and melanoma, with limited expression in healthy tissue, rendering it an ideal target for noninvasive and specific tumor delineation. In this study, we report the development of 5 novel IL13Rα2-targeted human monoclonal antibodies (mAbs) KLG-1–5;in subsequent in vitro and in vivo studies after radiolabeling with ⁸⁹Zr, we evaluate their performance to identify a lead candidate. Methods: Five novel human anti-IL13Rα2 mAbs KLG-1–5 were developed and in vitro binding properties and target specificity assessed. In vivo ⁸⁹Zr-immuno-PET using KLG-1–5 was conducted in a subcutaneous U-87 MG glioblastoma mouse model, and a mass dose titration study was conducted with lead candidate KLG-3. Ex vivo biodistribution results were used to derive prospective dosimetry of ¹⁷⁷Lu-labeled KLG-3. Targeting with KLG-3 was also verified in an A-375 melanoma model using the optimized conditions determined in the U-87 MG xenograft model. Results: In vitro studies confirmed target specificity and pico- to low nanomolar binding affinity. Immuno-PET studies with KLG-1–5 in U-87 MG xenografts demonstrated continuously increasing tumoral uptake with maximal uptake at 144 h after tracer injection, clearance of the unbound tracer from the blood pool, and little uptake in any other normal tissues, leading to high-contrast images. KLG-3 provided the highest tumoral uptake and tumor–to–normal tissue ratios and was chosen as the lead candidate, and further dose optimization with this antibody led to tumoral uptake of 97 6 6 maximum percent of injected dose per gram at 144 h after tracer injection. Ex vivo biodistribution-derived prospective dosimetry for ¹⁷⁷Lu-labeled KLG-3 predicted a favorable therapeutic index, encouraging the development of IL13Rα2-targeted radioimmunotherapy. Of note, KLG-3 performed similarly well in a melan

关键词： temporomandibular joint osteoarthritis   umbilical cord mesenchymal stem cells   stem cell priming   macrophage   M2  

摘要： Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disorder affecting the temporomandibular joint (TMJ), marked by persistent inflammation and structural damage to the joint. Only symptomatic treatment is available for managing TMJOA. Human umbilical cord mesenchymal stem cells (hUC-MSCs) show potential for treating TMJOA via their immune-modulating actions in the disease area. In addition, stimulation of inflammatory cytokines such as interferon-gamma in hUC-MSCs improves the therapeutic activity of na & iuml;ve stem cells. Emerging evidence indicates that macrophages play significant roles in regulating joint inflammation through diverse secreted mediators in the pathogenesis of TMJOA. This study was conducted to evaluate the effects of inflammatory cytokine-stimulated hUC-MSCs in repairing TMJOA-induced cartilage lesions and the role of macrophages in the disease. Our in vitro data showed that stimulated hUC-MSCs induce M2 polarization of macrophages and enhance the expression of anti-inflammatory molecules. These effects were subsequently validated in vivo. In a rat model of TMJOA, stimulated hUC-MSCs ameliorated inflammation and increased M2 macrophages ratio. Our results indicate that hUC-MSCs stimulated by inflammatory cytokines modulate the activation of M2 macrophages, thereby shifting the local osteoarthritis microenvironment toward a prochondrogenic state and facilitating cartilage repair in inflammatory conditions. Stimulating hUC-MSCs with inflammatory cytokines could potentially offer an effective therapeutic approach for TMJOA, with macrophages playing a pivotal role in immune modulation. Impact Statement Temporomandibular joint osteoarthritis (TMJOA) is marked by chronic inflammation and degeneration of the joint. This research focuses on human umbilical cord stem cells (hUC-MSCs), stimulated with inflammatory cytokines, to repair osteoarthritis (OA)-related cartilage lesions. In vitro results show that these stimulated cells promote M2

关键词： 止抽汤   多发性抽动   T淋巴细胞亚群   Th1/Th2   免疫  

摘要： 目的:探究止抽汤(Zhichou Decoction,ZCD)对多发性抽动症(Tourette syndrome,TS)模型大鼠外周血T淋巴细胞亚群及T辅助(Th)淋巴细胞Th1/Th2细胞平衡的影响,以明确该方对TS大鼠免疫调控作用。方法:建立TS模型成功后将大鼠随机分为模型组、氟哌啶醇组、ZCD高、中、低剂量组,同时设立对照组;连续给药4周后处死大鼠,称定大鼠脾脏、胸腺质量,计算脏器系数;苏木素-伊红(HE)染色观察大鼠脑组织形态,ELISA法检测纹状体中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)白细胞介素-6(interleukin-6,IL-6)及血清中γ干扰素(interferon-γ,IFN-γ)和白细胞介素-4(interleukin-4,IL-4)水平;流式细胞术检测外周血中CD3^(+)T、CD4^(+)T、CD8^(+)T淋巴细胞及Th1、Th2各细胞亚群比例变化。结果:与模型组比较,给药4周后ZCD高、中剂量组大鼠刻板运动评分均降低(P<0.05),脾脏、胸腺指数增加(P<0.05,P<0.01),TNF-α、IL-6及IFN-γ水平降低(P<0.05),外周血中CD3^(+)占比增加(P<0.01、P<0.05);CD8^(+)占比降低(P<0.05),CD4^(+)/CD8^(+)比例增加(P<0.05);ZCD高剂量组还可增加CD4^(+)百分比(P<0.05)并具增加血清中IL-4水平的趋势;在Th淋巴细胞亚群中,ZCD高剂量组Th1细胞占比降低,Th2细胞比例增加(P<0.05),Th1/Th2细胞比值降低(P<0.05);ZCD中剂量组Th1细胞占比显著降低,Th2细胞稍有增加,Th1/Th2细胞比值呈降低趋势;ZCD低剂量组脾脏指数增加(P<0.05),IL-6水平降低(P<0.05),但对其他指标均无明显调控作用。结论:ZCD可显著改善TS大鼠症状,降低脑内神经炎性分子水平,其机制可能与调控外周血T淋巴细胞亚群及Th1/Th2细胞平衡,改善免疫功能相关。

关键词： Sepsis   Microglia   Delirium   Cognitive   Systemic inflammation   Cytokines   TNF   IL-1   Encephalopathy  

摘要： Sepsis is characterised by dysregulated immune responses to infection, leading to multi-organ dysfunction and high rates of mortality. With increasing survival rates in recent years long-term neurological and psychiatric consequences have become more apparent in survivors. Many patients develop sepsis associated encephalopathy (SAE) which encompasses the profound but usually transient neuropsychiatric syndrome delirium but also new brain injury that emerges in the months and years post-sepsis. It is now clear that systemic inflammatory signals reach the brain during sepsis and that very significant neuroinflammation ensues. The major brain resident immune cell population, the microglia, has been implicated in acute and chronic cognitive dysfunction in animal models of sepsis based on a growing number of studies using bacterial endotoxin and in polymicrobial sepsis models such as cecal ligation and puncture. The current review explores the effects of sepsis on the brain, focussing on how systemic insults translate to microglial activation and neuroinflammation and how this disrupts neuronal function and integrity. We examine what has been demonstrated specifically with respect to microglial activation, revealing robust evidence for a role for neuroinflammation in sepsis-induced brain sequelae but less clear information on the extent of the specific microglial contribution to this, arising from findings using global knockout mice, non-selective drugs and treatments that equally target peripheral and central compartments. There is, nonetheless, clear evidence that microglia do become activated and do contribute to brain consequences of sepsis thus arguing for improved understanding of these neuroinflammatory processes toward the prevention and treatment of sepsis-induced brain dysfunction.

关键词： 流式荧光免疫法   米酵菌酸   抗原   抗体   食品安全  

摘要： 建立了一种定量检测米酵菌酸(BA)含量的流式荧光免疫法。首先通过合成BA-BSA完全抗原,免疫获得效价高的抗BA单克隆抗体。随后将BA-BSA合成抗原与藻红蛋白标记,并与样品中的BA竞争结合偶联有荧光微球的抗BA单克隆抗体,通过采用流式荧光仪检测微球表面的平均荧光强度,实现了样品中BA的定量测定。BA的线性范围为1.01~97.96μg/L,半数抑制浓度(IC_(50))为9.92μg/L,相关系数(r^(2))为0.9998,检出限为0.56μg/kg。加标回收率为90.4%~104%,相对标准偏差为5.0%~9.8%。方法特异性良好,与赭曲霉毒素A、黄曲霉素B1、黄曲霉素M1、伏马菌素B1、伏马菌素B2的交叉反应均<0.1%。实际样品测定结果与高效液相色谱-串联质谱法检测结果一致。所建立的流式荧光免疫法方法简单、快速、灵敏、准确,并可推广到各类食品等复杂基质中其他真菌毒素的分析和检测。

关键词： 食管癌   预后   淋巴细胞   单核细胞   临床病理特征  

摘要： 目的:研究淋巴细胞单核细胞比值(Lymphocytemonocyte ratio,LMR)在食管癌预后评估中的临床价值。方法:选择2020年5月-2023年5月我院治疗的90例食管癌患者。所有患者均行食管癌根治手术治疗,术前1周检测LMR。患者术后进行12个月随访,统计患者的生存情况,绘制受试者工作特征(Receiver operating characteristic,ROC)曲线,确定LMR最佳截断值,计算LMR对食管癌患者预后的预测价值,比较高LMR组与低LMR组患者的临床病理特征,采用Logistic回归方法分析影响食管癌患者预后的危险因素。结果:所有食管癌患者术后1年生存率为78.89%(71/90);绘制ROC曲线计算LMR预测食管癌患者预后的曲线下面积(Area under curve,AUC)为0.753,95%CI为0.663~0.843,最佳截断值为4.42,预测食管癌患者的总生存期敏感度为78.65%,特异度为71.19%;高LMR组肿瘤分期Ⅰ期加Ⅱ期患者占比高于低LMR组,差异有统计学意义(P<0.05);两组在性别、肿瘤位置、病理类型、饮酒及吸烟方面比较,差异无统计学意义(P>0.05);肿瘤位置、肿瘤分期及LMR与食管癌患者预后有关,差异有统计学意义(P<0.05);两组在性别、病理类型、饮酒及吸烟方面比较,差异无统计学意义(P>0.05);采用Logistic回归分析显示,肿瘤位置、肿瘤分期及LMR是影响食管癌患者预后的危险因素(P<0.05,且OR≥1)。结论:LMR对评估食管癌患者预后具有重要价值,LMR越低则患者生存期越短,可将LMR作为食管癌患者预后的独立预测因子。

关键词： 细胞免疫   胞内细胞因子染色   方法验证  

摘要： 目的对胞内细胞因子染色法检测抗原特异性T细胞免疫反应的方法进行验证。方法以重组带状疱疹病毒gE蛋白为抗原免疫小鼠,取小鼠脾脏淋巴细胞,通过细胞表面抗原和细胞内细胞因子染色进行细胞免疫反应评价。从专属性、重复性、批间精密度、区间精密度、稳定性五个指标进行方法验证。结果无肽刺激条件下免疫组小鼠和PBS组小鼠细胞因子CD4^(+)TNF-α、CD4^(+)IFN-γ、CD4^(+)IL-2均不表达,肽库刺激条件下PBS组小鼠细胞因子CD4^(+)TNF-α、CD4^(+)IFN-γ、CD4^(+)IL-2不表达,但免疫组小鼠细胞因子CD4^(+)TNF-α、CD4^(+)IFN-γ、CD4^(+)IL-2阳性表达。重复性、区间精密度、批间精密度和稳定性考察结果的CV值均小于20%。结论方法有良好的专属性,重复性、批间精密度、区间精密度和稳定性均符合要求。