课程文献中心 更多>>

关键词： CAR-T细胞   急性淋巴细胞白血病   细胞因子释放综合征   免疫疗法  

摘要： 急性淋巴细胞白血病作为血液系统恶性肿瘤,在传统治疗方式上存在预后差和疗效有限等问题。嵌合抗原受体T细胞免疫治疗(CAR-T),作为一种发展迅速且非常有前景的新型免疫疗法,在急性淋巴细胞白血病的治疗上取得了较大的突破和进展,但其安全性是治疗的一个挑战,特别是细胞因子释放综合征(CRS)。本文回顾了CAR-T细胞疗法的发展、治疗机制以及在急性淋巴细胞白血病中的治疗进展,详细阐述了CAR-T在急性淋巴细胞白血病发生CRS的临床现状和研究进展,探讨了近年来对于防治CRS的方法,为后续相关研究提供参考依据。

关键词： Anti-TG2   Celiac disease diagnosis   Ema   Gluten challenge   HLA  

摘要： Celiac disease (CeD) diagnosis traditionally relies on detecting serum antibodies against gluten, transglutaminase 2, and anti-endomysial antibodies, as well as confirming mucosal damage via intestinal biopsy. While serology is useful in diagnosing CeD, guidelines for adults often recommend an upper endoscopy and duodenal biopsy to assess mucosal atrophy. Human leukocyte antigens (HLA) testing is also valuable; Histology remains essential in presence of low-titer serology. In the presence of serology positive at high titers, in children and adults CeD cases can be diagnosed without biopsy. A gluten challenge may be necessary for accurate diagnosis in individuals already on a gluten-free diet. Research is in progress to develop less invasive diagnostic methods.

关键词： bispecific antibody   cytokine mimetic   IL-18   immunotherapy   nanobody  

摘要： Cytokines are promising in cancer immunotherapy, but their pleiotropic effects limit specificity and clinical utility. Through binding to IL-18R alpha and IL-18R beta, interleukin-18 (IL-18) stimulates innate lymphocytes and effector T cells for antitumor immunity. However, clinical trials of recombinant IL-18 have been hampered by IL-18 binding protein (IL-18BP), a secreted high-affinity decoy receptor. Here, we developed decoy-resistant bispecific nanobodies that maintain IL-18 signaling potential. Based on agonistic nanobodies targeting IL-18R alpha and IL-18R beta, bispecific nanobody A4B2-mdFc effectively enhanced CD8+ T cell responses with distinct transcriptomic profiles. Systemic delivery of A4B2-mdFc boosted CD8+ T cell infiltration and activation, demonstrating dose-dependent antitumor efficacy in cell-line-derived xenograft and patient-derived xenograft models. Interestingly, PDCD1 and CTLA4 expressions were drastically increased on CD8+ T cells when treated with A4B2-mdFc. Injection of A4B2-mdFc significantly improved the antitumor efficacy of immune checkpoint inhibitors (ICIs) targeting both PD-1 and CTLA-4. Our findings demonstrated that nanobody-based bispecific IL-18 mimetics elicited superior antitumor activity via CD8+ T cell activation and IL-18BP resistance, providing the potential application of cytokine-targeting bispecific nanobody monotherapy or in combination with ICIs for cancer immunotherapy.

摘要： Environmental exposures are linked to precancerous hematologic conditions, but studies in cohorts with well-defined exposures are limited. We sequenced blood samples from a large cohort of first-responders exposed to the aerosolized dust and carcinogens from the 9/11 World Trade Center (WTC) disaster and observed a significantly higher prevalence of clonal hematopoiesis (CH) mutations when compared to two sets of control cohorts after controlling for age, race, and sex. Younger exposed first-responders exhibited unconventional CH mutations, with defective DNA repair signatures. Leukemia risk was elevated (3.7% vs. 0.6%, OR=5.73) in WTC-exposed responders with CH versus without CH. Exposure to particulate matter collected from WTC site impaired healthy stem cell while expanding Tet2-mutant CH clones in mice. Inflammation sensor, IL1RAP, was overexpressed in murine CH, and genetic knockdown inhibited mutant clone growth in-vivo. This study links discrete environmental exposure to hematopoietic mutations and leukemia, identifying IL1RAP as a novel therapeutic target in CH.

关键词： 急性淋巴细胞白血病   T细胞免疫球蛋白黏蛋白分子-3   C-myc   T淋巴细胞亚群  

摘要： 目的:分析急性淋巴细胞白血病(ALL)患者Tim-3、C-myc、T淋巴细胞亚群比例与预后的相关性。方法:研究组选取2019年12月到2021年12月本院收治的60例ALL患者,对照组选取于本院进行体检的健康志愿者55例。对两组患者Tim-3、C-myc mRNA表达量、T淋巴细胞亚群比例进行检测。统计患者死亡率,分析Tim-3、C-myc、T淋巴细胞亚群比例与病理特征、预后的相关性。结果:与对照组相比,研究组Tim-3、C-myc、CD8^(+)水平明显升高,而CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平明显降低(均P<0.001)。Tim-3、C-myc mRNA表达量、CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)水平与危险度分型、髓外浸润相关(均P<0.05)。Tim-3、C-myc、CD8^(+)低表达患者生存率高于高表达患者,而CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)高表达患者生存率高于低表达患者(均P<0.05)。单因素分析结果显示,与存活患者相比,死亡患者有髓外浸润、高危分型占比、Tim-3、C-myc、CD8^(+)水平较高,CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平较低(均P<0.01)。多因素Logistic回归分析结果显示,髓外浸润、危险度分型、Tim-3、C-myc、CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)为影响ALL患者预后的主要因素(均P<0.05)。ROC曲线显示,与Tim-3、C-myc、CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)单项诊断相比,Tim-3、C-myc、T淋巴细胞亚群联合预测ALL患者预后的敏感性、准确性较高(P<0.05)。结论:ALL患者Tim-3、C-myc mRNA表达量、CD8^(+)水平较高,CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平较低,且Tim-3、C-myc、CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)表达水平与患者髓外浸润、高危分型、预后相关。

摘要： Immune check-point blockade for the treatment of malignancies has been focused on reversing inhibitory pathways in T lymphocytes. Natural killer (NK) cells are a potent innate defense against tumors and virally infected cells, but their therapeutic manipulation for anti-cancer immunity has been inadequately explored. Considerable attention has been focused on approaches to blocking inhibitory receptors on NK and myeloid cells. Most effort has been directed to the killer immunoglobulin-like receptors (KIR) and CD94/NKG2A on NK cells. Another set of receptors with similar function in both NK cells and myeloid cells is the leukocyte immunoglobulin like receptors (LILR) that interact with a wide variety of HLA molecules. Using pan-anti-HLA mAbs that recognize a conserved epitopic region on HLA also seen by LILR, we investigated their functional effects in several models of tumor immunity. The pan-anti-HLA-mAbs blocked the binding of most LILRs, did not block killer cell immunoglobulin-like receptors (KIR) or CD94/NKG2A/C or TCR recognition. They also activated dysfunctional NK cells explanted from a variety of human cancers, and resulted in enhancement of tumor immunity in humanized mice. The mAbs also exert direct anti-tumor effects. These results suggest that activation of innate immunity via disruption of HLA/LILR interactions is a potent approach for control of both primary tumors and potentially tumor metastases.

关键词： 白细胞介素-1β   中枢神经特异蛋白   神经元特异性烯醇化酶   脑瘫   诊断  

摘要： 目的探讨血清神经元特异性烯醇化酶(NSE)、白细胞介素-1β(IL-1β)、中枢神经特异蛋白(S100-β)对脑瘫患儿的诊断价值。方法选取70例脑瘫患儿作为研究组,另选取20例参与体检的健康儿童作为对照组。检测并比较两组血清NSE、IL-1β、S100-β水平;比较两组体质量指数;分析血清IL-1β、S100-β、NSE对脑瘫的诊断效能。结果研究组体质量指数为(13.874±3.250)kg/m2,低于对照组的(17.294±3.547)kg/m2,差异有统计学意义(P<0.05)。研究组和对照组血清NSE、IL-1β、S100-β水平比较,差异均无统计学意义(P>0.05)。血清IL-1β的受试者工作特征曲线(ROC曲线)的曲线下面积(AUC)为0.583[95%CI=(0.432,0.734)],最佳截断值为1.985 pg/ml,敏感度为65.70%,特异度为55.00%;血清S100-β的AUC为0.573[95%CI=(0.430,0.715)],最佳截断值为0.475μg/L,敏感度为77.10%,特异度为30.00%;血清NSE的AUC为0.600[95%CI=(0.461,0.740)],最佳截断值为2.275 ng/ml,敏感度为77.10%,特异度为40.00%。结论血清NSE对脑瘫的诊断价值较低,血清IL-1β、S100-β对脑瘫不具有诊断价值。

关键词： 富血小板血浆   Wiltse肌间隙入路   伤椎置钉内固定   胸腰椎骨折   白细胞介素-6   丙二醛  

摘要： 目的评价富血小板血浆(PRP)+Wiltse肌间隙入路伤椎置钉内固定对胸腰椎骨折患者白细胞介素-6(IL-6)、丙二醛(MDA)水平的影响。方法104例胸腰椎骨折患者,依据随机数表法分为对照组和观察组,各52例。对照组行Wiltse肌间隙入路伤椎置钉内固定治疗,观察组在对照组手术基础上联合PRP治疗。比较两组手术相关指标,血清相关指标(血清IL-6、MDA),视觉模拟评分法(VAS)评分和Oswestry功能障碍指数(ODI)评分,椎体相关参数(椎体前缘高度、伤椎矢状面Cobb角),并发症发生率。结果两组手术时间进行差异性分析,所得结果无统计学意义(P>0.05);观察组患者术中出血量(80.19±8.14)ml、术后引流量(50.66±4.19)ml、住院时间(9.11±1.88)d均优于对照组的(112.62±10.53)ml、(70.07±6.38)ml、(12.06±2.73)d,组间差异有意义(P<0.05)。治疗后,观察组患者的血清IL-6(2.22±0.31)ng/L、MDA(6.27±1.16)μmol/L均低于对照组的(4.44±0.55)ng/L、(9.51±1.87)μmol/L,组间差异有意义(P<0.05)。两组患者的VAS和ODI评分治疗前进行差异性分析,所得结果无统计学意义(P>0.05);治疗后,观察组患者的VAS评分(2.14±0.34)分和ODI评分(8.05±1.56)分均比对照组的(3.88±0.57)、(12.27±2.42)分更低,组间差异有意义(P<0.05)。治疗前两组椎体相关参数进行差异性分析,所得结果无统计学意义(P>0.05);治疗后,观察组患者的椎体前缘高度(69.94±6.92)mm、伤椎矢状面Cobb角(12.75±1.19)°优于对照组的(50.55±5.15)mm、(17.66±2.44)°,组间差异有意义(P<0.05)。观察组患者治疗期间的并发症发生率比对照组低(3.85%vs.17.31%),组间差异有意义(P<0.05)。结论PRP联合Wiltse肌间隙入路伤椎置钉内固定治疗胸腰椎骨折,可减少术中创伤,缩短住院时间,有效减轻机体的炎症反应和氧化应激损伤,减轻疼痛,促进椎体功能恢复,且安全性较高,值得临床采纳。

关键词： 小儿感染性肺炎   人免疫球蛋白   布地奈德   雾化吸入   临床效果   治疗安全  

摘要： 目的 探讨静脉注射人免疫球蛋白联合雾化吸入布地奈德治疗小儿感染性肺炎的临床疗效。方法 选取2021年2月—2024年2月在秦皇岛市妇幼保健院治疗的小儿感染性肺炎患儿82例,采用随机数字表法分为对照组41例(布地奈德雾化吸入治疗)和联合组41例(在对照组基础上静脉注射人免疫球蛋白)。对比两组患儿治疗前后的临床特征(啰音消失时间、咳嗽消失时间、住院时间)、炎症指标[白细胞介素-8(IL-8)、高敏C反应蛋白(hs-CRP)、降钙素原(PCT)]、免疫球蛋白[免疫球蛋白A(IgA)、免疫球蛋白G(IgG)、免疫球蛋白M(IgM)]水平、预后评分[急性生理与慢性健康状况评分Ⅱ(APACHE Ⅱ)、肺炎严重指数(PSI)评分]及不良反应的发生情况。结果 联合组患儿啰音消失时间、咳嗽消失时间、住院时间均短于对照组(P<0.05)。联合组治疗后PCT、hs-CRP和IL-8均低于对照组,联合组治疗前后PCT、hs-CRP和IL-8的差值均大于对照组(P<0.05)。联合组治疗后IgA、IgG和IgM均高于对照组,联合组治疗前后IgA、IgG和IgM的差值均大于对照组(P<0.05)。联合组治疗后APACHE Ⅱ评分、PSI评分均低于对照组,联合组治疗前后APACHE Ⅱ评分、PSI评分的差值均大于对照组(P<0.05)。联合组与对照组患儿不良反应总发生率比较,差异无统计学意义(P >0.05)。结论 静脉注射人免疫球蛋白联合雾化吸入布地奈德治疗能显著提高小儿感染性肺炎的治疗效果,加快症状改善,治疗安全,适合临床广泛应用。

关键词： 高级别浆液性卵巢癌   新辅助化疗   肿瘤浸润淋巴细胞   KELIM评分   铂敏感性  

摘要： 目的:检测高级别浆液性卵巢癌(HGSOC)患者新辅助化疗(NACT)前后配对肿瘤组织中肿瘤浸润淋巴细胞(TILs)及其亚型CD4^(+)TILs、CD8^(+)TILs、CD20^(+)TILs及Foxp3^(+)TILs的表达差异,分析其与化疗敏感性及预后的关系。方法:回顾性分析40例2017年8月至2023年2月就诊于河北医科大学第四医院行NACT及间歇性肿瘤细胞减灭术(IDS)的HGSOC患者临床资料,免疫组化法检测NACT前后配对肿瘤组织中CD4^(+)TILs、CD8^(+)TILs、CD20^(+)TILs及Foxp3^(+)TILs表达。依据KELIM评分及铂敏感性将患者分为两组,比较肿瘤组织中TILs、CD4^(+)TILs、CD8^(+)TILs、CD20^(+)TILs及Foxp3^(+)TILs表达差异,并分析其与预后的相关性。结果:KELIM评分≥1及铂敏感患者NACT后肿瘤组织TILs(P=0.003,P=0.01)、CD8^(+)TILs(P<0.001,P=0.014)、CD20^(+)TILs(P<0.001,P=0.003)密度较NACT前显著增加,而KELIM评分<1及铂耐药患者NACT前后TILs密度无明显变化。NACT前CD8^(+)TILs高表达患者无进展生存期(PFS)及总生存期(OS)较低表达患者延长(P<0.001,P=0.011);NACT后TILs高表达患者PFS及OS较低表达患者延长(P<0.001,P=0.009);NACT后CD20^(+)TILs高表达患者PFS较低表达患者延长(P=0.005)。多因素分析中,NACT前CD8^(+)TILs密度(HR=0.309,P=0.032)、NACT后TILs密度(HR=0.192,P=0.014)、年龄(HR=2.962,P=0.036)均为PFS的独立预后因素。结论:HGSOC患者NACT后TILs密度增加患者铂敏感可能性更高,肿瘤局部TILs、CD8^(+)TILs、CD20^(+)TILs表达可作为预后的有效预测因子。