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关键词： 5′ UTR   CAR-T cell therapy   Caspase 7   IFN-γ   on-target off-tumor effect  

摘要： On-target off-tumor effects precipitate severe adverse reactions in patients, significantly hindering the application of chimeric antigen receptor (CAR) T cells in both hematological and solid tumors. The underlying mechanisms remain elusive due to the absence of suitable preclinical models. To elucidate these mechanisms, a human epidermal growth factor receptor 2 (Her2) transgenic mouse model was developed to investigate CAR-T cell-induced on-target off-tumor effects. CAR-T cells initially migrated to the lungs, targeting alveolar epithelial cells and resulting in interferon-y (IFN-y)-dependent acute lung injury. Additionally, a regulatory mechanism involving IFNy-induced degradation of caspase-7 mRNA 50 untranslated regions (UTR), which amplifies acute lung injury mediated by CAR-T cells, was identified. Consequently, a strategy was validated to antagonize IFN-y during CAR-T cell infusion, thereby mitigating acute lung injury without compromising antitumor efficacy. These findings elucidate the mechanisms of CAR-T cell-induced acute lung injury and demonstrate the viability of targeting IFN-y to prevent this adverse reaction.

关键词： 表面等离子共振   脊髓灰质炎灭活疫苗   D抗原  

摘要： 目的建立Sabin株脊髓灰质炎灭活疫苗(Sabin strain inactivated polio vaccine,sIPV)单价原液D抗原含量表面等离子共振(surface plasmon resonance,SPR)快速检测方法,并对方法进行验证。方法分别将牛抗Ⅰ、Ⅱ、Ⅲ型D抗原多克隆抗体标记至SPR芯片表面,捕获脊髓灰质炎病毒Ⅰ、Ⅱ、Ⅲ型D抗原,监测芯片表面信号响应值变化,确定D抗原含量与响应信号的关系,建立检测D抗原含量的SPR方法,并对方法进行线性、专属性、精密性、准确性验证。分别采用建立的SPR法和ELISA法检测6批次Ⅰ、Ⅱ、Ⅲ型sIPV单价原液D抗原含量,对2种方法的检测结果进行比较分析,以对该方法的可行性进行补充验证。结果3个型别D抗原含量与响应值均呈较好的线性关系,相关系数(R^(2))均在0.99以上;3个型别之间有一定程度的交叉反应,但交叉反应响应值明显低于阳性反应响应值;3个型别重复检测的相对标准偏差(relative standard deviation,RSD)分别为3.1%、1.2%、1.4%,中间精密度验证的RSD分别为5.6%、2.0%、2.7%,均在8%以内,低于ELISA法可接受的15%以内;准确性验证的回收率分别为85.8%、105.1%、88.4%,在80%~120%范围内;6批次单价原液与ELISA法测定D抗原含量结果比较,Ⅰ、Ⅱ型差异无统计学意义(t分别为1.924和-0.901,P分别为0.083和0.389),Ⅲ型差异有统计学意义(t=-2.617,P=0.026)。结论建立了可快速、大通量检测sIPVⅠ、Ⅱ、Ⅲ型D抗原含量的SPR方法,该方法精密性和准确性良好,为疫苗生产全流程监测和质量检测提供了更多的方案。

关键词： 哮喘   胸腺基质淋巴细胞生成素   双阴性T淋巴细胞   哮喘控制  

摘要： 目的探讨支气管哮喘儿童血清中胸腺基质淋巴细胞生成素(TSLP)、双阴性T淋巴细胞(DNT)水平的临床意义。方法回顾性分析2024年1月—3月西安市儿童医院诊治的147例支气管哮喘患儿(研究组)的临床资料,选取同期在本院进行健康体检的120例儿童(对照组)的临床相关资料。所有受试者均行血清TSLP和DNT检测。根据哮喘控制水平将研究组分为控制组(116例)和未控制组(31例)。比较两组受试者TSLP、DNT水平,并分析影响支气管哮喘患儿哮喘控制水平的因素;采用受试者工作特征(ROC)曲线分析TSLP、DNT预测患儿哮喘控制水平的价值。结果研究组血清TSLP水平高于对照组,DNT水平低于对照组(均P<0.05)。未控制组患儿TSLP水平及病情程度为重症占比、有哮喘家族史占比均高于控制组患儿,DNT水平、年龄、第一秒用力呼气容积/用力肺活量(FEV_(1)/FVC)均低于控制组患儿(均P<0.05)。多因素逐步logistic回归分析显示,TSLP水平(OR=3.656、95%CI:2.091~6.392)、病情程度(OR=2.561、95%CI:1.230~5.330)是影响患儿哮喘控制水平的独立危险因素,DNT水平(OR=0.233、95%CI:0.122~0.442)、FEV_(1)/FVC水平(OR=0.287、95%CI:0.127~0.647)是独立保护因素(均P<0.05)。ROC曲线分析显示,TSLP、DNT及二者联合预测患儿哮喘控制水平的灵敏度分别为74.20%、71.00%、90.30%,特异度分别为75.90%、73.30%、91.40%,曲线下面积(AUC)分别为0.821、0.805、0.923(均P<0.05)。结论支气管哮喘患儿血清TSLP水平异常升高,DNT异常降低。TSLP是影响患儿哮喘控制水平的独立危险因素,DNT是独立保护因素。临床通过联合检测TSLP、DNT,可较好预测患者哮喘控制情况。

关键词： 微小RNA-147   Ki-67   癌胚抗原   浸润性肺腺癌   淋巴结转移   受试者工作特征曲线   免疫组化   TNM分期  

摘要： 目的探讨微小RNA-147(miR-147)、Ki-67以及癌胚抗原(CEA)表达水平与浸润性肺腺癌淋巴结转移的关系。方法选取浸润性肺腺癌患者160例为研究对象,根据患者淋巴结转移情况,分为有淋巴结转移组(n=74)和无淋巴结转移组(n=86)。采用免疫组化法检测患者癌组织中miR-147、Ki-67的表达水平。采用化学发光法检测患者血清CEA水平。分析miR-147和Ki-67以及血清CEA表达水平与患者临床病理特征的关系。采用受试者工作特征(ROC)曲线分析miR-147、Ki-67、CEA预测淋巴结转移的价值。结果有淋巴结转移组的miR-147表达水平低于无淋巴结转移组,Ki-67、血清CEA表达水平高于无淋巴结转移组,差异有统计学意义(P<0.05)。肿瘤直径≥3 cm、TNM分期为Ⅲ~Ⅳ期患者的癌组织miR-147表达水平低于肿瘤直径<3 cm、TNM分期为Ⅰ~Ⅱ期患者,差异有统计学意义(P<0.05)。肿瘤直径≥3 cm患者的癌组织Ki-67表达水平高于肿瘤直径<3 cm患者,差异有统计学意义(P<0.05)。TNM分期为Ⅲ~Ⅳ期患者的血清CEA水平高于TNM分期为Ⅰ~Ⅱ期患者,差异有统计学意义(P<0.05)。miR-147表达水平与Ki-67、血清CEA、淋巴结转移呈负相关(P<0.05);Ki-67、血清CEA与淋巴结转移呈正相关(P<0.05);Ki-67与血清CEA呈正相关(P<0.05)。miR-147、Ki-67、CEA预测淋巴结转移的ROC曲线的曲线下面积分别为0.785、0.835和0.798(P<0.05)。结论癌组织miR-147、Ki-67表达水平以及血清CEA水平与浸润性肺腺癌淋巴结转移存在相关性。

摘要： Type 1 Diabetes Mellitus (T1DM) is a chronic progressive autoimmune disease characterized by destruction of insulin-producing beta cells in the pancreas. The immune system plays a critical role in this illness, particularly regarding micro ribonucleic acid (miRNA) expression and cytokines levels. This study aimed to investigate the role of miRNA-155 and interleukin-2 (IL-2) in diagnosis of T1DM with related to antibodies against glutamic acid decarboxylase 65 (anti-GAD65) and Connecting peptide (C-peptide). This case-control study involved 120 participants, of whom 80 were T1DM patients and 40 apparently healthy subjects as controls. The patients' age ranged from 3 to 17 years of both sexes, collected from the Department of Diabetic in Al-Sader medical city in AL- Najaf Al-Ashraf province during October 2023 till February 2024. Their diagnoses were made based on clinical and serological parameters. Blood samples were collected from all participants to detect IL-2 serum level by an enzyme linked immunosorbent assay and miRNA155 by the reverse transcription polymerase chain reaction (RT-PCR), whereas anti-GAD65 and C-peptide diagnosis by a chemiluminescence immunoassay. The results showed that serum IL-2 was significantly lower in T1DM patients (330.66 ±129.92 ng/ml) compared to the control group (960.67 ±188.05 ng/ml). The expression of miR-155 was significantly higher in the patients' group (2.61 ± 1.17) versus the control group (1.0 ± 0.71) (p < 0.001). The serum level of anti-GAD antibodies among patients with T1DM was significantly higher than in controls (375.01 U/ml vs 5.66 U/ml). While the serum level of C-peptide in the patients was lower than in controls. In conclusion, the elevated expression of miRNA-155, along with significantly reduced blood IL-2 levels in T1DM patients indicates their potential as valid biomarkers for the diagnosis and progress of T1DM. Copyright© by the Egyptian Association of Immunologists.

关键词： 轮状病毒性肠炎   维生素D   赖氨葡锌   酪酸梭菌二联活菌散   免疫球蛋白   胃肠激素  

摘要： 目的探讨采用维生素D联合赖氨葡锌、酪酸梭菌二联活菌散治疗轮状病毒性肠炎患儿的效果,并分析对其免疫球蛋白及胃肠激素水平的影响。方法选取2019年6月至2023年5月郑州人民医院收治的106例轮状病毒性肠炎患儿为研究对象,依据掷硬币法将患儿分为对照组(53例)与观察组(53例)。两组患儿均接受补液、调整饮食干预,对照组接受赖氨葡锌、酪酸梭菌二联活菌散治疗,观察组在对照组基础上联合维生素D治疗,两组均连续治疗7 d,比较两组治疗前、治疗7 d时血清免疫球蛋白[免疫球蛋白A(IgA)、免疫球蛋白G(IgG)、免疫球蛋白M(IgM)]、胃肠激素[胃泌素(GAS)、胃动素(MOT)、血管活性肠肽(VIP)]及炎症因子[C反应蛋白(CRP)、降钙素原(PCT)、白细胞介素-6(IL-6)]水平,并统计两组不良反应。结果治疗7 d时,两组血清IgA、IgG、IgM水平均高于治疗前,血清GAS、MOT、VIP、CRP、PCT、IL-6水平均低于治疗前,且观察组血清IgA、IgG、IgM水平均高于对照组,血清GAS、MOT、VIP、CRP、PCT、IL-6水平均低于对照组,差异有统计学意义(P<0.05);治疗期间,两组不良反应比较,差异无统计学意义(P>0.05)。结论维生素D联合赖氨葡锌、酪酸梭菌二联活菌散可改善轮状病毒性肠炎患儿免疫球蛋白及胃肠激素水平,且不增加不良反应。

关键词： 多柔比星脂质体   日间病房   超敏反应   多学科团队   化疗   专科护理  

摘要： 本文总结1例日间病房输注多柔比星脂质体(PLD)诱发Ⅱ级超敏反应的乳腺癌患者护理经验。组建日间病房多学科管理团队(MDT),制定标准化输注方案,执行超敏反应应急流程,并由专科护士依托互联网护理门诊进行随访管理,提供优质的院外延续性护理。基于MDT的同质化输注方案与标准化超敏反应处置流程,患者顺利完成第一周化疗。

关键词： 肠致病性大肠杆菌   脂多糖   O-抗原   血清型   结构鉴定  

摘要： O-抗原是细菌脂多糖最外层的组成部分,其结构的复杂性与多样性对细菌的免疫逃逸、致病性及宿主相互作用具有重要影响。本研究开展了肠源性大肠杆菌EPEC080菌株脂多糖O-抗原的提取纯化。通过分子量测定、单糖组分分析、红外光谱分析以及核磁共振谱分析完成了该细菌脂多糖O-抗原化学结构的解析。该O-抗原的平均分子量为14.3 kDa,由五糖重复单元→4)-[α-D-GalpNAc-(1→3)]-α-L-Rhap-(1→2)-[β-D-GalpNAc-(1→3)]-α-L-Rhap-(1→2)-α-L-Rhap-(1→构成,其化学结构与已知的大肠杆菌各血清型O-抗原结构均不同,表明EPEC080菌株是一种新的大肠杆菌血清型。本研究结果可为肠致病性大肠杆菌的致病机制探索,以及相关疾病的预防和治疗方法研发提供基础。

关键词： 重组抗RANKL全人单克隆抗体注射液(LY01011)   实体瘤骨转移   临床试验   有效性   安全性  

摘要： 目的:比较LY01011(重组全人源抗RANKL单克隆抗体注射液)与地舒单抗注射液治疗实体瘤骨转移的有效性和安全性。方法:开展了一项随机、双盲、阳性药物平行对照、多中心临床试验。共850名受试者被随机分配(1:1比例)至试验组(424名受试者)或对照组(426名受试者)。试验组接受13剂LY01011治疗,对照组先接受3剂地舒单抗治疗,随后再接受10剂LY01011治疗。结果:主要疗效指标第13周尿肌酐校正的尿I型胶原交联N端肽(urinary N-terminal telopeptide of type I collagen corrected by urinary creatinine,uNTX/uCr)相对于基线的自然对数变化值。试验组的变化值为−1.740(0.0420),对照组为−1.745(0.0421)。组间最小二乘均值差为0.005(90%置信区间:−0.088~0.097),表明无统计学显著差异(P>0.05)。安全性方面,包括治疗期间出现的不良事件、实验室检查、生命体征、体格检查和心电图结果,两组间具有可比性(P>0.05)。结论:LY01011是地舒单抗注射液的生物类似药,整体安全耐受性良好,安全性较高,临床可继续推广运用。

关键词： IFN gamma-IL8 signaling   immune response   neutrophils   publicly accessible dataset   single-cell transcriptomic profiles  

摘要： Streptococcus agalactiae is a significant pathogen in both humans and animals, yet the immune cell subtype dynamics during infection remain poorly defined. Leveraging the high susceptibility and tractability of Nile tilapia (Oreochromis niloticus), 113,356 single immune cells are profiled from head kidney and spleen across multiple infection time points (0, 1, 5, 10, 75 days post-infection and 3 days post-reinfection). This single-cell transcriptomic and flow cytometry analyses revealed distinct activation and transition patterns among neutrophils, macrophages, T cells, and B cells. Neutrophils exhibited early transcriptional remodeling enriched in inflammatory and interferon gamma (IFN gamma) signaling pathways. Cross-species integration identified a conserved IFN gamma-driven transition toward il8(+) neutrophils. Furthermore, recombinant interleukin-8 (IL8) enhanced antibacterial responses in tilapia and human neutrophils, while inhibition of STAT1 reduced IL8 expression. IL8 stimulation increased phagocytosis and reactive oxygen species (ROS) production, supporting its role in neutrophil-mediated bacterial clearance. Together, this findings establish IFN gamma-IL8 as a conserved mechanism in vertebrate immunity and a potential target for antibacterial therapies.