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关键词： 玉屏风颗粒   乙酰半胱氨酸   肺炎支原体肺炎   T淋巴细胞亚群   临床疗效  

摘要： 目的探讨玉屏风颗粒联合乙酰半胱氨酸对支原体肺炎患儿的疗效及T淋巴细胞亚群的影响。方法选取2021年1月至2023年1月于延安大学附属医院就诊102例支原体肺炎患儿进行回顾性分析,根据治疗方法将患者分为对照组(乙酰半胱氨酸治疗)51例和试验组(乙酰半胱氨酸联合玉屏风颗粒治疗)51例。比较两组患儿临床疗效、症状消退时间、T淋巴细胞亚群变化及不良反应。结果试验组治疗后总有效率为96.08%(49/51)高于对照组的82.35%(42/51)(χ^(2)=4.993,P=0.025)。试验组患儿咳嗽、发热、喘息、啰音消退时间[分别为(5.35±0.89)d、(3.23±0.65)d、(2.67±0.58)d、(5.74±0.78)d]均短于对照组[分别为(6.12±1.32)d、(4.01±0.96)d、(3.54±0.84)d、、(6.45±1.12)d](t=3.454、4.805、6.087、3.715,均P<0.001)。试验组和对照组T淋巴细胞亚群CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平[分别为(65.87±7.23)%、(36.87±7.23)%、(1.47±0.42)、(61.23±6.18)%、(31.23±6.12)%、(1.26±0.25)]均高于治疗前[分别为(54.46±5.59)%、(26.45±5.59)%、(0.95±0.24)、(54.14±5.37)%、(26.14±5.37)%、(0.93±0.21)],且试验组高于对照组(t=3.484、4.252、3.068,均P<0.05)。两组不良反应总发生率分别为9.80%(5/51)、5.88%(3/51),差异无统计学意义(χ^(2)=0.136,P=0.713)。结论玉屏风颗粒联合乙酰半胱氨酸治疗支原体肺炎患儿疗效良好,能够更快缓解症状,改善T淋巴细胞亚群分布,且安全性良好。

关键词： 徐氏参芪苡术汤   脾虚瘀毒   癌因性疲乏   细胞因子  

摘要： 目的:评价徐氏参芪苡术汤治疗胃癌术后化疗癌因性疲乏(CRF)脾虚瘀毒型的临床疗效,并探讨其可能机制。方法:选取50例胃癌术后CRF脾虚瘀毒型患者,采用随机数字表法分为观察组、对照组,每组各25例。对照组予FLOT方案化疗(多西紫杉醇50 mg·m^(-2)第1天静脉滴注+奥沙利铂85 mg·m^(-2)第1天静脉滴注+亚叶酸钙200 mg·m^(-2)第1天静脉滴注+氟尿嘧啶2600 mg·m^(-2)第1天24 h持续静脉滴注,3周/次)及基础、对症支持治疗,观察组在对照组的基础上同时予徐氏参芪苡术汤治疗(水煎2次,200 mL口服,2次/d)。3周为1个疗程,共4疗程。观察两组治疗前后Piper疲乏量表(PFS)评分、Karnofsky Performance Status(KPS)量表评分、欧洲癌症治疗研究组织生命质量核心(EORTC-QLQ-C30)量表评分、中医证候评分,酶联免疫吸附测定法(ELISA)检测血清肿瘤坏死因子-α(TNF-α)、γ干扰素(IFN-γ)、白细胞介素-6(IL-6)水平,记录两组患者治疗前后安全性检查结果及治疗期间不良事件发生情况。从基因表达综合数据库(GEO)下载胃腺癌患者及正常人外周血样本的转录组测序数据,并鉴定肿瘤组和正常组间的差异表达基因,根据京都基因与基因组百科全书(KEGG)和基因本体(GO)进行差异基因富集分析。从基因卡片(GeneCards)数据库获取基因的CRF相关性评分。结果:(1)与本组治疗前比较,观察组PFS总疲乏评分明显降低(P<0.05);与对照组治疗后比较,观察组PFS总疲乏评分明显降低(P<0.05);(2)与本组治疗前比较,观察组KPS评分明显降低(P<0.05);与对照组治疗后比较,观察组KPS评分明显降低(P<0.05);与本组治疗前比较,观察组EORTCQLQ-C30量表功能领域(躯体功能、角色功能、情绪功能、社会功能)及总体健康领域评分明显增高,症状领域评分(疲乏、气促、食欲不振、便秘、腹泻)明显降低(P<0.05);与对照组治疗后比较,观察组EORTC-QLQ-C30量表功能领域(躯体功能、情绪功能、社会功能)及总体健康领域评分明显增高(P<0.05),症状领域评分疲乏、恶心呕吐、气促、食欲不振、腹泻明显降低(P<0.05);与本组治疗前比较,观察组中医证候评分(食少纳呆、体倦乏力、食后腹胀、大便异常、神疲乏力、总分)明显降低(P<0.05);与对照组治疗后比较,观察组中医证候评分(食少纳呆、体倦乏力、恶心呕吐、面色萎黄)明显降低(P<0.05),观察组疗效优于对照组(χ^(2)=7.996,P<0.05);血清TNF-α、IL-6、IFN-γ水平之间呈两两相关(P<0.01)。与本组治疗前比较,观察组血清细胞因子TNF-α、IL-6、IFN-γ水平明显降低(P<0.05);与对照组治疗后比较,观察组血清细胞因子TNF-α、IL-6、IFN-γ水平明显降低(P<0.05);(3)两组患者治疗前后安全性检查结果的组内和组间比较差异均无统计学意义;治疗期间,两组患者不良反应发生率差异无统计学意义。(4)与正常组外周血比较,肿瘤组患者外周血中共有328个基因表达明显上调(P<0.05),KEGG和GO分析显示其明显富集于TNF等信号通路(P<0.05)。(5)TNF、IL6、IFNG等细胞因子编码基因可能是CRF关键致病基因。结论:徐氏参芪苡术汤可缓解胃癌术后化疗患者CRF的疲乏等症状,提高患者功能状况、生命质量,其机制可能与改善细胞因子失调有关。

关键词： 慢性阻塞性肺疾病   清金化痰汤   IL-6/STAT3/HIF-1α通路   细胞凋亡   炎症   地塞米松  

摘要： 目的:探讨清金化痰汤(QJHTD)抑制白介素-6(IL-6)/信号转导与转录激活因子3(STAT3)/低氧诱导因子1α(HIF-1α)通路介导的细胞凋亡和炎症治疗慢性阻塞性肺疾病(COPD)的机制。方法:采用烟熏联合气管内注射脂多糖的方法建立大鼠COPD模型。将50只SPF级SD雄性大鼠随机分为对照组(CON组)、模型组(COPD组)、清金化痰汤低剂量组(QJHTD-L组)、清金化痰汤高剂量组(QJHTD-H组)以及地塞米松组(DXMS组),每组10只。给药结束后,观察各组大鼠的生存状态;HE染色检测大鼠肺组织的病理变化以及支气管肺泡灌洗液(BALF)中炎症细胞的数量;TUNEL法检测大鼠的肺上皮细胞凋亡情况;ELISA试剂盒检测大鼠BALF中肿瘤坏死因子-α(TNF-α)、IL-6、白介素-1β(IL-1β)的含量;WB检测大鼠BALF中IL-6、STAT3、HIF-1α的蛋白相对表达量。结果:与CON组相比,COPD组大鼠呼吸困难、精神萎靡、皮毛发黄;肺组织病理显示肺泡部分融合,有大量炎性细胞浸润;肺上皮细胞凋亡细胞指数显著增加(P<0.05);BALF中的中性粒细胞、巨噬细胞、淋巴细胞数量显著增加(均P<0.05),TNF-α、IL-6、IL-1β水平明显升高(均P<0.05),IL-6、STAT3、HIF-1α蛋白相对表达量显著增加(均P<0.05)。与COPD组相比,QJHTD-H和DXMS组大鼠表观症状明显缓解;QJHTD-H和DXMS组的中性粒细胞、淋巴细胞数量显著减少(均P<0.05),QJHTD-L、QJHTD-H和DXMS组的巨噬细胞数量显著减少(均P<0.05),TNF-α、IL-6、IL-1β水平明显下降(均P<0.05),IL-6、STAT3、HIF-1α的蛋白相对表达量显著减少(均P<0.05)。QJHTD-H组和DXMS组的治疗效果更接近。结论:清金化痰汤能够通过抑制IL-6/STAT3/HIF-1α通路介导的细胞凋亡和炎症治疗COPD。

关键词： Cytokine   Abscopal   Colorectal Cancer   Gastric Cancer   Immune modulatory  

摘要： Background Curative responses to immunotherapy require the generation of robust systemic immunity with limited toxicity. Recruitment of T cell populations such as precursor exhausted T cells (Tpex) from lymphoid tissues to tumors is a hallmark of effective treatment. However, the ability to efficiently induce this recruitment is lacking in current immunotherapy approaches. Furthermore, systemic administration of immunotherapies frequently results in dose-limiting toxicities, yielding an inadequate therapeutic window for eliciting durable *** In this investigation, we evaluated the safety and antitumor efficacy of locally administered interleukin 12 (IL-12) using a clinically translatable cytokine delivery platform (NCT05538624) to identify Tpex recruitment capabilities at tolerable cytokine *** We show IL-12 cytokine factories can effectively treat a broad spectrum of cancer types. Single-cell RNA sequencing data suggests that the antitumor efficacy seen in our studies was due to retinal pigmented epithelial cells-mIL12 treatment inducing differentiation of Tpex cells within the tumor microenvironment. When administered in combination with checkpoint therapy, IL-12 cytokine factory treatment generated systemic abscopal immunity, preventing subcutaneous tumor outgrowth in 8/9 mice with colorectal cancer and lung metastasis in mice with melanoma. Furthermore, this platform was well tolerated in a non-human primate without signs of *** Our new immunotherapy approach provides a robust strategy for inducing Tpex recruitment and systemic immunity against a range of solid peritoneal malignancies, many incurable with current immunotherapy strategies. Notably, these features were achieved using IL-12, and by leveraging our technology, we avoided the toxicities that have prevented the translation of IL-12 to the clinic. Our findings provide a strong rationale for the clinical development of IL-12 cytokine factories.

关键词： Multifunctional microfluidic chip   Perfusion culture of A549 cell   SERS detection of IL-6 secretion from LPS-   Stimulated A549 cells   Bubble trap  

摘要： A multifunctional microfluidic chip integrated with perfusion cell culture and in situ SERS detection of cell secretion was designed and developed for the detection of IL-6 secretion from LPS-stimulation of A549 cells in this paper. Researching works were focused on A549 cell activity and secretion in the constructed LPS-stimulated A549 cells model. On the designed microchip, a bubble trap chamber was designed to remove the bubbles in the culture medium which could also be simultaneously preheated by a split hot plate. Then, a long-time perfusion culture process of 549 cells could be realized. Under the optimized conditions the A549 cells could be cultured and kept in good activity for more than 36 h. Subsequently, the model of interaction between LPS and A549 cells was established on the designed microchip. When LPS-stimulated A549 cells, the IL-6 which was one of the secretions formed in this process was detected quantitatively by SERS spectral technique. The silver-coated gold nano-stars were prepared and taken as a sensitive enhancing probe for the SERS detection of IL-6 secreted from LPS-stimulated A549 cells. The immunomagnetic beads, IL-6 antigen, and SERS probes were mixed and incubated in the microchip and form a sandwich structure which was captured by the permanent magnet in the detection zone for SERS detection. The reference material of IL-6 was used to establish the calibration curve, and the linear range and detection limit were 1-10000 pg/mL and 0.75 pg/mL, respectively. Then, the IL-6 secretion from LPS-stimulated A549 cells was detected hourly for 7 h by this established method. The process of LPS stimulation of A594 cells did not lead to a sustained increase in the SERS spectral signature of IL-6. Instead, IL6 secretion initially increased sharply, then decreased and eventually stabilized. It could be due to a potential mechanism that the cells self-regulated to mitigate the inflammatory effects in response to sustained stimulation. The proposed m

关键词： CAR-T   IL7R alpha   Immune escape   Tumor microenvironment   Glioblastoma  

摘要： Tumor heterogeneity and an immunosuppressive microenvironment pose significant challenges for immunotherapy against solid tumors, particularly glioblastoma multiforme (GBM). Recent studies have highlighted the crucial role of glioma stem cells (GSCs) in tumor recurrence and therapeutic resistance. In this context, we developed a tandem chimeric antigen receptor (CAR)-T cell targeting CD44 and CD133 (PROM1), containing a truncated IL-7 receptor alpha intracellular domain (Delta 7R) between the CD28 costimulatory receptor and the CD3 zeta signaling chain (Tan zeta-T28-Delta 7R). Our target identification and validation were carried out using GSCs, samples from GBM patients, and the corresponding sequencing data. The antitumor efficacy of CAR-T cells was evaluated in patient-derived GSCs, intracranial xenograft models, patient-derived xenograft models, and glioblastoma organoids (GBOs). Single-cell RNA sequencing and mass cytometry were used to determine the immune phenotypes of CAR-T cells. We showed that locoregionally administered Tan zeta-T28-Delta 7R CAR-T cells induced longterm tumor regression with the desired safety outcomes. Patient-derived autologous Tan zeta-T28-Delta 7R CAR-T cells showed robust antitumor activity against GBOs. Our pre-clinical data has demonstrated the translational potential of Tan zeta-T28-Delta 7R CAR-T cell against GBM.

关键词： 急腹症   脓毒症   肝素结合蛋白   降钙素原   白细胞   淋巴细胞  

摘要： 目的:调查急腹症患者的肝素结合蛋白(HBP)、白细胞计数(WBC)、降钙素原(PCT)以及外周血淋巴细胞Fas的表达水平,分析其对患者脓毒症风险的预测价值。方法:回顾性分析2020年11月-2023年11月我院收治的126例急腹症患者的临床资料,所有患者基线资料与各指标的检测结果等资料基本完整,根据治疗期间是否并发脓毒症,将其分为脓毒症组(n=47)与非脓毒症组(n=79),比较两组各指标检测结果,并通过受试者工作特征(ROC)曲线分析,探讨各指标的预测价值。结果:脓毒症组的Fas、WBC、PCT、HBP水平均高于非脓毒症组(P<0.05)。ROC曲线分析结果表明,HBP的曲线下面积(AUC)最大,为0.933,PCT、Fas、WBC的AUC值依次为0.853、0.811、0.749。采用HBP指标预测患者脓毒症风险,最佳截断值为80.900ng/mL,对应敏感度及特异度分别为85.1%、96.2%。结论:在急腹症患者中,HBP、PCT、WBC以及Fas表达水平对脓毒症风险具有一定的预测价值,临床应对入院后相关指标的检测结果引起高度重视。

关键词： 弥漫性大B细胞淋巴瘤   IFN-γ   IL-2   T淋巴细胞   NK细胞   预后   预测  

摘要： 目的探讨血浆IFN-γ、IL-2及外周血T淋巴细胞亚群、NK细胞对弥漫性大B细胞淋巴瘤患者预后的预测价值。方法选取弥漫性大B细胞淋巴瘤患者106例,通过门诊或电话随访,其中生存74例(生存组),死亡32例(死亡组)。采用流式细胞仪检测IFN-γ、IL-2、CD3+、CD3+CD4+T、CD3+CD8+T、NK细胞,多因素Logistic回归分析影响弥漫性大B细胞淋巴瘤患者预后因素,ROC曲线分析血浆IFN-γ、IL-2及外周血T淋巴细胞亚群、NK细胞预测弥漫性大B细胞淋巴瘤患者预后的价值。结果生存组与死亡组基线资料性别、年龄、BMI、病理类型、临床分期比较,差异无统计学意义(P>0.05);生存组与死亡组IFN-γ、IL-2及外周血T淋巴细胞亚群(CD3+、CD3+CD4+T、CD3+CD8+T)、NK细胞水平比较,差异有统计学意义(P<0.05);多因素Logistic回归分析显示IFN-γ(OR=0.144,95%CI:0.057~0.364)、IL-2(OR=0.951,95%CI:0.933~0.970)、CD3+(OR=0.648,95%CI:0.549~0.765)、CD3+CD4+T(OR=0.777,95%CI:0.710~0.850)、NK细胞(OR=0.397,95%CI:0.270~0.586)水平均为弥漫性大B细胞淋巴瘤患者预后的保护性因素(P<0.001)。ROC曲线分析显示,与单一检测指标比较,联合检测价值更高。结论血浆IFN-γ、IL-2及外周血T淋巴细胞亚群、NK细胞可能成为弥漫性大B细胞淋巴瘤患者预后评估的潜在生物标志物,为临床诊断和治疗弥漫性大B细胞淋巴瘤提供重要的参考依据。

关键词： 过敏性紫癜   正五聚蛋白3   CXC趋化因子配体16   T淋巴细胞亚群   诊断价值  

摘要： 目的:探究正五聚蛋白3(PTX3)、CXC趋化因子配体16(CXCL16)联合T淋巴细胞亚群在过敏性紫癜(HSP)患儿诊断中的价值。方法:选取我院从2020年10月-2022年10月收治的120例HSP患儿作为研究组。另取同期健康体检儿童100例记作健康体检组。对比两组血清PTX3、CXCL16与T淋巴细胞亚群指标水平。此外,将HSP患儿按照病情严重程度的差异分作轻度组(n=47)、中度组(n=42)及重度组(n=31)。对比三组血清PTX3、CXCL16与T淋巴细胞亚群指标水平。结果:研究组血清PTX3、CXCL16水平均高于健康体检组(均P<0.05)。研究组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平均低于健康体检组,而CD8^(+)水平高于健康体检组(均P<0.05)。重度组患儿血清PTX3、CXCL16水平均高于轻度组与中度组,且中度组高于轻度组(均P<0.05)。重度组患儿CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平均低于轻度组与中度组,且中度组低于轻度组;重度组患儿CD8^(+)水平高于轻度组与中度组,且中度组高于轻度组(均P<0.05)。结论:PTX3、CXCL16联合T淋巴细胞亚群作为HSP病情发生、发展的重要监测指标,在临床诊断及病情严重程度评估方面具有重要作用。

关键词： 白鹇   蓝鹇   MHC   遗传多样性  

摘要： 为探究白鹇和蓝鹇两种雉鸡在主要组织相容性复合体(Major Histocompatibility Complex,MHC)BF基因的遗传多样性和双拷贝结构,通过设计引物、PCR扩增其MHC-BF基因第2外显子序列,采用高通量测序PCR产物,进而检测与分析这2个雉鸡物种的多态性。结果表明:扩增得到白鹇和蓝鹇的MHC-BF基因第2外显子序列长度为259bp或265bp,存在1个6bp“CCTGGG”的插入缺失,可作为MHC-BF基因2个拷贝的识别位点。白鹇包含了本次检测到的全部80个变异位点,而蓝鹇只有其中的62个。白鹇共有29个单倍型,蓝鹇仅有13个单倍型,两者共享8个单倍型。白鹇比蓝鹇的遗传多样性高,核酸多样性分别为0.104和0.076,单倍型多样性分别为0.959和0.868。蓝鹇作为岛屿物种,其MHC-BF基因的遗传多样性低于白鹇这个大陆物种,为2个物种的遗传管理提供了理论基础。