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国际免疫学杂志
国际免疫学杂志

李殿俊

双月刊

1673-4394

guojimianyi@126.com

0451-86669596

150081

黑龙江省哈尔滨市南岗区保健路157号

国际免疫学杂志/Journal International Journal of Immunology北大核心CSTPCD
查看更多>>1978年创刊，中华人民共和国卫生部主管，中华医学会、哈尔滨医科大学主办。本刊原名《国外医学》免疫学分册，公开发行的国家级学术期刊。期刊适合于从事免疫学以及相关学科、交叉学科的科研、教学和广大的临床医务工作者参考和交流。
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    利用斑马鱼模型进行中性粒细胞迁移相关作用药物的高通量筛选

    吕美王洪高薛容涛王莹...
    109-116页
    查看更多>>摘要：目的 建立半自动化高通量药物筛选系统，探索影响中性粒细胞迁移能力的药物，并探究药物对中性粒细胞免疫能力的作用，以期高效寻找可以用于治疗炎症和自身免疫性疾病的新型药物。 方法 应用荧光延时追踪技术记录斑马鱼卵黄囊内中性粒细胞的迁移，结合TrackMate软件建立半自动化检测与G蛋白偶联受体作用相关的不同药物处理后对中性粒细胞速度影响情况，从而进行高通量药物筛选，通过三轮重复独立筛选试验得到影响中性粒细胞迁移能力的药物；结合斑马鱼尾鳍横断实验及大肠杆菌感染实验进一步探讨该药物对中性粒细胞免疫反应能力的作用。 结果 建立了可靠、稳定、高效的半自动化高通量药物筛选系统，通过系统筛选得到丁香酚能够促进中性粒细胞迁移能力(0.08 μm/s比0.14 μm/s，t＝6.01，P<0.05)，氯化腾喜龙则抑制其迁移能力(0.08 μm/s比0.05 μm/s，t＝3.93，P<0.05)。斑马鱼尾尾鳍横断损伤和斑马鱼耳蜗内大肠杆菌感染实验表明，丁香酚可抑制损伤部位中性粒细胞的趋化迁移(1、2、3 h的t值分别为1.65、1.45、1.36，P值均<0.05)，而氯化腾喜龙在损伤/感染情况下对中性粒细胞免疫能力的影响差异无统计学意义(P>0.05)。 结论 高通量药物筛选系统可用于开发调控中性粒细胞迁移相关作用药物的研究，进而发现可用于治疗炎症和自身免疫性疾病相关的新型药物，或可以用于其他免疫相关疾病的研究和筛选任务。 Objective To establish a semi-automated high-throughput drug screening system to explore drugs that affect neutrophil migration ability, and to investigate the effects of drugs on neutrophil immune function, with the aim of efficiently identifying novel drugs for the treatment of inflammation and autoimmune diseases. Methods Taking advantage of the fluorescence time-lapse tracking technology to record the migration of neutrophils on the yolk sac of Zebrafish, a semi-automated high-throughput drug screening system for detecting of neutrophils velocity related to the action of G protein-coupled receptors was established by TrackMate cell tracking software. The drugs affecting the migration ability of neutrophils were obtained through 3 repeated independent screening tests. Zebrafish tail transection and Ecoli: RFP bacteria infection experi ments were conducted to further explore the effects of these drugs on neutrophil immune response. Results The reliable, stable and efficient semi-automated high-throughput drug screening system was established. Through the screening process, Eugenol was found to promote neutrophil migration (0.08 μm/s vs 0.14 μm/s, t=6.01, P<0.05), while Edrophonium chloride inhibits neutrophil migration (0.08 μm/s vs 0.05 μm/s,t=3.93, P<0.05). Zebrafish tail fin transection andEcoli: RFP infection experiments showed that Eugenol inhibited the chemotactic migration of neutrophils in the case of infection(t1h , 2h, 3h values are 1.65, 1.45, 1.36, respectively, all P values <0.05), while edrophonium chloride did not exhibit significant statistical differences under injury/infection conditions. Conclusion The high-throughput drug screening system can be used to develop drugs that regulate neutrophil migration and discover novel drugs for the treatment of inflammation and autoimmune diseases, or other immune-related disease research and screening tasks.

    细胞追踪G蛋白偶联受体中性粒细胞药物筛选

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    630 nm LED红光通过AKT/FOXO3a信号通路抑制人巨噬细胞炎症因子释放的研究

    潘昱霖林默楠张凯波曹国丁...
    117-123页
    查看更多>>摘要：目的 探讨630 nm发光二极管(light emitting diode，LED)红光照射对人外周血单核细胞系THP-1来源巨噬细胞炎症反应的作用，寻找其可能发挥作用的信号通路与分子机制。 方法 人外周血单核细胞THP-1，经佛波酯(phorbol myristate acetate，PMA)诱导为THP-1来源巨噬细胞，并用脂多糖(lipopolysaccharide，LPS)处理制备巨噬细胞炎症模型；未经630 nm LED红光照射的细胞设为对照组，实验组各组细胞接受光照能量强度分别为14.4 、28.8和43.2 J/cm2；对不同能量强度LED红光照射处理后的巨噬细胞进行实时荧光定量PCR(real-time reverse transcription polymerase chain reaction，RT-qPCR)和酶联免疫吸附试验(enzyme linked immunosorbent assay，ELISA)，检测炎症因子白细胞介素(interleukin，IL)-1β和肿瘤坏死因子(tumor necrosis factor，TNF)-α的mRNA与蛋白表达，Western blot检测蛋白激酶B(protein kinase B，AKT)和叉头框蛋白O3a(forkhead box O3a，FOXO3a)蛋白及其磷酸化(p-AKT、p-FOXO3a)表达，并分析其分子通路。 结果 巨噬细胞经LPS诱导后，与对照组相比，实验组细胞中iNOS的mRNA表达显著升高，同时伴随炎症因子IL-1β、TNF-α的mNRA表达水平显著提升，差异有统计学意义(t值分别为－48.73、－80.96、－38.45，P值均<0.001)。M1巨噬细胞经630 nm LED红光照射处理后，细胞中炎症因子IL-1β、TNF-α的mRNA表达水平明显降低，同时IL-1β、TNF-α的蛋白表达水平下降，p-AKT/AKT蛋白比值和p-FOXO3a/FOXO3a蛋白比值明显降低，差异有统计学意义(t值分别为60.18、25.30、14.79、17.31、23.64、87.50，P值均<0.05)。SC79干预后，M1巨噬细胞的p-AKT/AKT蛋白比值显著升高，IL-1β的mRNA、蛋白表达显著增加，差异有统计学意义(t值分别为－18.08、－26.43、－18.06，P值均<0.05)。SC79激活M1巨噬细胞AKT磷酸化后，630 nm LED红光可以明显降低SC79干预后M1巨噬细胞中p-AKT/AKT蛋白比值，同时明显下调IL-1β、TNF-α的mRNA表达和IL-1β、TNF-α的蛋白表达，差异有统计学意义(t值分别为15.59、33.56、70.00、5.79、36.25，P值均<0.05)。然而与对照组相比，单独SC79干预后，M1巨噬细胞中TNF-α的mRNA与蛋白表达未显著改变(P>0.05)。 结论 630 nm LED红光主要通过下调AKT和FOXO3a蛋白磷酸化通路，抑制巨噬细胞中炎症因子释放。 Objective To investigate the effect of 630 nm light emitting diode(LED) red light irradiation on the inflammatory response of human peripheral blood mononuclear cells THP-1-derived macrophages, and its potential signaling pathways and molecular mechanisms. Methods Human peripheral blood mononuclear cells, THP-1, were induced into THP-1-derived macrophages by phorbol myristate acetate(PMA) and treated with lipopolysaccharide(LPS) to prepare a macrophage inflammation model. The cells not irradiated with 630 nm LED red light were set as the control group, the cells in each experimental group received light energy intensities of 14.4, 28.8 and 43.2 J/cm2. Real-time reverse transcription polymerase chain reaction(RT-qPCR) and enzyme linked immunosorbent assay(ELISA) were performed to detect the mRNA and protein expression of inflammatory factors interleukin(IL)-1β and tumor necrosis factor(TNF)-α in macrophages after treatment with LED red light irradiation of different energy intensities, and Western blot to detect the protein expression of kinase B(AKT) and forkhead box O3a(FOXO3a) protein and their phosphorylation(p-AKT, p-FOXO3a), and their molecular pathways were analyzed. Results After macrophages were induced by LPS, the mRNA expression of iNOS in the cells of the experimental group was significantly elevated compared with the control group, accompanied by a significant increase in the mRNA expression level of the inflammatory factors IL-1β and TNF-α, and the difference was statistically significant(t values were-48.73, -80.96, -38.45, respectively, all P values<0.001). After M1 macrophages were treated with 630 nm LED red light irradiation, the mRNA expression levels of the inflammatory factors IL-1β and TNF-α in the cells were significantly reduced, along with the protein expression levels of IL-1β and TNF-α , and the p-AKT/AKT protein ratios and p-FOXO3a/FOXO3a protein ratios were significantly reduced, with statistically significant differences(t values were 60.18, 25.30, 14.79, 17.31, 23.64, 87.50, respectively, all P values<0.05). After SC79 intervention, the p-AKT/AKT protein ratio of M1 macrophages was significantly increased, and the mRNA and protein expression of IL-1β was significantly increased, with statistically significant differences(t values were -18.08, -26.43, -18.06 , respectively, all P values<0.05). After SC79 activated AKT phosphorylation in M1 macrophages, 630 nm LED red light could significantly reduce the p-AKT/AKT protein ratio in M1 macrophages after SC79 intervention, and at the same time significantly down-regulate the mRNA and protein expression of IL-1β and TNF-α, with statistically significant differences(t=15.59, 33.56, 70.00, 5.79, 36.25, all P values <0.05). However, the mRNA and protein expression of TNF-α in M1 macrophages was not significantly altered after SC79 intervention alone compared to controls( P>0.05). Conclusion The 630 nm LED red light mainly inhibits the release of inflammatory factors in macrophages by down-regulating the AKT and FOXO3a protein phosphorylation pathways.

    630nmLED红光巨噬细胞蛋白激酶B叉头蛋白O3a

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    IL-35与非小细胞肺癌患者疾病状态和疗效的相关性研究

    徐晓波石磊
    124-128页
    查看更多>>摘要：目的 研究非小细胞肺癌(non-small-cell lung cancer，NSCLC)患者外周血中白细胞介素(interleukin，IL)-35的表达水平及临床意义。 方法 收集2017年6月至2021年12月合肥市第八人民医院呼吸内科56例NSCLC患者以及30例健康志愿者外周血，采用酶联免疫吸附试验(enzyme-linked immunosorbent assay，ELISA)检测IL-35水平；采用反转录聚合酶链反应(RT-PCR)方法检测P35 mRNA和EB病毒诱导基因3(Epstein-Barr virus induced gene 3, EBI3) mRNA表达水平；采用流式细胞术检测调节性T细胞(regulatory T cells，Tregs)的表达水平；分析IL-35与临床病理征和疗效的相关性。 结果 56例NSCLC患者外周血中IL-35、P35 mRNA、EBI3 mRNA和Tregs表达水平相比对照组均明显升高，差异具有统计学意义[IL-35：(124.58±36.41)pg/mL比(31.38±15.34)pg/mL；P35 mRNA: (53.19±7.69)比(15.12±6.91) EBI3 mRNA: (23.18±3.41)比(6.16±1.93)；Tregs: (23.18±3.41) %比(6.16±1.93) %, t值分别为14.72，9.34，4.99，8.39, P值均<0.05]；Ⅲ-Ⅳ患者IL-35水平显著高于Ⅰ-Ⅱ患者，差异具有统计学意义[(135.81±38.88)pg/mL比(115.23±31.21)pg/mL t＝4.44, P<0.05]；伴有淋巴结转移患者相比无淋巴结转移患者IL-35水平亦显著升高，差异具有统计学意义[(141.81±39.71)pg/mL比(112.13± 32.61)pg/mL，t＝3.67, P<0.05]；IL-35和P35 mRNA水平与Tregs水平呈正相关(r值分别为0.761，0.663, P值均<0.05)；经过治疗后，IL-35、P35 mRNA、EBI3 mRNA表达水平显著下降，差异具有统计学意义[IL-35：(132.53±37.12)pg/mL比(56.18±19.35)pg/mL, P35 mRNA: (61.11±7.98)比(25.42±6.12), EBI3 mRNA: (28.14±4.25)比(12.17±2.67),t值分别为31.97，22.35，9.03，P值均<0.05]。 结论 IL-35表达增加可能加速NSCLC患者的进展和转移；IL-35可作为评估NSCLC疾病状态和疗效的标志物。 Objective To study the expression and clinical significance of interleukin-35 in patients with non-small cell lung cancer(NSCLC). Methods The peripheral blood of 56 patients with NSCLC and 30 healthy volunteers from June 2017 to December 2021 in the department of respiratory medicine of the Eighth People's Hospital of Hefei City were collected. The levels of IL-35 were detected by enzyme-linked immunosorbent assay (ELISA). The levels of P35 mRNA and EBI3 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). The levels of regulatory T cells (Tregs) were detected by flow cytometry. The relationship between IL-35 and clinical features and treatment outcome were analyzed. Results The levels of IL-35, P35 mRNA, EBI3 mRNA and Tregs in peripheral blood of 56 NSCLC patients were significantly higher than those in the control group [IL-35: (124.58±36.41)pg/mL vs (31.38±15.34)pg/mL, P35 mRNA: (53.19±7.69) vs (15.12±6.91), EBI3 mRNA: (23.18±3.41) vs (6.16±1.93), Tregs: (23.18±3.41) % vs (6.16±1.93) %, t values were 14.72, 9.34, 4.99, 8.39, all P values<0.05]. The level of IL-35 in patients with Ⅲ-Ⅳ was significantly higher than that in patients with Ⅰ-Ⅱ [(135.81 ±38.88) pg/mL vs (115.23 ±31.21) pg/mL,t=4.44, P<0.05]. Compared with patients without lymph node metastasis, the level of IL-35 was significantly higher in patients with lymph node metastasis [(141.81±39.71)pg/mL vs (112.13± 32.61)pg/mL,t=3.67, P<0.05] . IL-35 and P35 mRNA levels were positively correlated with Tregs (r values were 0.761, 0.663, both P values<0.05). After treatment, IL-35, P35 mRNA and EBI3 mRNA expression levels were significantly decreased[IL-35: (132.53±37.12)pg/mL vs (56.18±19.35)pg/mL, P35 mRNA: (61.11±7.98) vs (25.42±6.12), EBI3 mRNA: (28.14±4.25) vs (12.17±2.67),t values were 31.97, 22.35, 9.03, all P values<0.05]. Conclusion The increased expression of IL-35 may contribute to the progression and metastasis of NSCLC patients. IL-35 can be used as a marker to assess the disease status and treatment outcome of NSCLC patients.

    非小细胞肺癌白细胞介素-35疾病状态

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    系统性红斑狼疮与肺动脉高压患者外周血共有差异表达基因研究

    刘丽刘瑛琦郜赵伟
    129-135页
    查看更多>>摘要：目的 筛选系统性红斑狼疮(systemic lupus erythematosus, SLE)与肺动脉高压(pulmonary arterial hypertension, PAH)患者外周血单个核细胞(peripheral blood monocyte，PBMC)中的共有差异表达基因并分析其功能。 方法 在GEO数据库中筛选SLE数据集(GSE50772和GSE81622)和PAH数据集(GSE703和GSE131793)；筛选各数据集中的差异表达基因；筛选两组SLE数据集共有的差异表达基因，并利用DAVID进行功能分析；筛选PAH数据集共有差异表达基因并进行功能富集分析；筛选四组数据集中共有差异表达基因，并利用荧光定量PCR在临床样本中进行验证。 结果 SLE数据集-GSE50772和GSE81622共筛选出232个共有表达差异基因，其中156个基因表达上调，76个基因表达下调。功能分析显示，差异基因主要参与Ⅰ型干扰素信号通路、病毒基因组复制调控、免疫应答等生物过程；主要分子功能与寡腺苷酸合成酶活性、丝氨酸型肽链内切酶活性、核糖核酸酶活性及蛋白结合相关。PAH数据集-GSE703和GSE131793共筛选出18个表达差异基因。功能分析显示，差异基因主要参与细胞粘附、细胞基质粘附、细胞迁移等生物过程；主要分子功能与锚定蛋白及蛋白结合相关。SLE与PAH数据集共筛选出3个共有差异表达基因：PLSCR1、TCN2、S100A12。荧光定量PCR鉴定结果显示，在SLE和PAH患者PBMC中，S100A12表达水平上调(W＝194.50，P<0.05)。 结论 转录组数据分析和临床样本的实验验证表明S100A12在SLE和PAH患者PBMC中表达升高，提示S100A12可能在SLE并发PAH的过程中发挥作用。 Objective To screen the shared differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) and pulmonary arterial hypertension (PAH). Methods SLE datasets (GSE50772 and GSE81622) and PAH datasets (GSE703 and GSE131793) were screened from GEO database. Firstly, DEGs in each dataset were screened. Secondly, the shared DEGs in the two SLE datasets and in the two PAH datasets were screened respectively, and DAVID was used for functional analysis. Then, the shared DEGs among the four datasets were screened and verified by real-time fluorescence quantitative PCR (qRT-PCR) in clinical samples. Results A total of shared 232 DEGs (156 up-regulated and 76 down-regulated genes) were screened from SLE datasets. Functional analysis showed that these DEGs were mainly involved in type I interferon signaling pathway, viral genome replication regulation, immune response biological processes. The main molecular functions are related to oligosine synthase activity, serine endopeptidase activity, ribonuclease activity and protein binding. For PAH datasets, 18 shared DEGs were screened. Functional analysis showed that differential genes were mainly involved in cell adhesion, cell matrix adhesion, cell migration and other biological processes. The main molecular functions were related to anchored proteins and protein binding. Three shared DEGs(PLSCR1, TCN2 and S100A12), were screened from SLE and PAH datasets. qRT-PCR showed that S100A12expression were up-regulated in PBMC from SLE and PAH patients(W=194.50, P<0.05). Conclusion S100A12 expression were up-regulated in SLE and PAH patients.Based on GEO database and qRT-PCR in PBMC from clinical sample, the result demonstrated that S100A12 maybeinvolved in the process of SLE complicated with PAH.

    系统性红斑狼疮肺动脉高压差异表达基因功能分析

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    丁苯酞通过调控小胶质细胞极化在创伤性脑损伤中的神经保护作用研究

    郭温晗李杭黄成科许凤燕...
    136-142页
    查看更多>>摘要：目的 探讨丁苯酞(3-n-butylphthalide，NBP)调控小胶质细胞的极化反应在创伤性脑损伤(traumatic brain injury，TBI)中的神经保护作用。 方法 27只雄性C57BL/6小鼠随机分配(每组9只)：假手术组(Sham组)、TBI组和NBP组。Sham组和TBI组给予植物油，NBP组给予等体积100 mg/kg NBP，连续7 d。TBI 3 d后，干湿法评估小鼠脑水肿情况。应用改良版小鼠神经功能缺损评分(modified neurological severity score，mNSS)和转棒疲劳试验检测小鼠损伤后第1、3、7天的神经运动功能恢复情况。免疫组织化学法检测损伤皮层周围区抗离子钙结合适配器分子1(ionized calcium binding adapter molecule 1，Iba1)标记的小胶质细胞活化情况，免疫荧光染色检测胶质纤维酸性蛋白(glial fibrillary acidic protein，GFAP)标记的星形胶质细胞活化情况。通过精氨酸酶1(arginase-1，Arg1)与Iba1，诱导型一氧化氮合酶(inducible nitric oxide synthase，iNOS)与Iba1双重染色检测损伤周围区小胶质细胞M1型标志物iNOS及M2型标志物Arg1表达量；髓鞘碱性蛋白(myelinbasic protein，MBP)检测髓鞘丢失情况。 结果 在mNSS实验中，与TBI组相比，NBP组分别在损伤后的第1、3、7天，小鼠的神经功能评分逐渐降低(P第1天＝0.012，P第3天＝0.020，P第7天＝0.046)。与TBI组相比，匀速转棒实验中，NBP组小鼠停留时间在第3天明显增加(P第3天＝0.031)；随NBP治疗时间延长，小鼠在第3、7天的匀加速转棒中停留时间逐渐增加(P第3天＝0.024，P第7天＝0.039)。进一步病理学检测发现，与TBI组相比，NBP组损伤区MBP髓鞘完整性部分恢复(P＝0.026)；小胶质细胞和星形胶质细胞活化标志物Iba1和GFAP表达降低(PIba1＝0.007，PGFAP＝0.006)。与TBI组相比，NBP组M2型的小胶质细胞标志物Arg1增加(PArg1/Iba1＝0.004)，M1型小胶质细胞标志物iNOS减少(PiNOS/Iba1＝0.012)。 结论 NBP可以部分改善TBI小鼠神经运动功能障碍，抑制小胶质细胞和星形胶质细胞的活化，促进小胶质细胞向M2表型的极化。 Objective To investigate the neuroprotective effect of 3-n-butylphthalide (NBP) by regulating microglial polarization in traumatic brain injury (TBI). Methods Twenty-seven male C57BL/6 mice were randomly assigned to Sham group, TBI group and NBP group. Sham group and TBI group were given vegetable oil, and NBP group was given an equal volume of 100 mg/kg butylphthalein for 7 consecutive days. After 3 days, the brain edema of the mice was evaluated by wet and dry method.The modified neurological severity score (mNSS) and fatigue rotarod test were used to detect the recovery of neuromotor function in mice at 1, 3 and 7 days after TBI. The activation of ionized calcium binding adapter molecule 1 (Iba1)-labeled microglia was verified by immunohistochemistry, and the activation of glial fibrillary acidic protein(GFAP)-labeled astrocytes was confirmed by immunofluorescence staining. Through co-locating with Iba1, the expression of inducible nitric-oxide synthase (iNOS), M1 polarization marker, and arginase-1 (Arg1), M2 polarization marker , were indicated by immunofluorescence stainin. Myelinbasic protein (MBP) immunofluorescence staining was used to detect myelin loss. Results In the mNSS experiment, compared with the TBI group, the neural function scores of mice in the NBP group were gradually decreased on day 1, day 3 and day 7 after injury (Pday 1=0.012, Pday 3=0.020, Pday 7=0.046). In constant rotarod test the stick rotation residence time in NBP group was significantly increased on day 3 compared with TBI group (Pday 3=0.031) With the extension of NBP treatment time, the rotation retention time of mice increased in the uniformly accelerated rod rotation experiment on day 3 and day 7(Pday 3=0.024, Pday 7=0.039). Further pathological examination showed that, compared with TBI, the MBP marked-myelin integrity was partially recovered in NBP group (P=0.026). Expressions of microglia and astrocyte activation markers Iba1 and GFAP were decreased (PIba1=0.007, PGFAP=0.006). Compared with TBI group, M2-type microglial marker Arg1 increased (PArg1/Iba1=0.004) and M1-type microglial marker iNOS decreased (PiNOS/Iba1=0.012) in NBP group. Conclusion NBP can partly improve the recovery of neuromotor function in TBI mice, inhibit the activation of microglia and astrocytes, and promote the polarization of microglia to M2 phenotype.

    丁苯酞创伤性脑损伤神经炎症小胶质细胞极化

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    妊娠期糖尿病患者外周血NK细胞TIM-3表达与妊娠结局的相关性研究

    陈薇王琛琛章杨韦丁其培...
    143-148页
    查看更多>>摘要：目的 探究妊娠期糖尿病(gestational diabetes mellitus，GDM)患者外周血自然杀伤(natural killer，NK)细胞中T细胞免疫球蛋白黏蛋白-3(T cell immunoglobulin mucin domain containing molecules-3，TIM-3)表达与妊娠结局的相关性。 方法 选取于海安市人民医院2019年6月至2022年6月确诊为妊娠期糖尿病的孕妇52例作为研究组，并抽取同期于我院住院分娩的健康孕妇41例作为对照组。采集两组患者清晨空腹外周血，采用密度梯度离心法分离外周血单个核细胞(peripheral blood mononuclear cell，PBMC)；采用流式细胞仪检测所有患者外周血CD56＋ CD16- NK细胞表达及TIM-3在NK细胞中的表达。采用Spearman相关分析对外周血CD56＋CD16－ NK细胞表达及TIM-3在NK细胞中表达与孕妇妊娠结局的相关性。 结果 研究组孕期口服糖耐量试验(oral glucose tolerance test，OGTT)血糖水平空腹时、服糖后1及2 h时均明显高于对照组[mmol/L：(5.73±0.87)比(4.65±0.59)；(11.58±3.85)比(8.76±1.79)；(10.53±2.84)比(7.03±1.12)；t值分别为6.81、4.33、7.44，P值均<0.05]；且妊娠不良结局孕妇明显多于对照组，差异均有统计学意义[34.62%比7.32%，t＝9.77，P<0.05]。流式细胞术检测结果显示，研究组孕妇外周血CD56＋ CD16－ NK细胞表达及TIM-3在NK细胞中表达均明显低于对照组，差异有统计学意义[%：(35.44±2.58)比(78.62±8.45)；(21.33±1.63)比(70.22±7.57)；t值分别为34.89、45.32，P值<0.05]。不良组孕期OGTT血糖水平空腹时、服糖后1及2 h时均明显高于良好组，差异有统计学意义[mmol/L：(6.23±0.85)比(5.25±0.61)，(12.53±3.96)比(10.56±2.61)，(11.42±3.22)比(9.35±1.52)，t值分别为4.80、2.16、3.16，P值均<0.05)]。研究组中不良组孕妇外周血CD56＋ CD16－ NK细胞表达及TIM-3在NK细胞中表达均明显低于良好组，差异有统计学意义[%：(25.86±2.15)比(40.35±3.57)，(16.48±1.24)比(23.68±2.32)；t值分别为15.73，12.24，P值均<0.05]。Spearman分析结果显示，外周血CD56＋ CD16－ NK细胞表达与孕妇良好妊娠结局、TIM-3表达与孕妇良好妊娠结局均呈显著正相关，差异有统计学意义(r＝0.62、0.58，P值均<0.05)。 结论 GDM孕妇外周血CD56＋CD16－ NK细胞表达及TIM-3表达均明显降低，并且与孕妇良好妊娠结局呈正相关，外周血CD56＋CD16－ NK细胞表达及TIM-3表达越低GDM孕妇出现不良妊娠结局的可能性越大，提示外周血NK细胞TIM-3表达可作为预测GDM孕妇妊娠结局的参考指标。 Objective To explore the correlation between T cell immunoglobulin domain and mucin domain-3 (TIM-3) expression on peripheral blood natural killer (NK) cells and pregnancy outcome in patients with gestational diabetes mellitus (GDM). Methods A total of 52 GDM cases in Hai'an People's Hospital from June 2019 to June 2022 were selected as study group, and another 41 healthy pregnant women were concurrently enrolled as control group. Milliliters of fasting blood samples were collected. Peripheral blood mononuclear cell(PBMC) were isolated by centrifugation over Ficoll gradient density. Flow cytometry was utilized to detect the expression of CD56+ CD16- NK cells in peripheral blood and the expression of TIM-3 on NK cells. Spearman correlation analysis was performed to discuss the correlation of peripheral blood CD56+ CD16- NK cells expression and TIM-3 expression on NK cells with the maternal pregnancy outcome in GDM. Results The oral glucose tolerance test(OGTT) blood glucose levels during pregnancy in the study group were significantly higher than those in the control group at fasting and 1 and 2 hours after glucose administration[mmol/L: (5.73±0.87)vs(4.65±0.59), (11.58±3.85)vs(8.76±1.79), (10.53±2.84)vs(7.03±1.12) t values are 6.81, 4.33 and 7.44, respectively, , all P values<0.05] Moreover, the number of pregnant women with adverse pregnancy outcomes was significantly higher than that of the control group, and the differences were statistically significant(34.62 vs 7.32%,t=9.77, P<0.05). The results of flow cytometry showed that the expression of CD56+ CD16 NK cells and TIM-3 in NK cells in the peripheral blood of pregnant women in the study group were significantly lower than those in the control group, with statistical significance[%: (35.44±2.58)vs(78.62±8.45), (21.33±1.63)vs(70.22±7.57) t values are 34.89 and 45.32, both P value <0.05)]. The OGTT blood glucose levels during pregnancy in the poor group were significantly higher than those in the good group at fasting, 1 hour and 2 hours after glucose administration, with statistical significance[mmol/L: (6.23±0.85)vs(5.25±0.61), (12.53±3.96)vs(10.56±2.61), (11.42±3.22)vs(9.35±1.52), t values are 4.80, 2.16 and 3.16, respectively, all P values<0.05)]. The expression of CD56+ CD16 NK cells and TIM-3 in NK cells in the peripheral blood of pregnant women in the study group were significantly lower than those in the good group, with statistical significance[%: (25.86±2.15)vs(40.35±3.57), (16.48±1.24)vs(23.68±2.32) tvalues are 15.73, 12.24, both P values<0.05]. Spearman correlation analysis denoted that both the peripheral blood CD56+ CD16-NK cell expression and the TIM-3 expression were positively correlated with good pregnancy outcome(r=0.62, 0.58, both P values <0.05). Conclusion The peripheral blood CD56+ CD16- NK cell expression and TIM-3 expression are notably down-regulated in GDM women, and are positively correlated with good pregnancy outcome, suggesting that women with lower expression of CD56+ CD16- NK cell and TIM-3 suffer a greater risk of adverse pregnancy outcome, so the TIM-3 expression on peripheral blood NK cells can be used as a reference index to predict the pregnancy outcome of GDM women.

    妊娠期糖尿病外周血外周血自然杀伤细胞T细胞免疫球蛋白黏蛋白-3

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    血清miR-322-5p、IL-1β诊断不明原因复发性流产的临床价值及与Th17/Treg平衡的关系研究

    陈娟葛仁美董业峰
    149-154页
    查看更多>>摘要：目的 探讨血清微小RNA(microRNA，miR)-322-5p、白细胞介素(interleukin，IL)-1β诊断不明原因复发性流产(unexplained recurrent spontaneous abortion，URSA)的临床价值及与辅助性T细胞(helper T cell，Th)17/调节性T细胞(regulatory T cells，Treg)平衡的关系。 方法 选取2020年9月至2022年9月海安市人民医院收治的103例URSA患者作为URSA组。另外选取同时期来院产检的120例健康孕妇作对照组。采用实时荧光定量聚合酶链反应检测血清miR-322-5p水平；采用酶联免疫吸附法检测血清IL-1β水平；采用流式细胞仪检测Th17、Treg细胞，计算两者比值。采用Pearson相关分析探讨miR-322-5p、IL-1β与Th17/Treg的关系，采用受试者工作特征(receiver operating characteristic，ROC)曲线评估miR-322-5p、IL-1β对URSA的诊断价值。 结果 与对照组相比，URSA组血清miR-322-5p表达水平明显降低，IL-1β表达水平明显升高，差异有统计学意义[(3.17±1.24)比(1.05±0.43)，(62.14±7.53)pg/L比(81.42±9.16)pg/L，t值分别为16.52，17.25，P值均<0.05]。与对照组相比，URSA组血清Th17水平及Th17/Treg值明显升高，Treg水平明显降低，差异有统计学意义[(1.52±0.42)%比(2.57±0.74)%，(0.28±0.08)比(0.65±0.12)，(6.15±1.52)%比(4.02±1.03)%，t值分别为13.26，27.42，12.04，P值均<0.05]。Pearson相关分析结果显示，URSA患者血清miR-322-5p与Th17、Th17/Treg呈负相关，与Treg呈正相关(r＝－0.41、－0.37、0.50，P值均<0.05)；血清IL-1β与Th17、Th17/Treg呈正相关，与Treg呈负相关(r＝0.37、0.49、－0.42，P值均<0.05)。miR-322-5p、IL-1β预测URSA特异度分别为61.17%、66.02%，敏感度分别为92.50%、83.33%；两者联合预测的特异度为85.44%，敏感度为85.83%。两者联合的诊断价值高于单独检测(Z＝4.102，P＝0.015)。 结论 URSA患者血清miR-322-5p水平明显降低、IL-1β水平明显升高，两者可作为辅助诊断URSA的生物学指标，且与Th17/Treg平衡密切相关。 Objective To explore the clinical value of serum microRNA(miR)-322-5p and interleukin(IL)-1β in diagnosing unexplained recurrent spontaneous abortion(URSA)and its relationship with helper T cell(Th)17/regulatory T cell(Treg)balance. Methods A total of 103 URSA patients admitted to Haian People's Hospital from September 2020 to September 2022 were selected as the URSA group.In addition, 120 healthy pregnant women who came to the hospital during the same period were selected as the control group.Serum miR-322-5p was detected by real-time fluorescence quantitative polymerase chain reaction.Serum IL-1β levels were detected by enzyme-linked immunosorbent assay.The ratio of Th17 and Treg cells was calculated by flow cytometry.Pearson correlation analysis was used to investigate the relationship between miR-322-5p, IL-1β and Th17/Treg.receiver operating characteristic was adopted.ROC curve evaluated the diagnostic value of miR-322-5p and IL-1β in URSA. Results Compared with the control group, the serum miR-322-5p expression level in URSA group was significantly decreased, and IL-1β level was significantly increased[(3.17±1.24) vs (1.05±0.43), (62.14±7.53)pg/L vs (81.42±9.16)pg/L,t=16.52, 17.25, both P values <0.05]. Compared with the control group, the serum Th17 level and Th17/Treg value in URSA group were significantly higher, and the Treg level was significantly lower, the difference was statistically significant[(1.52±0.42)% vs (2.57±0.74)%, (0.28±0.08) vs (0.65±0.12), (6.15±1.52)% vs (4.02±1.03)%, t values were 13.26, 27.42, 12.04, all P values <0.05]. Pearson correlation analysis showed that serum miR-322-5p was negatively correlated with Th17 and Th17/Treg, and positively correlated with Treg ( r values were -0.413, -0.369, 0.502, all P values <0.05). Serum IL-1β was positively correlated with Th17, Th17/Treg, and negatively correlated with Treg ( r values were 0.372, 0.485, -0.416, all P values <0.05). The area under curve(AUC) (95% CI) of miR-322-5p and IL-1β predicted URSA was 0.806 (0.755~0.857) and 0.844 (0.793~0.895), the cut-off values 2.11 and 71.78 pg/L, and the specificity was 61.17% and 66.02%, respectively, the sensitivity 92.50% and 83.33%, respectively. The both combined prediction AUC (95%CI) was 0.921 (0.870~0.972), the specificity 85.44%, and the sensitivity was 85.83%. The diagnostic value of combined detection was higher than that of single detection (Z=4.102, P=0.015). Conclusion The serum miR-322-5p level in Ursa patients was significantly decreased, and IL-1β was increased.Both of them can be used as biological indicators for the diagnosis of URSA, and are closely related to Th17/Treg balance.

    miR-322-5p白细胞介素-1β不明原因复发性流产辅助性T细胞17调节性T细胞

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    不同剂量的甲泼尼松龙联合免疫球蛋白治疗RMPP的临床疗效及对患儿炎症因子及免疫功能的影响

    闵婕郭斐刘怀彬
    155-161页
    查看更多>>摘要：目的 探讨甲泼尼松龙联合免疫球蛋白治疗难治性小儿肺炎支原体肺炎(refractory mycoplasma pneumoniae pneumonia，RMPP)疗效及对炎症因子及免疫功能的影响。 方法 选取徐州医科大学附属徐州儿童医院2019年12月至2021年12月收治的180例RMPP患儿，按照随机数字表法分成对照组和研究组，每组90例，所有患儿均给予阿奇霉素和免疫球蛋白治疗，基础上对照组给予1～2 mg/(kg·d)甲泼尼松龙治疗，研究组给予10～12 mg/(kg·d)甲泼尼松龙治疗，对比对照组和研究组患儿治疗前后临床疗效、临床症状变化、炎症因子、T淋巴细胞表面分子表达及不良反应发生情况。 结果 研究组患儿咳嗽消失时间、肺啰音消失时间及发热消失时间少于对照组[d：(7.20±2.20)比(11.41±3.30)、(5.21±1.50)比(8.12±1.63)、(2.20±0.61)比(3.80±0.90)，t值分别为8.41、10.49、11.74，P值均<0.05]。研究组治疗总有效率高于对照组[n(%): 88(88.89)比65(72.22)，χ2＝8.01，P<0.05)]。治疗后，对照组和研究组红细胞沉降率(erythrocyte sedimentation rate, ESR)、C反应蛋白(C-reactive protein，CRP)、白细胞介素(interleukin-4，IL)-4、干扰素-γ(interferon- γ，IFN-γ)、IL-17和IL-18与治疗前比较均明显降低，差异均具有统计学意义[mm/h: (13.42±3.20)比(15.81±4.70)、mg/L：(12.91±2.92)比(16.62±4.02)、pg/mL：(23.54±3.63)比(29.32±4.53)、(26.21±3.50)比(33.40±3.70)、(13.40±2.21)比(20.22±2.83)、(25.42±3.71)比(30.30±4.50)，t值分别为5.63、6.43、6.96、6.57、6.68、6.63，P值均<0.05]。与治疗前对比，治疗后对照组和研究组患儿血清可溶性CD4明显升高、CD8明显降低，但研究组比对照组变化更显著[%：(35.54±2.73)比(31.43±2.32)、(3.20±0.80)比(4.40±0.90)，t值分别为7.35、7.91，P值均<0.05]。对照组和研究组不良反应率差异无统计学意义(P>0.05)。 结论 大剂量甲泼尼松龙联合免疫球蛋白治疗RMPP患儿的疗效更佳，可改善患儿病情，降低炎症因子水平、提高患儿机体免疫功能。 Objective To explore the therapeutic effect of methylprednisolone combined with immunoglobulin in the treatment of refractory mycoplasma pneumonia(RMPP) and the impact on inflammatory factors and immune function. Methods A total of 180 children with RMPP admitted to Xuzhou Children's Hospital affiliated with Xuzhou Medical University from December 2019 to December 2021 were selected.According to the random number table method, the patients were divided into a control group and a study group, with 90 cases in each group.All patients were treated with azithromycin and immunoglobulin. On this basis, the control group was treated with 1~2 mg/(kg·d) methylprednisolone, while the study group was treated with 10~12 mg/(kg·d). The clinical efficacy, clinical symptom changes, inflammatory factors, T lymphocyte surface molecules, and adverse reactions before and after treatment were compared. Results The disappearance time of cough, lung rales, and fever in the study group was shorter than that in the control group [d: (7.20±2.20) vs (11.41±3.30), (5.21±1.50) vs (8.12±1.63), (2.20±0.61) vs (3.80±0.90), t values were 8.41, 10.49, 11.74, all P values <0.05]. The total effective rate of treatment in the research group was higher than that in the control group[n(%): 88(88.89) vs 65(72.22), χ2=8.01, P<0.05)]. After treatment, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin (IL)-4, interferon-γ(IFN-γ), IL-17 and IL-18 of two groups were significantly reduced compared to before treatment. After treatment, all indicators in the study group were lower than those in the control group [mm/h: (13.42±3.20) vs (15.81±4.70), mg/L: (12.91±2.92) vs (16.62±4.02), pg/mL: (23.54±3.63) vs (29.32±4.53), (26.21±3.50) vs (33.40±3.70), (13.40±2.21) vs (20.22±2.83), (25.42±3.71) vs (30.30±4.50),t values were 5.63, 6.43, 6.96, 6.57, 6.68, 6.63, all P values <0.05]. Compared with before treatment, after treatment, the serum soluble CD4 in both groups of children were significantly increased, while CD8 were significantly decreased. The study group was more significant than the control group [%: (35.54±2.73) vs (31.43±2.32), (3.20±0.80) vs (4.40±0.90), t values were 7.35, 7.91, both P values <0.05]. There was no statistically significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusion The combination of high-dose methylprednisolone and immunoglobulin has a better therapeutic effect on children with RMPP, which can significantly improve their condition, reduce the levels of inflammatory factors and inhance immune function.

    甲泼尼松龙免疫球蛋白肺炎支原体肺炎炎症因子

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    幽门螺杆菌的感染诊断及环介导等温扩增技术在该领域的研究进展

    董莉真王成雪李瑶瑶罗微...
    162-170页
    查看更多>>摘要：幽门螺杆菌(Helicobacter pylori, Hp)与很多胃肠道疾病甚至是胃肠外疾病密切相关。目前幽门螺杆菌的常规检测技术包括快速尿素酶试验、病理组织学检查、血清抗体检测、粪便抗原检测、尿素呼气试验等，随着在临床应用中发现这些技术均存在不同程度的缺陷，因此需要探索新技术来弥补。恒温核酸扩增技术中的环介导等温扩增(loop-mediated isothermal amplification，LAMP)技术近年发展迅速，具有快速、特异、敏感、简便等特点，使该技术在核酸检测领域得到了广泛的应用。文章就Hp感染诊断及LAMP技术在诊断、毒力分型领域内的研究进展进行综述，期望为后续研究者们提供更多信息。 Helicobacter pylori (Hp) is closely related to many gastrointestinal diseases and even parenteral diseases. The detection technologies for Hp include rapid urease test, histopathological examination, serum antibody detection, stool antigen detection, urea breath test, etc. As found in clinical applications, these technologies have various degrees of defects. Therefore, new technologies need to be explored to compensate. Loop mediated isothermal amplification (LAMP), one of thermostatic nucleic acid amplification techniques, has developed rapidly in recent years. This review focuses on the research progress of HP infection diagnosis and LAMP in the diagnosis, virulence typing of Hp, we hoping to provide more information for subsequent researchers.

    环介导等温扩增幽门螺杆菌核酸检测

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    miRNA在自身免疫性疾病中的研究进展

    刘子玉罗玥高天舒杨潇...
    171-177页
    查看更多>>摘要：自身免疫性疾病(autoimmune diseases，AID)是机体自身耐受被打破后，发生自身免疫反应引起局部或全身器官、组织的病理性损伤所致的疾病。微小RNA(microRNA，miRNA)是一类长度在18到25个核苷酸之间的单链内源性非编码RNA，在多种疾病中发挥重要作用，具有潜在的诊断和治疗意义。大量研究发现miRNA在AID发病机制中发挥着重要调控作用，文章总结了miRNA在AID中的研究进展。 Autoimmune disease (AID) is a disease caused by pathological damage of local or systemic organs and tissues caused by autoimmune reaction after the body's self-tolerance is broken. MicroRNA(miRNA) is a kind of single-stranded endogenous non-coding RNA with a length of between 18 and 25 nucleotides, which plays an important role in many diseases and has potential diagnostic and therapeutic significance. A large number of studies have found that miRNA plays an important regulatory role in the pathogenesis of AID. This paper will review the research progress of miRNA in AID.

    微小RNA自身免疫性疾病免疫

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