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Adjuvant Effects of Dual Co-stimulatory Molecules on Cellular Responses to HIV Multiple-epitope DNA Vaccination 被引量:2
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作者 SHEN Zhen-wei JIN Hong-tao +4 位作者 LI Chang CONG Yan-zhao NAN Wen-long BAI Liang JIN Ning-yi 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2009年第3期347-352,共6页
Designing adjuvants that can induce strong cytotoxic T cell responses is largely required for preparing DNA vaccines. In this study we explored dual costimulatory molecules 4-1BBL and OX40L as adjuvants to improve the... Designing adjuvants that can induce strong cytotoxic T cell responses is largely required for preparing DNA vaccines. In this study we explored dual costimulatory molecules 4-1BBL and OX40L as adjuvants to improve the efficiency of the HIV multiple-epitope DNA vaccine. When explored in the human dendritic cell-T cell based coculture system, dual costimulatory molecules significantly enhanced the anti-HIV T cell response of the HIV multiple-epitope DNA vaccine, as detected by intracellular cytokine staining to HIV antigens, cytokines accumulation in the cultures, and antigen-specific cytotoxic T lymphocyte responses. These results suggest that dual costimulatory molecules 4-1BBL and OX40L can effectively increase the potential of the HIV multiple-epitope antigen DNA vaccine and may provide an exciting approach for HIV therapy. 展开更多
关键词 HIV DNA vaccine co-stimulatory molecules 4-1BBL OX40L Dendritic cells
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Adjusting amplitude of the stored optical solitons by inter-dot tunneling coupling in triple quantum dot molecules
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作者 王胤 周驷杰 +1 位作者 邓永和 陈桥 《Chinese Physics B》 SCIE EI CAS CSCD 2023年第5期433-441,共9页
We study the propagation properties of a probe field in an aligned asymmetric triple quantum dot molecule with both sides inter-dot tunneling coupling effect. It is shown that the probe field can form optical soliton ... We study the propagation properties of a probe field in an aligned asymmetric triple quantum dot molecule with both sides inter-dot tunneling coupling effect. It is shown that the probe field can form optical soliton due to the destructive quantum interference induced by the quantum inter-dot tunneling coupling effect. Interestingly, these optical solitons can be stored and retrieved by adjusting single or double inter-dot tunneling coupling effect, different from that light memory in the ultra-cold atom system. Furthermore, we also find that the amplitude of the stored optical soliton can be adjusted by the strength of the single or double inter-dot tunneling coupling. It is possible to improve the stability and the fidelity of the optical information in the process of the storage and retrieval in semiconductor quantum dots devices. 展开更多
关键词 tunneling induced transparency triple quantum dot molecules the storage and retrieval of the optical solitons
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Expression of co-stimulatory molecules B7-2 and PD-L1 on peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection
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作者 Lingxia Fei Shipin Wu Hongtao Chen 《Journal of Nanjing Medical University》 2009年第5期347-351,共5页
Objective: To explore the roles of the expression of the co-stimulatory molecule, B7-2, and the co-inhibitory molecule, PD-L1, on peripheral blood mononuclear cells in the mechanism of immunotolerance in chronic hepa... Objective: To explore the roles of the expression of the co-stimulatory molecule, B7-2, and the co-inhibitory molecule, PD-L1, on peripheral blood mononuclear cells in the mechanism of immunotolerance in chronic hepatitis B virus infection. Methods: Thirty HBV infected patients in the immunoreactive phase and 20 patients in the immunotolerant phase were enrolled in the study, while 20 healthy volunteers were used as controls. RT- PCR and real-time PCR methods were used to detect the expression levels of B7-2 and PD-L1 mRNA in peripheral blood mononuclear cells in chronic HBV infected patients. Results: The B7-2 expression in irnrnunoreactive and immunotolerant patients was significantly lower than that in the controls (P all 〈 0.01 ); B7-2 expression in immunoreactive patients was significantly lower than in immunotolerant patients (P 〈 0.01). PD-L1 expression in irnmunoreactive patients and immunotolerant patients was significantly higher than that in normal controls (P all 〈 0.01). The PD-L1/BT-2 ratios in immunoreactive and immunotolerant patients were significantly higher than that of the healthy controls (P all 〈 0.01); the PD-L1/ B7-2 ratio was significantly higher in the immunoreactive patients than in the immunotolerant patients (P 〈 0.01). Conclusion: In chronic HBV infection, changes in the expression of co-stimulatory and co-inhibitory molecules imply a protective adjustment against the patient' s immune response that may result in increased immunotolerance and persistent HBV infection. 展开更多
关键词 co-stimulatory molecule B7-2 PD-L1 Hepatitis B virus
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Expression of Inducible Co-stimulator in Peripheral Blood T Lymphocytes in the Patients with Systemic Lupus Erythematosus
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作者 陈志平 刘贞富 +1 位作者 郑舜华 梁智辉 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2005年第3期357-359,共3页
The expression of inducible co-stimulator (ICOS) in peripheral blood T lymphocytes from the patients with systemic lupus erythematosus (SLE) and the role in the pathogenesis of SLE was investigated. By using two-color... The expression of inducible co-stimulator (ICOS) in peripheral blood T lymphocytes from the patients with systemic lupus erythematosus (SLE) and the role in the pathogenesis of SLE was investigated. By using two-color immunofluorescent staining and flow cytometric assay, the expression levels of ICOS in peripheal blood T lymphocytes from 33 patients with SLE and 16 healthy volunteers were detected. SLE diseases activity index (SLEDAI) of the patients with SLE was used to evaluate the disease activity. The correlation between the ICOS expression and SLEDAI was analyzed among the groups. The results showed that the expression levels of ICOS in T lymphocytes in active SLE group was markedly higher than those in the control and inactive SLE groups (both P<0.01). There was no significant difference in the expression levels of ICOS between the inactive SLE and the control groups (P>0.05). In active SLE and inactive SLE groups, positive linear correlation was found between the levels of the ICOS expression in T lymphocytes and SLEDAI (r=0.711, P=0.001; r=0.561, P=0.03). It was suggested that the expression of ICOS in peripheral blood T lymphocytes from the patients with active SLE was up-regulated and and ICOS might be related to the pathogenesis of SLE. 展开更多
关键词 lupus erythematosus systemic inducible co-stimulatory
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Historical evolution,overview,and therapeutic manipulation of costimulatory molecules
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作者 Henry Velazquez-Soto Fernanda Real Maria C Jimenez-Martinez 《World Journal of Immunology》 2022年第1期1-8,共8页
Co-stimulatory molecules are key mediators in the regulation of immune responses and knowledge of its different families,structure,and functions has improved in recent decades.Understanding the role of co-stimulatory ... Co-stimulatory molecules are key mediators in the regulation of immune responses and knowledge of its different families,structure,and functions has improved in recent decades.Understanding the role of co-stimulatory molecules in pathological processes has allowed the development of strategies to modulate cellular functions.Currently,modulation of co-stimulatory and co-inhibitory molecules has been applied in clinical applications as therapeutic targets in diseases and promising results have been achieved. 展开更多
关键词 co-stimulatory molecules Immune modulation Monoclonal antibodies Biological therapy Autoimmune diseases Oncological diseases
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COPD合并肺源性心脏病患者血清ICOS、ICOSL水平变化及临床意义
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作者 钱王燕 虞鸣娟 +4 位作者 陈访 李妍妍 张赛 葛小宁 陈润祥 《疑难病杂志》 CAS 2024年第3期282-286,共5页
目的观察慢性阻塞性肺疾病(COPD)合并肺源性心脏病(PHD)患者血清诱导性共刺激分子(ICOS)和诱导性共刺激分子配体(ICOSL)水平变化及临床意义。方法选择2020年6月—2023年2月上海交通大学医学院苏州九龙医院心内科收治COPD患者172例,根据... 目的观察慢性阻塞性肺疾病(COPD)合并肺源性心脏病(PHD)患者血清诱导性共刺激分子(ICOS)和诱导性共刺激分子配体(ICOSL)水平变化及临床意义。方法选择2020年6月—2023年2月上海交通大学医学院苏州九龙医院心内科收治COPD患者172例,根据患者是否合并PHD分为合并PHD组82例和COPD组90例。根据肺动脉收缩压(PASP)将PHD患者分为轻度亚组(30~50 mmHg,21例)、中度亚组(51~70 mmHg,37例)和重度亚组(≥71 mmHg,24例),再根据纽约心脏病协会(NYHA)分级将PHD患者分为Ⅰ~Ⅱ级亚组(44例)、Ⅲ~Ⅳ级亚组(38例)。酶联免疫吸附试验检测血清ICOS、ICOSL水平,分析ICOS、ICOSL与PASP、NYHA分级之间的相关性,受试者工作特征(ROC)曲线分析ICOS、ICOSL诊断COPD合并PHD的价值。结果合并PHD组血清ICOS、ICOSL水平高于COPD组(t=14.526、34.508,P均<0.001)。重度亚组血清ICOS、ICOSL及PASP水平高于中度亚组和轻度亚组(F/P=125.351/<0.001、163.591/<0.001、84.292/<0.001),Ⅲ~Ⅳ级亚组血清ICOS、ICOSL水平均高于Ⅰ~Ⅱ级亚组(t/P=11.658/<0.001、27.345/<0.001)。PHD患者血清ICOS、ICOSL水平与PASP、NYHA分级均呈正相关(r=0.439、0.416、0.501、0.497,P均<0.001)。血清ICOS、ICOSL及二者诊断COPD患者合并PHD的曲线下面积分别为0.780、0.723、0.926,二者联合高于单独ICOS、ICOSL诊断(Z=4.021、5.194,P均<0.001)。结论COPD合并PHD患者血清ICOS、ICOSL水平显著增高,且与肺动脉高压以及心功能降低有关,联合检测ICOS、ICOSL可有效评估COPD患者PHD风险。 展开更多
关键词 慢性阻塞性肺疾病 肺源性心脏病 肺动脉高压 诱导性共刺激分子 诱导性共刺激分子配体
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慢性HBV感染者外周血可诱导共刺激分子在CD8+ T淋巴细胞的表达及其临床意义
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作者 陈春林 张华堂 +4 位作者 苏密龙 郑怡娟 苏智军 余雪平 任岚 《转化医学杂志》 2024年第2期196-202,共7页
目的 探讨慢性乙型肝炎病毒(HBV)感染者外周血可诱导共刺激分子(ICOS)在CD8+T淋巴细胞的表达特点及临床意义。方法 选取2017年5月—2018年10月就诊的慢性乙型肝炎(CHB)100例、HBV-肝硬化(LC)25例和HBV-慢加急(或亚急)性肝衰竭(ACLF)26... 目的 探讨慢性乙型肝炎病毒(HBV)感染者外周血可诱导共刺激分子(ICOS)在CD8+T淋巴细胞的表达特点及临床意义。方法 选取2017年5月—2018年10月就诊的慢性乙型肝炎(CHB)100例、HBV-肝硬化(LC)25例和HBV-慢加急(或亚急)性肝衰竭(ACLF)26例分别纳入CHB组、HBV-LC组和HBV-ACLF组,健康对照(NC)组35例来自同期门诊体检健康者。采用流式细胞仪检测各组ICOS在CD8+T淋巴细胞的表达情况;分析CD8+T淋巴细胞ICOS表达水平与慢性HBV感染者疾病严重程度、HBV-ACLF预后及并发症的相关性;动态观察HBV-ACLF患者治疗过程中CD8+T淋巴细胞ICOS表达变化。结果 HBV-ACLF组外周血CD8+T淋巴细胞ICOS表达比率及平均荧光强度(MFI)均高于CHB组、HBV-LC组和NC组(P<0.05)。慢性HBV感染者ICOS的MFI与白蛋白、胆碱酯酶、总胆固醇、血红蛋白呈负相关(r=-0.263、-0.269、-0.273、-0.302,P=0.003、0.003、0.011、0.004);与直接胆红素、天冬氨酸转氨酶、凝血酶原时间、国际标准化比值呈正相关(r=0.248、0.208、0.331、0.315,P=0.005、0.020、0.003、0.009);与HBV-DNA、腹水及感染无明显相关性(P>0.05)。治疗过程中,HBV-ACLF患者ICOS的MFI无明显改变。但生存组ICOS的MFI在治疗第1周时较治疗前上升(P<0.05)。结论 HBV-ACLF患者外周血CD8+T淋巴细胞ICOS的表达水平明显升高,并与肝脏合成功能、炎症程度及预后相关,治疗早期ICOS水平变化有助于预测慢性HBV感染者的预后。 展开更多
关键词 乙型肝炎病毒 乙型肝炎 慢性 肝衰竭 肝硬化 可诱导共刺激因子 CD8+T淋巴细胞 腹水 预后
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河北省枣树枣疯病发病情况调查与防治技术研究
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作者 王希 候如月 +4 位作者 霍立勇 孟晓鑫 王晓玲 王彦立 毛永民 《河北农业科学》 2024年第1期55-59,65,共6页
枣疯病是枣树(Zizyphus jujuba Mill.)的一种毁灭性病害,发病后常常导致树体死亡,对枣产业可持续健康发展造成严重威胁。为了明确河北省枣疯病的发病情况和特点,本研究采用重点调查与田间普查相结合的方法,对河北省枣主要产区的枣树枣... 枣疯病是枣树(Zizyphus jujuba Mill.)的一种毁灭性病害,发病后常常导致树体死亡,对枣产业可持续健康发展造成严重威胁。为了明确河北省枣疯病的发病情况和特点,本研究采用重点调查与田间普查相结合的方法,对河北省枣主要产区的枣树枣疯病发病情况进行调查。本次调查涉及到7个市21个县(市),枣树种植面积占河北省枣树种植总面积的81.60%;9个枣树品种;2种地形,分别是平原区和山区(太行山区、燕山山区)。结果显示,调查的21个县(市)枣树枣疯病发病面积比例平均为2.13%,其中唐县枣树发病最重(发病面积比例最高,为12.32%),黄骅市发病最轻(发病株仅有1株);枣树品种和地形对枣疯病的发生程度影响较大,其中,婆枣发病最重(发病面积比例最高,为4.87%)、冬枣未见发病树体,山区种植的枣树发病程度(发病面积比例为3.64%,发病株率为96.88%)重于平原区种植的枣树(发病面积比例为0.17%,发病株率为3.12%)。为了探索枣疯病的防治方法,我们采用叶面喷施和树干注射2种方式施用小分子诱导剂进行枣疯病树体的治疗康复试验,结果显示,叶面喷施和树干注射小分子诱导剂均对枣疯病树体具有康复效果,树体康复有效率为50%~70%。河北省枣疯病发病情况较为普遍,发病程度与地形和枣树品种有关,小分子诱导剂有望成为治疗枣疯病的较为有效方法。 展开更多
关键词 枣疯病 小分子诱导剂
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肿瘤坏死因子α诱导蛋白8样分子1在小鼠急性肝损伤中的作用及机制
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作者 常勇生 田雪钦 +4 位作者 赵雨欣 宋苗苗 王涵 娄运伟 常廷民 《新乡医学院学报》 CAS 2024年第8期712-717,共6页
目的探讨肿瘤坏死因子α诱导蛋白8样分子1(TNFAIP8L1)在小鼠急性肝损伤中的作用及机制。方法选择C57BL/6J雄性野生型(WT)小鼠和C57BL/6J雌性TNFAIP8L1+/-小鼠杂交繁殖的第2代TNFAIP8L1+/-小鼠和WT小鼠,进一步自交繁殖出第3代雄性TNFAIP8... 目的探讨肿瘤坏死因子α诱导蛋白8样分子1(TNFAIP8L1)在小鼠急性肝损伤中的作用及机制。方法选择C57BL/6J雄性野生型(WT)小鼠和C57BL/6J雌性TNFAIP8L1+/-小鼠杂交繁殖的第2代TNFAIP8L1+/-小鼠和WT小鼠,进一步自交繁殖出第3代雄性TNFAIP8L1-/-小鼠和第3代WT雄性小鼠。分别取5只正常第3代雄性WT小鼠和5只正常第3代雄性TNFAIP8L1-/-小鼠,检测比较2种正常小鼠的血清丙氨酸氨基转移酶(ALT)水平,苏木精-伊红(HE)染色观察2种正常小鼠肝组织中炎症细胞浸润及细胞坏死情况,采用流式细胞术检测2种正常小鼠肝组织髓系细胞亚群中性粒细胞(Neu)、嗜酸性粒细胞(EOS)、树突状细胞(DC)、骨髓来源的巨噬细胞(BMDMs)、骨髓来源的单核细胞(BMNCs)所占百分比。另取5只第3代雄性WT小鼠和4只第3代雄性TNFAIP8L1-/-小鼠,采用脂多糖(LPS)/D-半乳糖胺(D-Gal)诱导制备急性肝损伤小鼠模型,24 h后采取上述方法检测比较2种急性肝损伤小鼠血清ALT水平,观察2种急性肝损伤小鼠肝组织中炎症细胞浸润及细胞坏死情况,并检测2种急性肝损伤小鼠肝组织髓系细胞亚群Neu、EOS、DC、BMDMs、BMNCs所占百分比。结果正常WT小鼠和TNFAIP8L1-/-组小鼠肝组织中髓系细胞亚群Neu、EOS、DC、BMDMs、BMNCs百分比及血清ALT水平比较差异无统计学意义(P>0.05)。正常WT小鼠和TNFAIP8L1-/-小鼠的肝组织HE染色结果均显示肝小叶结构完整清晰,肝细胞形态正常、排列整齐,无明显炎症细胞浸润及细胞坏死。急性肝损伤24 h后,TNFAIP8L1-/-小鼠肝组织髓系细胞亚群中Neu、BMNCs百分比及血清ALT水平显著高于WT小鼠(P<0.05);2组小鼠肝组织髓系细胞亚群EOS、DC、BMDMs百分比比较差异无统计学意义(P>0.05)。急性肝损伤WT小鼠肝组织中肝小叶结构模糊,肝细胞肿胀、散在空泡样脂肪变性,有少量炎症细胞浸润。急性肝损伤TNFAIP8L1-/-小鼠肝组织中肝小叶结构几乎不存在,肝细胞损伤严重且大量坏死,并有大量炎症细胞浸润。结论TNFAIP8L1基因缺陷不影响小鼠肝组织中髓系细胞的发育和小鼠肝脏稳态。TNFAIP8L1在急性肝损伤的发生发展过程中起抑制作用。TNFAIP8L1基因缺陷加重LPS/D-Gal诱导的急性肝损伤,有可能是通过增加Neu和BMNCs浸润而招募其他类型的免疫细胞浸润入肝组织,从而加重肝细胞的坏死。 展开更多
关键词 肿瘤坏死因子α诱导蛋白8样分子1 急性肝损伤 中性粒细胞 单核细胞
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冠心病患者经皮冠状动脉介入术相关造影剂急性肾损害的影响因素分析及KIM-1、NGAL、NHE3的预测价值 被引量:1
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作者 陈西 羡微微 +3 位作者 盛勇 张国民 孙生健 于翠迪 《中国现代医学杂志》 CAS 2024年第4期51-57,共7页
目的探究冠状动脉粥样硬化性心脏病(以下简称冠心病)患者经皮冠状动脉介入术(PCI)相关造影剂急性肾损害(CIAKI)的影响因素,并分析尿液中肾损伤分子-1(KIM-1)、中性粒细胞明胶酶相关脂质结合蛋白(NGAL)、钠/氢交换蛋白3(NHE3)预测CIAKI... 目的探究冠状动脉粥样硬化性心脏病(以下简称冠心病)患者经皮冠状动脉介入术(PCI)相关造影剂急性肾损害(CIAKI)的影响因素,并分析尿液中肾损伤分子-1(KIM-1)、中性粒细胞明胶酶相关脂质结合蛋白(NGAL)、钠/氢交换蛋白3(NHE3)预测CIAKI发生的价值。方法回顾性分析2021年7月—2022年6月在齐齐哈尔医学院附属第一医院行PCI的142例冠心病患者的病历资料,根据患者术后是否发生CIAKI,分为CIAKI组和非CIAKI组。分析影响PCI术后发生CIAKI的因素,评估PCI前后KIM-1差值、NGAL差值及NHE3差值对PCI术后发生CIAKI的预测价值。结果142例行PCI的冠心病患者中发生CIAKI 25例(17.61%)。CIAKI组糖尿病占比及造影剂使用剂量高于非CIAKI组(P<0.05),术前GFR水平低于非CIAKI组(P<0.05)。CIAKI组手术前后尿KIM-1、NGAL及NHE3的差值均高于非CIAKI组(P<0.05)。多因素逐步Logistic回归分析结果显示:糖尿病[OR=3.350(95%CI:1.145,9.802)]、造影剂使用剂量[OR=3.377(95%CI:1.154,9.880)]、KIM-1差值[OR=4.958(95%CI:1.695,14.506)]、NGAL差值[OR=4.446(95%CI:1.519,13.008)]、NHE3差值[OR=4.446(95%CI:1.519,3.008)]是冠心病患者PCI术后发生CIAKI的危险因素(P<0.05);GFR[OR=0.262(95%CI:0.089,0.765)]是冠心病患者PCI术后发生CIAKI的保护因素(P<0.05)。受试者工作特征曲线分析结果表明,KIM-1差值、NGAL差值、NHE3差值单一及联合预测冠心病患者PCI术后发生CIAKI的敏感性为75.32%(95%CI:0.594,0.831)、68.59%(95%CI:0.537,0.762)、62.77%(95%CI:0.514,0.735)、80.93%(95%CI:0.629,0.924),特异性为74.01%(95%CI:0.583,0.826)、83.16%(95%CI:0.652,0.941)、78.92%(95%CI:0.603,0.875)、81.15%(95%CI:0.638,0.945),曲线下面积为0.743、0.748、0.762和0.837,联合诊断效能最高。结论糖尿病、GFR、造影剂使用剂量和PCI前后KIM-1、NGAL、NHE3的变化影响CIAKI的发生,PCI前后KIM-1差值、NGAL差值及NHE3差值联合预测CIAKI的效能较好。 展开更多
关键词 冠状动脉粥样硬化性心脏病 经皮冠状动脉介入术 造影剂急性肾损害 肾损伤分子-1 中性粒细胞明胶酶相关脂质结合蛋白 钠/氢交换蛋白3
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γδT淋巴细胞及其亚型在毒性弥漫性甲状腺肿中的分布研究
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作者 王姜琳 梁冬雨 +3 位作者 汪国庆 赵江峰 汤明明 杨慧健 《检验医学与临床》 2024年第5期592-595,602,共5页
目的研究γδT淋巴细胞及其亚型在毒性弥漫性甲状腺肿(GD)中的分布并探讨γδT淋巴细胞在GD免疫学发病机制中的作用。方法选取2022年6-12月上海市嘉定区中心医院内分泌门诊确诊的GD患者59例作为GD组,另选择同期65例健康志愿者作为对照... 目的研究γδT淋巴细胞及其亚型在毒性弥漫性甲状腺肿(GD)中的分布并探讨γδT淋巴细胞在GD免疫学发病机制中的作用。方法选取2022年6-12月上海市嘉定区中心医院内分泌门诊确诊的GD患者59例作为GD组,另选择同期65例健康志愿者作为对照组。检测两组相关甲状腺指标[包括游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)、甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TG-Ab)、抗促甲状腺激素受体抗体(TRAb)],采用流式细胞术检测两组外周血中γδT淋巴细胞及其亚型的比例,分析γδT淋巴细胞表面活化分子CD69、HLA-DR及协同刺激分子CD40配体(CD40L)与诱导性共刺激分子(ICOS)的表达水平。结果GD组TSH水平低于对照组,FT3、FT4、TPOAb、TG-Ab、TRAb水平均高于对照组,差异均有统计学意义(P<0.05)。两组γδT淋巴细胞比例比较,差异无统计学意义(P>0.05);GD组Vδ1γδT淋巴细胞比例高于对照组,Vδ2γδT淋巴细胞比例低于对照组,差异均有统计学意义(P<0.05)。GD组γδT淋巴细胞表面活化分子CD69、HLA-DR表达水平及协同刺激分子CD40L、ICOS的表达水平均明显高于对照组,差异均有统计学意义(P<0.05)。结论GD患者外周血γδT淋巴细胞亚型改变表现为Vδ1γδT淋巴细胞比例上调与Vδ2γδT淋巴细胞比例下调,γδT淋巴细胞功能活化并表达协同刺激分子CD40L、ICOS可能是促进GD产生自身抗体及自身体液免疫应答的重要病理机制。 展开更多
关键词 毒性弥漫性甲状腺肿 ΓΔT淋巴细胞 表面活化分子 协同刺激分子 诱导性共刺激分子
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小分子组合诱导大鼠胚胎成纤维细胞重编程为功能性神经元
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作者 高群伟 代振佳 +2 位作者 杨新康 刘长青 刘高峰 《浙江大学学报(医学版)》 CAS CSCD 北大核心 2024年第4期498-508,共11页
目的:建立通过小分子化合物将大鼠胚胎成纤维细胞(REF)重编程为化学诱导神经元(ciNC)的方法体系,为细胞移植治疗神经退行性疾病提供安全有效的供体细胞。方法:以裴钢研究团队建立的人成纤维细胞直接重编程为神经元的方法为基础,通过更... 目的:建立通过小分子化合物将大鼠胚胎成纤维细胞(REF)重编程为化学诱导神经元(ciNC)的方法体系,为细胞移植治疗神经退行性疾病提供安全有效的供体细胞。方法:以裴钢研究团队建立的人成纤维细胞直接重编程为神经元的方法为基础,通过更换包被液、缓解氧化应激损伤、添加神经源性保护因子、调整毛喉素浓度和小分子去除实验对诱导培养基和成熟培养基进行优化,并通过免疫荧光法和蛋白质印迹法验证不同诱导阶段细胞的相关蛋白质。结果:以原方案进行诱导时,细胞存活率仅(34.24±2.77)%。包被液更换为基质胶后,细胞存活率上升到(45.41±4.27)%;添加褪黑素后细胞存活率提高至(67.95±5.61)%,(23.43±1.42)%的细胞转变为神经样细胞;添加小分子P7C3-A20后细胞存活率进一步提升至(76.27±1.41)%,(39.72±4.75)%的细胞转变为神经样细胞;毛喉素浓度提升至30μmol/L时,神经样细胞比例达到(55.79±1.90)%;去除SP600125后,(86.96±2.15)%细胞存活,神经样细胞生成率提高至(63.43±1.60)%。以优化后的方案诱导,可经过神经前体细胞将REF诱导为ciNC。其中,神经前体细胞能够高表达神经前体细胞标志物SRY-box转录因子2、配对盒6以及神经元特异性标志物Ⅲ类β-微管蛋白,而成纤维相关蛋白波形蛋白表达量减少。神经前体细胞在成熟培养基中诱导两周后,可见大部分细胞呈神经样细胞形态,诱导后的ciNC高表达Ⅲ类β-微管蛋白和微管相关蛋白2,而成纤维相关蛋白波形蛋白表达减少。结论:优化后的小分子组合在常氧条件下能将REF重编程为ciNC。 展开更多
关键词 体细胞重编程 小分子化合物 胚胎成纤维细胞 化学诱导神经元 大鼠
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CD147、ESM-1、sdLDL-C与ACI患者颈动脉斑块类别及狭窄程度的关联性
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作者 王晓燕 刘艳秋 +2 位作者 张辉 刘亚君 尹红蕾 《脑与神经疾病杂志》 CAS 2024年第6期361-366,共6页
目的 探究细胞外基质金属蛋白酶诱导因子(CD147)、内皮细胞特异性分子-1 (ESM-1)、小而密低密度脂蛋白胆固醇(sdLDL-C)与急性脑梗死(ACI)患者颈动脉斑块类别及狭窄程度的关联性。方法 选择淄博一四八医院2021年3月至2022年3月收治的80例... 目的 探究细胞外基质金属蛋白酶诱导因子(CD147)、内皮细胞特异性分子-1 (ESM-1)、小而密低密度脂蛋白胆固醇(sdLDL-C)与急性脑梗死(ACI)患者颈动脉斑块类别及狭窄程度的关联性。方法 选择淄博一四八医院2021年3月至2022年3月收治的80例ACI患者,测定患者颈动脉斑块类别及狭窄程度。比较不同颈动脉斑块类别及狭窄程度患者一般资料、血清CD147、ESM-1、sdLDL-C水平;分析血清CD147、ESM-1、sdLDL-C水平与患者颈动脉斑块类别及狭窄程度的关系;探讨患者颈动脉斑块类别及狭窄程度的影响因素。结果 80例ACI患者中存在不稳定斑块49例(61.25%),稳定斑块17例(21.25%),无斑块14例(17.50%);存在重度狭窄7例(8.75%),中度狭窄16例(20.00%),轻度狭窄30例(37.50%),无狭窄27例(33.75%)。不同颈动脉斑块类别及狭窄程度患者血清CD147、ESM-1、sdLDL-C水平比较,差异有统计学意义(P<0.001);Spearman相关性分析可知,血清CD147、ESM-1、sdLDL-C水平与患者颈动脉斑块类别及狭窄程度呈显著正相关,血清CD147、ESM-1、sdLDL-C水平越高患者颈动脉斑块越不稳定,狭窄程度越严重(P<0.001);Logistic回归分析显示,低密度脂蛋白胆固醇、血清CD147、ESM-1、sdLDL-C均为颈动脉斑块类别的影响因素(P<0.05),总胆固醇、低密度脂蛋白胆固醇、血清CD147、ESM-1、sdLDL-C均为颈动脉狭窄程度的影响因素(P<0.05)。结论 血清CD147、ESM-1、sdLDL-C水平与ACI患者颈动脉斑块类别及狭窄程度有关,可用于预测斑块类别及狭窄程度,指导临床治疗。 展开更多
关键词 细胞外基质金属蛋白酶诱导因子 内皮细胞特异性分子-1 小而密低密度脂蛋白胆固醇 急性脑梗死 颈动脉斑块类别 狭窄程度
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基于VEGF/PI3K/Akt通路基因表达探讨骨坏死康复丸对激素性股骨头坏死大鼠血管新生的影响
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作者 李文茜 田亮玉 +5 位作者 张谨 沈彩红 杨志敏 冯小艳 郭家巧 曹玉举 《广州中医药大学学报》 CAS 2024年第8期2127-2135,共9页
【目的】观察骨坏死康复丸对激素性股骨头坏死(SONFH)大鼠的治疗作用及机制。【方法】将60只大鼠随机分为空白组,模型组,仙灵骨葆胶囊组及骨坏死康复丸低、中、高剂量组,每组10只。除空白组,其他各组大鼠采用脂多糖联合糖皮质激素诱导... 【目的】观察骨坏死康复丸对激素性股骨头坏死(SONFH)大鼠的治疗作用及机制。【方法】将60只大鼠随机分为空白组,模型组,仙灵骨葆胶囊组及骨坏死康复丸低、中、高剂量组,每组10只。除空白组,其他各组大鼠采用脂多糖联合糖皮质激素诱导法建立SONFH模型。干预结束后,分别进行股骨头的血管造影观察骨髓内微血管变化、苏木素-伊红(HE)染色并计算空骨陷窝率、Micro-CT扫描分析、压缩实验,采用实时定量聚合酶链反应(RT-qPCR)法检测全血磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(Akt)1、血管内皮生长因子(VEGF)、血小板内皮细胞黏附分子1(CD31)基因表达。【结果】与空白组比较,模型组股骨头髓腔内血供差,空骨陷窝率增加(P<0.05),骨密度、骨体积分数显著降低(P<0.05),股骨头最大载荷及弹性模量降低(P<0.05),全血Akt1、PI3K、VEGF、CD31 mRNA表达水平降低(P<0.05);与模型组比较,骨坏死康复丸高剂量组和仙灵骨葆胶囊组股骨头髓腔内血供较好,空骨陷窝率减少(P<0.05),骨密度、骨体积分数、骨小梁数量、骨小梁厚度显著升高(P<0.05)及骨小梁分离度显著减小(P<0.05),股骨头最大载荷及弹性模量升高(P<0.05),全血Akt1、PI3K、VEGF、CD31 mRNA表达水平升高(P<0.05);骨坏死康复丸高剂量组上述各指标与仙灵骨葆胶囊组比较,差异均无统计学意义(P>0.05)。【结论】骨坏死康复丸可改善大鼠激素性股骨头坏死,其机制与促进VEGF/PI3K/Akt通路基因表达,进而促进血管新生有关。 展开更多
关键词 骨坏死康复丸 激素性股骨头坏死 血管新生 磷脂酰肌醇3-激酶(PI3K) 蛋白激酶B(Akt)1 血管内皮生长因子(VEGF) 血小板内皮细胞黏附分子1(CD31) 大鼠
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Change of hs-CRP,sVCAM-1,NT-proBNP levels in patients with pregnancy-induced hypertension after therapy with magnesium sulfate and nifudipine 被引量:46
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作者 Li Wang Zhi-Qiang Liu +3 位作者 Ying-Qian Huo Li-Juan Yao Xue-Gong Wei Yun-Fang Wang 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2013年第11期897-901,共5页
Objective:To investigate the change of the hs-CRP,sVC AM-1,NT-proBNP levels of the patients with pregnancy-induced hypertension(PIH) syndrome.Methods:A total of 200 patients with PIH were divided into mild,moderate an... Objective:To investigate the change of the hs-CRP,sVC AM-1,NT-proBNP levels of the patients with pregnancy-induced hypertension(PIH) syndrome.Methods:A total of 200 patients with PIH were divided into mild,moderate and severe group,and 50 healthy pregnancy patients served as the control group.The serum sVCAM-1 levels were detected by enzyme-linked immunosorbent assay,hs-CRP were detected by immunity transmission turbidity,and NT-proBNP levels were determined by the colloidal gold method.Patients were treated with magnesium sulfate and nifudipine and the contrastive analysis was performed before and after treatment.And the pathological changes in placental of PIH patients were delected by hematoxylin-eosin staining at the same time.Results:The hs-CRP,sVCAM-l,NT-proBNP levels of patients in the mild, moderate and severe PHI group were significantly higher than that in the control group(P<0.05). The hs-CKP,sVCAM-l,NT-proBNP levels in the severe group were significantly higher than the mild group and the moderate group,the difference was statistically significant(P<0.05).The hsCRP,sVCAM-l,NT-proBNP of the moderate group were significantly higher than the mild group(P<0.05).There was a positive correlation between hs-CRP,sVCAM-1,NT-proBNP expression levels and the degree of the PIH.The expression of hs-CRP,sVCAM-1,NT-proBNP levels of the moderate and the severe group were significantly decreased(P<0.05).The number of placental villi and interstitial blood vessel in the moderate and severe PIH group were significantly less than the control group(P<0.05).Conclusions:The increased levels of serum hs-CRP,sVCAM-1, NT-proBNP may be involved in the process of vascular endothelial cell injury of the PIH,and the hs-CRP,sVCAM-1,NT-proBNP can be used as the auxiliary index for diagnosis of PIH and determination of PIH severity. 展开更多
关键词 Pregnancy-induced hypertension SOLUBLE vascular cell adhesion moleculE-1 Ultra-sensitivity C-reactive protein Amino-terminal pro-brain NATRIURETIC peptide
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Expression of TGF-β1 in Placenta of the Patients with Pregnancy-induced Hypertension and Its relationship with Serum VCAM-1 被引量:4
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作者 相文佩 徐晓燕 陈汉平 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2005年第1期82-84,共3页
The expression of transforming growth factor-β1 (TGF-β1) in placental tissue of pregnancy-induced hypertension (PIH) and the relationship between the level of expression of TGF-β1 and the amount of vascular cell ad... The expression of transforming growth factor-β1 (TGF-β1) in placental tissue of pregnancy-induced hypertension (PIH) and the relationship between the level of expression of TGF-β1 and the amount of vascular cell adhesion molecule-1 (VCAM-1) in serum was studied. Immunohistochemistry ABC was used to detect the expression and distribution of TGF-β1 in placental tissues in 40 PIH women and 20 normal pregnancy women. High resolution pathological image analysis system was used to determine the quality of TGF-β1. The VCAM-1 in serum was examined by enzyme linked immunoabsorbent assay (ELISA). The results showed that TGF-β1 could be express in syncytiotrophoblast. The levels of TGF-β1 expression in placental tissues of the patients with moderate and severe PIH were significantly higher (P<0.05), while the serum VCAM-1 was significantly lower than in normal group (P<0.01). There was a significant positive correlation between the expression of TGF-β1 in placental tissues and the serum VCAM-1 (r=0.969, P<0.01). It was concluded that the level of TGF-β1 expression in PIH was increased and was positively correlated with the amount of serum VCAM-1, indicating that they might be involved in the pathogenesis of PIH. 展开更多
关键词 pregnancy-induced hypertension PLACENTA transforming growth factor-β1 cell adhesion molecule-1
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Transient Folate Deprivation in Combination with Small-molecule Compounds Facilitates the Generation of Somatic Cell-derived Pluripotent Stem Cells in Mice 被引量:1
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作者 胡文涛 闫秋月 +2 位作者 方瑜 邱占东 张苏明 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2014年第2期151-156,共6页
Induced pluripotent stem cells (iPSCs) can be propagated indefinitely, while maintaining the capacity to differentiate into all cell types in the body except for the extra-embryonic tissues. This iPSC technology not... Induced pluripotent stem cells (iPSCs) can be propagated indefinitely, while maintaining the capacity to differentiate into all cell types in the body except for the extra-embryonic tissues. This iPSC technology not only represents a new way to use individual-specific stem cells for regenerative medicine but also constitutes a novel method to obtain large numbers of disease-specific cells for biomedical re- search. However, the low efficiency of reprogramming and genomic integration of oncogenes and viral vectors limit the potential application of iPSCs. Chemical-induced reprogramming offers a novel ap- proach to generating iPSCs. In this study, a new combination of small-molecule compounds (SMs) (so- dium butyrate, A-83-01, CHIR99021, Y-27632) under conditions of transient folate deprivation was used to generate iPSC. It was found that transient folate deprivation combined with SMs was sufficient to permit reprogramming from mouse embryonic fibroblasts (MEFs) in the presence of transcription factors, Oct4 and Klf4, within 25 days, replacing Sox2 and c-Myc, and accelerated the generation of mouse iPSCs The resulting cell lines resembled mouse embryonic stem (ES) cells with respect to proliferation rate, morphology, pluripotency-associatedmarkers and gene expressions. Deprivation of folic acid, combined with treating MEFs with SMs, can improve the inducing efficiency of iPSCs and reduce their carcino- genicity and the use of exogenous reprogramming factors. 展开更多
关键词 folic acid deprivation small-molecule compounds induced pluripotent stem cells
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Suppression of Allogeneic T Cells Proliferation by CD3/CD46-Induced T-regulatory 1 Cells
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作者 陈栋 张艳 +5 位作者 李明 张弛 陈刚 陈知水 陈实 张伟杰 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2010年第3期332-336,共5页
CD46 is not only identified as a complement regulatory protein which protects host cells from complement attack,but also a new co-stimulatory molecule for human T cells.CD3/CD46 co-stimulation can induce a T-regulator... CD46 is not only identified as a complement regulatory protein which protects host cells from complement attack,but also a new co-stimulatory molecule for human T cells.CD3/CD46 co-stimulation can induce a T-regulatory 1 cell(Tr1)-specific cytokine phenotype in human CD4+ T cells.However,the role of CD46 as a co-stimulatory molecule in the modulation of the acquired immunity,such as transplant immunology,remains unclear.In this study,CD4+ T cells were isolated from human CD46-transgenic C57BL/6 mice by magnetic-activated cell sorting,and further induced by anti-CD3,anti-CD28 and anti-CD46 antibodies respectively,and anti-CD3/anti-CD28 antibodies,anti-CD3/anti-CD46 antibodies,or the monoclonal antibody panel against CD3/CD28/CD46.The levels of interleukin-2(IL-2),γ-interferon(γ-IFN),interleukin-10(IL-10) and transforming growth factor-β(TGF-β) were detected in the supernatants of different groups.Suppression of allogeneic T cell proliferation were assessed by using mixed lymphocyte reaction(MLR) assay,in which monoclonal antibodies against CD46 were added to the culture.The results showed that CD3/CD28,CD3/CD46 and CD3/CD28/CD46 co-stimulation could significantly induce stronger proliferation of T cells than CD3 stimulation(P<0.05),and CD3/CD28/CD46 co-stimulation significantly increased the proliferation of T cells when compared with CD3/CD28 or CD3/CD46 co-stimulation(P<0.05 for each).IL-2 and γ-IFN levels were much higher in CD3/CD28 co-stimulation group than in CD3,CD28,CD46 and CD3/CD46 groups(P<0.05 for each).IL-10 and TGF-β levels were dramatically increased in CD3/CD46 co-stimulation group as compared with those in the CD3,CD28,CD46 and CD3/CD28 groups(P<0.05 for each).CD3/CD46 co-stimulation significantly inhibited the T cell proliferation and allogenic immune responses through the secretion of IL-10 and TGF-β in MLR(P<0.05).These results suggested that CD3/CD46 can induce Tr1 cells to modulate allogenic immune responses,and it may become a novel target for the development of new therapeutic approach for T-cell-mediated diseases.CD46 plays an important role in regulating the T cell-mediated immune responses by bridging innate and acquired immunity. 展开更多
关键词 CD46 co-stimulatory molecule T-regulatory 1 cells allogenic immune response
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The Expression of PLF in Placenta in Pregnancy-Induced Hypertension and the Relationship between the PLF and Serum VCAM-1
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作者 徐晓燕 相文佩 陈汉平 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2003年第2期184-186,共3页
To study the expression of placental isoferritin (PLF) in placental tissue of pregnancy-induced hypertension (PIH) and the relationship between the level of expression of PLF and the amount of vascular cell adhesion m... To study the expression of placental isoferritin (PLF) in placental tissue of pregnancy-induced hypertension (PIH) and the relationship between the level of expression of PLF and the amount of vascular cell adhesion molecule-1 (VCAM-1) in serum, immunohistochemical technique was used to detect the expression of PLF in placenta tissue in 45 PIH patients (PIH group) and 15 normal pregnant women (normal group). High resolution pathological image analysis system (HPIAS-100) was employed to determine the quantity of PLF. The VCAM-1 in serum was examined by enzyme linked immunoabsorbent assay (ELISA). The results showed that the levels of PLF expressions in moderate and severe PIH patients were significantly lower than that of normal group (P<0. 01). The serum VCAM-1 was significantly decreased in PIH group (1310±177 ρ/ng/ml) than that of normal group (609±72 ρ/ng/ml, P<0. 01). The significant negative correlation existed between the expression of PLF in placental tissue and the serum VACM-1 (r=-0. 58, P<0. 01). It was concluded that the level of PLF expression in PIH decreases and is negatively correlated with the amount of serum VCAM-1, indicating that these may be involved in the pathogenesis of PIH. 展开更多
关键词 pregnancy-induced hypertension PLACENTA FERRITIN cell adhesion molecules
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Studies on Ion-molecule Reaction of Disubstituted Benzene with Ion System of Acetyl Chloride in Gas Phase
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作者 LI Zhi-li (Shandong Non-metallic Material Research Institute, Jinan 250031, P. R. China) 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2000年第4期334-340,共7页
The ion-molecule reactions of disubstituted benzenes with the ion system of acetyl chloride under the chemical ionization condition were examined and the fragmentation reactions of the adduct ions formed by the ion-mo... The ion-molecule reactions of disubstituted benzenes with the ion system of acetyl chloride under the chemical ionization condition were examined and the fragmentation reactions of the adduct ions formed by the ion-molecule reactions were studied by using collision-induced dissociation technique. It was found that the electron-releasing groups favored the adduct reactions and the electron-withdrawing groups did not. The position and properties of substituting groups had an effect on the relative abundance of the adduct ions. The fragmentation reaction of the adduct ions formed by ortho-benzene diamine with the acetyl ion was similar to the reductive alkylation reaction of amine in condensed phase. 展开更多
关键词 Disubstituted benzene Ion-molecule reaction Collision-induced dissociation technique ADDUCTION
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