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《Vaccine》2022,40(6):934-944
Respiratory Syncytial Virus (RSV) remains a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously described the derivation of an RSV Fusion protein (F) stabilized in its prefusion conformation (preF) as vaccine immunogen and demonstrated superior immunogenicity in naive mice of preF versus wild type RSV F protein, both as protein and when expressed from an Ad26 vaccine vector. Here we address the question if there are qualitative differences between the two vaccine platforms for induction of protective immunity. In naïve mice, both Ad26.RSV.preF and preF protein induced humoral responses, whereas cellular responses were only elicited by Ad26.RSV.preF. In RSV pre-exposed mice, a single dose of either vaccine induced cellular responses and strong humoral responses. Ad26-induced RSV-specific cellular immune responses were detected systemically and locally in the lungs. Both vaccines showed protective efficacy in the cotton rat model, but Ad26.RSV.preF conferred protection at lower virus neutralizing titers in comparison to RSV preF protein. Factors that may contribute to the protective capacity of Ad26.RSV.preF elicited immunity are the induced IgG2a antibodies that are able to engage Fcγ receptors mediating Antibody Dependent Cellular Cytotoxicity (ADCC), and the induction of systemic and lung resident RSV specific CD8 + T cells. These data demonstrate qualitative improvement of immune responses elicited by an adenoviral vector based vaccine encoding the RSV preF antigen compared to the subunit vaccine in small animal models which may inform RSV vaccine development. 相似文献
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目的:探讨血清糖类抗原125(carbohydrate antigen 125,CA125)、人附睾蛋白4(human epididymis protein 4,HE4)、中性粒细胞与淋巴细胞比值(neutrophil-lymphocyte ratio,NLR)联合检测在子宫内膜癌诊断中的作用。方法:选取42例子宫内膜癌患者、50例子宫内膜良性疾病患者和50例健康体检人群。采用SYSMEX XN550全自动血液分析仪计数术前外周血中性粒细胞和淋巴细胞,计算NLR;采用Maglumi4000全自动化学发光仪检测术前血清CA125、HE4水平。采用ROC曲线分析CA125、HE4、NLR和三者联合指标在诊断子宫内膜癌中的作用。结果:外周血NLR在健康组、良性组和子宫内膜癌组中逐渐增高,且差异有统计学意义(P<0.05);子宫内膜癌组HE4表达量显著高于良性组与健康组(P<0.05),而良性组与健康组之间差异无统计学意义(P>0.05);CA125表达量在三组中差异无统计学意义(P>0.05)。CA125、HE4、NLR及三者联合标记物的AUC分别为0.530、0.733、0.795、0.823,当分别取它们的临界值时,特异性分别为70.8%、85.1%、61.7%、83.0%,敏感性分别为40.0%、63.3%、86.7%、73.3%。单项指标NLR的敏感性最高,HE4的特异性最高,联合指标的特异性和敏感性都很高。结论:术前血清CA125、HE4和NLR联合检测具有较高的特异性和敏感性,联合检测可以互为补充,提高子宫内膜癌的诊断准确率,对子宫内膜癌的诊断具有指导意义。 相似文献
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目的探讨程序性死亡受体1(PD-1)和程序性死亡受体配体1(PD-L1)在非小细胞肺癌(NSCLC)组织中的表达情况及临床意义。方法选择150例NSCLC患者的NSCLC组织及其癌旁组织,采用实时荧光定量聚合酶链反应(PCR)检测两种组织中PD-1 mRNA和PD-L1 mRNA的相对表达量。采用免疫组织化学染色法检测NSCLC组织中PD-1和PD-L1的表达情况,分析PD-1和PD-L1表达情况与患者临床特征的关系。采用流式细胞术检测NSCLC组织和癌旁组织中CD4^+-PD-1、CD8^+-PD-1、CD14^+-PD-L1、CD68^+-PD-L1的表达水平。结果NSCLC组织中PD-1 mRNA和PD-L1 mRNA的相对表达量分别为(5.03±1.92)和(4.95±1.09),分别高于癌旁组织的(1.72±0.81)和(1.25±0.24),差异均有统计学意义(P﹤0.05)。TNM分期为Ⅲ~Ⅳ期、低分化、有淋巴结转移、有远处转移的NSCLC患者NSCLC组织中PD-1和PD-L1的高表达率均明显高于TNM分期为Ⅰ~Ⅱ期、高+中分化、无淋巴结转移、无远处转移的患者,差异均有统计学意义(P﹤0.01)。NSCLC组织中CD4^+-PD-1、CD8^+-PD-1、CD14^+-PD-L1、CD68^+-PD-L1的表达水平均明显高于癌旁组织,差异均有统计学意义(P﹤0.01)。结论PD-1和PD-L1在NSCLC组织中高表达,可能成为一种新的生物标志物,PD-1/PD-L1信号通路可能参与了NSCLC的免疫逃逸过程,对其逃逸机制进行研究可以为NSCLC患者的临床治疗提供新靶点。 相似文献
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Therapeutic efficacy of intense pulsed light in patients with refractory meibomian gland dysfunction
Purpose
To evaluate the efficacy and safety of intense pulsed light (IPL) combined with meibomian gland expression (MGX) for treatment of refractory meibomian gland dysfunction (MGD).Methods
Ninety eyes of 45 patients were randomly assigned to receive either the combination of IPL and MGX or MGX alone (control). Each eye underwent eight treatment sessions at 3-week intervals. Parameters were evaluated before and during treatment as well as at 3–11 weeks after the last treatment session. Measured parameters included the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire score, noninvasive breakup time (NIBUT), fluorescein breakup time (BUT), lipid layer grade, lipid layer thickness (LLT), lid margin abnormalities, corneal and conjunctival fluorescein staining (CFS) score, meibum grade, and meiboscore.Results
A significant improvement in lipid layer grade was apparent in the IPL-MGX group from 6 to 32 weeks after treatment onset (adjusted P?<?0.001) but was not observed in the control group. The IPL-MGX group also showed significant improvements in LLT, NIBUT, BUT, lid margin abnormalities, and meibum grade compared with the control group at 24 and 32 weeks (adjusted P?<?0.001) as well as significant improvements in the SPEED score at 32 weeks (adjusted P?=?0.044) and in CFS score at 24 (adjusted P?=?0.015) and 32 (adjusted P?=?0.006) weeks.Conclusions
The combination of IPL and MGX improved homeostasis of the tear film and ameliorated ocular symptoms in patients with refractory MGD and is thus a promising modality for treatment of this condition. 相似文献6.
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Béla Nagy Zsolt Bene Zsolt Fejes Sonya L. Heltshe David Reid Nicola J. Ronan Yvonne McCarthy Daniel Smith Attila Nagy Elizabeth Joseloff György Balla János Kappelmayer Milan Macek Scott C. Bell Barry J. Plant Margarida D. Amaral István Balogh 《Journal of cystic fibrosis》2019,18(2):271-277
Background
We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.Methods
In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6?months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI).Results
After 1?month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6?months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r?=??0.5376; P?<?.001 and r?=??0.3285; P?<?.001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β?=??0.57, P?=?.019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581–0.863]; P?=?.029) were used as classifier, especially in the first 2?months of treatment (0.806 [95% CI 0.665–0.947]; P?<?.001).Conclusions
This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy. 相似文献8.
《European journal of surgical oncology》2020,46(6):1080-1087
IntroductionRecent reports on gene expression profiling (GEP) show several genes associated with malignant progression of GIST. However, genes associated with malignant transformation have not been clarified. Here, we aimed to reveal distinct genes in aggressive malignant GIST, using comprehensive gene expression analysis.Materials and methodsWe investigated GEP obtained by microarrays for 43 gastric GISTs, which mostly harbored KIT and PDGFRA mutations and integrated clinicopathological risk information. RT-PCR and immunohistochemistry were performed for FZD7, a receptor of Wnt ligands.ResultsGEP divided 43 gastric GISTs into two clusters. A cluster included seven of eight high-risk GISTs (88%) in modified NIH classification and was defined as high-risk cluster; the other cluster was defined as low-risk cluster. The number of probes with over 3-fold changes between the two clusters was 1,177, in which probes corresponding to 16 oncogenes were included. Genes involved in the Wnt signaling pathway were the most abundant among the 16 oncogenes. Focusing on 73 Wnt signaling pathway genes of the 21,578 probes, 12 upregulated and 5 downregulated genes were found in the high-risk cluster. Major cascade genes promoting the Wnt/β-catenin signaling pathway, including WNT11, FZD family, and DVL2, were upregulated in the high-risk cluster. SNAI1, SNAI2, and BIRC5, which are activated by this pathway and increase cell proliferation, were also upregulated. These gene expression alterations were consistent in the positive direction of this pathway. GISTs in high-risk cluster strongly expressed FZD7.ConclusionWnt/β-catenin signaling pathway may play an important role in malignant transformation of indolent GIST. 相似文献
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目的: 探讨人胃癌组织中乙酰肝素酶(HPA)、上皮标志物E-cadherin、间质标志物N-cadherin和vimentin蛋白的表达及其与人胃癌临床病理指标的关系,以及HPA与E-cadherin、N-cadherin、vimentin蛋白之间的关系。方法: 应用免疫组织化学方法检测91例人胃癌组织中HPA、E-cadherin、N-cadherin和vimentin蛋白表达情况;采用卡方检验,检测这几种蛋白阳性表达率与人胃癌不同病理指标的关系;同时采用Spearman等级相关分析HPA与E-cadherin、N-cadherin、vimentin蛋白之间的关系。结果: 人胃癌组织中HPA、E-cadherin、N-cadherin和vimentin蛋白阳性表达率为75.82%、51.65%、54.95%和23.08%。91例人胃癌组织中HPA、E-cadherin、N-cadherin和vimentin蛋白的阳性表达率与胃癌患者年龄、性别、胃癌大小均无明显相关(P > 0.05),而与人胃癌发生部位、分化程度和有无淋巴结转移、侵袭程度有关(P < 0.05)。HPA、N-cadherin和vimentin蛋白在贲门部阳性表达率明显高于胃体、幽门及胃窦胃癌;低分化者、有淋巴结转移者和胃癌侵袭深处这3种蛋白阳性表达率明显高于高分化者、无淋巴结转移者和胃癌起始部位;E-cadherin蛋白在幽门及胃窦部胃癌阳性表达率明显高于贲门和胃体胃癌;高中分化者、无淋巴结转移者明显高于低分化者和有淋巴结转移者。E-cadherin蛋白阳性表达率在侵袭深处明显低于起始部位。经Spearman等级相关分析显示,人胃癌组织中HPA与E-cadherin蛋白的阳性表达率呈负相关(r=-0.341,P < 0.05);而与N-cadherin(r=0.366,P < 0.05)和vimentin(r=0.284,P < 0.05)蛋白阳性表达率呈正相关。结论: 人胃癌组织中HPA、N-cadherin和vimentin蛋白在低分化者、有淋巴结转移者和胃癌侵袭深处高表达;E-cadherin蛋白在高中分化胃癌,无淋巴结转移者和起始部位高表达。HPA与N-cadherin、vimentin蛋白阳性表达率呈正相关,HPA与E-cadherin蛋白的阳性表达率呈负相关,可见HPA蛋白与间质标志物N-cadherin和vimentin蛋白表达增强有关,而与上皮标志物E-cadherin蛋白缺失或减少有关,因此HPA可能诱导人胃癌组织发生上皮间质转化。 相似文献
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