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《Vaccine》2019,37(31):4382-4391
Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8+ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα+ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice. 相似文献
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《Nutrition Clinique et Métabolisme》2016,30(1):83-87
Chylous ascitis is a rare cause of ascitis. Most of the time, it results of retroperitoneal lymph node or duct dissection during abdominal or urological surgery; it is rarely due to lymphatic obstruction (neoplasia). Nutritional damage is major and severely impairs prognosis. Malnutrition is due to the necessity to avoid fatty acid in meal to reduce chylous leakage. Diagnosis is based on patient's clinical history and cytologic and biochemical ascitis analyses. Treatment combines the correction of nutritional status and therapy of the causative disease. Oral diet or enteral nutrition with low content of long chain triglyceride, thus enriched in medium chain triglyceride, is the major therapeutic option of chylous ascitis. 相似文献
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朱晓东 《中国小儿急救医学》2020,(4):268-271
电阻抗断层成像技术(electrical impedance tomography,EIT)作为一项新兴的功能性成像技术,具有无损伤、便携、图像监护等突出特点。肺功能成像是目前EIT最主要的应用领域,可以实现实时动态监测肺通气及血流灌注。本文对肺EIT在儿童呼吸系统疾病及其诊疗过程中的应用基础及临床研究进展进行总结,为未来EIT技术在儿科临床急救领域的推广应用提供帮助。 相似文献
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Although hepatitis E virus (HEV) is the primary cause of enterically transmitted acute hepatitis and jaundice in developing countries, locally acquired HEV infections are increasing in nonendemic countries. As such, HEV is emerging as an underdiagnosed cause of infection. This report describes three clinically variable cases of HEV infection with unusual clinical presentations. These cases highlight the fact that HEV should be considered in the differential diagnosis of patients with unexplained hepatitis (acute or chronic) with or without extrahepatic manifestations. HEV should also be considered in patients with persistently elevated liver enzymes who have not travelled to known HEV-endemic regions. Lack of knowledge among physicians and an absence of standardized diagnostic tests may result in increased morbidity and mortality from HEV infection. 相似文献
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《Vaccine》2016,34(24):2663-2670
Human metapneumovirus (HMPV) is a major cause of morbidity and mortality from acute lower respiratory tract illness, with most individuals seropositive by age five. Despite the presence of neutralizing antibodies, secondary infections are common and can be severe in young, elderly, and immunocompromised persons. Preclinical vaccine studies for HMPV have suggested a need for a balanced antibody and T cell immune response to enhance protection and avoid lung immunopathology. We infected transgenic mice expressing human HLA-A*0201 with HMPV and used ELISPOT to screen overlapping and predicted epitope peptides. We identified six novel HLA-A2 restricted CD8+ T cell (TCD8) epitopes, with M39–47 (M39) immunodominant. Tetramer staining detected M39-specific TCD8 in lungs and spleen of HMPV-immune mice. Immunization with adjuvant-formulated M39 peptide reduced lung virus titers upon challenge. Finally, we show that TCD8 from HLA-A*0201 positive humans recognize M39 by IFNγ ELISPOT and tetramer staining. These results will facilitate HMPV vaccine development and human studies. 相似文献
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《Sleep medicine》2020
Study objectivesTo analyze the association between sleep-related symptoms and sleep length in parents and their children in relation to other risk factors in both generations.MethodThe participants were parents (n = 5,855, age 54.3 ± 6.5 years, 45.2% men) who participated in the community-based Respiratory Health in Northern Europe (RHINE) study and one random member of their adult offspring (n = 5,855, age 30.2 ± 7.7 years, 41.5% men) who participated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) study. Both generations responded to identical questionnaires on sleep symptoms, including difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), early morning awakening (EMA), snoring, nocturnal sweating, nocturnal gastroesophageal reflux (nGER), sleep time and excessive daytime sleepiness (EDS). Insomnia was defined as either, or both, DIS and DMS in combination with EDS.ResultsAll sleep variables except nocturnal sweating were more common in offspring whose parents had reported the same symptom. After adjusting for age, gender, BMI, smoking, physical activity, education, center and parents' total number of children, there were independent associations between sleep symptoms in parents and offspring for DIS (adj. OR, 95% CI: 1.52, 1.20–1.93), DMS (1.34, 1.15–1.56), snoring (1.45, 1.15,1.83), nGER (1.65, 1.15–2.37), insomnia (1.39, 1.13–1.73), short sleep time (<6 h/night) (2.51, 1.72–3.68) and EDS (1.48, 1.26,1.72). There were no independent relationships between symptoms in parents and offspring for EMA, nocturnal sweating or long sleep time (>9 h/night).ConclusionThe familiar aggregation of many sleep disturbances was not explained by investigated lifestyle and environmental factors. This supports a heritable factor in sleep problems. 相似文献
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