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1.
《Vaccine》2022,40(42):6048-6054
BackgroundLive vaccines potentially have non-specific effects that protect against other infections than those the vaccines are targeted against. The national vaccination program (NVP) in Finland was changed on September 1st, 2006: before BCG vaccine was given to all newborn babies and afterwards to babies in risk groups only. We used this natural experiment to study the non-specific effects of BCG in the frame of NVP using before-after design.MethodsWe compared the incidence of several outcomes obtained from Finnish health registers between children born between July 1st, 2004, and June 30th, 2006 (BCG-eligible) and an age- and season-matched reference cohort born between July 1st, 2007, and June 30th, 2009 (BCG-non-eligible) using Poisson regression. These cohorts were restricted to full-term children whose parents were born in Finland. Follow-up began at birth and lasted 3 months, which is the scheduled age for DTaP-IPV-Hib vaccination, and from 4 months until first birthday. The outcomes included all infections, pneumonia and injuries as a negative control outcome.ResultsThe incidence rate ratio (IRR) of the BCG-eligible cohort (N = 93,658) compared to BCG-non-eligible cohort (N = 94,712) for hospital-diagnosed infections was 0.89 (95 %Cl 0.86–0.93) for the 3-month follow-up. The decrease was mainly caused by respiratory infections. In 4–12 months follow-up the BCG-eligible had slightly more infections than BCG-non-eligible children (IRR 1.03, 1.01–1.06).ConclusionsBCG vaccination was associated with a lower incidence of all hospital-diagnosed infections during the first three months of life. The difference cannot be attributed to lung tuberculosis, since only few paediatric cases occurred in Finland during 2000s. The disappearance of non-specific effect after administration of an inactivated vaccine is compatible with previous studies.  相似文献   
2.

Background

Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.

Methods

Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.

Results

Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).

Conclusions

Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF.  相似文献   
3.

Background

Acute myocardial infarction (AMI) causes irreversible myocardial damage and release of inflammatory mediators, including cytokines, chemokines and miRNAs. We aimed to investigate changes in the levels of cytokines (IL-6, TNF-α and IL-10), miRNAs profiles (miR-146 and miR-155) and distribution of different monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) in the acute and post-healing phases of AMI.

Methods

In eighteen consecutive AMI patients (mean age 56.78?±?12.4 years, mean left ventricle ejection fraction – LVEF: 41.9?±?9.8%), treated invasively, monocyte subsets frequencies were evaluated (flow cytometry), cytokine concentrations were analyzed (ELISA) as well as plasma miRNAs were isolated twice – on admission and after 19.2?±?5.9 weeks of follow-up. Measurements were also performed among healthy volunteers.

Results

AMI patients presented significantly decreased frequencies of classical cells in comparison to healthy controls (median 71.22% [IQR: 64.4–79.04] vs. 84.35% [IQR: 81.2–86.7], p?=?0.001) and higher percent of both intermediate and non-classical cells, yet without statistical significance (median 6.54% [IQR: 5.14–16.64] vs. 5.87% [IQR: 4.48–8.6], p?=?0.37 and median 5.99% [IQR: 3.39–11.5] vs. 5.26% [IQR: 3.62–6.2], p?=?0.42, respectively). In AMI patients both, analyzed plasma miRNA concentrations were higher than in healthy subjects (miR-146: median 5.48 [IQR: 2.4–11.27] vs. 1.84 [IQR: 0.87–2.53], p?=?0.003; miR-155: median 25.35 [IQR: 8.17–43.15] vs. 8.4 [IQR: 0.08–16.9], p?=?0.027, respectively), and returned back to the values found in the control group in follow-up. miR-155/miR-146 ratio correlated with the frequencies of classical monocytes (r=0.6, p?=?0.01) and miR-155 correlated positively with the concentration of inflammatory cytokines ? IL-6 and TNF-α.

Conclusions

These results may suggest cooperation of both pro-inflammatory and anti-inflammatory signals in AMI in order to promote appropriate healing of the infarcted myocardium.  相似文献   
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Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system (ADDS) for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. Uptake of BGs loaded with Doxorubicin (Dox) by CaCo2 cells led to effective Dox release from endo-lysosomal compartments and accumulation in the nucleus. Viability and proliferative capacity of the cells were significantly decreased (2–3 orders of magnitude) after internalization of Dox loaded BGs as compared to cells incubated with free Dox. The same effect was observed with leukemia cells. Melanoma cells also revealed a high capability to internalize BGs. These results indicate that BGs are able to target a range of types of cancer. BGs have also been investigated as DNA delivery vectors. Studies show DNA loaded BGs are efficiently phagocytosed and internalized by both professional APCs and tumor cells with up to 82% of cells expressing the plasmid-encoded reporter gene. Our studies with BGs as an ADDS system contribute (i) to optimize drug delivery for the treatment of cancer; (ii) define specific conditions for selection and preparation of BG formulations; (iii) and provide a background for the clinical application of BGs in cancer therapy.  相似文献   
7.
目的:探讨柴苓小方对大鼠肾小球系膜细胞(GMCs)异常增殖的影响及相关机制。方法:采用脂多糖刺激系膜细胞异常增殖。MTT法检测柴苓小方对㈣异常增殖的影响;免疫细胞化学方法检测药物作用后增殖细胞核抗原(PCNA)的表达;乳酸脱氢酶释放实验检测柴苓小方的细胞毒作用。采用RT—PCR检测药物作用不同时间点细胞周期蛋白依赖性激酶抑制剂p21的表达。结果:柴苓小方可以剂量依赖性的抑制系膜细胞异常增殖并显著减少PCNA阳性细胞数而没有明显的细胞毒作用。并且柴苓小方可以显著地上调p21基因的表达(P〈0.05)。结论:柴苓小方可剂量依赖性的抑制GMC8异常增殖.其机制可能与上调p21mRNA表达有关。  相似文献   
8.
对石家市结核病的流行情况进行了随机抽样调查,共抽取24个调查点(市区8个、郊县16个)35745人。调查结果:平均患病率及菌阳患病率为0.63%和1.27%,其中郊县与市区分别为0.67%和0.54%及1.60‰和0.42‰(Ρ<0.01);15岁以下儿童有卡痕者,其结素反应阳性率年龄曲线,在7岁和12岁表现为低谷;1~3岁卡痕检出率,市区与郊县分别为90.5%与35.4%(Ρ<0.01)。通过本调查表明,我市结核病患病率高于全国1985年调查的平均数值。  相似文献   
9.
卡介苗激活杀伤细胞抗膀胱肿瘤作用研究   总被引:1,自引:0,他引:1  
为了进一步探讨BCG抗膀胱肿瘤的作用机理,采取15例膀胱肿瘤患者外周血单个核细胞(PBMC),置于含BCG或IL2的培养基中培养,计算扩增倍数,检测培养细胞抗自体及异体膀胱癌细胞活性。结果:卡介苗激活杀伤细胞(BAK)与淋巴因子激活杀伤细胞(LAK)分别于培养第7和第3天达增殖高峰,对自体瘤杀伤率分别为36.2%和31.4%,差异有显著性(P<0.05);对异体瘤杀伤率分别为25.2%和28.3%,差异无显著性。结果表明:BAK细胞抗自体瘤活性高于LAK细胞,死BCG对PBMC无激活作用,BAK细胞抗肿瘤效应可能是BCG抗膀胱肿瘤重要作用机理之一。  相似文献   
10.
目的分析评价汕头地区新生儿卡介苗接种工作质量;方法对2001-2004年我市四家大医院新生儿卡介苗接种工作记录和质量监控结果记录进行统计,汇总分析。结果2001-2004年,汕头市新生儿卡介苗接种率保持在94.69%以上,12周结素试验阳转率稳定在90.96%以上,卡痕率在97%以上,结素试验平均反应直径、卡痕平均直径指标均比较稳定。结论汕头市区卡介苗接种质量较高。  相似文献   
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