Midterm Outcomes of the Dissected Aorta Repair Through Stent Implantation Trial

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Plasma matrix metalloproteinase 7, CC-chemokine ligand 18, and periostin as markers for pulmonary sarcoidosis

BackgroundSome patients with sarcoidosis experience worsening of pulmonary lesions. However, no biomarker has been identified that reflects pulmonary disease status in sarcoidosis. We investigated the usefulness of potential markers of pulmonary fibrosis in patients with sarcoidosis.MethodsPlasma matrix metalloproteinase 7 (MMP-7), CC-chemokine ligand 18 (CCL-18), and periostin levels were evaluated in 60 patients with sarcoidosis and 30 healthy controls; bronchoalveolar lavage fluid levels were analyzed in 22 patients with sarcoidosis. To determine the usefulness of these markers, we explored potential correlations between these markers and sarcoidosis clinical characteristics.ResultsPlasma MMP-7, CCL-18, and periostin concentrations were significantly higher in patients with sarcoidosis than those in healthy controls. MMP-7 concentrations in plasma and bronchoalveolar lavage fluid were higher in patients with sarcoidosis with parenchymal infiltration than in those without lung lesions. Moreover, MMP-7 concentration was negatively correlated with pulmonary function.ConclusionAmong these novel biomarkers, MMP-7 most precisely reflected pulmonary sarcoidosis disease status and thus, might be useful for diagnosing and evaluating sarcoidosis, particularly in patients with pulmonary parenchymal lesions.     

PROP test: prediction of caries risk by genetic taste perception among the visually impaired children

The study sample consisted of 100 children with visual impairment aged 6–14 years. 6‐n‐propylthiouracil (PROP) sensitivity test was carried out. The Caries experience was recorded, estimation of Streptococcus mutans done and their taste likes and dislikes assessed through a food preference questionnaire. The Caries experience and S. mutans levels were highest in the non‐tasters, comparatively low in medium tasters and the least in the supertasters. Dietary preferences indicated tasters were sweet dislikers and non‐tasters, sweet likers. PROP test can be a useful tool in determining genetic taste sensitivity levels amongst the visually impaired children and thus used as a screening tool in those children who are at a high risk of developing dental caries.     

白细胞介素-6对初次膝关节置换术后早期假体周围感染筛查作用研究

目的探讨白细胞介素-6(IL-6)对膝关节置换术后早期假体周围感染的诊断价值。方法选取2014年12月至2016年1月在沈阳军区总医院行初次膝关节置换的患者44例,对其术前及术后3、6、9 d血液中IL-6、血沉(ESR)、C-反应蛋白(CRP)的检测结果进行分析。结果所有患者术后IL-6值快速回落,但直至术后第9天,IL-6值也未回落到正常范围内。本研究患者术后3、6、9 d的血清IL-6、CRP回落曲线具有相关性,IL-6值的回落曲线更迅速,而ESR值回落曲线变化幅度较小。结论 IL-6可作为筛查膝关节置换术后早期假体周围感染的敏感指标,动态监测患者术后IL-6值回落曲线,能够提高膝关节置换术后早期假体周围感染的诊断率。     

Understanding the immune landscape in atopic dermatitis: The era of biologics and emerging therapeutic approaches

Atopic dermatitis (AD) is a chronic, systemic, inflammatory disease that affects the skin and is characterized by persistent itch and marked redness. AD is associated with an increased risk of skin infections and a reduced quality of life. Most AD treatment options to date were not designed to selectively target disease‐causing pathways that have been established for this indication. Topical therapies have limited efficacy in moderate‐to‐severe disease, and systemic agents such as corticosteroids and immunosuppressants present with tolerability issues. Advances in the understanding of AD pathobiology have made possible a new generation of more disease‐specific AD therapies. AD is characterized by the inappropriate activation of type 2 T helper (Th2) cells and type 2 innate lymphoid (ILC2) cells, with a predominant increase in type 2 cytokines in the skin, including interleukin (IL)‐13 and IL‐4. Both cytokines are implicated in tissue inflammation and epidermal barrier dysfunction, and monoclonal antibodies targeting each of these interleukins or their receptors are in clinical development in AD. In March 2017, dupilumab, a human anti–IL‐4Rα antibody, became the first biologic to receive approval in the United States for the treatment of moderate‐to‐severe AD. The anti–IL‐13 monoclonal antibodies lebrikizumab and tralokinumab, which bind different IL‐13 epitopes with potentially different effects, are currently in advanced‐stage trials. Here, we briefly review the underlying pathobiology of AD, the scientific basis for current AD targets, and summarize current clinical studies of these agents, including new research to develop both predictive and response biomarkers to further advance AD therapy in the era of precision medicine.     

Poly(I:C) source,molecular weight and endotoxin contamination affect dam and prenatal outcomes,implications for models of maternal immune activation

The viral mimetic polyinosinic:polycytidylic acid (poly(I:C)) is increasingly used to induce maternal immune activation (mIA) to model neurodevelopmental disorders (NDDs). Robust and reproducible phenotypes across studies are essential for the generation of models that will enhance our understanding of NDDs and enable the development of improved therapeutic strategies. However, differences in mIA-induced phenotypes using poly(I:C) have been widely observed, and this has prompted the reporting of useful and much needed methodological guidelines. Here, we perform a detailed investigation of molecular weight and endotoxin variations in poly(I:C) procured from two of the most commonly used suppliers, Sigma and InvivoGen. We demonstrate that endotoxin contamination and molecular weight differences in poly(I:C) composition lead to considerable variability in maternal IL-6 response in rats treated on gestational day (GD)15 and impact on fetal outcomes. Specifically, both endotoxin contamination and molecular weight predicted reductions in litter size on GD21. Further, molecular weight predicted a reduction in placental weight at GD21. While fetal body weight at GD21 was not affected by poly(I:C) treatment, male fetal brain weight was significantly reduced by poly(I:C), dependent on supplier. Our data are in agreement with recent reports of the importance of poly(I:C) molecular weight, and extend this work to demonstrate a key role of endotoxin on relevant phenotypic outcomes. We recommend that the source and batch numbers of poly(I:C) used should always be stated and that molecular weight variability and endotoxin contamination should be minimised for more robust mIA modelling.     

Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) rs10845498 Polymorphism Is Associated with a Decreased Risk of Non-Small Cell Lung Cancer

Objectives: Low-density lipoprotein receptor-related protein 6 (LRP6) modulates Wnt signaling transduction. Altered LRP6 expression leads to abnormal Wnt protein activation, cell proliferation and tumorigenesis. This study investigated the association between LRP6 single-nucleotide polymorphisms (SNPs) and non-small-cell lung cancer (NSCLC) in a Chinese population. Methods: A total of 500 NSCLC patients and 500 healthy controls were recruited for assessment of four LRP6 SNPs using the SEQUENOM MassARRAY matrix-assisted laser desorption ionization-time of flight mass spectrometry. The association between genotype and NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) with multivariate unconditional logistic regression analyses. Results: The frequency of the LRP6 rs10845498 genotype was 60.9% (A/A), 35.5% (AG) and 3.6% (GG) in patients with lung squamous cell carcinoma (SCC) and 69.2% (A/A), 27.2% (A/G) and 3.6% (GG) in controls. Logistic regression analysis revealed that the LRP6 rs10845498 A/A major allele was associated with a reduced risk in developing lung SCC (OR = 0.69; 95% CI, 0.48-1.00; P=0.04), and tobacco smokers had a 2.21 fold greater risk in developing SCC than nonsmokers (p<0.01, 95% CI, 1.72-2.85), and tobacco smokers who carried an “A” allele (AA+AG) in rs6488507 had a 2.34-fold greater risk in developing NSCLC than other patients (p< 0.01, 95%CI, 1.74-3.13). Conclusions: The LRP6 rs10845498 SNP is associated with a reduced risk of lung SCC, while tobacco smoke increases the risk. LRP6 rs6488507 polymorphism synergistically increased the risk of NSCLC in tobacco smokers. Further studies are needed to elucidate the functional impact of LRP6 expression and activity in NSCLC.