Novel immune signatures associated with dysplastic naevi and primary cutaneous melanoma in human skin

Dysplastic naevi (DN) are benign lesions with atypical features intermediate between that of common melanocytic naevi (CMN) and malignant melanoma (MM). Debate remains over whether DN represent progressive lesions from CMN. Through gene expression profiling and analysis of molecular gene signatures, our study revealed progressive increases in immune activation and regulation, along with pathways implicated in melanomagenesis, from CMN to DN to MM. Using criteria of 1.5‐fold change and false discovery rate ≤0.05, we found differential expression of 7186 probes (6370 unique genes) with the largest difference detected between DN and MM from the standpoint of genomic melanoma progression. Despite progressive increases in the T‐helper type 1 (Th1)‐inducing gene (IL‐12), RT‐PCR indicated impaired Th1 or cytotoxic T‐cell response (decreased IFN‐γ) in MM. Concordantly, our results indicated progressive increases in molecular markers associated with regulatory T cells, exhausted T cells and tolerogenic dendritic cells, including detection of increased expression of suppressor of cytokine signalling 3 (SOCS3) in dendritic cells associated with MM. All together, our findings suggest that the increased immunosuppressive microenvironment of melanoma may contribute to unhampered proliferation of neoplastic cells. In addition, the detection of increased markers associated with tolerogenic dendritic cells in MM suggests that targeting these suppressive immune cell types may represent an alternative avenue for future immunotherapy.     

Why We Need Continuous Pharmaceutical Manufacturing and How to Make It Happen

We make the case for why continuous pharmaceutical manufacturing is essential, what the barriers are, and how to overcome them. To overcome them, government action is needed in terms of tax incentives or regulatory incentives that affect time.     

Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

Long-term follow-up of camouflage effects following resin infiltration of post orthodontic white-spot lesions in vivo

Objectives:To reassess the long-term camouflage effects of resin infiltration (Icon, DMG, Hamburg, Germany) of white spot lesions (WSL) and sound adjacent enamel (SAE) achieved in a previous trial. The null hypothesis was tested that there were no significantly different CIE-L*a*b*-ΔE-values between WSL and SAE areas of assessment after at least 24 months (T24) compared to those at baseline (T0).Materials and Methods:Of twenty subjects who received previous resin infiltration treatment of n_teeth = 111 nonrestored, noncavitated postorthodontic WSL after multibracket treatment during a randomized controlled trial and were contacted 20 months after baseline, eight subjects (trial teeth n_teeth = 40; m/f ratio 1/7; age range (mean; SD) 12–17 [15.25; 2.12] years); response rate: 40%) were available for follow-up after at least 24 months (T24). CIE-L*a*b* differences between summarized color and lightness values (ΔE_WSL/SAE) of WSL and SAE were assessed using a spectrophotometer and compared to baseline data assessed prior to infiltration (T0), and those after 6 (T6), and 12 (T12) months using paired t tests at a significance level of α = 5%.Results:T24 assessments were performed after a mean 33.86 (SD: 8.64; Min: 24; Max: 45) months following T0. Mean (SD) ΔE_WSL/SAE units of available teeth were 8.76 (5.33) at baseline; 5.5 (2.75) at T6; 5.2 (2.41) at T12; and 5.57 (2.6) at T24. Comparisons of T6, T12, and T24 with T0 yielded highly significant differences, whereas T6–T24 and T12–T24 differences were found to be not significant.Conclusions:Assimilation of infiltrated WSL to the color of adjacent enamel by resin infiltration is considered to be suitable for the long-term improvement in the esthetic appearance of postorthodontic WSL.     

Chemical isotope labeling liquid chromatography mass spectrometry for investigating acute dietary effects of cow milk consumption on human urine metabolome

Biomarker discovery has been increasingly important in the field of metabolomics for the detection and understanding of diseases. Of the many biofluids available for metabolomics, urine is a preferred option as it is non-invasive to collect and contains a wide range of metabolites reflective of the health status of the testing individual. However, urine also contains many exogenous metabolites which are introduced through various sources such as diet. This complicates the data interpretation when searching the metabolome for disease-related endogenous metabolites. Since diet is difficult to control, this work aims to study the acute effects of diet (particularly cow milk) consumption on the human urine amine/phenol submetabolome by utilizing differential chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS). LC-MS analysis of 62 urine samples collected before and after (1 hour and 2 hours) milk intake resulted in the detection of 4985 metabolites with an average of 3815 ± 206 (n = 62) detected per sample. The work aims to differentiate the exogenous “food” metabolites from the endogenous metabolite pool and to determine any dietary effects from milk intake on the human urine metabolome.     

量化体育锻炼对维持性血液透析患者生活质量和疾病转归的影响

目的:观察量化体育锻炼对维持性血液透析(MHD)患者的应用效果,探讨临床治疗体会。方法:将64例MHD患者随机分成2组各32例,对照组给予常规健康宣教、干预治疗和自主锻炼,观察组在其基础上给予量化体育锻炼干预治疗;观察2组患者的运动量指标变化情况,比较生活质量和疾病转归等相关指标。结果:干预6个月后,2组的上肢锻炼时间和步行运动量均较干预前明显提高(P0.01,0.05),观察组的提高幅度更高于对照组(P0.01);2组的疲乏状态、日常生活活动能力(ADL)、焦虑自评量表(SAS)和睡眠质量评分量表(SPIEGEL)等指标均较干预前明显降低(均P0.05),改良SGA评分明显提高(P0.01,0.05),观察组的改善幅度更高于对照组(P0.01)。治疗后,观察组的内瘘血管良好率和肾功能平稳率高于对照组(均P0.05),并发症率和再入院率降低(P0.05)。结论:对MHD患者给予量化体育锻炼干预治疗,能显著提高康复锻炼的运动量和优化锻炼效果,提高患者的生活质量,改善疾病预后。     

原料配比对胆南星成分及药效影响

目的考察原料配比对胆南星成分和药效作用的影响。方法采用UPLC⁃MS/MS法及负离子多反应监测(MRM)模式进行不同原料配比的胆南星中鹅去氧胆酸、猪去氧胆酸、猪胆酸、牛磺鹅去氧胆酸、牛磺猪去氧胆酸、甘氨鹅去氧胆酸的含有量测定。胆南星甲醇溶液的分析采用Waters Acquity UPLC BEH C18柱(50 mm×2.1 mm,1.7μm);流动相乙腈⁃0.1%甲酸水,梯度洗脱;体积流量0.25 mL/min;柱温45℃。药效学采用大鼠酵母致热实验、小鼠气管段酚红法和小鼠氨水引咳实验考察不同原料配比对胆南星药效作用影响。结果不同原料配比的胆南星中胆汁酸含有量差异明显,胆汁占原料比大于1∶1时,胆南星的解热、祛痰、止咳作用有统计学差异(P<0.05),胆汁占配比为1∶2时解热、祛痰作用较差(P>0.05)。结论胆汁比例对胆南星的成分和药效作用有显著影响,胆汁占原料比不应低于1∶1。