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.     

Electrophysiological differences between upper and lower limb movements in the human subthalamic nucleus

ObjectiveFunctional processes in the brain are segregated in both the spatial and spectral domain. Motivated by findings reported at the cortical level in healthy participants we test the hypothesis in the basal ganglia of Parkinson’s disease patients that lower frequency beta band activity relates to motor circuits associated with the upper limb and higher beta frequencies with lower limb movements.MethodsWe recorded local field potentials (LFPs) from the subthalamic nucleus using segmented “directional” DBS leads, during which patients performed repetitive upper and lower limb movements. Movement-related spectral changes in the beta and gamma frequency-ranges and their spatial distributions were compared between limbs.ResultsWe found that the beta desynchronization during leg movements is characterised by a strikingly greater involvement of higher beta frequencies (24–31 Hz), regardless of whether this was contralateral or ipsilateral to the limb moved. The spatial distribution of limb-specific movement-related changes was evident at higher gamma frequencies.ConclusionLimb processing in the basal ganglia is differentially organised in the spectral and spatial domain and can be captured by directional DBS leads.SignificanceThese findings may help to refine the use of the subthalamic LFPs as a control signal for adaptive DBS and neuroprosthetic devices.     

基于血管内皮功能相关多生物标记物的哮喘预后研究

目的 分析哮喘儿童血清中血管内皮功能相关标记物的变化情况及其与疾病预后的关系,为儿童哮喘预后的评估提供依据。方法 收集2016年10月-2017年12月在南通大学附属常州儿童医院就诊的89例5～14岁哮喘患儿在哮喘发作期的血清样本和92例健康儿童的血清样本,运用ELISA和其他商用测试盒检测其中内皮功能相关标志物血管内皮生长因子(VEGF)、精氨酸酶I(Arg I)、骨膜蛋白(POSTN)、脂联素(APN)和瘦素的浓度以及诱导型一氧化氮合酶(iNOS)活性,并用高效液相串联质谱(HPLC-MS/MS)检测L-精氨酸、甲基化精氨酸ADMA和SDMA的浓度。此后对哮喘组患儿进行为期1年的随访,记录在此期间出现喘息发作的次数。运用正交偏最小二乘法-判别分析(OPLS-DA)分析数据,筛选对哮喘疾病预后有关键影响的血管内皮功能相关标记物。结果 哮喘组儿童血清中Arg I、POSTN、VEGF和瘦素的含量显著增加,iNOS活性显著增高,L-精氨酸浓度显著下降(P<0.05)。OPLS-DA模型显示,基于内皮功能多标记物哮喘组可以和对照组显著区分,且Arg I、iNOS活性以及VEGF水平的变量重要性因子(VIP)值分别为2.11、1.23、1.09,是区分哮喘组和对照组的关键内皮标记物。随访后1年,随访成功70例,其中反复喘息组(n=27)与非反复喘息组(n=43)相比,血清ADMA和Arg I的含量显著增加,POSTN和APN含量显著减少(P<0.05)。OPLS-DA模型的S-plot图和VIP值排序都表明区分两组的关键内皮标记物是APN、POSTN和Arg I。结论 哮喘儿童血清中多种内皮功能相关的生物标记物稳态失衡,其中APN、POSTN和Arg I对儿童哮喘的疾病预后有较高的预测价值。     

散聚汤加味对宫颈癌术后放化疗患者的癌因性疲乏和免疫功能的改善研究

[目的]探讨散聚汤加味改善宫颈癌术后放化疗患者的癌因性疲乏和免疫功能的疗效。[方法]筛选在洛阳解放军534医院行宫颈癌手术后患者共82例作为研究对象,按随机数字表法随机分为对照组和观察组各41例。对照组给予同步放疗+TP化疗方案[紫杉醇(TAX)+顺铂(DDP)]。观察组在对照组基础上给予散聚汤加味治疗,每日1剂,每日2次,连续服用12周。比较两组患者癌因性疲乏评分、毒性反应、T淋巴细胞亚群水平以及血清免疫球蛋白(IgA、IgG、IgM)水平。[结果]治疗12周后,观察组患者的癌因性疲乏(情绪、感觉、行为、认知)评分显著低于对照组(P0.01);观察组患者的消化道反应、膀胱刺激发生率明显少于对照组(P0.05);治疗12周后,观察组患者CD3+、CD3+CD4+以及IgA、IgG、IgM水平显著高于对照组,CD3+CD8+明显低于对照组(P0.01)。[结论]散聚汤加味能改善宫颈癌术后放化疗患者的癌因性疲乏,增强免疫功能,且可降低毒副反应。     

丁苯酞对轻度血管性认知障碍患者执行功能的影响

目的 评估口服丁苯酞对血管性轻度认知障碍患者执行能力的影响。 方法 选择轻度血管性认知功能障碍患者48例，分为观察组24例，对照组24例。观察组服用丁苯 酞200 mg，每日3次，对照组服用维生素E 100 mg，每日3次，共90 d。比较两组治疗前及治疗后连线A 和连线B测试、数字广度顺背倒背、言语流畅性测验（verbal fluency test，VFT）、画钟测验量表评分， 评价丁苯酞对患者执行功能的影响。 结果 治疗前，两组认知和执行功能差异无统计学意义。治疗后，观察组连线A（[ 53.65±0.88）vs （56.22±0.87）]和连线B（[ 174.95±1.99）vs（177.41±1.44）]测试评分低于对照组，差异有统计学意义； 数字广度顺背倒背测试（[ 5.05±1.22）vs（4.59±0.33）]和VFT（[ 13.29±0.88）vs（12.43±1.02）]评分 高于对照组，差异有统计学意义；两组画钟测试差异无统计学意义。 结论 丁苯酞可以改善轻度血管性认知障碍患者执行功能。