Characteristics and clinical significance of augmentation spectra in solar urticaria

Solar urticaria has unique spectra, such as inhibition and augmentation. The clinical significance of these spectra, especially augmentation, is not well understood. Reported cases of solar urticaria with augmentation spectra are extremely rare in the published English-language work. The purposes of this study were to evaluate the clinical features of solar urticaria with augmentation spectra and to elucidate the mechanisms and clinical importance of the spectra. We experienced 11 cases (five females, six males; mean age, 40.1 years; range, 1–74) of solar urticaria with augmentation spectra from April 2007 to July 2019. Augmentation spectra were UV-B in three cases, UV-A in two, visible light in four, UV-A and UV-B in one, and UV-A and visible light in one. Augmentation spectra were observed before action spectra in four cases, after in six, and before and after in one. Injection of sera irradiated with action spectra and augmentation spectra in vitro induced stronger immediate reactions than those of only action spectrum-irradiated sera in four of five cases. The results of injection tests suggested that augmentation spectra enhance the production of urticaria-forming factor. Clinically, we observed severe urticarial reactions in four cases, including anaphylaxis in three and moderate urticarial reactions in three. These results suggest that augmentation spectra are not as rare as previously thought and that they are associated with the severity of solar urticaria. Therefore, phototesting for both augmentation and action spectra should be performed to provide appropriate guidance for patients with solar urticaria.     

恶性黑素瘤免疫检查点抑制疗法研究进展

【摘要】 免疫检查点抑制剂在过去几年中已成为许多恶性黑素瘤患者的重要治疗选择，其旨在恢复并促进效应T细胞特异性识别和杀伤肿瘤细胞的功能，系统性增强全身的抗肿瘤免疫反应，对于手术切除后具有高复发风险或处于疾病晚期（不可切除或存在转移）的患者都是较好的治疗选择。目前免疫检查点抑制的主要目标是程序性死亡受体 1与细胞毒性T淋巴细胞相关抗原4，它们分别是中枢和外周免疫耐受的两个关键受体。本文主要讨论不同免疫检查点抑制剂的临床效应、可能存在的药物反应性预测标志物与相关不良反应。     

欧前胡素抗肿瘤作用机制及治疗的研究进展

欧前胡素是从中药当归中提取的呋喃香豆素类化合物,临床上常用于治疗头痛、炎症、心血管疾病等。近年来研究发现,欧前胡素对多种类型的肿瘤细胞增殖均有抑制作用,能发挥抗肿瘤的功效。本文就欧前胡素对肿瘤及相关疾病的治疗作用和机制进行探讨,以期从不同的角度为肿瘤治疗提供新思路、新方法,并对欧前胡素的进一步研究和开发利用提供理论基础。     

Predictions of genotoxic potential,mode of action,molecular targets,and potency via a tiered multiflow® assay data analysis strategy

The in vitro MultiFlow® DNA Damage Assay multiplexes γH2AX, p53, phospho-histone H3, and polyploidization biomarkers into a single flow cytometric analysis. The current report describes a tiered sequential data analysis strategy based on data generated from exposure of human TK6 cells to a previously described 85 chemical training set and a new pharmaceutical-centric test set (n = 40). In each case, exposure was continuous over a range of closely spaced concentrations, and cell aliquots were removed for analysis following 4 and 24 hr of treatment. The first data analysis step focused on chemicals' genotoxic potential, and for this purpose, we evaluated the performance of a machine learning (ML) ensemble, a rubric that considered fold increases in biomarkers against global evaluation factors (GEFs), and a hybrid strategy that considered ML and GEFs. This first tier further used ML output and/or GEFs to classify genotoxic activity as clastogenic and/or aneugenic. Test set results demonstrated the generalizability of the first tier, with particularly good performance from the ML ensemble: 35/40 (88%) concordance with a priori genotoxicity expectations and 21/24 (88%) agreement with expected mode of action (MoA). A second tier applied unsupervised hierarchical clustering to the biomarker response data, and these analyses were found to group certain chemicals, especially aneugens, according to their molecular targets. Finally, a third tier utilized benchmark dose analyses and MultiFlow biomarker responses to rank genotoxic potency. The relevance of these rankings is supported by the strong agreement found between benchmark dose values derived from MultiFlow biomarkers compared to those generated from parallel in vitro micronucleus analyses. Collectively, the results suggest that a tiered MultiFlow data analysis pipeline is capable of rapidly and effectively identifying genotoxic hazards while providing additional information that is useful for modern risk assessments—MoA, molecular targets, and potency. Environ. Mol. Mutagen. 60:513–533, 2019. © 2019 Wiley Periodicals, Inc.     

当归芍药散改善认知功能的研究进展

当归芍药散（danggui shaoyao san，DSS）是收录在汉代张仲景《金匮要略》中的著名方剂，原为治疗“妇人怀妊，腹中㽲痛”、“妇人腹中诸疾痛”而设，为中医健脾祛湿、养血调肝的著名方剂。临床多用于妇科疾病的治疗。近年发现当归芍药散具有神经保护作用，尤其对认知功能具有一定改善作用，其作用机制主要与调控雌激素水平、抑制氧化应激以及神经元突触等转导通路及相关信号分子有关。当归芍药散作为潜在的阿尔茨海默病及其他中枢神经退行性疾病治疗药物将日益受到关注，该文对当归芍药散化学成分和药理作用的研究进展进行综述。     

基于FPGA的神经突触的硬件实现及放电性能比较

目前专门对化学突触硬件实现的研究较少,采用FPGA芯片技术硬件实现化学突触,对神经元网络的硬件实现具有重要价值。运用DSP Builder软件,对以Hodgkin-Huxley神经元为突触前神经元和突触后神经元的化学突触数学模型进行建模。在DSP Builder模型的基础上,将化学突触的DSP Builder模型进行合理的拆分,然后分别将各个模块在FPGA所对应的软件环境下进行编译运行,最后下载到FPGA核心芯片中,硬件实现5种基于不同机理的化学突触模型。采用相关系数法,对仿真结果和硬件结果在同一个周期内的突触前神经元动作电位、突触后神经元动作电位以及突触电流的幅值进行对比,验证硬件实现的准确性。5种硬件实现的化学突触均可以较好地传递动作电位,但是各个模型消耗资源不同,模型3所消耗的内部乘法器资源(69%),约为模型5资源(31%)的2倍,表明突触模型数学复杂度越高,其消耗的乘法器资源越多。相关系数法的对比结果显示,模型3相关度最高,为0.791 3,模型4相关度最低,为0.693 5。虽然模型3数学复杂度高、硬件资源消耗多,但是其表现的生物性最好。硬件实现的5种突触模型均能较好地呈现化学突触的单向传递性,其中模型5硬件资源消耗少、相关度高,建议以其作为化学突触硬件实现的首选。     

八珍汤对肺癌化疗致白细胞减少症临床疗效及部分机制研究

目的:探究八珍汤对肺癌化疗所致白细胞减少症的疗效及作用机制,有助于精准治疗并提高疗效。方法:选取2017年4月至2018年4月哈尔滨医科大学附属第一医院收治的肺癌化疗所致白细胞减少症患者66例作为研究对象,采用数字随机表法按就诊顺序号,分为对照组和观察组,每组33例。对照组予利血生20 mg口服,3次/d;鲨肝醇100 mg口服,3次/d,升白治疗,观察组在对照组基础上加用八珍汤化裁治疗,均治疗4周,观察不同方法治疗后在白细胞水平含量比较,比较治疗前、治疗末神疲乏力、心悸气短、头晕目眩、面色淡白、畏寒肢冷、纳呆食少中医症候积分和免疫功能指标CD4^+、CD8^+、CD4^+/CD8^+、NK细胞变化情况,治疗过程中收集不良反应情况,结束治疗后观察疗效情况。结果:1)2组治疗1周、2周、3周、4周后白细胞计数菌显著高于治疗前(P<0.05),观察组治疗1周、2周、3周、4周后显著优于对照组(P<0.05);2)2组患者治疗前神疲乏力、心悸气短、头晕目眩、面色淡白、畏寒肢冷、纳呆食少,比较差异无统计学意义(P>0.05),完成治疗方案后,2组患者以上指标较治疗前均显著下降(P<0.05)。治疗末观察组患者以上指标显著低于对照组(P<0.05)。3)2组患者治疗前CD4^+、CD8^+、CD4^+/CD8^+、NK细胞比较,差异无统计学意义(P>0.05),完成治疗方案后,2组患者CD8^+较治疗前均显著下降,CD4^+、CD4^+/CD8^+、NK细胞较治疗前显著升高(P<0.05),治疗末观察组患者以上指标显著优于对照组(P<0.05)。4)完成治疗后观察组患者显效率、总有效率明显高于对照组(P<0.05)。5)2组在不良反应发生率上比较,差异无统计学意义(P>0.05)。结论:八珍汤对肺癌化疗所致白细胞减少症能升高白细胞水平,提高疗效,改善症状。可能和该药能提高机体免疫力,促使骨髓造血功能有关。     

The link between language and action in aging

ObjectiveMany studies have demonstrated the existence of a link between action verb processing and action. However, little is known about the changes in this relationship with aging.MethodTo assess this point, we compare the performances of younger and older people during a priming task consisting of judging whether an image contains a human after listening to an action verb.ResultsIn accordance with previous literature, the results showed that younger people were faster to detect the presence of a human in the image in congruent conditions, namely, when the action verb and the image refer to the same action. However, this effect was not present in older adults’ participants.ConclusionThese findings suggest that the link between action and language decreases with age. We discuss these findings in the context of the embodied view of cognition.