Cytotoxic antimelanoma drugs suppress the activation of M2 macrophages

Together with regulatory T cells (Tregs), tumor‐associated macrophages (TAMs) play roles in maintaining the tumor microenvironment. Although cytotoxic antimelanoma drugs such as dacarbazine (DTIC), nimustine hydrochloride (ACNU) and vincristine (VCR) have been used for the treatment of malignant melanoma as adjuvant therapy in Japan, the detailed mechanisms of their immunomodulatory effects are not fully understood. As the majority of TAMs are alternatively activated M2 macrophages that favour tumor development, the aim of this study was to elucidate the immunomodulatory effects of these reagents on human monocyte‐derived M2 macrophages. First, mRNA expressions and protein production of immune checkpoint molecules, PD‐L1 and chemokines by CD163⁺ CD206⁺ M2 macrophages derived from peripheral blood mononuclear cells were investigated to determine the immunomodulatory effects of DTIC, ACNU, and VCR. DTIC and VCR significantly decreased PD‐L1 mRNA expression, which was confirmed by flow cytometry. Moreover, the mRNA expression and production of CCL22 were significantly decreased by DTIC, which suggested that DTIC might suppress the recruitment of Tregs in the tumor site. Furthermore, the decreased expression of PD‐L1 and production of CCL22 were validated in vivo, using the B16F10 mouse melanoma model, leading to abrogation of the suppressive function of T‐cell proliferation. The present report suggests one of the possible antimelanoma mechanisms of DAV combination chemotherapy for melanoma patients.     

肿瘤干细胞标志物在鼻咽癌细胞株中的表达

目的探索肿瘤干细胞(CSC)标志物ABCG2、CD44、CD34在鼻咽癌细胞株CNE2、5-8F和6-10B中的表达情况,为选择CSC标志物进行鼻咽癌CSC样研究奠定基础。方法常规培养CNE2、5-8F和6-10B这3种鼻咽癌细胞株,用流式细胞仪检测3种鼻咽癌细胞株中ABCG2、CD44、CD34细胞比例及其交互情况。结果 ABCG2在CNE2、5-8F和6-10B这3种鼻咽癌细胞株中表达率分别为0.1%、18.6%、19.9%;CD44在CNE2、5-8F和6-10B中表达率分别为99.5%、93.2%、99.1%;CD34在CNE2、5-8F和6-10B中表达率分别为0、3.0%、0.1%。在5-8F中,ABCG2+CD44+细胞交互比例为11.6%,ABCG2+CD34+细胞交互比例为0。结论 5-8F和6-10B中CD34+细胞比例与CSC理论中CSC的比例相符。CD34可以作为鼻咽癌CSC的候选标志物。     

Anomalous functional connectivity within the default-mode network in treatment-naive patients possessing first-episode major depressive disorder

Background and Objective:Previous studies have shown that the default-mode network (DMN) has a substantial role in patients with major depressive disorder (MDD). However, there is a shortage of information regarding variations in the functional connectivity (FC) of the DMN of treatment-naive patients with first-episode MDD. The present study aims to explore the FC of the DMN in such patients.Methods:The study population consisted of 33 patients and 35 controls, paired regarding age, gender, education level, and health condition. Depression severity was assessed through the Hamilton Depression Scale (HAM-D), and subjects underwent evaluation during the resting-state through functional magnetic resonance imaging (rs-fMRI). To assess the result, we used FC and ICA. We used Spearman''s correlation test to detect potential correlations between anomalous FC and severity of HAM-D scores.Results:We have found a decreased FC in the left medial orbitofrontal gyrus (MOFG) and right marginal gyrus (SMG) in depressive patients compared to controls. There was a negative correlation between abnormal FC in the right SMG and HAM-D scores. We have not found any increase in FC of the DMN in treatment-naive, first-episode of MDD patients.Conclusions:Our study provided evidence of a negative correlation between abnormal FC in the DMN and severity of depression symptoms measured by HAM-D in treatment-naive MDD patients. This finding could shed some light on the relevance of DMN for understanding the pathophysiology of cognitive impairment in MDD.     

Novel research synergized by Chinese medicine pattern classification in rheumatoid arthritis

Clinical Rheumatology -     

N-Acetyl-l-leucine-polyethylenimine-mediated miR-34a delivery improves osteogenesis and bone formation in vitro and in vivo

Oral bone defects are difficult to treat. Recently, endogenous miR-34a was shown to be involved in bone anabolism. Clinical application of such microRNAs requires the inherent instability of microRNAs to be overcome by an efficient delivery system. In this study, we employed N-acetyl-l-leucine-modified polyethylenimine (N-Ac-l-Leu-PEI) as an miR-34a carrier and evaluated its delivery ability, transfection efficiency, cytotoxicity and whether it enhanced osteogenic differentiation and bone formation in vitro and in vivo. Stable N-Ac-l-Leu-PEI/miR-34a nanocomplexes were synthesized at a mass ratio of 4 and had a small size (190.34 nm), a low zeta potential (21.1 mV), a high transfection efficiency (69.39%) and no cytotoxicity in MG63 cells. N-Ac-l-Leu-PEI-mediated miR-34a delivery in vitro promoted ALP activity and expression of osteogenic differentiation markers, Runx2, SP7 and ColI to higher levels than those produced by Lipofectamine 2000-mediated delivery. N-Ac-l-Leu-PEI also achieved delivery of miR-34a in vivo to a local cranial bone defect area with miR-34a retaining the ability to initiate significant new bone formation 12 weeks post-implantation. This demonstrates the potential for N-Ac-l-Leu-PEI as a gene therapy vehicle for the regeneration of bone defects.

We employ N-acetyl-l-leucine-modified polyethylenimine as an miR-34a carrier and evaluate its delivery ability, transfection efficiency, cytotoxicity and whether it enhances osteogenic differentiation and bone formation in vitro and in vivo.     

Layer-by-layer assembled polyaniline/carbon nanomaterial-coated cellulosic aerogel electrodes for high-capacitance supercapacitor applications

Traditional layer-by-layer (LbL) assembled electrodes are mostly multilayer composites formed on two-dimensional membrane materials. In this case, the electroactive material cannot enter the interior of the substrate. With porous aerogels as the substrate, the LbL assembly of the electroactive material into the three-dimensional aerogel skeleton can be realised, greatly improving the utilisation and the electrochemical performance of the electroactive material. To create a promising aerogel electrode for high-performance energy storage devices, we herein report an aerogel based on wood pulp fibre (WPF) and cellulose nanocrystals (CNC), for use as a porous substrate for LbL assembly of nanostructural polyaniline (PANI) and graphene oxide (GO) or carboxylic multi-walled carbon nanotubes (CMCNT). Owing to the uniformly distributed multilayer nanoarchitecture, interpenetrating channels, and hydrophilic character of the cellulosic aerogel substrate, the produced electrodes of (PANI/CMCNT)₁₀ and (PANI/CMCNT)₁₀ both display high specific capacitances, favourable capacitance retention, good cycling stabilities, and structural flexibility. In the three-electrode test, their gravimetric specific capacitances are as high as 716.62 and 636.63 F g⁻¹, respectively. In addition, the assembled symmetric supercapacitors show good areal specific capacitances (1.95 and 1.49 F cm⁻²) in addition to high areal specific energies (168.64 and 113.57 mW h cm⁻², respectively). These results demonstrate that the integration of the LbL-assembled electroactive materials and porous cellulosic aerogel substrate can be a promising strategy to design high-efficiency green energy storage devices.

Cellulosic aerogel was used as a porous lightweight substrate to layer-by-layer assembly polyaniline and carbon nanomaterials for high capacitance supercapacitor applications.     

中国慢性病前瞻性研究:10个项目地区成年人肺功能指标水平和气流受限现患率的差异分析

目的 描述中国慢性病前瞻性研究(CKB)10个地区人群肺功能指标水平和气流受限现患率的地区差异。方法 剔除基线调查时肺功能指标异常个体后,分析10个地区512 495名30～79岁调查对象肺功能指标水平(FEV₁和FVC)和气流受限(分别采用GOLD标准和LLN标准进行判断)现患率的地区差异。结果 10个地区男性的FEV₁(2.66 L)和FVC(3.16 L)均高于女性(1.99 L和2.35 L);河南和哈尔滨人群FEV₁和FVC高于其他地区。基于GOLD标准的气流受限现患率:男性(5.13%)高于女性(3.75%);农村人群高于城市(男性:6.32% vs. 3.47%;女性:4.26% vs. 2.97%);四川人群现患率最高(男性为13.34%,女性为10.70%),其次是苏州、河南和湖南。基于LLN标准的气流受限现患率(男性为6.93%,女性为6.29%)略高于GOLD标准,但地区差异近似。结论 CKB的10个地区人群无论在肺功能指标水平和气流受限现患率上均存在明显的地区差异。     

中国1995－2012年双生子出生体重变化趋势分析

目的 描述分析中国双生子出生体重变化趋势。方法 使用中国双生子登记系统在中国8个省份收集的1995-2012年出生的双生子人群(共10 827对),采用病例回顾方法分析出生体重各指标情况和变化趋势。结果 调整性别、卵型、出生地区后,出生年份每推迟5年,双生子出生体重平均值降低0.01 kg(P=0.041).随着时间变化,双生子优势方出生体重、劣势方出生体重均不同程度地降低,出生体重相对差与出生体重不一致率在2007年以后有升高趋势。结论 1995-2012年中国双生子出生体重呈下降趋势,出生体重不一致率逐渐上升。考虑到出生体重不一致与某些不良健康结局的风险存在关联,应对双生子出生体重不一致予以重视。     

中国9省/自治区成年居民膳食胆固醇摄入与高胆固醇血症关系的前瞻性研究

目的 探讨成年居民膳食胆固醇摄入与高胆固醇血症的关系. 方法 利用“中国健康与营养调查”数据,本研究中纳入的研究对象为同时参加2004年和2009年2轮调查、且在2009年调查时年龄为25～65岁、血样检测和膳食调查数据完整的成年居民,共4 244人.以《中国成人血脂异常防治指南2007》为标准,血清TC≥6.22 mmol/L时,判定为高胆固醇血症.采用非条件logistic回归方法,研究膳食胆固醇摄入与高胆固醇血症的关系.结果 2009年成年居民平均血清TC水平为4.9 mmol/L,高胆固醇血症患病率为9.6%.2004－2009年膳食胆固醇摄入量总体呈大幅增长,尤其是低摄入量组的增幅最大.男性成年居民中2004年膳食胆固醇摄入中低水平者和2009年膳食胆固醇摄入高水平者,高胆固醇血症患病风险增加.女性膳食胆固醇摄入与高胆固醇血症之间未见统计学关联.结论 膳食胆固醇摄入与高胆固醇血症的关系具有性别差异.膳食胆固醇摄入水平升高,可增加男性居民发生高胆固醇血症的危险性.