干扰肿瘤相关巨噬细胞的P2X4受体表达可抑制胶质瘤细胞的迁移和侵袭

目的研究P2X4受体在小鼠胶质瘤中肿瘤相关巨噬细胞（TAMs）的表达对胶质瘤细胞侵袭迁移的影响及分子机制。方法将16只健康C57BL/6小鼠随机分为肿瘤组、对照组（8只/组），利用小鼠胶质瘤GL261细胞接种于小鼠大脑尾状核，建立小鼠脑胶质瘤模型。术后第21天处死小鼠，取荷瘤小鼠及正常小鼠脑组织，采用HE染色观察小鼠胶质瘤形态，利用免疫荧光检测Iba-1、P2X4受体的表达情况；应用GL261条件培养基将RAW264.7细胞诱导为TAMs，采用RT-qPCR检测巨噬细胞极化相关标志物及P2X4受体在TAMs的mRNA表达情况；采用Western blot检测P2X4受体在TAMs的蛋白表达情况；采用siRNA P2X4，下调TAMs中P2X4受体的蛋白表达，RT-qPCR、Western blot检测siRNA P2X4转染后TAMs中IL-1β、IL-18的mRNA及蛋白表达；利用transwell侵袭及迁移实验检测siRNA P2X4转染后TAMs对GL261细胞侵袭迁移能力的影响。结果与对照组相比，荷瘤小鼠脑胶质瘤组织中有较高数量的Iba-1阳性细胞（P < 0.0001），且P2X4受体在Iba-1阳性细胞中的表达增高（P=0.001）；使用GL261条件培养基刺激RAW264.7细胞转化为TAMs后，M2型巨噬细胞标志基因Arg-1、IL-10表达上调（P=0.0001、0.001），M1型巨噬细胞标志基因iNOS、TNF-α表达也上调（P=0.006、0.001），但以M2型巨噬细胞标志基因Arg-1、IL-10表达上调更为显著，同时TAMs中P2X4受体蛋白表达水平及mRNA水平均增高（P=0.005、0.014）。干扰TAMs中P2X4受体表达引起其IL-1β、IL-18的mRNA（P < 0.01）及蛋白表达水平（P < 0.01，P < 0.05）降低，并抑制TAMs促进胶质瘤细胞侵袭和迁移的能力（P=0.004、0.017）。结论降低肿瘤相关巨噬细胞P2X4受体表达可能通过IL-1β、IL-18影响胶质瘤细胞的迁移和侵袭。     

Low Complement C1q/TNF-related Protein-13 Levels are Associated with Childhood Obesity But not Binge Eating Disorder

Objective:C1q/tumor necrosis factor-related proteins (CTRPs) are recently described members of the adipokine family. CTRP-13, a new member of this family, has been shown to increase insulin sensitivity and had an anorexigenic effect on food intake in experimental studies. The aim was to investigate serum CTRP-13 levels in children with obesity, and its relationship with other adipokines, metabolic parameters, or binge eating disorder (BED).Methods:A cross-sectional study was conducted with 105 pubertal children attending a single center. Clinical (metabolic syndrome, BED) and biochemical (glucose, insulin, lipids, leptin, adiponectin, CTRP-13 levels) parameters were assessed.Results:Sixty children with obesity [24 males (40%); median age 14.7 (13.0-16.4) years] and 45 healthy controls [15 males (33.3%); median age 15.2 (14.1-16.5) years] were included. Serum adiponectin and CTRP-13 levels were significantly lower in children with obesity than controls (7.1 vs 20.1 μg/mL, p<0.001; 64.7 vs 103.8 ng/mL, p<0.001, respectively). CTRP-13 levels correlated negatively with body mass index (Spearman rho=-0.230, p=0.018) and positively with high-density lipoprotein-cholesterol levels (Spearman rho=0.218, p=0.026). There was no significant difference in serum CTRP-13 concentrations in terms of the presence of metabolic syndrome or BED.Conclusion:Childhood obesity seems to be causing dysregulation in adipokine production and function, including the down-regulation of CTRP-13. The positive correlation between CTRP-13 and HDL-C levels suggested a possible effect of this adipokine on lipid metabolism. Thus CTRP-13 may be a novel biomarker for dyslipidemia in childhood obesity.     

子宫内膜腺癌组织中KAI1蛋白的表达及其与临床病理因素的关系

目的探讨子宫内膜腺癌组织中转移抑制基因1(KAI1)蛋白的表达及其意义。方法应用免疫组织化学EnviSion法检测20例正常子宫内膜和70例子宫内膜腺癌组织中KAI1蛋白的表达水平。结果子宫内膜腺癌组织中KAI1蛋白阳性表达率明显低于正常子宫内膜组织(χ2=12.22,P<0.01);子宫内膜腺癌组织中KAI1蛋白的表达与病理分级、手术-临床分期、肌层浸润深度及淋巴结转移有关(2χ=10.80~14.91,P<0.01)。结论KAI1蛋白表达下调可能是子宫内膜腺癌发生发展及浸润和转移的重要原因之一。     

人脑胶质瘤组织HIF-1α和COX-2及CD105蛋白表达与临床病理学关系的研究

目的:探讨缺氧诱导因子-1α(HIF-1α)、环氧化酶-2(COX-2)及CD105在人脑胶质瘤组织中的表达及与临床病理特征的关系。方法:应用免疫组化SP法检测70例胶质瘤和10位正常人脑组织中HIF-1α、COX-2和CD105的表达,并测定CD105标记的MVD。结果:1)胶质瘤组织中HIF-1α、COX-2和CD105蛋白的阳性表达率分别为64.3%、61.4%和74.3%,明显高于正常人脑组织。2)HIF-1α、COX-2表达和MVD与胶质瘤病理分级密切相关。3)胶质瘤组织中HIF-1α和COX-2蛋白表达的一致符合率为70.35%,且两者表达呈正相关,r=0.5837,P=0.004。4)HIF-1α和COX-2阳性表达组的MVD(35.87±4.55和36.00±4.57)均高于阴性表达组(29.19±4.69和29.48±4.71),P值均为0.0000;两者均为阳性表达时的MVD(36.22±4.62)最大,明显高于其他各组(33.75±3.59和28.29±4.33),P=0.0001;两者表达均与MVD呈正相关,r值分别为0.5405和0.4652,P值分别为0.005和0.014。结论:HIF-1α、COX-2和CD105过表达可能在胶质瘤的恶性进展中发挥重要作用,并与肿瘤血管形成密切相关,三者的联合检测可更准确地揭示胶质瘤的生物学特性。     

糖化血清蛋白测定对排除假性高血糖的临床应用价值

目的观察糖化血清蛋白(GSP)的测定是否对排除假性高血糖有临床应用价值。方法对一些血糖高的病人进行GSP检测、糖化血红蛋白(HBA1C)检测、餐后2小时血糖的检测,观察经临床确诊确属假性血糖升高的非糖尿病病人的GSP水平。结果凡经临床确诊的属假性血糖升高的非糖尿病病人的GSP水平为:1.61±0.56mmol/L,而糖尿病组为2.55±0.59mmol/L,经统计处理,两组的GSP结果差别有显著性(P<0.05)。结论GSP的检测对排除假性的一次性高血糖有一定的临床应用价值。     

Hypercalcemia in Pregnancy Due to CYP24A1 Mutations: Case Report and Review of the Literature

Pathogenic mutations of CYP24A1 lead to an impaired catabolism of vitamin D metabolites and should be considered in the differential diagnosis of hypercalcemia with low parathyroid hormone concentrations. Diagnosis is based on a reduced 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D ratio and confirmed by genetic analyses. Pregnancy is associated with an upregulation of the active vitamin D hormone calcitriol and may thus particularly trigger hypercalcemia in affected patients. We present a case report and a narrative review of pregnant women with CYP24A1 mutations (13 women with 29 pregnancies) outlining the laboratory and clinical characteristics during pregnancy and postpartum and the applied treatment approaches. In general, pregnancy triggered hypercalcemia in the affected women and obstetric complications were frequently reported. Conclusions on drugs to treat hypercalcemia during pregnancy are extremely limited and do not show clear evidence of efficacy. Strictly avoiding vitamin D supplementation seems to be effective in preventing or reducing the degree of hypercalcemia. Our case of a 24-year-old woman who presented with hypercalcemia in the 24th gestational week delivered a healthy baby and hypercalcemia resolved while breastfeeding. Pathogenic mutations of CYP24A1 mutations are rare but should be considered in the context of vitamin D supplementation during pregnancy.     

Effects of Interleukin-17A on the Early Stages of Arterial Thrombosis in Mice

PurposeInterleukin (IL)-17A has been suggested to play a role in the growth and organization of thrombi. We examined whether IL-17A plays a role in the early stages of thrombosis and whether there are sex differences in the effects of IL-17A.Materials and MethodsWe performed a blinded, randomized, placebo-controlled study to compare time to thrombotic occlusion and sex differences therein between mice treated with IL-17A and those treated with saline using a ferric chloride-induced model. We also assessed thrombus histology, blood coagulation, and plasma levels of coagulation factors.ResultsTime to occlusion values did not differ between the IL-17A group and the control group (94.6±86.9 sec vs. 121.0±84.4 sec, p=0.238). However, it was significantly shorter in the IL-17A group of female mice (74.6±57.2 sec vs. 130.0±76.2 sec, p=0.032). In rotational thromboelastometry, the IL-17A group exhibited increased maximum clot firmness (71.3±4.5 mm vs. 66.7±4.7 mm, p=0.038) and greater amplitude at 30 min (69.7±5.2 mm vs. 64.5±5.3 mm, p=0.040) than the control group. In Western blotting, the IL-17A group showed higher levels of coagulation factor XIII (2.2±1.5 vs. 1.0±0.9, p=0.008), monocyte chemoattractant protein-1 (1.6±0.6 vs. 1.0±0.4, p=0.023), and tissue factor (1.5±0.6 vs. 1.0±0.5, p=0.003).ConclusionIL-17A plays a role in the initial st ages of arterial thrombosis in mice. Coagulation factors and monocyte chemoattractant protein-1 may be associated with IL-17A-mediated thrombosis.     

Research Progress on Emerging Viral Pathogens of Small Ruminants in China during the Last Decade

China is the country with the largest number of domestic small ruminants in the world. Recently, the intensive and large-scale sheep/goat raising industry has developed rapidly, especially in nonpastoral regions. Frequent trading, allocation, and transportation result in the introduction and prevalence of new pathogens. Several new viral pathogens (peste des petits ruminants virus, caprine parainfluenza virus type 3, border disease virus, enzootic nasal tumor virus, caprine herpesvirus 1, enterovirus) have been circulating and identified in China, which has attracted extensive attention from both farmers and researchers. During the last decade, studies examining the etiology, epidemiology, pathogenesis, diagnostic methods, and vaccines for these emerging viruses have been conducted. In this review, we focus on the latest findings and research progress related to these newly identified viral pathogens in China, discuss the current situation and problems, and propose research directions and prevention strategies for different diseases in the future. Our aim is to provide comprehensive and valuable information for the prevention and control of these emerging viruses and highlight the importance of surveillance of emerging or re-emerging viruses.