Quantitative chemical exchange saturation transfer (qCEST) MRI – omega plot analysis of RF‐spillover‐corrected inverse CEST ratio asymmetry for simultaneous determination of labile proton ratio and exchange rate

Chemical exchange saturation transfer (CEST) MRI is sensitive to labile proton concentration and exchange rate, thus allowing measurement of dilute CEST agent and microenvironmental properties. However, CEST measurement depends not only on the CEST agent properties but also on the experimental conditions. Quantitative CEST (qCEST) analysis has been proposed to address the limitation of the commonly used simplistic CEST‐weighted calculation. Recent research has shown that the concomitant direct RF saturation (spillover) effect can be corrected using an inverse CEST ratio calculation. We postulated that a simplified qCEST analysis is feasible with omega plot analysis of the inverse CEST asymmetry calculation. Specifically, simulations showed that the numerically derived labile proton ratio and exchange rate were in good agreement with input values. In addition, the qCEST analysis was confirmed experimentally in a phantom with concurrent variation in CEST agent concentration and pH. Also, we demonstrated that the derived labile proton ratio increased linearly with creatine concentration (P < 0.01) while the pH‐dependent exchange rate followed a dominantly base‐catalyzed exchange relationship (P < 0.01). In summary, our study verified that a simplified qCEST analysis can simultaneously determine labile proton ratio and exchange rate in a relatively complex in vitro CEST system. Copyright © 2015 John Wiley & Sons, Ltd.     

互动式歌唱表演对轻中度阿尔茨海默病患者抑郁、精神行为和运动训练参与率的影响

目的 观察互动式歌唱表演对轻中度阿尔茨海默病（AD）患者抑郁、精神行为症状及运动训练参与率的影响。方法 选取符合入组条件≥60周岁AD患者63例，随机分为研究组（31例）和对照组（32例）。所有受试患者常规药物治疗及常规运动训练，对照组接受被动性音乐治疗，研究组接受以互动歌唱为主的主动性音乐治疗，1次/d，每次1小时，每周训练5天，持续干预6个月。于治疗前、治疗1个月后、治疗3个月后、治疗6个月后分别采用康奈尔痴呆抑郁量表（CSDD）评分、阿尔茨海默病病理行为（BEHAVE AD）评分、参与率进行评估。结果 治疗1个月、3个月后，研究组CSDD评分较治疗前均降低（P<0.05）；治疗6个月后，研究组患者CSDD评分较治疗前、治疗1个月、3个月后均显著降低（P<0.05），且与对照组比较差异有统计学意义（P<0.05）。治疗1个月、3个月后，研究组BEHAVE AD评分较治疗前均降低（P<0.05）；治疗6个月后，研究组患者BEHAVE AD评分较治疗前、治疗1个月、3个月后均显著降低（P<0.05），且与对照组比较差异有统计学意义（P<0.05）。治疗6个月后，两组运动训练参与率组间比较差异有统计学意义（P<0.05）。结论 互动式歌唱表演可能对改善轻中度AD患者的抑郁和精神行为症状有着积极的疗效，同时对提高受试者运动训练的参与率可能有着更积极的疗效。     

Prospective observation: Clinical utility of plasma Epstein–Barr virus DNA load in EBV-associated gastric carcinoma patients

Epstein–Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) may account for 8–9% of all gastric cancer (GC) patients. All previous reports on EBVaGC were retrospective. Prospective study is warranted to evaluate the exact role of EBV status in predicting the prognosis of GC. It is of special interest to figure out whether dynamic detection of plasma EBV-DNA load could be a feasible biomarker for the monitor of EBVaGC. From October 2014 to September 2017, we consecutively collected GC patients (n = 2,760) from Sun Yat-sen University Cancer Center for EBER examination. We detected EBV-DNA load in plasma and tissue samples of EBVaGC patients at baseline. Subsequently, plasma EBV-DNA load was dynamically monitored in EBVaGC patients. The overall prevalence of EBVaGC is 5.1% (140/2,760). The incidence rate of EBVaGC decreased with advanced AJCC 7th TNM stage (p < 0.001), with the corresponding percentages of 9.3, 9.9, 6.7 and 1.4% for Stage I, II, III and IV patients. EBVaGC patients were predominately young males with better histologic differentiation and earlier TNM stage than EBV-negative GC (EBVnGC) patients. EBVaGC patients were confirmed to had a favorable 3-year survival rate (EBVaGC vs. EBVnGC: 76.8% vs. 58.2%, p = 0.0001). Though only 52.1% (73/140) EBVaGC patients gained detectable EBV-DNA and 43.6% (61/140) reached a positive cutoff of 100 copies/ml, we found the plasma EBV-DNA load in EBVaGC decreased when patients got response, while it increased when disease progressed. Our results suggested that plasma EBV-DNA is a good marker in predicting recurrence and chemotherapy response for EBVaGC patients.     

极低/超低出生体重儿甲状腺功能减退的临床分析

目的 分析极低/超低出生体重（VLBW/ELBW）患儿甲状腺功能减退的危险因素和治疗情况。方法 选择2018年9月至2019年12月诊断为甲状腺功能减退的VLBW/ELBW患儿为病例组（n=29），按照1：3比例匹配甲状腺功能正常的VLBW/ELBW患儿作为对照组（n=87），比较两组患儿的临床特征，分析甲状腺功能与出生胎龄、出生体重的相关性及甲状腺功能减退的危险因素。结果 符合纳入标准的VLBW/ELBW患儿共162例，其中病例组29例，甲状腺功能减退发生率为17.9%。出生体重越低，甲状腺功能减退发生率越高（P < 0.05）；三碘甲状腺原氨酸（T3）、游离三碘甲状腺原氨酸（FT3）与出生胎龄呈正相关（P < 0.05），T3、游离甲状腺素（FT4）与出生体重呈正相关（P < 0.05）。小于胎龄儿、多胎、孕母≥35岁、使用多巴胺是发生甲状腺功能减退的独立危险因素（P < 0.05）。病例组中16例患儿给予左旋甲状腺素（每日5~10 μg/kg）治疗，甲状腺功能在治疗2周后恢复正常。结论 VLBW/ELBW患儿甲状腺功能减退的发生率较高，小于胎龄儿、多胎、孕母高龄、应用多巴胺是其发生甲状腺功能减退的危险因素，应用左旋甲状腺素治疗的患儿需定期随访，以保证用药剂量适宜。     

LPS对骨肉瘤细胞迁移、侵袭及TLR4/HOTAIR通路的影响

目的探讨脂多糖(LPS)对骨肉瘤细胞迁移和侵袭的影响及其潜在的作用机制。方法将人MG-63骨肉瘤细胞随机分为2组:对照组和LPS组。LPS组细胞用10 g/ml的LPS干预24 h,对照组用生理盐水干预。ELISA检测干预后培养基中促炎因子的水平,Transwell实验检测细胞迁移和侵袭能力,Western Blot检测相关蛋白的表达。结果与对照组相比,LPS组培养基中促炎因子TNF-α、IL-1和IL-6的释放水平均显著增高(P<0.05),LPS组迁移细胞数和侵袭细胞数均显著增高(P<0.05),LPS组中E-cadherin的表达显著降低(P<0.05),而N-cadherin、α-SMA、波形蛋白、TLR4和HOTAIR的表达均显著增高(P<0.05)。结论LPS诱导的肿瘤微环境可促进骨肉瘤细胞的迁移和侵袭,其机制与TLR4/HOTAIR途径介导的EMT过程的发生有密切关系。     

Role of macrophages in peripheral nerve injury and repair

Resident and inflammatory macrophages are essential effectors of the innate immune system. These cells provide innate immune defenses and regulate tissue and organ homeostasis. In addition to their roles in diseases such as cancer, obesity and osteoarthritis, they play vital roles in tissue repair and disease rehabilitation. Macrophages and other inflammatory cells are recruited to tissue injury sites where they promote changes in the microenvironment. Among the inflammatory cell types, only macrophages have both pro-inflammatory(M1) and anti-inflammatory(M2) actions, and M2 macrophages have four subtypes. The co-action of M1 and M2 subtypes can create a favorable microenvironment, releasing cytokines for damaged tissue repair. In this review, we discuss the activation of macrophages and their roles in severe peripheral nerve injury. We also describe the therapeutic potential of macrophages in nerve tissue engineering treatment and highlight approaches for enhancing M2 cell-mediated nerve repair and regeneration.     

肝细胞癌患者血清外泌体mRNA表达谱及临床意义分析

背景与目的:外泌体是包含了复杂RNA和蛋白质的小膜泡,其中肿瘤细胞分泌的外泌体中的mRNA携带了大量肿瘤细胞遗传信息,因此对外泌体中特异性mRNA的分析,有望找到肿瘤诊断的新型分子标志物和治疗靶点。本研究通过高通量筛选与生物信息学方法探讨肝细胞癌(HCC)患者血清外泌体mRNA的表达特征及其潜在功能。方法:采集3例HCC患者及3例正常人的静脉血,用外泌体提取试剂盒提取血清外泌体,用Magen试剂盒提取外泌体RNA,对血清外泌体mRNA进行纯化、行反转录形成cDNA、PCR扩增、测序,最后将对所得数据质量进行评价后与参考数据进行比对,分析得到差异表达外泌体mRNA,并采用GO和KEGG通路富集分析对差异基因进行功能与通路注释。结果:与正常人比较,HCC患者有397个外泌体mRNA表达上调,192个外泌体mRNA表达下调;其中,NRGN、PF4、RGS18等17个基因表达明显上调,CXCL8、MORF4L2、SYCP1等14个基因显明显下调。GO富集分析显示,表达上调的外泌体mRNA的靶基因与蛋白质结合、蛋白质异二聚化活性、免疫系统过程的调节、胞外囊泡、细胞外细胞器、应激反应等有关,表达下调的外泌体mRNA的靶基因与嗅觉受体活性、细胞因子活性、CXCR趋化因子受体结合、中间丝、中间丝状细胞骨架等有关;KEGG通路分析显示,在上调的外泌体mRNA中,30条通路被显著富集,在下调的外泌体mRNA中9条通路被显著富集,其中,在上调的外泌体mRNA中,血小板激活、Rap 1信号通路、吞噬体、病毒致癌、肌动蛋白细胞骨架的调节与抗原处理和呈递等是最丰富和最有意义的通路;在下调的外泌体mRNA中,基础转录因子和细胞因子-细胞因子受体相互作用分别是最丰富和最有意义的通路。结论:HCC患者与正常人的血清外泌体mRNA表达特征存在较大差异,其与HCC发生、发展、转移可能密切相关,这为寻找新的诊断标志物及治疗靶点提供了依据。     

CA153联合CA199对良恶性腹腔积液的鉴别诊断价值

目的探讨腹腔积液中CA153联合CA199对良恶性腹腔积液的鉴别诊断价值。方法选择98例腹腔积液患者,经手术病理诊断为恶性腹腔积液者为观察组(48例),良性腹腔积液者为对照组(50例)。检测并比较2组患者腹腔积液中的CA153、CA199水平及CA153、CA199的阳性结果,分析CA153及CA155单用及联合应用对恶性腹腔积液的诊断效能。结果观察组腹腔积液中的CA153及CA199水平均明显高于对照组,P <0. 05。观察组CA153及CA199阳性率明显高于对照组,P <0. 05。CA153、CA199对恶性腹腔积液诊断的敏感性、特异性及准确性对比,差异无统计学意义(P> 0. 05);CA153+CA199的敏感性、特异性及准确性明显高于单项CA153及CA199(P <0. 05)。结论 CA153与CA199单项检测对恶性腹腔积液的诊断价值有限,CA153+CA199对恶性腹腔积液的诊断价值较高,值得临床推广应用。