淫羊藿苷对骨微血管内皮细胞自噬及外泌体产生的影响

目的评估淫羊藿苷对低浓度糖皮质激素诱导的骨微血管内皮细胞（bone microvascular endothelial cells，BMECs）自噬和外泌体分泌的影响。方法从行全髋关节置换术切取的股骨头中分离 BMECs，用一系列低浓度梯度氢化可的松（0、0.03、0.06、0.10 mg/mL）干预（设为 A、B、C、D 组），在此基础上再用 5×10⁻⁵ mol/L 淫羊藿苷干预（设为 A1、B1、C1、D1 组），24 h 后采用 Western blot 检测自噬相关蛋白微管相关蛋白轻链 3B（microtubule-associated protein 1 light chain 3B，LC3B）及死骨片 1（p62）的表达。从经淫羊藿苷处理（干预组）和未经淫羊藿苷处理（未干预组）的 BMECs 中提取外泌体，纳米颗粒跟踪分析技术检测其直径和浓度，BCA 法检测外泌体总蛋白质含量，Western blot 检测外泌体 CD9、CD81、TGF-β₁ 和 VEGFA 蛋白的表达。进一步将 BMECs 分为 3 组，实验组和对照组分别分离经或未经淫羊藿苷处理的 BMECs 分泌的外泌体，与 BMECs 共培养；空白对照组为单纯 BMECs。氢化可的松处理后，采用 Western blot 检测 LC3B 和 p62 表达，划痕实验检测细胞迁移能力，并观察血管生成能力。 结果随氢化可的松浓度升高，各组 LC3B-Ⅱ蛋白相对表达量逐渐增加，p62 蛋白相对表达量减少，各组间差异均有统计学意义（P<0.01）；相同激素浓度下，淫羊藿苷干预后，LC3B-Ⅱ蛋白相对表达量减少，p62 蛋白相对表达量增加（P<0.01）。干预组外泌体浓度显著高于未干预组（t=−10.191，P=0.001）；两组外泌体直径和总蛋白质含量比较差异均无统计学意义（P>0.05）。未干预组和干预组 CD9 和 CD81 蛋白均高度表达；干预组 VEGFA/CD9 和 TGF-β₁/CD9 蛋白相对表达量比值均显著高于未干预组（P<0.01）。外泌体共培养后，空白对照组、对照组和实验组中 p62 蛋白相对表达量呈递增趋势，LC3B-Ⅱ蛋白相对表达量呈递减趋势，各组间比较差异均有统计学意义（P<0.05）。氢化可的松处理 12、24 h 时，对照组和实验组划痕闭合率明显高于空白对照组（P<0.05），实验组明显高于对照组（P<0.05）；氢化可的松处理 4、8 h 时，实验组和对照组管腔数、出芽数和小管分支长度均显著大于空白对照组（P<0.05）；实验组小管分支长度和管腔数显著大于对照组（P<0.05）。 结论淫羊藿苷及 BMECs 产生的外泌体能改善低浓度激素诱导的 BMECs 自噬，对内皮细胞起到保护作用。     

Circular RNA hsa_circ_0005114-miR-142-3p/miR-590-5p-adenomatous polyposis coli protein axis as a potential target for treatment of glioma

Glioma is the most common type of brain tumor and is associated with a high mortality rate. Despite recent advances in treatment options, the overall prognosis in patients with glioma remains poor. Studies have suggested that circular (circ)RNAs serve important roles in the development and progression of glioma and may have potential as therapeutic targets. However, the expression profiles of circRNAs and their functions in glioma have rarely been studied. The present study aimed to screen differentially expressed circRNAs (DECs) between glioma and normal brain tissues using sequencing data collected from the Gene Expression Omnibus database ({"type":"entrez-geo","attrs":{"text":"GSE86202","term_id":"86202"}}GSE86202 and {"type":"entrez-geo","attrs":{"text":"GSE92322","term_id":"92322"}}GSE92322 datasets) and explain their mechanisms based on the competing endogenous (ce)RNA regulatory hypothesis. In total, 424 commonly downregulated DECs (with the Gene_symbol annotated in the circBase database) in these two datasets were identified. Using the CircInteractome and Starbase databases, 18 micro (mi)RNAs (miRs) were predicted to interact with DECs, while 22 glioma-related genes obtained from the Comparative Toxicogenomics Database were predicted to be regulated by 15 miRNAs via the miRwalk 2.0 database. A ceRNA network was established based on 115 DECs, 15 miRNAs and 22 mRNAs. LinkedOmics online analysis using The Cancer Genome Atlas (TCGA) data showed that hsa-miR-142-3p/hsa-miR-590-5p and their target gene adenomatous polyposis coli protein (APC) were all significantly associated with overall survival rate and their prognosis trend was opposite, revealing that high expression levels of hsa-miR-142-3p/hsa-miR-590-5 were associated with a poor overall survival rate, while high APC expression with a good overall survival rate. UALCAN analysis using TCGA data of glioblastoma multiforme and the {"type":"entrez-geo","attrs":{"text":"GSE25632","term_id":"25632"}}GSE25632 and {"type":"entrez-geo","attrs":{"text":"GSE103229","term_id":"103229"}}GSE103229 microarray datasets showed that hsa-miR-142-3p/hsa-miR-590-5p was upregulated and APC was downregulated. Thus, hsa-miR-142-3p/hsa-miR-590-5p-APC-related circ/ceRNA axes may be important in glioma, and hsa_circ_0005114 interacted with both of these miRNAs. Functional analysis showed that hsa_circ_0005114 was involved in insulin secretion, while APC was associated with the Wnt signaling pathway. In conclusion, hsa_circ_0005114-miR-142-3p/miR-590-5p-APC ceRNA axes may be potential targets for the treatment of glioma.     

股骨转子间骨折的稳定性重建概念演化与研究进展

目的总结近年来股骨转子间骨折在稳定性重建方面的概念演化与研究进展。方法查阅国内外相关文献并结合自身经验，从股骨转子间骨折的解剖特点、稳定型骨折与不稳定型骨折分类、稳定性复位与不稳定性复位、术中加压初始稳定与术后滑动二次稳定、内固定术后稳定性评估、早期下地站立负重等方面进行总结分析。结果股骨转子间骨折发生于股骨颈干骺端转换区，具有天然的内翻不稳定倾向。骨折复位质量是影响后续内固定物安放的最重要前提因素。判断骨折复位质量有对线和对位两方面，对线采用 Garden 指数；在对位方面，随着皮质对位理念（正性、中性、负性）的提出，特别强调前内侧皮质的相互砥住支撑（解剖、正性），是获得骨折稳定性复位的关键，而不再强调后内侧小转子骨块的作用。术后影像学的稳定性评分为早期下地站立负重提供了量化指标。但术中的前内侧皮质支撑复位，在术后头颈骨块滑动获得二次稳定的过程中，仍有皮质对位丢失现象，需研究其危险因素和防范措施。结论股骨转子间骨折在取得良好对线的基础上，只要获得了前内侧皮质的相互砥住和支撑，并用内固定器械维持住，就获得了术后稳定性。术后稳定性评分优良者，可以安全地早期下地负重、站立行走活动。     

Nation's compensation for war wounds and work incapacities. The creation of a new welfare system for physically disabled veterans and civilians of the First World War in Interwar Belgium, 1918–1928

This article explores the creation of a new social welfare system for physically disabled veterans and civilians of the Great War in Belgium during the early interwar period. Through an analysis of debates among ministers and legislators, doctor's opinions and the member's periodicals of the two largest national associations for war-wounded veterans and civilians it examines how these actors shaped a new set of benefits that caused significant socio-economic inequalities inside and between both groups of victims and in relation to physically disabled citizens without war injuries. Consequently, this article reveals how the welfare system characterised a reimagining of war compensation, the physically disabled worker and disability equality in Belgium.     

Assessment of gas chromatography methodology approach for the trace evaluation of carcinogenic impurity,methyl chloride,in trimetazidine dihydrochloride

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Nutraceuticals use and type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a complicated metabolic disease and has become one of the significant medical problems worldwide. Researchers aim to provide fine-tuned treatment for T2DM with minimal exposed side effects. Nutraceuticals are compounds or materials and emerging evidence suggests that the use of nutraceuticals has recently been recognized as a promising option for the prevention and management of T2DM, such as probiotics and prebiotics, Vitamin D, n-3 long-chain polyunsaturated fatty acids, and Plant-derived nutraceuticals. This review attempts to show the most popular nutraceuticals and review their effects and possible mechanisms in the prevention or glycemic control of T2DM.     

脂质纳米粒-mRNA递送系统及其在嵌合抗原受体T细胞治疗中的应用

尽管嵌合抗原受体（CAR）T细胞治疗在血液系统恶性肿瘤患者中取得了显著的临床疗效，但需要进一步优化。脂质纳米粒（LNP）-信使核糖核酸（mRNA）递送系统作为一种非病毒性基因载体运用于CAR-T细胞治疗研究中，一方面通过LNP将密封蛋白-6 mRNA靶向递送至抗原提呈细胞，从而实现抗原提呈细胞辅助性增强密封蛋白-6靶向的CAR-T细胞的功能，以进一步诱导对实体瘤的清除；另一方面，通过LNP将成纤维细胞激活蛋白（FAP）CARmRNA靶向递送至T细胞，实现体内FAP靶向的CAR-T细胞的制备，以通过阻断心脏纤维化过程达到治疗急性心肌损伤的目的。在CAR-T细胞研究和治疗中，LNP-mRNA递送系统具有不与细胞基因组整合、价格便宜、毒副作用小及可修饰等优点，亦存在蛋白瞬时表达导致调控细胞功能的持久性不足及制备等方面的技术局限性。本文综述了LNP-mRNA递送系统及其在CAR-T细胞治疗中的应用研究。     

长链非编码RNA THOR在生殖与肿瘤中调控的研究现状

睾丸相关的高度保守的致癌性lncRNA(Testis-associated Highly-conserved Oncogenic long non-coding RNA,THOR)是一类非编码RNA,在哺乳动物睾丸及肿瘤组织中特异性表达,参与雄性生殖过程,调控肿瘤细胞的发生发展。本文对lnc-THOR在生殖和肿瘤中的研究进展进行综述,为雄性生殖有关疾病和肿瘤的表观遗传机制研究提供新的见解,并为其寻找潜在的治疗靶点。     

Tfh-cell-derived interleukin 21 sustains effector CD8+ T cell responses during chronic viral infection

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