Immune checkpoint inhibitor-induced inflammatory arthritis: identification and management

ABSTRACT

Introduction

Immune checkpoint inhibitors (ICIs) have proved to be groundbreaking in the field of oncology. However, immune system overactivation from ICIs has introduced a novel medical entity known as immune-related adverse events (irAEs), that can affect any organ or tissue. ICI-induced inflammatory arthritis (ICI-IIA) is the most common musculoskeletal irAE and can lead to significant morbidity and limitation in anti-cancer therapy.     

Pharmacological evaluation and mechanistic study of compound Xishu Granule in hepatocellular carcinoma

ObjectiveIn this study, we used HepG2 human hepatocellular carcinoma cells to study the effects of Compound Xishu Granule (CXG) on cell proliferation, apoptosis, and the cell cycle in vitro. We also used a xenograft tumor model to study the anti-tumor effects of CXG and related mechanisms in vivo.MethodsThe effect of CXG on cell viability was measured using Cell Counting Kit-8 and a colony formation assay. The effect of CXG on apoptosis and the cell cycle was analyzed using flow cytometry. The in vivo anti-tumor effect of CXG was assessed by measuring the volume change in xenograft tumors after drug administration. The CXG anti-tumor mechanism was studied using western blotting assay to detect cell cycle and apoptotic associated proteins.ResultsCXG suppressed HepG2 cell proliferation in a time- and dose-dependent manner in vitro. Colony formation experiments showed that CXG administration for 24 h significantly reduced HepG2 cell formations (P < .01). Flow cytometric analysis showed that CXG treatment for 48 h promoted apoptosis and blocked HepG2 cells in the G2/M phase. Western blotting results showed that Bax was significantly up-regulated and Bcl-2 was down-regulated in graft tumor tissues and HepG2 cells after CXG administration, which increased the Bax/Bcl-2 ratio. PLK1, CDC25C, CDK1, and Cyclin B1 expression were up-regulated. CXG had a good inhibitory effect on graft tumor growth in vivo.ConclusionCXG has good anti-tumor effects in vitro and in vivo. In vitro, CXG promoted HepG2 cell apoptosis and induced G2/M phase arrest. In vivo, CXG significantly inhibited graft tumor growth. The CXG mechanism in treating hepatocellular carcinoma may be that CXG can induce abnormal apoptotic and cell cycle associated protein expression, leading to mitotic catastrophe and apoptosis.     

m6A结合蛋白IGF2BP1在肝细胞癌中的基因调控网络分析

目的 分析m6A阅读器胰岛素样生长因子2-mRNA结合蛋白1（insulin-like growth factor 2 mRNA-binding protein 1，IGF2BP1）在肝细胞癌（hepatocellular carcinoma，HCC）中的表达水平及其对HCC患者预后的影响，并探讨IGF2BP1在HCC发生发展中的作用及其潜在机制。方法 基于5对HCC癌及相应癌旁组织mRNA-seq数据和TCGA数据库LIHC的mRNA-seq数据综合分析IGF2BP1在HCC中的表达情况，同时利用TCGA数据库中343例HCC患者的临床随访资料分析IGF2BP1表达水平对HCC患者总生存期的影响。基于TCGA数据库筛选IGF2BP1的共表达mRNA，并利用m6Avar在线网站预测mRNA的m6A位点及其RNA结合蛋白等信息，最终构建IGF2BP1的基因调控网络。结果 IGF2BP1基因在HCC中表达上调（log2FC HCC转录组数据=10.684，P<0.001；log2FC TCGA-LIHC数据集=7.032，P<0.001）。生存分析显示IGF2BP1低表达的HCC患者中位生存时间为5.84年，IGF2BP1高表达患者为4.44年，高表达患者总生存期缩短（P=0.011）。22个差异表达的mRNA与IGF2BP1存在靶向结合关系，并与其表达水平呈正相关。其中，HMGA2等15个高表达mRNA的HCC患者总生存期缩短。HMGA2、PEG10、CEP55、RHO、CDC6和KIF23基因中的潜在m6A甲基化位点位于mRNA 3'UTR端的miRNA结合区域。结论 IGF2BP1在HCC中高表达且导致患者总生存期缩短。IGF2BP1可能通过m6A甲基化及miRNA抑制作用的方式上调mRNA的表达，促进HCC发生并导致不良预后。     

Characterization of Malignant Portal Vein Thrombosis with Contrast-Enhanced Ultrasonography

We prospectively evaluated the effectiveness of contrast-enhanced ultrasonography (CEUS) for differentiation of benign versus malignant portal vein thrombosis (PVT). We studied a total of 43 patients with chronic liver disease, hepatocellular carcinoma-suggestive nodules and confirmed PVT, in whom the nature of the PVT was confirmed by follow-up imaging (US, computed tomography and/or magnetic resonance imaging) performed up to 6 mo after CEUS. PVT was assessed by US, Doppler US and CEUS with respect to vessel wall disruption and/or invasion, color Doppler vascularization, pulsed Doppler vascularization pattern and CEUS enhancement and vascularization pattern, and thrombi were classified as benign or malignant based on these findings. Follow-up studies revealed malignant PVT in 22 of the 43 patients (51%) and benign PVT in 21 patients (49%). CEUS findings were consistent with follow-up studies in 41 of the 43 patients (95%), with κ?=?0.903 (p < 0.0001), sensitivity?=?91% and specificity?=?100%, indicating that CEUS can be confidently used to differentiate benign from malignant portal vein thrombosis in the setting of chronic liver disease.     

二维斑点追踪技术评价低温兔左室纵向功能

目的:探讨应用二维斑点追踪技术评价低温条件下兔左心室纵向功能的价值。方法:30只新西兰兔随机分成对照组(n=10),低温组A(n=10),低温组B(n=10)。先行常规心脏数据测量,然后采用组织多普勒(TDI),之后应用斑点追踪成像(STI)中的获取基底段、中间段、心尖段及整体水平SL、SrLs.SrL E,SrL A及分层应变技术获取3个长轴切面心内膜下、中层和心外膜下心肌收缩期纵向峰值应变(SL)。结果:①与对照组相比,A组心内膜下心肌LS值的减低,差异有统计学意义(P<0.05),B组3层心肌SL值的减低明显,差异有统计学意义(P<0.01)②与对照组相比,A组大部分纵向应变及应变率减低(P<0.05);B组基底段、中间段、心尖段及整体水平SL,SrL S、SrLE、SrLA均减低(P<0.01)结论:随低温时间延长,左室壁3层心肌SL值受累程度不同,心内膜应变较心外膜更加敏感,二维班点追踪技术比LVEF及TDI更早发现左室功能减低。     

偏瘫性肩痛患者腋囊的MRI观测及临床意义

目的通过MRI技术观察偏瘫患者肩疼痛腋囊形态变化,为影像诊断提供依据。方法对47例偏瘫性肩疼痛患者(疼痛组)和47例正常肩部(对照组),运用MRI技术对肩关节腋囊进行测量,观察腋囊下肱盂韧带信号。结果偏瘫性肩疼痛的腋囊厚度(4.1±1.45)mm,高于对照组。腋囊腔高度(8.70±1.80)mm,腋囊腔宽度(4.31±0.56)mm,小于对照组。偏瘫性肩痛下肱盂韧带呈高信号出现率达21%,腋囊厚度与VAS呈正相关,与肩关节外展外旋呈负相关。结论脑中风中后期肩周炎是引起偏瘫性肩疼痛患者的常见原因,腋囊厚度是限制肩关节活动度的重要因素。     

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。     

Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.     

A Novel Nomogram to Identify Candidates for Extended Pelvic Lymph Node Dissection Among Patients with Clinically Localized Prostate Cancer Diagnosed with Magnetic Resonance Imaging-targeted and Systematic Biopsies

Background

Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.