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.     

附件炎性包块的诊断

附件炎性包块是指盆腔炎性疾病引起的附件区包块，多由性传播疾病的病原体（如淋病奈瑟菌和沙眼衣原体）感染引起，性生活活跃的年轻女性是高危人群。附件炎性包块会严重影响女性的生殖健康，故预防重于治疗。盆腔炎性疾病的临床表现差异较大，尚无敏感且特异的实验室检查指标，阴道超声诊断附件炎性包块的准确性较高，是临床常用的检查手段。     

The effect of Benson’s relaxation response on sleep quality and anorexia in cancer patients undergoing chemotherapy: A randomized controlled trial

Background and objectivesPatients with cancer experience many side effects due to its nature and usual treatments. Sleep disorders and anorexia are the most commonly reported symptoms in cancer patients undergoing chemotherapy. The present study aimed to investigate the effect of Benson's Relaxation Response (BRR) on sleep quality and anorexia in cancer patients undergoing chemotherapy.Methodology and participantsIn the present clinical trial, a total of 84 patients were enrolled and randomly divided into two groups of experimental and control. Benson's relaxation response was administered to the experimental group twice a day over 5 consecutive days. Data was collected using St. Mary's Hospital Sleep Questionnaire (SMHSQ) and anorexia questionnaire with Visual Analog Scale (VAS).ResultsThe results of our study showed a significant improvement in the sleep quality in the experimental group at 24 (p = 0.02) and 48 (p = 0.001) hours after the intervention compared to the control group. Benson's relaxation response (BRR) also had a significant effect on the anorexia in the experimental group at 24 (7.5 ± 1.6) and 48 (6.9 ± 2.1) hours after the intervention compared to the control group. No side effects were reported during the study and follow-up period.ConclusionBenson's relaxation response as a complementary method may improve sleep quality and anorexia in cancer patients undergoing chemotherapy. Further studies with greater sample size and longer follow-up period are needed to confirm the current findings.     

基于蛋白质组学分析色胺酮抑制小鼠乳腺癌的作用机制

目的:采用非标记定量(Label-free)蛋白质组学技术研究色胺酮抗小鼠体内乳腺癌的作用机制。方法:采用超高效液相色谱-质谱联用技术检测色胺酮抗小鼠乳腺癌的表达蛋白,选择Ionoptics nano UPLC C18色谱柱(0.075 mm×250 mm,1.6μm),流动相0.1%甲酸水溶液-0.1%甲酸乙腈溶液梯度洗脱,正离子模式,扫描范围m/z 100～1 700,使用MaxQuant 1.6.5.0进行数据库检索。采用Label-free高分辨质谱的蛋白质组学技术筛选4T1乳腺癌小鼠模型组与色胺酮(100 mg·kg~(-1))口服给药组之间的差异表达蛋白,进行色胺酮抗乳腺癌的蛋白质组学研究。结果:共鉴定出3 997个蛋白质,其中有2 911个蛋白可定量。模型组与色胺酮组共750个差异表达蛋白,其中286个蛋白上调,464个蛋白下调。基因本体分析表明,这些差异表达蛋白主要参与增殖、细胞迁移、凋亡、免疫、血管生成和炎症调节等生物学过程。京都基因与基因组百科全书通路分析进一步表明,这些蛋白主要集中于T细胞受体,B细胞受体,Toll样受体,核转录因子-κB(NF-κB),Ras蛋白,白细胞介素-17,肿瘤坏死因子,磷脂酰肌醇3-激酶/蛋白激酶B(PI3K-Akt)和丝裂原活化蛋白激酶(MAPK)等信号通路。结论:与色胺酮抗4T1乳腺癌作用密切相关的差异表达蛋白包括上调蛋白白细胞分化抗原14(CD14),前列腺素G/H合酶2(PTGS2),泛素蛋白连接酶E3和下调蛋白CD44,70 kDa热休克蛋白1A(HSPA1A),巨噬细胞移动抑制因子(MIF),NF-κB,核糖体蛋白S6激酶α-4(RPS6KA4)和高迁移率族蛋白B1(HMGB1),提示色胺酮主要通过调节肿瘤炎症微环境来达到抑制小鼠乳腺癌的作用。     

碘乙酸钠诱导的大鼠膝骨关节炎模型肠道菌群变化及其潜在影响

目的:研究碘乙酸钠诱导的大鼠膝骨关节炎(KOA)模型肠道菌群变化情况,探究肠道菌群与KOA的潜在联系。方法:将SPF级大鼠分为空白对照组和KOA组,通过膝关节局部注射碘乙酸钠制造大鼠KOA模型。通过16SrDNA检测大鼠粪便中的肠道菌群变化情况,蛋白印记法检测结肠组织中NF-κB和TNF-α蛋白表达,RT-qPCR检测结肠组织中Caspase-1和IL-1β基因表达情况,苏木精-伊红染色观察结肠黏膜通透性变化,苏木精-伊红染色观察关节滑膜和软骨组织的病理变化情况。ELISA检测血液上清中LBP,IL-1β,TNF-α及IL-10炎症因子水平。结果:与空白对照组相比,从KOA组中筛选出明显变化的肠道菌群,以Akkermansia和疣微菌门变化最为显著,结肠黏膜通透性增加,结肠组织中NF-κB p65及TNF-α蛋白表达升高,结肠组织中Caspase-1和IL-1β基因表达升高,血液中促炎因子LBP,IL-1β及TNF-α蛋白含量升高,抗炎因子IL-10蛋白含量降低。结论:KOA病理状态下肠道菌群发生变化,结肠炎症反应增强,结肠炎症反应或许在提高全身炎症反应水平、促进与肠道菌群相关的KOA的病理进程中起到重要的桥梁作用。     

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.