Cellular functions regulated by deubiquitinating enzymes in neurodegenerative diseases

Neurodegenerative diseases are one of the most common diseases in mankind. Although there are reports of several candidates that cause neurodegenerative diseases, the exact mechanism of pathogenesis is poorly understood. The ubiquitin-proteasome system (UPS) is an important posttranslational modification for protein degradation and control of homeostasis. Enzymes such as E1, E2, E3 ligases, and deubiquitinating enzymes (DUBs) participating in UPS, regulate disease-inducing proteins by controlling the degree of ubiquitination. Therefore, the development of treatments targeting enzymes for degenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), is emerging as an attractive perspective. In particular, as DUBs are able to regulate one or more degenerative disease-related proteins, the potential as a therapeutic target is even more evident. DUBs influence the regulation of toxic proteins that cause neurodegenerative diseases by not only their removal, but also by regulating signals associated with mitophagy, autophagy, and endoplasmic reticulum-associated degradation (ERAD). In this review, we analyze not only the cellular processes of DUBs, which control neurodegenerative disease-inducing proteins, but also their potentials as a therapeutic agent for neurodegenerative diseases.     

浙江省2013-2015年学生男男性行为人群HIV-1亚型与分子传播簇特征分析

目的 了解浙江省12～30岁学生MSM HIV-1亚型及传播簇的特征。方法 以2013-2015年浙江省新确诊290例经男男性行为感染的学生HIV感染者（学生MSM感染者）为研究对象,开展HIV分子流行病学研究。收集流行病学相关信息,从采集的血浆中提取RNA,运用RT-PCR和巢式PCR扩增HIV-1的pol区基因,进行系统进化和分子传播簇分析。结果 290例学生MSM感染者中,杭州市确诊的占50.3%,大专及以上文化程度占81.0%。成功获取178例序列,有10种亚型,以CRF01_AE（49.4%,88/178）和CRF07_BC（39.3%,70/178）亚型为主。共形成18个分子传播簇（簇大小：2～4例/簇）,成簇比例为23.6%（42/178）,簇内学生MSM感染者所在学校为同一县（区、市）的占61.9%（26/42）,其性伴类型为学生和非学生并存。中学生MSM感染者的成簇比例为38.2%（13/34）,高于大学生MSM感染者的成簇比例20.1%（29/144）（χ²=4.996,P<0.05）。结论 2013-2015年浙江省学生MSM感染者的HIV-1亚型多样,提示HIV-1感染来源的多样化,HIV-1分子传播簇内的毒株呈现地理的相对聚集性,应加强性伴追踪和针对性干预,有效遏制艾滋病的传播。     

纳米蜂胶对实验性高脂血症大鼠脂质代谢的影响

 目的探讨纳米蜂胶对实验性高脂血症大鼠脂质代谢的影响。方法采用动物实验法,观察不同剂量纳米蜂胶对高脂血症大鼠体重、肝重、血清总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)浓度及脂蛋白脂酶(LPL)、肝脂酶(HL)、卵磷脂胆固醇酰基转移酶(LCAT)活性的影响。结果纳米蜂胶对高脂血症大鼠的体重、肝重及HDL-C含量无显著影响,但各剂量组纳米蜂胶均可显著提高LPL、HL的活力(P<0.01,P<0.05),中、高剂量纳米蜂胶可显著降低血清TC值和显著提高LCAT活力(P<0.05,P<0.01),高剂量组纳米蜂胶可使LDL-C含量、肝指数和动脉硬化指数(AI)显著下降(P<0.05)。结论纳米蜂胶具有明显降低血清胆固醇的作用,可能与提高血酯蛋白相关酶活性有关。     

基于脂肪抑制增强T1WIDelta影像组学预测鼻咽癌患者放射治疗后口干分级

目的 基于脂肪抑制(FS)增强T1WI构建预测放射治疗(放疗)后鼻咽癌(NPC)患者口干级别的Delta影像组学模型，并评估其效能。方法 回顾性分析227例于诱导化学治疗(IC)后接受放疗或同步放化疗(CCRT)NPC患者IC前2周内及IC结束后鼻咽部MRI。于放疗结束后1周根据放射治疗肿瘤协作组标准评估患者口干分级(0～4级),将0、1级口干归为轻度口干(n=81),≥2级口干归为重度口干(n=146)。基于IC前、后FS增强T1WI提取双侧腮腺影像组学特征，计算Delta影像组学特征值。采用最小绝对收缩和选择算子和随机森林算法降维，筛选最优Delta影像组学特征，构建Delta影像组学模型。按8∶2比例将患者分为训练集(n=182)及测试集(n=45),绘制受试者工作特征(ROC)曲线，计算曲线下面积(AUC),评估Delta影像组学模型预测训练集及测试集NPC患者放疗后口干分级的效能；绘制校准曲线，评估模型性能。结果 分别基于IC前、后FS增强T1WI提取2 286个影像组学特征，最终筛选出8个最优Delta影像组学特征并以之构建模型，其预测训练集和测试集NPC患者放疗后口干分级...     

热疗联合免疫检查点抑制剂的基础研究和临床应用进展北大核心CSCD

恶性肿瘤传统治疗方法对晚期转移患者疗效欠佳。近年来免疫检查点抑制剂治疗发展迅速,极具潜力,但整体临床有效率不高。肿瘤通过多种机制改变肿瘤微环境,产生免疫耐药,从而大大降低了免疫检查点抑制剂的疗效。热疗不仅可发挥热效应的抗肿瘤优势,还可通过多种途径起到直接和间接免疫增敏作用,将"冷肿瘤"转变为"热肿瘤",从而多方面起到增强免疫检查点抑制剂疗效的作用。大量基础实验证明,在小鼠体内进行热疗联合免疫检查点抑制剂已取得较好效果。目前,部分正在开展的热疗联合免疫检查点抑制剂临床试验也已取得较好进展。本文从免疫检查点抑制剂、热疗、热疗联合免疫检查点抑制剂3个层面分析了联用优势,并展望了未来热疗联合免疫检查点抑制剂治疗的重点研究方向。     

Effectiveness of mind-body exercise via Baduanjin on physical and psychological outcomes in patients with pulmonary ground-glass nodules: A non-randomized controlled pilot study

BackgroundWith the increasing incidence and mortality of lung cancer, ground-glass nodules (GGNs) have become an ongoing public health concern. In clinical practice, the physical and psychological distress of GGN patients is easy to overlook during the follow-up after diagnosis. Such patients typically have limited medical options and few of these options involve mind-body exercises.ObjectiveThe purpose of this pilot study was to explore the effectiveness of the mind-body exercise Baduanjin on physical and psychological outcomes among GGN patients.DesignWe conducted a prospective, non-randomized, controlled, assessor-blinded trial (ClinicalTrials.gov: NCT03420885).SettingThis trial was conducted at three medical sites, both located in Shanghai, China, between April 2017 and January 2020.ParticipantsPatients with GGN.InterventionSixty GGN participants were divided into a health education control group only receiving health education (n = 30) and a Baduanjin intervention group receiving health education plus a Baduanjin training program (n = 30). Both groups were treated for 16 weeks.Outcome measurementsOutcomes were assessed at baseline and week 16. The primary outcomes included pulmonary function (FVC, FVC%, FEV₁, FEV₁/FVC, PEF) and psychological condition (SAS score, SDS score). The secondary outcome was quality of life (SF-36).ResultsCompared with the health education control group, the Baduanjin intervention group had significant improvements in pulmonary function (FVC, FVC%, FEV₁), psychological outcomes (SAS score, SDS score), and quality of life (SF-36). The significant differences in pre-intervention and post-intervention between groups were as follows: FVC (MD = 0.21, 95%CI: 0.10 to 0.33, P = 0), FVC% (MD = 6.90, 95%CI: 3.10 to 10.70, P = 0.001), FEV₁ (MD = 0.18, 95%CI: 0.07 to 0.29, P = 0.001); SAS score (MD = −4.90, 95%CI: −8.28 to −1.52, P = 0.005), SDS score (MD = −5.83, 95%CI: −9.46 to −2.21, P = 0.002); physical component summary (PCS) of SF-36 (MD = 5.03, 95%CI: 2.54 to 7.51, P = 0), mental component summary (MCS) of SF-36 (MD = 5.78, 95%CI: 2.64 to 8.92, P = 0.001). Linear regression analysis was performed to study the influence of confounder variables on the improvements of primary outcomes, and no significant change was found. Moreover, Pearson correlation coefficient analysis demonstrated that ameliorations in lung function (FVC, FVC%, FEV₁, FEV₁/FVC, and PEF) were significantly associated with a decrease in anxious symptoms and depressive symptoms.ConclusionGGN patients in the Baduanjin intervention group showed greater benefits in pulmonary function and psychological outcomes than those in the health education control group, and the effectiveness was stable. The findings support Baduanjin as an effective, safe, enjoyable, and promising complementary intervention for management of GGN in patients with physical and psychological distress.