沙库巴曲缬沙坦在心力衰竭治疗中的应用

心力衰竭是一种慢性疾病，是心脏无法泵出足够的血液为其他身体器官提供氧气，从而引发呼吸短促、疲劳和水肿等症状。目前其治疗包括病因治疗、一般治疗、药物治疗及非药物治疗等，其中血管紧张素受体脑啡肽酶抑制剂（ARNI）是当前新研发出的一类抗心衰药物，沙库巴曲缬沙坦是其代表药物，具有阻断肾素-血管紧张-醛固酮系统（RAAS）及抑制脑啡肽酶（NEP）的双重作用，新的欧美指南均推荐用于射血分数降低心力衰竭（HFrEF）的治疗。本文现就沙库巴曲缬沙坦在心力衰竭治疗中的作用机理、临床试验、药物安全性作一综述，旨在为该病的临床治疗提供参考。     

华细辛和北细辛HPLC特征图谱识别与抗炎靶点及抗炎成分分析

建立华细辛和北细辛HPLC特征图谱并结合聚类分析研究2种来源细辛的识别方法;应用网络药理学方法预测细辛潜在抗炎靶点并寻找潜在抗炎成分。对89批细辛药材(12批华细辛和77批北细辛)的数据进行分析确定了11个特征峰,用对照品、紫外光谱和LC-MS指认了11个特征成分。特征峰面积聚类分析显示华细辛和北细辛被分为2类,且利用特征峰面积比值可实现两者区分,当特征峰9(细辛素)/参照峰S(卡枯醇)峰面积比值大于5时为华细辛,小于2时为北细辛。对119种细辛成分进行网络药理学分析的结果表明细辛抗炎作用可能与COX-2,COX-1,iNOS,MAPK14,LAT4H,NR3C1,PPARG和TNF等8个靶点相关,其中COX-2最为关键,与5种特征成分细辛脂素、芝麻脂素、细辛素、甲基丁香酚和黄樟醚均存在相互作用。此外,细辛脂素、芝麻脂素与iNOS,MAPK14也存在相互作用关系,黄樟醚和细辛素可作用于iNOS,COX-1,LAT4H,甲基丁香酚可作用于COX-1,LAT4H。细辛脂素与芝麻脂素均可作用在COX-2,iNOS和MAPK143个靶点上,提示它们是细辛发挥抗炎作用的活性成分;COX-2分子对接结果和COX-2活性实验结果验证了细辛脂素、芝麻脂素可抑制COX-2活性,为细辛抗炎作用活性成分。基于HPLC特征图谱的华细辛和北细辛识别方法简便易行;预测到的细辛抗炎靶点和抗炎成分为完善细辛质量评价体系奠定了基础。     

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.     

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。     

多原发结直肠癌的临床特征和预后

目的探讨多原发结直肠癌的临床特征和预后。方法回顾性分析南京医科大学第一附属医院2013年1月至2018年12月收治的42例多原发结直肠癌患者的临床资料,对其临床病理特征、诊治及预后进行总结。结果符合多原发结直肠癌诊断的患者42例,占同期收治的所有结直肠癌患者的1.20%(42/3499),病理类型以腺癌为主。其中,同时性多原发癌32例,年龄38~86岁,中位年龄66岁,共发现73处结直肠癌灶,多位于近端结肠、乙状结肠及直肠;共检出淋巴结527枚,阳性10枚(1.9%),淋巴结阳性患者占同时性多原发癌的37.5%(12/32);27例为双原发癌,3例为三原发癌,2例为五原发癌;1、3年总生存率分别为83.75%和74.38%。异时性多原发癌10例,年龄33~86岁,第一癌多位于直肠和乙状结肠区域,第二癌多位于升结肠区域;共检出淋巴结276枚,阳性率12.3%(34枚),1、3年总生存率分别为100.00%和66.67%。结论多原发结直肠癌在临床上不少见,其分布有一定规律。临床中应引起重视,提高早期诊断率。应早期手术治疗以提高患者的生存率。     

Learning to Discretize: Solving 1D Scalar Conservation Laws via Deep Reinforcement Learning

Conservation laws are considered to be fundamental laws of nature. It has broad applications in many fields, including physics, chemistry, biology, geology, and engineering. Solving the differential equations associated with conservation laws is a major branch in computational mathematics. The recent success of machine learning, especially deep learning in areas such as computer vision and natural language processing, has attracted a lot of attention from the community of computational mathematics and inspired many intriguing works in combining machine learning with traditional methods. In this paper, we are the first to view numerical PDE solvers as an MDP and to use (deep) RL to learn new solvers. As proof of concept, we focus on 1-dimensional scalar conservation laws. We deploy the machinery of deep reinforcement learning to train a policy network that can decide on how the numerical solutions should be approximated in a sequential and spatial-temporal adaptive manner. We will show that the problem of solving conservation laws can be naturally viewed as a sequential decision-making process, and the numerical schemes learned in such a way can easily enforce long-term accuracy. Furthermore, the learned policy network is carefully designed to determine a good local discrete approximation based on the current state of the solution, which essentially makes the proposed method a meta-learning approach. In other words, the proposed method is capable of learning how to discretize for a given situation mimicking human experts. Finally, we will provide details on how the policy network is trained, how well it performs compared with some state-of-the-art numerical solvers such as WENO schemes, and supervised learning based approach L3D and PINN, and how well it generalizes.     

极速实时荧光聚合酶链反应与常规方法对新型布尼亚病毒检测的评价

目的探讨极速实时荧光聚合酶链反应(polymerase chain reaction,PCR)、实时荧光PCR、酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)和胶体金免疫层析法(gold immunochromatography assay,GICA)4种方法检测新型布尼亚病毒的特异度和灵敏度,为发热伴血小板减少综合征的早期诊断提供依据。方法采集2017年6月1日至9月30日山东大学附属济南市传染病医院86例临床诊断为发热伴血小板减少综合征患者的血清样本,分别应用极速实时荧光PCR、实时荧光PCR、ELISA和GICA 4种方法进行检测。统计学分析采用χ^2检验。结果86份患者血清标本中,极速实时荧光PCR、实时荧光PCR、IgM-ELISA、IgG-ELISA、IgM-GICA、IgG-GICA的新型布尼亚病毒阳性分别为82份(95.34%)、79份(91.86%)、41份(47.67%)、8份(9.3%)、19份(22.09%)和3份(3.49%)。极速实时荧光PCR特异度为100%,灵敏度达到1×103拷贝/mL,3次重复扩增试验显示其Ct值变异系数均<2%。在发热伴血小板减少综合征进展的1期、2期、3期病程中,极速实时荧光PCR的阳性检出率为41份(97.62%)、34份(94.44%)、7份(87.50%),实时荧光PCR的阳性检出率为39份(92.86%)、33份(91.67%)、7份(87.50%),在1期和2期两个病程,极速实时荧光PCR阳性检出率略高;IgM-ELISA阳性检出率从1期(28.57%)到3期(87.50%)显著增高,2期、3期与1期相比,差异均有统计学意义(χ^2=8.347、7.561,均P<0.01);IgM-GICA的阳性检出率从1期(14.29%)到2期(33.33%)也有增高,差异有统计学意义(χ^2=3.962,P<0.05),但与其他方法相比,其检出率偏低。1期,实时荧光PCR阳性检出率显著高于ELISA(IgM和IgG)和GICA(IgM和IgG),差异均有统计学意义(χ^2=33.740、55.080、49.010、64.340,均P<0.01)。2期,实时荧光PCR的阳性检出率高于ELISA(IgM和IgG)和GICA(IgM和IgG),差异均有统计学意义(χ^2=7.700、46.720、23.700、50.630,均P<0.01)。3期,极速实时荧光PCR、实时荧光PCR和IgM-ELISA表现出同样高的阳性检出率,远高于IgG-ELISA和GICA(IgM和IgG)。实时荧光PCR阳性检出率和IgG-ELISA、IgM-GICA、IgG-GICA之间差异均有统计学意义(均χ^2=6.250,P<0.05)。结论极速实时荧光PCR在新型布尼亚病毒的早期检测中有更高的灵敏度和特异度,且重复性好、稳定度高,与传统实时荧光PCR相比大大缩短了扩增时间,对发热伴血小板减少综合征的早期快速诊断具有重要价值。     

胃食管反流病与功能磁共振技术

随着对胃食管反流病研究的深入,大脑和食管感觉及胃排空的相互作用越来越受到重视,功能磁共振成像技术,有助于进一步了解胃食管反流病的发病机制。