关节镜联合富血小板血浆对膝关节半月板损伤患者膝关节功能和生活质量的影响

目的:探讨关节镜联合富血小板血浆对膝关节半月板损伤患者膝关节功能和生活质量的影响。方法:选取2017年12月-2019年9月期间我院收治的膝关节半月板损伤患者80例,根据随机数字表法分为对照组(n=40)和研究组(n=40),对照组予以关节镜下修整手术治疗,研究组在对照组基础上联合富血小板血浆治疗,比较两组患者优良率、生活质量及视觉模拟评分量表(VAS)、Lysholm评分量表、美国西安大略和麦克马斯特大学关节炎指数(WOMAC)评分。记录两组治疗期间不良反应情况。结果:研究组治疗后3个月的膝关节功能优良率高于对照组(P0.05)。两组治疗前、治疗后1个月、治疗后3个月VAS、WOMAC评分均逐步降低,Lysholm评分逐步升高(P0.05);研究组治疗后1个月、治疗后3个月VAS、WOMAC评分低于对照组,Lysholm评分高于对照组(P0.05)。两组治疗后3个月SF-36各维度评分均较治疗前升高,且研究组高于对照组(P0.05)。两组不良反应发生率对比未见统计学差异(P0.05)。结论:关节镜联合富血小板血浆治疗膝关节半月板损伤患者,可促进膝关节功能的恢复,可有效缓解手术治疗后的疼痛症状,改善患者生活质量,具有较好的临床应用价值。     

不同分级及转归脓毒症患者血清PCT、D-D、CRP及血小板相关参数检测的临床意义

目的:探讨不同分级及转归脓毒症患者的血清降钙素原(PCT)、D-二聚体(D-D)、C反应蛋白(CRP)及血小板相关参数检测的临床意义。方法:回顾性分析2015年3月至2018年8月期间中国人民解放军西部战区总医院收治的92例脓毒症患者的临床资料,分析不同分级及转归脓毒症患者的血清中PCT、D-D和CRP水平、急性病生理与慢性健康评价系统Ⅱ(APACHEⅡ)评分及血小板相关参数[血小板计数(PLT)、血小板平均容积(MPV)、血小板分布宽度(PDW)、大型血小板比率(P-LCR)],并分析脓毒症患者PCT、D-D、CRP水平以及血小板相关参数与APACHEⅡ评分的相关性。结果:全身炎症反应综合征组、轻度脓毒症组、严重脓毒症组、脓毒性休克组血清PCT、D-D和CRP水平、MPV、PDW、P-LCR、APACHEⅡ评分逐渐升高(P0.05),PLT逐渐降低(P0.05)。存活组患者血清PCT、D-D、CRP水平、MPV、PDW、P-LCR、APACHEⅡ评分均低于死亡组(P0.05),PLT高于死亡组(P0.05)。Pearson相关分析显示,脓毒症患者血清PCT、D-D、CRP、MPV、PDW、P-LCR与APACHE II评分呈正相关(P0.05),PLT与APACHE II评分呈负相关(P0.05)。结论:脓毒症患者血清PCT、D-D、CRP及血小板相关指标可能参与了脓毒症的发展,通过检测其血清PCT、D-D、CRP水平及血小板相关参数可评估脓毒症患者的病情和预后。     

A Prognostic Model to Predict Recovery of COVID-19 Patients Based on Longitudinal Laboratory Findings

Virologica Sinica - The temporal change patterns of laboratory data may provide insightful clues into the whole course of COVID-19. This study aimed to evaluate longitudinal change patterns of key...     

Aggregation properties of cold-active lipase produced by a psychrotolerant strain of Pseudomonas palleroniana (GBPI_508)

Abstract

The present study aims to exploit microbial potential from colder region to produce lipase enzyme stable at low temperatures. A newly isolated bacterium GBPI_508 from Himalayan environment, was investigated for the production of cold-active lipase emphasizing on its aggregation properties. Plate based assays followed by quantitative production of enzyme was estimated under different culture conditions. Further characterization of partially purified enzyme was done for molecular weight determination and activity and stability under varying conditions of pH, temperature, and in presence of organic solvents, inhibitors, and metal ions. The psychrotolerant bacterium was identified as Pseudomonas palleroniana following 16S rRNA gene sequencing. Maximum lipase production by GBPI_508 was recorded in 7?days at 25?°C utilizing yeast extract as nitrogen source and olive oil as substrate in the lipase production medium. Triton X-100 (1%) in the medium as emulsifier significantly enhanced the lipase production. Lipase produced by bacterium showed aggregation which was confirmed by dynamic light scattering and native PAGE. SDS-PAGE followed by zymogram analysis of partially purified enzyme showed two active bands of ～50?kDa and ～54?kDa. Optimum activity of partially purified enzymatic preparation was recorded at 40?°C while the activity remained nearly consistent from pH 7.0 to 12.0, whereas, maximum stability was recorded at pH values 7.0 and 11.0 at 25?°C. Interestingly, lipase in the partially purified fraction retained 60% enzyme activity at 10?°C. Medium chain pNP ester (C10) was the most preferred substrate for the lipase of GBPI_508. The lipase possessed >50% residual activity when incubated with different organic solvents (25% v/v) except toluene and dichloromethane which inhibited the activity below 50%. Partially purified enzyme was also stable in the presence of metal ions and inhibitors. The study suggests applicability of GBPI_508 lipase in low temperature conditions such as cold-active detergent formulations and cold bioremediation.     

Discovery of biphenyl pyrazole scaffold for neurodegenerative diseases: A novel class of acetylcholinesterase-centered multitargeted ligands

Multitargeted ligands have demonstrated remarkable efficiency as potential therapeutics for neurodegenerative diseases as they target multiple pathways involved in the progression of these diseases. Herein, we report first-in-class dual inhibitor of acetylcholinesterase (AChE) and tau aggregation as a novel class of multitargeted ligands for neurodegenerative diseases. The reported biphenyl pyrazole scaffold binds monomeric tau with submicromolar affinity and impedes the formation of tau oligomers at early stages. Additionally, the lead compound inhibited AChE activity with an IC₅₀ value of 0.35 ± 0.02 μM. Remarkably, the neuroprotective effect of this lead in induced cytotoxicity model of SH-SY5Y neuroblastoma cells is superior to single-targeted AChE and tau-aggregation inhibitors. This scaffold would enable development of new generation of multitargeted ligands for neurodegenerative diseases that function through dual targeting of AChE and monomeric tau.     

β‐amyloid model core peptides: Effects of hydrophobes and disulfides

The mechanism by which a disordered peptide nucleates and forms amyloid is incompletely understood. A central domain of β‐amyloid (Aβ21–30) has been proposed to have intrinsic structural propensities that guide the limited formation of structure in the process of fibrillization. In order to test this hypothesis, we examine several internal fragments of Aβ, and variants of these either cyclized or with an N‐terminal Cys. While Aβ21–30 and variants were always monomeric and unstructured (circular dichroism (CD) and nuclear magnetic resonance spectroscopy (NMRS)), we found that the addition of flanking hydrophobic residues in Aβ16–34 led to formation of typical amyloid fibrils. NMR showed no long‐range nuclear overhauser effect (nOes) in Aβ21–30, Aβ16–34, or their variants, however. Serial ¹H‐¹⁵N‐heteronuclear single quantum coherence spectroscopy, ¹H‐¹H nuclear overhauser effect spectroscopy, and ¹H‐¹H total correlational spectroscopy spectra were used to follow aggregation of Aβ16–34 and Cys‐Aβ16–34 at a site‐specific level. The addition of an N‐terminal Cys residue (in Cys‐Aβ16–34) increased the rate of fibrillization which was attributable to disulfide bond formation. We propose a scheme comparing the aggregation pathways for Aβ16–34 and Cys‐Aβ16–34, according to which Cys‐Aβ16–34 dimerizes, which accelerates fibril formation. In this context, cysteine residues form a focal point that guides fibrillization, a role which, in native peptides, can be assumed by heterogeneous nucleators of aggregation.     

Role of a noncanonical disulfide bond in the stability,affinity, and flexibility of a VHH specific for the Listeria virulence factor InlB

A distinguishing feature of camel (Camelus dromedarius) VHH domains are noncanonical disulfide bonds between CDR1 and CDR3. The disulfide bond may provide an evolutionary advantage, as one of the cysteines in the bond is germline encoded. It has been hypothesized that this additional disulfide bond may play a role in binding affinity by reducing the entropic penalty associated with immobilization of a long CDR3 loop upon antigen binding. To examine the role of a noncanonical disulfide bond on antigen binding and the biophysical properties of a VHH domain, we have used the VHH R303, which binds the Listeria virulence factor InlB as a model. Using site directed mutagenesis, we produced a double mutant of R303 (C33A/C102A) to remove the extra disulfide bond of the VHH R303. Antigen binding was not affected by loss of the disulfide bond, however the mutant VHH displayed reduced thermal stability (T_m = 12°C lower than wild‐type), and a loss of the ability to fold reversibly due to heat induced aggregation. X‐ray structures of the mutant alone and in complex with InlB showed no major changes in the structure. B‐factor analysis of the structures suggested that the loss of the disulfide bond elicited no major change on the flexibility of the CDR loops, and revealed no evidence of loop immobilization upon antigen binding. These results suggest that the noncanonical disulfide bond found in camel VHH may have evolved to stabilize the biophysical properties of the domain, rather than playing a significant role in antigen binding.     

西藏飞蝗蝗蝻群集迁移特性及其群集效应

西藏飞蝗Locusta migratoria tibetnsis Chen暴发成灾的重要原因之一是蝗蝻具有群集迁移危害习性。为阐明西藏飞蝗灾变的行为机制,为西藏飞蝗的监测预警和防治提供科学依据,利用视频跟踪技术测定了自然环境中西藏飞蝗蝗蝻群集迁移的运动速度、方向,建立自推进粒子模型模拟蝗蝻群集迁移行为,分析群集迁移效应。结果表明,①不同自然环境中的西藏飞蝗蝗蝻在群集迁移过程中,群体内个体的运动表现出定向集体运动,群集迁移速度为0.1256 m/s,0.2 m以内的个体蝗蝻方向趋向一致。沙滩、翻耕农田和草地蝗蝻群运动一致性参数均较高,分别为0.8502、0.7870和0.6987。②西藏飞蝗蝗蝻群由分散运动转变为群集迁移存在临界密度,密度较低时群体内个体分散运动,当蝗蝻密度达到12-15头/m²时,蝗蝻群体由分散运动转变为高度一致的群集迁移运动。③蝗蝻群通过群集迁移可以显著增加迁移距离,随机运动蝗蝻1 d扩展只有70-80 m,而群集迁移1 d最大距离可达2.5 km。蝗蝻群集迁移可以提高发现特别是远距离食物等资源的概率,使群体中更多的个体受益。④尽管未发现室外蝗蝻群存在先验个体,但模拟发现在群集迁移群体中,只需要少数先验个体（3%-5%）即可引导整个蝗蝻群运动。