血清中WBC、CRP和PCT检测对细菌性肺炎的临床价值

目的探讨血清白细胞计数(WBC)、C-反应蛋白(CRP)和降钙素原(PCT)对细菌性肺炎的临床价值。方法本院2015年5月-2017年9月收治肺炎患者160例,其中包括细菌性肺炎100例,非细菌性肺炎60例,选择同时期健康体检者60例,作为对照组,分别测定WBC、CRP、PCT的水平,同时比较细菌性肺炎患者预后不同指标的差异。结果与对照组比较,细菌性肺炎组和非细菌性肺炎组WBC、CRP和PCT这三项水平均升高(Ps0.05),且细菌性肺炎组这三项指标水平均显著高于非细菌性肺炎组(Ps0.05)。在细菌性肺炎组中,死亡者的这三项指标均明显高于存活者(Ps0.05)。在单项检测中,PCT敏感性和特异性最高,WBC最低(Ps0.05);三项联合检测敏感性和特异性高于单项检测(Ps0.05)。结论血清中WBC、CRP和PCT这三项指标对细菌性肺炎的诊断和预后有一定评估价值。     

血清降钙素原联合血培养对ICU患者菌血症的早期诊断价值

目的 评价血清降钙素原(PCT)对ICU重症患者菌血症早期诊断的临床应用价值.方法 用全自动快速定量法和免疫浊度法分别测定30例ICU重症菌血症患者的血清PCT和CRP浓度,并与血培养结果进行比较.结果 菌血症组血培养、PCT及PCT+血培养的阳性率高于非菌血症组(P＜0.0l),而CRP则在两组之间差异无统计学意义(P＞0.05).PCT联合血培养检测对菌血症诊断的灵敏度、特异性、阳性预测值、阴性预测值分别为96.7％、93.3％、90.0％和93.3％,均高于血培养、CRP及PCT.在研究的30例菌血症患者中,血培养出23株病原菌,主要包括表皮葡萄球菌和大肠埃希菌.结论 PCT和血培养联合检测对ICU患者菌血症的早期诊断有较高价值.     

脑脊液乳酸和血清降钙素原及C反应蛋白 对小儿细菌性脑膜炎的诊断价值

目的探讨脑脊液乳酸、血清降钙素原及C反应蛋白对小儿细菌性脑膜炎的诊断价值。方法选取我院2016年4月至2017年6月收治的50例细菌性脑膜炎患儿以及50例病毒性脑膜炎患儿进行作为研究对象,比较2类患儿脑脊液乳酸(LA)、血清降钙素原(PCT)及C反应蛋白(CRP)的水平,并分析其诊断价值。结果细菌性脑膜炎组患儿脑脊液LA、血清PCT及CRP水平显著高于病毒性脑膜炎患儿(均P0.05)。血清PCT诊断的灵敏度和特异度最高(96.4%、90.9%,P0.05)。3项指标联合检测的灵敏度(100.0%)和特异度(95.5%)明显高于任一单项指标(均P0.05)。经过Pearson相关性分析,脑脊液LA、血清PCT及CRP与小儿细菌性脑膜炎均呈显著正相关关系(均P0.05)。结论脑脊液乳酸、血清PCT及CRP对小儿细菌性脑膜炎的诊断和治疗效果监测有重要应用价值。     

CRP、PCT、WBC联合检测对中老年社区获得性肺炎的诊断效果

目的:研究C反应蛋白(C-reactive protein,CRP)、降钙素原(Procalcitonin,PCT)以及白细胞(White blood cell,WBC)联合检测对中老年社区获得性肺炎患者的诊断效果。方法:选择2018年1月～2019年1月我院收治的76例中老年社区获得性肺炎患者为观察组,同期在我院体检中心选取30例健康体检者为对照组。检测两组研究对象的CRP、PCT及WBC水平。采取肺炎严重程度CURB-65评分将观察组的76例患者分为低危组(n=63例),CURB-65评分3分,以及高危组(n=13例),CURB-65评分≥3分;依照观察组的转归情况分为存活组(n=70例)以及死亡组(n=6例),比较观察组和对照组患者,低危组和高危组患者,存活组和死亡组患者的CRP、PCT及WBC水平的差异。结果:观察组患者的CRP、PCT及WBC水平明显高于对照组(P0.05);高危组患者的CRP、PCT水平明显高于低危组患者(P0.05),而WBC水平两组无明显差异(P0.05);死亡组患者的CRP、PCT水平明显高于存活组患者(P0.05),而WBC水平两组无明显差异(P0.05)。经Pearson相关分析发现,CURB-65评分与PCT、CRP均呈明显的正相关(t=0.532,0.497,P均0.05)。结论:CRP、PCT以及联合检测可以为中老年社区获得性肺炎的诊断提供有利的信息,且CRP、PCT与患者的病情严重程度有一定的相关性。     

SAA和CRP联合检测在小儿感染性疾病鉴别诊断中的应用价值

目的探讨血清淀粉样蛋白A(SAA)和C-反应蛋白(CRP)联合检测在小儿感染性疾病鉴别诊断中的临床价值。方法选取2012年1月至2013年12月间住院患儿166例,分为细菌感染组72例,病毒感染组94例,采用免疫比浊法检测急性期和恢复期水平,并与30例健康儿童进行比较分析。结果细菌感染组SAA和CRP浓度显著高于病毒感染组和对照组,病毒感染组SAA显著高于对照组(P0.05)。细菌感染组中重症组SAA和CRP浓度显著高于轻症组,轻症组SAA和CRP浓度显著高于对照组(P0.05)。SAA和CRP单独检测阳性率较低,两者联合检测能提高检出率。结论 SAA和CRP联合检测在小儿感染性疾病鉴别诊断、疗效动态观察中有重要应用价值。     

肺癌胸腔镜术后肺部感染的危险因素探讨及术前CRP/Alb、PCT、SAA对感染风险的预测价值

摘要 目的：分析肺癌胸腔镜术后肺部感染的危险因素并探讨术前C反应蛋白/白蛋白比值（CRP/Alb）、降钙素原（PCT）、血清淀粉样蛋白A（SAA）对感染风险的预测价值。方法：选取2019年3月～2021年10月在徐州医科大学附属医院接受胸腔镜手术治疗的360例肺癌患者,根据肺癌胸腔镜术后72 h是否发生肺部感染分为肺部感染组57例和非肺部感染组303例。收集患者临床资料,术前1d检测患者血清CRP/Alb、PCT、SAA水平。通过单因素和多因素Logistic回归分析肺癌胸腔镜术后肺部感染的危险因素,受试者工作特征（ROC）曲线分析术前血清CRP/Alb、PCT、SAA水平对肺癌胸腔镜术后肺部感染的预测价值。结果：单因素分析显示,肺部感染组年龄≥60岁、吸烟史、糖尿病、手术时间≥3 h、术中出血量≥200 mL、机械通气时间≥12 h、胸腔引流时间≥5 d比例和血清CRP/Alb、PCT、SAA水平高于非肺部感染组（P＜0.05）。多因素Logistic回归分析显示,年龄≥60岁、吸烟史、糖尿病、手术时间≥3 h、机械通气时间≥12 h、胸腔引流时间≥5 d和血清CRP/Alb、PCT、SAA升高为肺癌胸腔镜术后肺部感染的独立危险因素（P＜0.05）。ROC曲线分析显示,术前血清CRP/Alb、PCT、SAA水平联合预测肺癌胸腔镜术后肺部感染的曲线下面积大于各指标单独预测。结论：年龄、吸烟史、糖尿病、手术时间、机械通气时间、胸腔引流时间和CRP/Alb、PCT、SAA升高为肺癌胸腔镜术后肺部感染的危险因素,术前血清CRP/Alb、PCT、SAA联合预测肺癌胸腔镜术后肺部感染的价值较高。     

血清PCT、CRP及IL-6联合检测诊断细菌性血流感染的临床价值分析

目的:探讨血清降钙素原(PCT)、C反应蛋白(CRP)及白介素-6(IL-6)联合检测诊断细菌性血流感染(BSI)的临床价值。方法:选取我院2015年8月到2016年10月收治的疑似细菌性BSI患者216例,入院后均送检血培养,根据培养结果将其分为阳性组(102例)和阴性组(114例)。统计细菌性BSI阳性率、革兰阳性菌感染率和革兰阴性菌感染率;检测血清PCT、CRP、IL-6水平,并比较两组患者的差异,同时绘制ROC曲线并计算出各指标及联合检测的灵敏度、特异度、阳性预测值、阴性预测值及约登指数值。结果:所有疑似BSI患者的细菌阳性检出率为47.22%,革兰阳性菌感染率与革兰阴性菌感染率对比无差异(P0.05);阳性组的血清PCT、CRP、IL-6水平均明显高于阴性组(P0.05);血清IL-6的AUC明显大于PCT和CRP(P0.05);PCT、CRP及IL-6联合检测的灵敏度、特异度、阳性预测值、阴性预测值及约登指数均明显高于单项检测(P0.05)。结论:血清PCT、CRP及IL-6对于BSI均有着一定诊断价值,而各指标联合检测诊断BSI的临床价值更高。     

SP-A、CRP和PCT在新生儿肺炎中的变化及诊断意义

为了考察肺泡表面活性物质蛋白A (SP-A)、血清C反应蛋白(CRP)、降钙素原(PCT)在新生儿肺炎中的变化及诊断意义,本研究检测了80例肺炎新生儿和40例健康新生儿血清SP-A、CRP和PCT水平。然后建立了肺炎克雷伯菌诱导的肺炎小鼠模型,每天按照200 mg/kg的剂量对小鼠腹腔注射SP-A蛋白溶液,共注射3 d。研究显示,肺炎新生儿血清中SP-A水平显著低于健康新生儿,而CRP和PCT水平均显著高于健康新生儿(p0.05)。肺炎新生儿血清SP-A与CRP和PCT水平显著负相关(p0.05),CRP和PCT水平显著正相关(p0.05)。SP-A、CRP和PCT联合诊断的敏感度、特异性和曲线下面积依次为0.864、0.829和0.845,均高于单独指标诊断。SP-A处理可显著减轻肺炎小鼠肺组织的病理改变,并显著升高肺组织和血清中的SP-A水平,降低血清CRP和PCT水平。本研究表明,肺炎新生儿血清SP-A水平明显降低,而CRP和PCT水平明显升高。SP-A、CRP和PCT联合检测对新生儿肺炎的诊断价值高于单独指标诊断。通过腹腔注射SP-A蛋白溶液可显著抑制小鼠肺组织病变,并降低血清CRP和PCT水平,从而抑制炎症反应。     

慢性阻塞性肺疾病急性加重期患者血清SAA水平与肺功能、炎性因子的相关性及其诊断价值分析

目的:探讨慢性阻塞性肺疾病急性加重期(AECOPD)患者血清淀粉样蛋白A(SAA)水平与肺功能及炎性因子的相关性,并分析其诊断价值。方法:选取2013年6月-2018年6月中国人民解放军第970医院收治的204例慢性阻塞性肺疾病(COPD)患者作为研究对象,其中COPD稳定期患者132例作为COPD稳定组,AECOPD患者72例作为AECOPD组。另选取同期于中国人民解放军第970医院进行健康体检的50例健康体检者作为健康组。比较三组受试者血清SAA水平、白细胞介素-8(IL-8)、白细胞介素-6(IL-6)、C反应蛋白(CRP)、降钙素原(PCT)水平及肺功能,采用Pearson相关性分析AECOPD患者血清SAA水平与肺功能及炎性因子的相关性,并分析SAA对AECOPD的诊断价值。结果:AECOPD组患者血清SAA、PCT、CRP、IL-6、IL-8水平较COPD稳定组及健康组升高(P0.05),COPD稳定组患者血清SAA、IL-6、IL-8、PCT、CRP水平均高于健康组,差异有统计学意义(P0.05);AECOPD组患者第一秒用力呼气容积(FEV1)、用力肺活量(FVC)、第一秒用力呼吸容积占用力肺活量的百分比(FEV1/FVC%)、第一秒用力呼气容积占预计值百分比(FEV1%)低于COPD稳定组及健康组,差异有统计学意义(P0.05),COPD稳定组患者FEV1、FVC、FEV1/FVC%、FEV1%低于健康组,差异有统计学意义(P0.05)。Pearson相关性分析显示,AECOPD患者血清SAA水平与IL-8、IL-6、CRP、PCT呈正相关,与FEV1%、FEV1/FVC%、FEV1、FVC呈负相关(P0.05)。受试者工作特征(ROC)曲线结果显示,SAA对AECOPD诊断的敏感度为80.85%,特异度为80.07%,曲线下面积为0.832。结论:AECOPD患者血清SAA水平明显升高,其与患者肺功能及炎症因子存在相关性,具有较高的诊断价值,可用于AECOPD患者病情的评估。     

脓毒症患儿血清SAA、PCT、CRP水平与预后的关系及其诊断价值分析

摘要 目的：探讨脓毒症患儿血清淀粉样蛋白A（SAA）、降钙素原（PCT）、C反应蛋白（CRP）与预后的关系,并分析三者对脓毒症的诊断价值。方法：纳入我院于2016年8月～2020年6月期间收治的脓毒症患儿60例开展回顾性研究,作为脓毒症组,选取同期于我院进行体检的健康儿童40例作为对照组,比较两组血清SAA、PCT、CRP水平。根据脓毒症患儿1个月内的生存、死亡情况,分成生存组（n=42）、死亡组（n=18）,比较两组临床资料及血清SAA、PCT、CRP水平,经COX回归模型分析脓毒症患儿死亡的危险因素。绘制受试者工作特征（ROC）曲线分析血清SAA、PCT、CRP对脓毒症的诊断价值。结果：脓毒症组血清SAA、PCT、CRP水平显著高于对照组（P＜0.05）。死亡组器官障碍数量＞2个、脓毒性休克患儿占比分别为55.56%、44.44%,显著高于生存组的19.05%、9.52%（P＜0.05）;死亡组入院后1 h内使用抗菌治疗患儿占比为38.89%,显著低于生存组的69.05%（P＜0.05）;死亡组血清SAA、PCT、CRP水平高于生存组（P＜0.05）。COX多因素分析结果显示,器官障碍数量＞2、脓毒性休克及血清SAA、PCT、CRP水平升高是脓毒症患儿死亡的危险因素（P＜0.05）,而入院后1 h内使用抗菌治疗是脓毒症患儿死亡风险的保护性因素（P＜0.05）。血清SAA、PCT、CRP单独及三者联合诊断脓毒症的曲线下面积（AUC）分别为0.808、0.780、0.761、0.912。结论：脓毒症患儿血清SAA、PCT、CRP明显升高,三者升高均为脓毒症患儿死亡的危险因素,且对脓毒症具有一定诊断价值。     

Symmetric primary and tertiary structure mutations within a symmetric superfold: a solution, not a constraint, to achieve a foldable polypeptide

In previous studies designed to increase the primary structure symmetry within the hydrophobic core of human acidic fibroblast growth factor (FGF-1) a combination of five mutations were accommodated, resulting in structure, stability and folding kinetic properties similar to wild-type (despite the symmetric constraint upon the set of core residues). A sixth mutation in the core, involving a highly conserved Met residue at position 67, appeared intolerant to substitution. Structural analysis suggested that the local packing environment of position 67 involved two regions of apparent insertions that distorted the tertiary structure symmetry inherent in the beta-trefoil architecture. It was postulated that a symmetric constraint upon the primary structure within the core could only be achieved after these insertions had been deleted (concomitantly increasing the tertiary structure symmetry). The deletion of these insertions is now shown to permit mutation of position 67, thereby increasing the primary structure symmetry relationship within the core. Furthermore, despite the imposed symmetric constraint upon both the primary and tertiary structure, the resulting mutant form of FGF-1 is substantially more stable. The apparent inserted regions are shown to be associated with heparin-binding functionality; however, despite a marked reduction in heparin-binding affinity the mutant form of FGF-1 is surprisingly approximately 70 times more potent in 3T3 fibroblast mitogenic assays. The results support the hypothesis that primary structure symmetry within a symmetric protein superfold represents a possible solution, rather than a constraint, to achieving a foldable polypeptide.     

Integrating statistical pair potentials into protein complex prediction

The biophysical study of protein-protein interactions and docking has important implications in our understanding of most complex cellular signaling processes. Most computational approaches to protein docking involve a tradeoff between the level of detail incorporated into the model and computational power required to properly handle that level of detail. In this work, we seek to optimize that balance by showing that we can reduce the complexity of model representation and thus make the computation tractable with minimal loss of predictive performance. We also introduce a pair-wise statistical potential suitable for docking that builds on previous work and show that this potential can be incorporated into our fast fourier transform-based docking algorithm ZDOCK. We use the Protein Docking Benchmark to illustrate the improved performance of this potential compared with less detailed other scoring functions. Furthermore, we show that the new potential performs well on antibody-antigen complexes, with most predictions clustering around the Complementarity Determining Regions of antibodies without any manual intervention.     

Protein microarrays as a discovery tool for studying protein–protein interactions

Exploring the function of the genome and the encoded proteins has emerged as a new and exciting challenge in the postgenomic era. Novel technologies come into view that promise to be valuable for the investigation not only of single proteins, but of entire protein networks. Protein microarrays are the innovative assay platform for highly parallel in vitro studies of protein–protein interactions. Due to their flexibility and multiplexing capacity, protein microarrays benefit basic research, diagnosis and biomedicine. This review provides an overview on the basic principles of protein microarrays and their potential to multiplex protein–protein interaction studies.     

The heat capacity of proteins

The heat capacity plays a major role in the determination of the energetics of protein folding and molecular recognition. As such, a better understanding of this thermodynamic parameter and its structural origin will provide new insights for the development of better molecular design strategies. In this paper we have analyzed the absolute heat capacity of proteins in different conformations. The results of these studies indicate that three major terms account for the absolute heat capacity of a protein: (1) one term that depends only on the primary or covalent structure of a protein and contains contributions from vibrational frequencies arising from the stretching and bending modes of each valence bond and internal rotations; (2) a term that contains the contributions of noncovalent interactions arising from secondary and tertiary structure; and (3) a term that contains the contributions of hydration. For a typical globular protein in solution the bulk of the heat capacity at 25°C is given by the covalent structure term (close to 85% of the total). The hydration term contributes about 15 and 40% to the total heat capacity of the native and unfolded states, respectively. The contribution of non-covalent structure to the total heat capacity of the native state is positive but very small and does not amount to more than 3% at 25°C. The change in heat capacity upon unfolding is primarily given by the increase in the hydration term (about 95%) and to a much lesser extent by the loss of noncovalent interactions (up to ～5%). It is demonstrated that a single universal mathematical function can be used to represent the partial molar heat capacity of the native and unfolded states of proteins in solution. This function can be experimentally written in terms of the molecular weight, the polar and apolar solvent accessible surface areas, and the total area buried from the solvent. This unique function accurately predicts the different magnitude and temperature dependences of the heat capacity of both the native and unfolded states, and therefore of the heat capacity changes associated with folding/unfolding transitions. © 1995 Wiley-Liss, Inc.     

A solubility-enhancement tag (SET) for NMR studies of poorly behaving proteins

Protein-fusion constructs have been used with great success for enhancing expression of soluble recombinant protein and as tags for affinity purification. Unfortunately the most popular tags, such as GST and MBP, are large, which hinders direct NMR studies of the fusion proteins. Cleavage of the fusion proteins often re-introduces problems with solubility and stability. Here we describe the use of N-terminally fused protein G (B1 domain) as a non-cleavable solubility-enhancement tag (SET) for structure determination of a dimeric protein complex. The SET enhances the solubility and stability of the fusion product dramatically while not interacting directly with the protein of interest. This approach can be used for structural characterization of poorly behaving protein systems, and would be especially useful for structural genomics studies.     

Improvement of protein stability in protein microarrays

Protein stability in microarrays was improved using protein stabilizers. PEG 200 at 30% (w/v) was the most efficient stabilizer giving over 4-fold improvement in protein stability compared to without the stabilizer. PEG 200 above 10% (w/v) in the array solution prevented the evaporation of water in the sample and thereby improved protein stability in the microarray. When the streptavidin-biotin binding reaction was performed under optimized conditions, biotin-BSA-fluorescein isothiocyanate (FITC) was detected from 1 ng ml^–1 to 5 g ml^–1 by fluorescence analysis.     

A large scale test of computational protein design: folding and stability of nine completely redesigned globular proteins

A previously developed computer program for protein design, RosettaDesign, was used to predict low free energy sequences for nine naturally occurring protein backbones. RosettaDesign had no knowledge of the naturally occurring sequences and on average 65% of the residues in the designed sequences differ from wild-type. Synthetic genes for ten completely redesigned proteins were generated, and the proteins were expressed, purified, and then characterized using circular dichroism, chemical and temperature denaturation and NMR experiments. Although high-resolution structures have not yet been determined, eight of these proteins appear to be folded and their circular dichroism spectra are similar to those of their wild-type counterparts. Six of the proteins have stabilities equal to or up to 7kcal/mol greater than their wild-type counterparts, and four of the proteins have NMR spectra consistent with a well-packed, rigid structure. These encouraging results indicate that the computational protein design methods can, with significant reliability, identify amino acid sequences compatible with a target protein backbone.     

Lethal mutations in the major homology region and their suppressors act by modulating the dimerization of the rous sarcoma virus capsid protein C‐terminal domain

An infective retrovirus requires a mature capsid shell around the viral replication complex. This shell is formed by about 1500 capsid protein monomers, organized into hexamer and pentamer rings that are linked to each other by the dimerization of the C‐terminal domain (CTD). The major homology region (MHR), the most highly conserved protein sequence across retroviral genomes, is part of the CTD. Several mutations in the MHR appear to block infectivity by preventing capsid formation. Suppressor mutations have been identified that are distant in sequence and structure from the MHR and restore capsid formation. The effects of two lethal and two suppressor mutations on the stability and function of the CTD were examined. No correlation with infectivity was found for the stability of the lethal mutations (D155Y‐CTD, F167Y‐CTD) and suppressor mutations (R185W‐CTD, I190V‐CTD). The stabilities of three double mutant proteins (D155Y/R185W‐CTD, F167Y/R185W‐CTD, and F167Y/I190V‐CTD) were additive. However, the dimerization affinity of the mutant proteins correlated strongly with biological function. The CTD proteins with lethal mutations did not dimerize, while those with suppressor mutations had greater dimerization affinity than WT‐CTD. The suppressor mutations were able to partially correct the dimerization defect caused by the lethal MHR mutations in double mutant proteins. Despite their dramatic effects on dimerization, none of these residues participate directly in the proposed dimerization interface in a mature capsid. These findings suggest that the conserved sequence of the MHR has critical roles in the conformation(s) of the CTD that are required for dimerization and correct capsid maturation. Proteins 2013. © 2012 Wiley Periodicals, Inc.