脑出血患者气管切开并发肺部感染的预测研究

目的探讨脑出血患者气管切开并发肺部感染的预测方法及价值。 方法选取亳州市人民医院重症医学科自2018年5月至2020年2月收治的142例脑出血气管切开患者为研究对象,按照脑出血气管切开患者并发肺部感染情况,分为发生组和未发生组。分析脑出血气管切开患者肺部感染危险因素,对比2组患者气管切开术后次日血清白蛋白（Alb）、降钙素原（PCT）及D-二聚体（D-D）水平。采用受试者工作特征（ROC）曲线分析血清Alb、PCT、D-D水平及三者联合预测脑出血气管切开并发肺部感染的价值。 结果本组患者中有33例（23.24%）并发肺部感染,纳入发生组,余109例患者纳入未发生组。发生组脑出血气管切开患者的血清Alb水平[（34.28±7.61）g/L]明显低于未发生组[（48.15±9.27）g/L],PCT[（0.25±0.06）ng/mL]和D-D水平[（253.16±41.27）μg/L]均明显高于未发生组[（0.17±0.05）ng/mL,（168.41±35.24）μg/L],差异均具有统计学意义（P<0.05）。慢性阻塞性肺疾病、吸烟史、低蛋白血症、气管切开距离发病时间≥5 d、气管插管、使用呼吸机、应用广谱抗菌药物、进行颅脑手术、血清Alb<40 g/L、PCT≥0.15 ng/L、D-D≥200 μg/L均是影响出血性气管切开患者肺部感染发生的独立危险因素（P<0.05）,入院GCS评分是其保护因素（OR=0.551,P=0.023）;ROC分析显示,血清Alb、PCT、D-D水平预测脑出血气管切开患者并发肺部感染的最佳截断点分别为36.29 g/L、0.23 ng/mL、228.05 μg/L;血清Alb、PCT及D-D三者联合预测脑出血气管切开患者并发肺部感染的灵敏度、特异度、曲线下面积（AUC）分别为69.70%、97.25%、0.912,特异度和AUC均高于单独预测（P<0.05）,灵敏度与单独预测差异无统计学意义（P>0.05）。 结论脑出血气管切开患者并发肺部感染风险高,且慢性阻塞性肺疾病、吸烟史、低蛋白血症等与血清Alb<40 g/L、PCT≥0.15 ng/L、D-D≥200 μg/L均是其影响因素,血清Alb、PCT、D-D水平联合可用于预测肺部感染。     

AaeAP1 and AaeAP2: Novel Antimicrobial Peptides from the Venom of the Scorpion,Androctonus aeneas: Structural Characterisation,Molecular Cloning of Biosynthetic Precursor-Encoding cDNAs and Engineering of Analogues with Enhanced Antimicrobial and Anticancer Activities

The main functions of the abundant polypeptide toxins present in scorpion venoms are the debilitation of arthropod prey or defence against predators. These effects are achieved mainly through the blocking of an array of ion channel types within the membranes of excitable cells. However, while these ion channel-blocking toxins are tightly-folded by multiple disulphide bridges between cysteine residues, there are additional groups of peptides in the venoms that are devoid of cysteine residues. These non-disulphide bridged peptides are the subject of much research interest, and among these are peptides that exhibit antimicrobial activity. Here, we describe two novel non-disulphide-bridged antimicrobial peptides that are present in the venom of the North African scorpion, Androctonus aeneas. The cDNAs encoding the biosynthetic precursors of both peptides were cloned from a venom-derived cDNA library using 3''- and 5''-RACE strategies. Both translated precursors contained open-reading frames of 74 amino acid residues, each encoding one copy of a putative novel nonadecapeptide, whose primary structures were FLFSLIPSVIAGLVSAIRN and FLFSLIPSAIAGLVSAIRN, respectively. Both peptides were C-terminally amidated. Synthetic versions of each natural peptide displayed broad-spectrum antimicrobial activities, but were devoid of antiproliferative activity against human cancer cell lines. However, synthetic analogues of each peptide, engineered for enhanced cationicity and amphipathicity, exhibited increases in antimicrobial potency and acquired antiproliferative activity against a range of human cancer cell lines. These data clearly illustrate the potential that natural peptide templates provide towards the design of synthetic analogues for therapeutic exploitation.     

Discovery of Quinazoline-Based Fluorescent Probes to α1-Adrenergic Receptors

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Pharmacokinetic and pharmacodynamic study of triptolide-loaded liposome hydrogel patch under microneedles on rats with collagen-induced arthritis

Triptolide (TP), a major active component of Tripterygium wilfordii Hook.F. (TWHF), is used to treat rheumatoid arthritis (RA). However, it has a narrow therapeutic window due to its serious toxicities. To increase the therapeutic index, a new triptolide-loaded transdermal delivery system, named triptolide-loaded liposome hydrogel patch (TP-LHP), has been developed. In this paper, we used a micro-needle array to deliver TP-LHP to promote transdermal absorption and evaluated this treatment on the pharmacokinetics and pharmacodynamics of TP-LHP in a rat model of collagen-induced arthritis (CIA). The pharmacokinetic results showed that transdermal delivery of microneedle TP-LHP yielded plasma drug levels which fit a one-compartment open model. The relationship equation between plasma concentration and time was C=303.59×(e^−0.064t−e^−0.287t). The results of pharmacodynamic study demonstrated that TP-LHP treatment mitigated the degree of joint swelling and suppressed the expressions of fetal liver kinase-1, fetal liver tyrosine kinase-4 and hypoxia-inducible factor-1α in synovium. Other indicators were also reduced by TP-LHP, including hyperfunction of immune, interleukin-1β and interleukin-6 levels in serum. The therapeutic mechanism of TP-LHP might be regulation of the balance between Th1 and Th2, as well as inhibition of the expression and biological effects of vascular endothelial growth factor.KEY WORDS: Pharmacokinetics, Pharmacodynamics, Triptolide, Micro-electro-mechanical system, Microneedles, Collagen-induced arthritis     

室间隔心肌切除术围手术期心房颤动的临床特征与危险因素分析

【摘要】 目的 观察肥厚型梗阻性心肌病（Hypertrophic obstructive cardiomyopathy,HOCM）患者行室间隔心肌切除术后新发房颤（Postoperative atrial fibrillation,POAF）的临床特点以及其发生的相关影响因素。方法 以2016年10月至2019年06月期间在阜外医院行室间隔心肌切除术的成人患者为研究对象,除外术前阵发性及持续性心房颤动的患者,进行临床资料及相关检查结果收集,分析POAF的临床特点,采用多因素logistic回归分析研究室间隔心肌切除术患者发生POAF的危险因素。结果 共498例患者入选,其中132例（26.5%）患者发生POAF,POAF首次发作于术后（50.9±27.2）h,即77.3%的患者在术后2~3 d内（24~72h）首次发作;平均发作（2±1.6）次,54.5%的患者发作1次;房颤平均发作持续时间（42.0±67.5）h,50.8%的患者房颤发作≤24h;发作POAF的患者平均年龄（54.0±9.7）岁,术后房颤发生率随着年龄段增长而增加,50~60岁、60~70岁、70~80岁的发生率分别为28.3%、36.0%、62.5%;性别间无统计学差异。将患者依据有无POAF分为术后房颤组（n=132）及术后无房颤组（n=366）,两组患者在手术年龄[（54.0±9.7）岁比（49.3±10.1）岁]、发病年龄[（46.8±10.4）岁比（43.1±10.8）岁]、病程时间[（84.1±78.0）m比（69.0±64.7）m]、X线提示肺淤血、术前左心房内径[（44.0±7.5）mm比（41.2±6.7）mm]及左心室舒张末内径[（43.2±6.1）mm比（41.3±5.1）mm]、合并左心室中部狭窄、术中合并冠状动脉狭窄、主动脉瓣病变及二尖瓣病变、进入ICU时心率[（73.9±12.3）次/min比（77.2±13.2）次/min]、术后左心房内径[（38.4±5.5）mm比（35.4±5.0）mm]均具有统计学差异（P＜0.05）,其中合并左心室中部狭窄和进入ICU时心率是POAF的保护因素;多因素 logistic回归分析发现年龄（OR=1.051,95%CI 1.027~1.075,P=0.000）、术前左心房内径（OR=1.045,95%CI 1.007~1.083,P=0.019）和术后左心房内径（OR=1.077,95%CI 1.029~1.128,P=0.001）是POAF颤的独立危险因素。结论 高龄、术前和术后左心房扩大是室间隔心肌切除术后POAF的独立危险素。 【关键词】 肥厚型梗阻性心肌病;室间隔心肌切除术;术后新发房颤;危险因素     

“勾股定理”测量的左右心室电极间距离与心脏再同步化治疗临床疗效的相关性和预测性分析

【摘要】背景：再同步化治疗能改善心力衰竭患者的预后,但大约有1/3患者不能从中获益,也就是无反应者。目的：探讨在勾股定理方法测量下的实际左右心室电极间距离与心脏再同步化治疗临床疗效的相关性和预测性。方法：回顾性的研究在我院所有因符合CRT指征而行CRT植入术的患者,采集患者术前、术后6个月基本资料（年龄、左心室射血分数（LVEF）、左心室舒张末内径（LVEDD）、左心房前后径（LAAPD）、QRS 时限（QRSd）、N-端脑利钠肽前体(NT-proBNP)、美国纽约心脏病协会（NYHA）心功能分级等）;在术后的透视影像下,用游标卡尺测量正侧位左右心室间电极直接距离（L）（水平距离 V ,垂直距离 H）,正前位心脏横径（C）、胸腔横径（T）,根据勾股定理左、右心室电极植入位置间直接距离（DD2=V12+L22）或（DD2=V22+L12）;计算左、右心室电极植入位置间 DD/C。并根据术后心脏彩超变化或临床症状评估分为显著有效（A组）,有效（B组）和无效（C组）。结果：共有108个患者（平均年龄 64.34±9.35岁,51.9%男性,57.4%扩心病）纳入研究,A组（31）、有效组（56）和无效组（31）;三组患者术后6月的LVEF、6-MWT、LVEDD、QRSd、NT-ProBNP较术前均有明显改善（P＜0.05）,DD及DD/C在组内及组间均有统计学意义（P＜0.05）;且A组＞B组＞C组;多因素Logistic回归分析示DD和DD/C是CRT临床疗效的独立影响因素;在ROC曲线分析中,DD（DD/C）曲线下面积分别为0.709（0.713）和0.741（0.835）,A组和B组、B组和C组之间的DD（DD/C）截断值分别为54.84mm（0.551）和43.5mm（0.395）（P＜0.05）。结论：在勾股定理方法测量下的实际心室间电极距离与CRT临床疗效呈正相关,DD（DD/C）越大,CRT临床效果越好,并且也是预测CRT临床效果的预测因素。     

Exploring the binding pattern between pepsin and deferasirox using detailed experimental and computer simulation methods

Steady-state fluorescence spectroscopy indicated that a ground state complex was formed between deferasirox (DFX) and pepsin. The binding parameters and thermodynamic parameters of pepsin–DFX complex formation suggested the presence of only one high affinity binding site in the binding process of DFX and pepsin and that the binding process was hydrogen bond dominated. According to the MD simulation optimal pepsin–DFX binding model analysis, the binding force between DFX and pepsin was mainly hydrogen bonding, and the hydrophobic interaction was supplemented. Synchronous fluorescence spectroscopy and 3D fluorescence spectroscopy indicated that the binding of DFX to pepsin had minor effect on the protein structure and function. Circular dichroism spectra showed that DFX had no significant effect on the main secondary structure of pepsin. MD analysis also showed that DFX did not affect the looseness of pepsin and the overall secondary structure, but it affected the amino acid residue sequence Leu48-Ala49-Cys50-Ser51-Asp52. Pepsin enzyme activity test showed that the addition of DFX had a slight enhancement effect on the activity of pepsin. Combined with the MD results, DFX bound to pepsin and was closer to the pepsin active site Asp-215, which may affect the electrical environment of Asp-215 residues and enhance the activity of pepsin.

Investigation on the binding properties of deferasirox to pepsin.     

Antitumor component recognition from the Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma herb pair extract by chemometrics and mean impact value

The purpose of this research is to recognize the active antitumor components from the mixed pair extract of Aconiti Lateralis Radix Praeparata (Fuzi in Chinese) and Glycyrrhizae Radix et Rhizoma (Gancao in Chinese) using chemometrics and mean impact value (MIV) methods. Firstly, 30 common components of 31 different samples were analyzed quantitatively and qualitatively by HPLC-UV and UPLC-Q-TOF tandem mass spectrometry, respectively. Meanwhile, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays were used to test the inhibition activities of the 31 different samples against HeLa cells. Then a back propagation (BP) neural network, support vector regression (SVR), and two optimization algorithms – genetic algorithm (GA) and particle swarm optimization (PSO) – were applied to construct composition–activity relationship (CAR) models for the Fuzi–Gancao extract. Based on the optimal CAR model, the MIV was introduced to evaluate the contribution of each individual component to the anticancer efficacy of the extract. Results indicated that the SVR-PSO model best depicted the complex relationship between the chemical composition and the inhibition effect of a Fuzi–Gancao extract. The 30 common components were ranked by their absolute MIVs, and the top 8, which corresponded to peaks 17, 25, 22, 13, 23, 28, 5, and 7 in the chromatogram, were tentatively deemed to be the main antitumor components. The integrated strategy shows a novel and efficient approach to understanding the potential contributions of components from complicated herbal medicines, and the identified results suggest certain directions for screening and research into new antitumor drugs.

CAR models for the Fuzi–Gancao herb pair were constructed by BP, SVR, GA and PSO, and used to fit experimental data. The main active antitumor components were recognized from MIVs based on the optimal CAR model.     

Morphology and electrical characteristics of p-type ZnO microwires with zigzag rough surfaces induced by Sb doping

Sb-doped p-type ZnO microwires with zigzag rough surfaces were synthesized by two zone chemical vapor deposition. The zigzag morphology characteristics analyzed by high resolution scanning electron microscopy and transmission electron microscopy show the existence of surface defects caused by Sb doping. The incorporation of Sb into a ZnO lattice induces lattice imperfection, which is the origin of the zigzag rough surface. Photoluminescence and electrical properties of the obtained Sb-doped ZnO microwires were determined. The crossed structure microwire-based p–n homojunction device was fabricated by applying as-synthesized Sb-doped p-type ZnO microwires and undoped n-type ZnO microwires. The doped microwires demonstrate reproducible p-type conduction and enhanced rectifying behavior with increasing Sb doping concentration. The results demonstrated that the optimizable optical and electrical characteristics, controlled by increasing the doping concentration, are reflected in the surface morphology changes which would be helpful for characterizing the doping effects in micro/nanoscale materials.

Sb-doped microwires which have a zigzag rough surface demonstrate p-type conduction and enhanced rectifying behavior with increasing Sb doping concentration.