慢性肾脏病患者五聚素3与血管内皮功能障碍的相关性研究

目的探讨慢性肾脏病(CKD)未透析患者五聚素3(PTX3)与血管内皮功能障碍的关系。方法选取2012年4月—2013年12月在首都医科大学附属北京朝阳医院肾内科住院或门诊治疗的符合纳入标准的CKD患者70例,采用简化MDRD公式计算估算肾小球滤过率(e GFR),并根据e GFR将患者分为CKD 1~3期组(A组,n=30)和CKD 4~5期组(B组,n=40)。另选取同期在首都医科大学附属北京朝阳医院体检中心体检健康者30例为对照组。采用ELISA法检测血清PTX3,采用外周动脉张力检测技术检测反应性充血指数(RHI)。收集3组一般资料[性别、年龄、糖尿病发生率、高血压发生率、吸烟率、收缩压(SBP)、舒张压(DBP)、脉压(PP)、平均动脉压(MAP)、体质指数(BMI)]、实验室检查指标[白细胞计数(WBC)、中性粒细胞分数(NE)、血红蛋白(HGB)、清蛋白(ALB)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、尿素氮(BUN)、血肌酐(Scr)、尿酸(UA)、血钙、血磷、全段甲状旁腺激素(PTH)]、炎性指标[超敏C反应蛋白(hs-CRP)、PTX3]、血管内皮功能指标(内皮素、RHI),并分析CKD患者PTX3与各指标的相关性。结果 A组SBP、MAP高于对照组(P<0.05);B组SBP、PP、MAP高于对照组、A组,DBP高于对照组(P<0.05)。A组NE、LDL-C、UA高于对照组,HGB、ALB低于对照组(P<0.05);B组NE、BUN、Scr、血磷、PTH高于对照组、A组,HGB、血钙低于对照组和A组,ALB低于对照组,LDL-C、UA高于对照组(P<0.05)。A组PTX3高于对照组,RHI低于对照组(P<0.05);B组hs-CRP、PTX3、内皮素高于对照组、A组,RHI低于对照组、A组(P<0.05)。Pearson相关性分析结果显示,PTX3与WBC(r=0.300,P=0.046)、NE(r=0.422,P=0.004)、Scr(r=0.320,P=0.032)、hs-CRP(r=0.342,P=0.022)、内皮素(r=0.307,P=0.036)呈正相关,与RHI(r=-0.374,P=0.011)呈负相关。结论 CKD患者PTX3与内皮素呈正相关,与RHI呈负相关。与hs-CRP相比,PTX3对于预测CKD患者血管内皮功能障碍可能是一个更好的指标。

胰液中CLDN5和NPTX2基因高甲基化在胰腺癌诊断中的意义

目的:探讨胰腺癌和慢性胰腺炎患者胰液中CLDN5和NPTX2基因高甲基化在胰腺癌诊断中的临床意义。方法:MSP方法检测21例胰腺癌和8例慢性胰腺炎患者胰液中CLDN5和NPTX2基因启动子区CpG岛高甲基化。结果:21例胰腺癌患者的胰液中,17例(81.0%)CLDN5基因高甲基化阳性;15例(71.4%)NPTX2基因高甲基化阳性。8例慢性胰腺炎患者的胰液中,各有1例(12.5%)CLDN5和NPTX2基因高甲基化阳性。结论:CLDN5和NPTX2基因高甲基化作为分子生物学标志物可用于胰腺癌的诊断,有较高的临床应用价值。

初诊多囊卵巢综合征患者空腹血清Pentraxin3的水平变化及意义

目的检测初诊多囊卵巢综合征(PCOS)患者空腹血清Pentraxin3(PTX3)水平,探讨其在PCOS发生发展中的可能作用。方法选取78例PCOS患者(PCOS组)和67例健康体检者(对照组),两组按体质指数(BMI)分为体重正常(PCOS-NW,对照-NW)亚组和超重/肥胖(PCOS-OW/OB,对照-OW/OB)亚组。测量身高、体重、腰围(WC)、臀围。测定各组空腹血清PTX3水平、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、黄体生成素(LH)、卵泡刺激素(FSH)、睾酮(T)、空腹血糖(FBG)、餐后2 h血糖(P2hB G)、空腹胰岛素(FINS);计算BMI、腰臀比(WHR)、稳态模型胰岛素抵抗指数(HOMA-IR)。结果(1)PCOS组和对照组中OW/OB组PTX3水平均低于NW组(P<0.05,P<0.01);(2)Pearson相关性分析显示空腹血清PTX3水平与BMI、FBG、P2hB G、FINS、HOMA-IR呈负相关性(P<0.05);(3)多元回归分析结果显示影响PTX3水平的重要因素是FBG;(4)二分类Logistic回归分析显示PTX3是PCOS发生的保护因素。结论 PTX3可能参与了PCOS的发生,低水平的PTX3可能是PCOS发生发展中的危险因素。

地尔硫卓联合血栓抽吸治疗老年急性心肌梗死的临床疗效及对pentraxin3、S100A8/A9水平的影响

目的探究地尔硫卓联合血栓抽吸治疗老年急性心肌梗死临床疗效及对五聚素(pentraxin)3、S100A8/A9水平的影响。方法120例老年急性心肌梗死患者随机分为观察组和对照组,对照组在经皮冠状动脉介入(PCI)后给予地尔硫卓进行治疗,观察组在对照组基础上给予联合血栓抽吸治疗。记录并比较两组PCI术前和术后1个月的心功能指标,术后1 h心肌灌注分级指标,术后72 h血清pentraxin3、S100A8/A9水平及术后6个月心脏不良事件发生率。结果术后1个月,两组左室射血分数(LVEF)均增加,且观察组增加更明显(P<0.01),两组左心室舒张末期内径LVEDD均下降,且观察组下降更明显(P<0.01);术后1 h,观察组TIMI心肌灌注分级(TMPG)优于对照组,差异有统计学意义(P<0.01);两组累积无主要不良心血管事件(MACE)生存率差异无统计学意义(93.3%vs 88.3%,log-rankχ^2=2.63,P=0.10);术后24 h,两组血清pentraxin3、S100A8/A9水平均下降,且观察组下降更明显(P<0.01)。结论PCI术后采用地尔硫卓联合血栓抽吸治疗老年急性心肌梗死患者较单用地尔硫卓更有利于改善心功能和心肌灌注水平,不增加MACE发生风险,且有效降低血清pentraxin3、S100A8/A9水平。

正五聚蛋白-3水平对慢性心力衰竭患者预后的价值研究

目的探讨血浆正五聚蛋白-3（PTX3）水平对慢性心力衰竭患者预后的预测价值。方法检测406例慢性心力衰竭患者入院后次日早晨血PTX3水平并前瞻性随访2年，观察全因死亡、心力衰竭再次住院、急性心肌梗死、卒中及周围动脉栓塞，分析PTX3水平与心血管事件的关系。结果共有376例患者完成随访，171例患者发生心血管事件。心血管事件组PTX3水平较无心血管事件组显著增高[（3.911＆#177;0.83）ng/ml vs（3.088＆#177;0.99）ng/ml，P＜0.01]；PTX3浓度与慢性心力衰竭严重程度呈正相关（P＜0.01），PTX3浓度增高（≥中位数3.438ng/ml）组患者出现心血管事件明显增加（63.5%vs 27.3%，P＜0.01），生存函数Kaplan-Meier曲线也显示PTX3≥3.438ng/ml患者无心血管事件生存率明显降低（P＜0.01），多因素逐步分析显示PTX3浓度增高是慢性心力衰竭患者出现心血管事件的独立危险因子（RR=4.224，P＜0.01；95%CI 1.130～15.783）。结论 PTX3浓度增高的慢性心力衰竭患者发生心血管事件风险显著增加，PTX3浓度增高可能是慢性心力衰竭患者预后的独立预测因子。

Pentraxin 3 （PTX3） promoter methylation associated with PTX3 plasma levels and neutrophil to lymphocyte ratio in coronary artery disease

Background Pentraxin 3 （PTX3） is expressed in the heart under inflammatory conditions and plays an important role in atherogenesis. Patients with increased PTX3 levels may suffer from higher rates of cardiac events. Regulation of specific genes by promoter methylation is important in atherogenesis. The factors influencing PTX3 levels and the association between epigenetics and PTX3 levels have not been investigated. Methods Blood samples were collected from 64 patients admitted to the Department of Cardiology, 35 who had coronary artery disease （CAD）, and 29 who were CAD-free. Plasma levels of PTX3 were measured by ELISA. PTX3 promoter methylation was evaluated via methyl-specific PCR. The severity of coronary artery lesion was evaluated by angiography. Results The level of PTX3 promoter methylation in the CAD group was 62.69% ± 20.57%, significantly lower than that of the CAD-free group, which was 72.45% ± 11.84% （P = 0.03）. Lower PTX3 promoter methylation levels in the CAD group were associated with higher plasma PTX3 concentrations （r = -0.29, P = 0.02）. Furthermore, lower PTX3 promoter methylation levels were associated with higher neutrophil to lymphocyte ratio （NLR） in men （r = -0.58, P = 0.002）. Conclusions The present study provides new evidence that methylation of the PTX3 promoter is associated with PTX3 plasma levels and NLR in coronary artery disease. This study also shows that modification of epigenetics by chronic inflamma- tion might be a significant molecular mechanism in the atherosclerotic processes that influence plasma PTX3 concentrations.

Aberrant methylation of the 3q25 tumor suppressor gene PTX3 in human esophageal squamous cell carcinoma

AIM:To identify the novel methylation-silenced gene pentraxin 3(PTX3) in esophageal squamous cell carcinoma(ESCC).METHODS:PTX3 mRNA expression was examined in six human ESCC cell lines,one human immortalized normal esophageal epithelial cell line,primary ESCC tumor tissue,and paired adjacent nontumor tissue using reverse transcription polymerase chain reaction(RTPCR).Semi-quantitative immunohistochemistry was used to examine cellular localisation and protein levels.Methylation specific PCR and bisulphite genomic sequencing were employed to investigate the methylation of the candidate gene.RESULTS:In the majority of ESCC cell lines,we found that PTX3 expression was down-regulated due to gene promoter hypermethylation,which was further confirmed by bisulphite genomic sequencing.Demethylation treatment with 5-aza-2'-deoxycytidine restored PTX3 mRNA expression in ESCC cell lines.Methylation was more common in tumor tissues(85%) than in adjacent nontumor tissues(25%)(P < 0.01).CONCLUSION:PTX3 is down-regulated through promoter hypermethylation in ESCC,and could potentially serve as a biomarker of ESCC.

Lipopolysaccharide Challenge Induces Long Pentraxin 3 Expression in Mice Independently from Acute Lung Injury

Objective To determine whether the onset of acute lung injury （ALl） induces the up-regulation of pentraxin 3 （PTX3） expression in mice and whether PTX3 concentration in the biofluid can help recognizing sepsis-induced ALI. Methods Wild-type C57BL/6 mice （12-14 weeks old） were randomly divided into 3 groups. Mice in the group 1 （n=12） and group 2 （n=12） were instilled with lipopolysaccharide via intratracheal or intraperitoneal routes, respectively. Mice in the group 3 （n=8） were taken as blank controls. Pulmonary morphological and functional alterations were measured to determine the presence of experimental ALl. PTX3 expression in the lung was quantified at both protein and mRNA levels. PTX3 protein concentration in blood and bronchoalveolar lavage fluid was measured to evaluate its ability to diagnose sepsis-induced ALI by computing area under receiver operator characteristic curve （AUROCC）. Results ALl was commonly confirmed in the group 1 but never in the other groups. PTX3 expression was up-regulated indiscriminately among lipopolysaccharide-challenged mice. PTX3 protein concentration in the biofluid was unable to diagnose sepsis-induced ALl evidenced by its small AUROCC. PTX3 concentration in bronchoalveolar lavage fluid did not correlate with that in serum. Conclusions Lipopolysaccharide challenges induced PTX3 expression in mice regardless of the presence ofALI. PTX3 may act as an indicator of inflammatory response instead of organ injury per se.

Early expression of PTX3 in Aspergillus fumigatus infected rat cornea

AIM： To investigate the expression of pentraxin 3（PTX3） in rat corneal epithelium at the early stage of Aspergillus fumigatus（A. fumigatus） infection. METHODS： A total of 50 Wistar rats were randomly divided into control group, Sham group and experimental group（fungal keratitis group, FK group）. The right eye was chosen as the experiment one and infected by A. fumigatus. Rats were executed at 8, 16 and 24 h after the experimental models being established. Corneal epithelia were collected to assess the expression of PTX3 by quantitative reverse transcription polymerase chain reaction（q RT-PCR） and Western blot analysis. RESULTS： Corneal inflammation scores increased as infection prolonged（P〈0.05, P〈0.001）. PTX3 m RNA expression was low in normal and Sham group rats＇ corneas. Level of PTX3 m RNA in infected rat cornea was elevated at 8 h and peaked at 16 h. The difference was significant compared with control group（P〈0.001）. Western blot analysis also showed a significant increase of PTX3 protein in experimental group at 8 h and peaked at 16 h（P〈0.001）. The synchronous expression of control group and experimental group were also in significant difference（P〈0.001）. CONCLUSION： PTX3 exists in cornea epithelium and is significantly increased after A. fumigatus infection. PTX3 plays an important role in the early stage of cornea innate immunity against A. fumigatus.

Pentraxin 3在肿瘤中作用的研究进展

五聚蛋白3(Pentraxin 3,PTX3)是一种存在于体液中的以环状多聚体结构为特征的炎症因子,可以参与伤口愈合、组织重塑、天然免疫、炎症等过程。近年的研究发现,PTX3参与多种肿瘤的进展,是肺癌、宫颈癌、结直肠癌、原发性骨髓纤维化等肿瘤的独立预后因子。PTX3可以被C-Jun氨基末端激酶(JNK)-Jun、磷脂酰肌醇3激酶-蛋白激酶B(PI3K-Akt)、核因子κB(NF-κB)、Wnt信号通路调控在肿瘤细胞中高表达,通过调控上皮-间质转分化(EMT)相关蛋白、基质金属蛋白酶(MMPs)、破骨细胞分化因子(RANKL)等而促进肿瘤细胞迁移侵袭及转移,通过参与Hedgehog和Hippo-YAP信号通路促进肿瘤细胞干性,从而促进肿瘤恶性进展;其也可以通过抑制成纤维细胞生长因子(FGFs)家族与受体的结合,抑制肿瘤中血管生成及肿瘤的恶性进展。

The implication of calcium score and pentraxin-3 in non-invasive identification of significant coronary artery stenosis in chronic stable angina pectoris

Objective: Coronary Artery Disease (CAD) would continue to concern medical society in the foreseeable future. Determining the extent of coronary luminal stenosis is a key factor in management of CAD. Methods presently used are costly and pose certain dangers, ranging from nephrotoxicity to death. Long Pentraxin or Pentraxin-3 (PTX3) has been used to predict survival or atherosclerotic process, but not to identify coronary stenosis. Calcium Score has been used to this end with some success. Methods: Individuals with chronic stable angina, without evidence of Myocardial Infarction (MI), who were categorized as intermediate-risk after completing a treadmill exercise test, according to Duke Protocol, underwent cardiac catheterization. In addition, blood samples were drawn for coronary sinus PTX3, and also PTX3, uric acid, high-sensitivity C-reactive protein (hs-CRP), cholesterol, glucose and High-Density Lipo-protein (HDL) in peripheral circulation. Calcium Scores were calculated using Agatston Score and non-contrast multi-slice CT scan. Participants were divided according to the number of stenotic coronary arteries (patent, one-, two-and three-vessel disease). Results: We found that PTX3 levels in coronary sinus and femoral vein correlated with each other, after log-transforming the values. Also we found that PTX3 levels and Calcium Scores differed among individuals with triple-vessel involvement and individuals without significant stenosis in any of coronary arteries. No significant differences were observed, regarding hs-CRP levels. Conclusion: PTX3 levels in periphery correlate with those in coronary arteries, and this variable can be measured with a less invasive procedure. In addition to Calcium Score, PTX3 levels are different in our four groups. The combined contribution of PTX3 and calcium score may help us identify individuals with significant coronary artery stenosis without needing to perform cardiac catheterization in a select group of patients.

Serum neuronal pentraxin 2 is related to cognitive dysfunction and electroencephalogram slow wave/fast wave frequency ratio in epilepsy

BACKGROUND Cognitive dysfunction in epileptic patients is a high-incidence complication.Its mechanism is related to nervous system damage during seizures,but there is no effective diagnostic biomarker.Neuronal pentraxin 2(NPTX2)is thought to play a vital role in neurotransmission and the maintenance of synaptic plasticity.This study explored how serum NPTX2 and electroencephalogram(EEG)slow wave/fast wave frequency ratio relate to cognitive dysfunction in patients with epilepsy.AIM To determine if serum NPTX2 could serve as a potential biomarker for diagnosing cognitive impairment in epilepsy patients.METHODS The participants of this study,conducted from January 2020 to December 2021,comprised 74 epilepsy patients with normal cognitive function(normal group),37 epilepsy patients with cognitive dysfunction[epilepsy patients with cognitive dysfunction(ECD)group]and 30 healthy people(control group).The minimental state examination(MMSE)scale was used to evaluate cognitive function.We determined serum NPTX2 levels using an enzyme-linked immunosorbent kit and calculated the signal value of EEG regions according to the EEG recording.Pearson correlation coefficient was used to analyze the correlation between serum NPTX2 and the MMSE score.RESULTS The serum NPTX2 level in the control group,normal group and ECD group were 240.00±35.06 pg/mL,235.80±38.01 pg/mL and 193.80±42.72 pg/mL,respectively.The MMSE score was lowest in the ECD group among the three,while no significant difference was observed between the control and normal groups.In epilepsy patients with cognitive dysfunction,NPTX2 level had a positive correlation with the MMSE score(r=0.367,P=0.0253)and a negative correlation with epilepsy duration(r=−0.443,P=0.0061)and the EEG slow wave/fast wave frequency ratio value in the temporal region(r=−0.339,P=0.039).CONCLUSION Serum NPTX2 was found to be related to cognitive dysfunction and the EEG slow wave/fast wave frequency ratio in patients with epilepsy.It is thus a potential biomarker for the diagnosis of cognitive impairment in patients with epilepsy.

Shenfu Injection(参附注射液) Suppresses Inflammation by Targeting Haptoglobin and Pentraxin 3 in Rats with Chronic Ischemic Heart Failure

Objective： To investigate the regulatory effects of Shenfu Injection （SFI, 参附注射液） on hemodynamic parameters and serum proteins in rats with post-infarction chronic heart failure （CHF）. Methods： Forty-five healthy Wistar rats were randomized into three groups： sham, heart failure （model） and SFI group. The CHF was induced by left coronary artery ligation. Seven days after the surgical operation, animals in the sham group and the model group received saline （6.2 mL/kg/d）, while animals in the SFI group received SFI （6.2 mL/kg.d） intraperitoneally. Four weeks later, cardiac hemodynamic parameters were measured via the carotid route. The expression of serum proteins was analyzed by two-dimensional electrophoresis and matrixassisted laser desorption/ionization time-of-flight mass spectrometer （MALDI-TOF MS）. Results： Recording of hemodynamic parameters showed that left ventricular systolic pressure （LVSP）, maximum rate of left ventricular pressure （＋dp/dtmax） rise, and maximum rate of left ventricular pressure （-dp/dtmax） decrease, while the left ventricular end diastolic pressure （LVEDP） rose in the model group compared to those in the sham group （P〈0.05）. The results of the MALDI-TOF MS indicated that haptoglobin （HP）, pentraxin 3 （PTX3） and alpha-1- antitrypsin were up-regulated, while serum albumin and 40S ribosomal protein were down-regulated in the model group （P〈0.05）. Compared with the model group, LVSP, ＋dp/dtmax and -dp/dtmax were higher, while LVEDP was lower in the SFI group （P〈0.05）. Expression levels of HP and PTX3 were lower than in the model group （P〈0.05）. Conclusion： SFI could improve hemodynamic function and decrease inflammatory reactions in the pathophysiology of CHF. The serum proteins HP and PTX3 could be potential biomarkers for chronic ischemic heart failure, and they could also be the serum protein targets of SFI.

血浆Pentraxin 3水平变化在急性胰腺炎患者中的临床意义

[目的]观察急性胰腺炎(AP)患者血浆Pentraxin 3的动态变化及临床意义。[方法]入组48例AP患者,含轻型急性胰腺炎(MAP)33例,重症急性胰腺炎(SAP)15例。在入院后第1、3、5天收集血标本,采用ELISA法检测Pentraxin 3、肿瘤坏死因子-α(TNF-α),C反应蛋白(CRP)。[结果]入院第1天,AP患者Pentraxin 3即达到峰值(P<0.01),随后逐渐下降,其峰值早于CRP;SAP患者Pentraxin 3水平明显高于MAP患者(P<0.01)。相关性分析发现,在第1天Pentraxin 3与TNF-α、CRP呈明显正相关(P<0.01)。[结论]Pentraxin 3可能是一个较好的SAP早期诊断指标。

Biomarkers in differentiating clinical dengue cases:A prospective cohort study

Objective:To evaluate five biomarkers(neopterin,vascular endothelial growth factor-A,thrombomodulin,soluble vascular cell adhesion molecule 1 and pentraxin 3)in differentiating clinical dengue cases.Methods:A prospective cohort study was conducted whereby the blood samples were obtained at day of presentation and the final diagnosis were obtained at the end of patients’follow-up.All patients included in the study were 15 years old or older,not pregnant,not infected by dengue previously and did not have cancer,autoimmune or haematological disorder.Median test was performed to compare the biomarker levels.A subgroup Mann-Whitney U test was analysed between severe dengue and non-severe dengue cases.Monte Carlo method was used to estimate the 2-tailed probability(P)value for independent variables with unequal number of patients.Results:All biomarkers except thrombomodulin has P value<0.001 in differentiating among the healthy subjects,non-dengue fever,dengue without warning signs and dengue with warning signs/severe dengue.Subgroup analysis for all the biomarkers between severe dengue and non-severe dengue cases was not statistically significant except vascular endothelial growth factor-A(P<0.05).Conclusions:Certain biomarkers were able to differentiate the clinical dengue cases.This could be potentially useful in classifying and determining the severity of dengue infected patients in the hospital.