Correlation between growth differentiation factor-15 and collagen metabolism indicators in patients with myocardial infarction and heart failure

BackgroundGrowth differentiation factor （GDF）-15, a divergent member of the transforming growth factor beta super-family does appear to be up-regulated in response to experimental pressure overload and progression of heart failure （HF）. HF frequently develops after myocardial infarction （MI）, contributing to worse outcome. The aim of this study is to assess the correlation between GDF-15 levels and markers related to collagen turnover in different stages of HF.MethodsThe study consists of a cohort of 179 patients, including stable angina pectoris patients （AP group,n= 50）, old MI patients without HF （OMI group,n = 56）, old MI patients with HF （OMI-HF group,n= 38） and normal Control group （n = 35）. Both indicators reflecting the synthesis and degradation rates of collagen including precollagen I N-terminal peptide （PINP）, type I collagen carboxy-terminal peptide （ICTP）, precollagen III N-terminal peptide （PIIINP） and GDF-15 were measured using an enzyme-linked inmunosorbent assay.ResultsThe plasma GDF-15 level was higher in OMI-HF group （1373.4 ± 275.4 ng/L） than OMI group （1036.1 ± 248.6 ng/L）, AP group （784.6 ± 222.4 ng/L） and Control group （483.8 ± 186.4 ng/L） （P〈 0.001）. The indi-cators of collagen turnover （ICTP, PINP, PIIINP） all increased in the OMI-HF group compared with Control group （3.03 ± 1.02μg/Lvs. 2.08 ± 0.95μg/L, 22.2 ± 6.6μg/Lvs. 16.7 ± 5.1μg/L and 13.2 ± 7.9μg/Lvs. 6.4 ± 2.1μg/L, respectively;P〈 0.01）. GDF-15 positively cor-related with ICTP and PIIINP （r = 0.302,P〈 0.001 andr= 0.206,P= 0.006, respectively）. GDF-15 positively correlated to the echocardio-graphic diastolic indicators E/Em and left atrial pressure （r= 0.349 and r= 0.358, respectively;P〈 0.01）, and inversely correlated to the systolic indicators left ventricular ejection fraction and the average of peak systolic myocardial velocities （Sm） （r=-0.623 and r=-0.365, respectively;P〈 0.01）.ConclusionPlasma GDF-15 is associated with the indicators of type I and III collagen turnover.

Macrophage inhibitory cytokine-1/growth differentiation factor-15 in premalignant and neoplastic tumours in a high-risk pancreatic cancer cohort

BACKGROUND Pancreatic cancer(PC)is a leading cause of cancer related mortality worldwide,with poor survival due to late diagnosis.Currently,biomarkers have limited use in early diagnosis of PC.Macrophage inhibitory cytokine-1 or growth differentiation factor-15(MIC-1/GDF15)has been implicated as a potential serum biomarker in PC and other malignancies.AIM To determine the role of MIC-1/GDF15 in detecting pre-malignant pancreatic lesions and neoplastic tumours in an asymptomatic high-risk cohort part of Australian Pancreatic Cancer Screening Program.METHODS A feasibility prospective single centre cohort study was performed.Participants recruited for yearly surveillance with endoscopic ultrasound(EUS)had serial fasting blood samples collected before EUS for MIC-1/GDF15,C-reactive protein and carbohydrate antigen 19-9.Patients were stratified into five groups based on EUS findings:Normal;pancreatic cysts,branch-duct intraductal papillary mucinous neoplasm;diffuse non-specific abnormalities;and neoplastic tumours.MIC-1/GDF15 serum levels were quantified using ELISA.Participants in whom EUS demonstrated abnormalities but not malignancy were closely followed up with magnetic resonance imaging(MRI)or computed tomography.RESULTS One hundred twenty participants were prospectively recruited from 2011-2018.Forty-seven participants(39.2%)had an abnormal EUS and five participants(4.2%)were diagnosed with neoplastic tumours,three by EUS(two pancreatic and one liver)and two by MRI/computed tomography(breast cancer,bladder cancer),which were performed for follow up of abnormal EUS.Baseline serum MIC-1/GDF15 was a significant predictor of neoplastic tumours on receiver operator characteristic curve analysis[area under curve(AUC)=0.814,P=0.023].Baseline serum MIC-1/GDF15 had moderate predictive capacity for branch-duct intraductal papillary mucinous neoplasm(AUC=0.644)and neoplastic tumours noted on EUS(AUC=0.793),however this was not significant(P=0.188 and 0.081 respectively).Serial serum MIC-1/GDF15 did not demonstrate a significant percentage change between a normal and abnormal EUS(P=0.213).Median baseline MIC-1/GDF15 was greater in those with neoplastic tumours(Median=1039.6,interquartile range=727.0-1977.7)compared to those diagnosed with a benign lesion(Median=570.1,interquartile range=460.7-865.2)on EUS and MRI(P=0.012).CONCLUSION In this pilot study MIC-1/GDF15 has predictive capacity for neoplastic tumours in asymptomatic individuals with a genetic predisposition for PC.Further imagining may be warranted in patients with abnormal EUS and raised serum MIC-1/GDF15.Larger multicentric prospective studies are required to further define the role of MIC-1/GDF15 as a serological biomarker in pre-malignant pancreatic lesions and neoplastic tumours.

Growth differentiation factor-15 is a prognostic marker in patients with intermediate coronary artery disease

Background Growth differentiation factor-15(GDF-15)is involved in multiple processes that are associated with coronary artery disease(CAD).However,little is known about the association between GDF-15 and the future ischemic events in patients with intermediate CAD.This study was conducted to investigate whether plasma GDF-15 constituted risk biomarkers for future cardiovascular events in patients with intermediate CAD.Methods A prospective study was performed based on 541 patients with intermediate CAD(20%–70%).GDF-15 of each patient was determined in a blinded manner.The primary endpoint was major adverse cardiac event(MACE),which was defined as a composite of all-cause death,nonfatal myocardial infarction,revascularization and readmission due to angina pectoris.Results After a median follow-up of 64 months,504 patients(93.2%)completed the follow-up.Overall,the combined endpoint of MACE appeared in 134 patients(26.6%)in the overall population:26 patients died,11 patients suffered a nonfatal myocardial infarction,51 patients underwent revascularization,and 46 patients were readmitted for angina pectoris.The plasma levels of GDF-15(median:1172.02 vs.965.25 pg/m L,P=0.014)were higher in patients with ischemic events than those without events.After adjusting for traditional risk factors,higher GDF-15 levels were significantly associated with higher incidence of the composite endpoint of MACE(HR=1.244,95%CI:1.048–1.478,Quartile 4 vs.Quartile 1,P=0.013).Conclusions The higher level of GDF-15 was an independent predictor of long-term adverse cardiovascular events in patients with intermediate CAD.

Elevated serum growth differentiation factor 15 in multiple system atrophy patients:A case control study

BACKGROUND Multiple system atrophy(MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15(GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA.AIM To determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson’s disease(PD) patients and healthy controls.METHODS A case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzymelinked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysiswas used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD.RESULTS Serum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls(P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels(P = 0.043 and 0.000;respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients(cutoff: 470.42 pg/m L, sensitivity: 85.7%, specificity: 88.0%;cutoff: 1075.91 pg/m L, sensitivity:51.0%, specificity: 96.0%;respectively).CONCLUSION Serum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.

GROWTH DIFFERENTIATION FACTOR-5 STIMULATES THE GROWTH AND ANABOLIC METABOLISM OF ARTICULAR CHONDROCYTES

Objective To observe the effect of growth differentiation factor-5 (GDF-5) on the growth and anabolic metabolism of articular chondrocytes. Methods The articular chondrocytes isolated from rats were treated with various concentrations of rmGDF-5, and the growth of chondrocytes measured by MTT assay, the cellular cartilage matrices formation detected sulfated glycosaminoglycan by Alcian blue staining and type Ⅱcollagen by RT-PCR. Results After 7 days culture, MTT assay showed that GDF-5 enhanced the growth of chondrocytes in a dose-dependent manner, RT-PCR showed that GDF-5 clearly induced the synthesis of type Ⅱ collagen because of the col2a1 mRNA band more and more strong in a dose-dependent. Chondrocytes were cultured with GDF-5 for 14 days, the intensity of Alcian blue staining was greatly enhanced, especially, at a high concentration of 1000ng/mL, and GDF-5 enhanced the accumulation of the Alcian blue-stainable material in a concentration-dependent manner and in a does-dependent manner. Conclusion GDF-5 enhanced the growth of mature articular chondrocytes, and stimulated the cellular cartilage matrices formation in mono-layer culture.

Growth differentiation factor 15 as an emerging novel biomarker in SARS-CoV-2 infection

BACKGROUND Growth differentiation factor(GDF)-15 is a member of a transforming growth factor-βcytokine superfamily that regulates metabolism and is released in response to inflammation,hypoxia and tissue injury.It has evolved as one of the most potent cytokines for predicting the severity of infections and inflammatory conditions,such as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To investigate the utility of GDF-15 in predicting the severity of SARS-CoV-2 infection.METHODS PubMed,Reference Citation Analysis,CNKI,and Goggle Scholar were explored by using related MeSH keywords and data such as the first author’s name,study duration,type and place of study,sample size and subgroups of participants if any,serum/plasma GDF-15 level in pg/mL,area under the curve and cut-off value in receiver operating characteristic analysis,method of measurement of GDF-15,and the main conclusion were extracted.RESULTS In all studies,the baseline GDF-15 level was elevated in SARS-CoV-2-infected patients,and it was significantly associated with severity,hypoxemia,viral load,and worse clinical consequences.In addition,GDF-15 levels were correlated with C-reactive protein,D-dimer,ferritin and procalcitonin,and it had superior discriminatory ability to detect severity and in-hospital mortality of SARS-CoV-2 infection.Hence,GDF-15 might be used to predict the severity and prognosis of hospitalized patients with SARS-CoV-2.CONCLUSION Serial estimation of GDF-15 levels in hospitalized patients with SARS-CoV-2 infection appeared to have useful prognostic value and GDF-15 can be considered a clinically prominent sepsis biomarker for SARS-CoV-2 infection.

生长分化因子15联合沉默信息调节因子1在老年急性心肌梗死患者介入治疗的预后预测价值分析

目的:探讨生长分化因子15(growth differentiation factor-15,GDF15)联合沉默信息调节因子1(silent information regulator 1,SIRT1)在老年急性心肌梗死(acute myocardial infarctio,AMI)患者PCI治疗后预后预测中的价值。方法:选取本院2019年1月至2021年8月收治的209例AMI行PCI老年患者纳入AMI组,另选同期健康体检人群90例纳入对照组,检测AMI患者术前、术后7d以及对照组血清GDF15、SIRT1表达水平,观察AMI术后3个月内AMI组主要不良心血管事件(major adverse cardiovascular events,MACE)发生情况,对比MACE发生与未发生患者血清GDF15、SIRT1表达差异,通过受试者工作曲线(ROC)评估其对患者MACE发生的预测价值。结果:AMI患者术前与术后血清GDF-15水平明显高于对照组,SIRT1水平明显低于对照组(P <0.05);血清GDF-15、SIRT1水平联合检测诊断AMI的发生ROC曲线下面积(AUC)显著高于两项指标单独评估的AUC(P <0.05);209例患者术后3个月内发生MACE者44例(21.1%),发生MACE患者术前及术后血清GDF-15水平高于未发生者,SIRT1水平低于未发生者(P <0.05);术前血清GDF-15、SIRT1水平联合检测评估老年PCI治疗AMI患者MACE的发生ROC曲线下面积为0.816,显著高于两项指标单独评估曲线下面积0.726、0.725(P <0.05);术后血清GDF-15、SIRT1水平联合检测评估老年PCI治疗AMI患者MACE的发生ROC曲线下面积为0.894,显著高于两项指标单独评估曲线下面积0.815、0.811(P <0.05);术后7d血清GDF-15、SIRT1水平检测评估老年PCI治疗AMI患者MACE的发生ROC曲线下AUC高于术前(P <0.05)。结论:AMI患者血清GDF-15呈高表达,SIRT1呈低表达,且其表达水平可在一定程度上预测患者PCI术后MACE的发生,反映患者预后状态。

母体血清GDF-15、ANGPTL8对胎儿先天性心脏病产前诊断的临床意义

目的探讨血清生长分化因子-15(GDF-15)、血管生成素样蛋白8(ANGPTL8)在先天性心脏病(CHD)胎儿母体中的表达及其诊断胎儿CHD的价值。方法收集2020年1月—2023年3月甘肃省妇幼保健院产前诊断中心产前筛查疑似胎儿CHD的120例孕妇作为研究对象,根据产前彩色多普勒超声心动图诊断结果分为CHD组(n=86)和非CHD组(n=34)。比较2组血清GDF-15、ANGPTL8水平;多因素Logistic回归分析胎儿CHD发病的影响因素;ROC曲线分析血清GDF-15、ANGPTL8对胎儿CHD的诊断效能。结果与非CHD组比较,CHD组血清GDF-15、ANGPTL8水平显著升高(t/P=7.860/<0.001、7.334/<0.001);多因素Logistic回归分析结果显示,孕次≥3次、CHD家族史及血清GDF-15、ANGPTL8升高均是胎儿CHD发病的危险因素[OR(95%CI)=1.383(1.082~1.767),1.596(1.148~2.218),3.596(1.694~7.633),3.175(1.571~6.417)];血清GDF-15、ANGPTL8及二者联合预测胎儿CHD的AUC分别为0.805、0.835、0.903,二者联合诊断胎儿CHD优于血清GDF-15、ANGPTL8各自单独诊断(Z=2.052、2.219,P=0.040、0.027)。结论CHD胎儿的母体血清GDF-15、ANGPTL8水平显著升高,二者联合对胎儿CHD具有较高的辅助诊断潜能。

代谢综合征患者血清25(OH)D和GDF15水平表达与并发甲状腺结节发生恶性风险的相关性研究

目的探讨代谢综合征(metabolic syndrome,MS)患者血清25羟基维生素D[25(OH)D],生长分化因子15(growth differentiation factor 15,GDF-15)水平表达与并发甲状腺结节(thyroid nodules,TN)发生恶性风险的相关性。方法选取2019年8月~2023年8月在新疆医科大学第一附属医院就诊的185例MS患者作为研究对象,按照甲状腺超声检查结果将其分为MS组(n=73)和MS+TN组(n=112),并根据甲状腺结节恶性分级将MS+TN组患者分为良性组(n=89)及恶性组(n=23);另选取同期体检的68例体检健康者作为对照组。采用酶联免疫吸附法(ELISA)测定各组血清25(OH)D和GDF-15水平;Pearson分析血清25(OH)D和GDF-15水平与MS并发TN患者临床指标之间的相关性;多因素Logistic回归分析MS并发TN患者发生恶性TN的影响因素;绘制受试者工作特征(ROC)曲线评估血清25(OH)D和GDF-15水平对MS并发恶性TN的诊断价值。结果对照组、MS组、MS+TN组血清25(OH)D(30.41±6.73ng/ml,27.23±6.15 ng/ml,24.67±4.38 ng/ml)和GDF-15(167.99±22.56 ng/L,239.75±25.92 ng/L,286.63±26.04 ng/L)水平比较,差异具有统计学意义(F=22.219,472.113,均P<0.05);且与良性组相比,恶性组患者血清25(OH)D(26.28±4.53 ng/ml vs 18.44±3.79 ng/ml)水平明显降低,GDF-15(276.93±24.53 ng/L vs 324.17±31.89 ng/L)水平明显升高,差异具有统计学意义(t=7.631,7.718,均P<0.05)。恶性组患者BMI,年龄、FPG,TG,TSH和TGAb水平明显高于良性组,差异具有统计学意义(t=2.868,3.523,3.542,3.603,4.581,5.516,均P<0.05).Pearson相关分析,MS并发TN患者血清25(OH)D水平与FPG,TSH,TG和TGAb水平均呈负相关(r=-0.302,-0.482,-0.524,-0.546,均P<0.05),GDF-15水平与TG,TSH,TGAb和FPG水平均呈正相关(r=0.467,0.541,0.578,0.623,均P<0.001)。多因素Logistic回归分析,GDF-15(OR=1.673,95%CI:1.146~2.442)为MS患者恶性TN发生的危险因素(P<0.05),25(OH)D(OR=0.744,95%CI:0.604~0.916)为恶性TN发生的保护因素(P<0.05);血清25(OH)D和GDF-15水平单独及联合诊断MS并发恶性TN的AUC分别为0.813,0.799,0.930,联合诊断优于单独诊断(Z=2.088,2.021,P=0.037,0.043)。结论MS并发TN患者血清25(OH)D,GDF-15水平与其结节性质明显相关,血清25(OH)D水平降低和GDF-15水平升高是MS患者发生恶性TN的危险因素。

血清TAFI和GDF-15在上消化道出血患者诊断及预后评估中的价值

目的 探讨上消化道出血患者的血清纤溶抑制物(TAFI)、生长分化因子-15(GDF-15)表达水平及其在诊断及预后评估中的价值。方法 选择2020年5月至2023年6月保定市第二中心医院收治的94例上消化道出血患者设为研究组,根据AIMS65评分系统对患者预后的评估结果,将患者分为预后良好组(n=65)和预后不良组(n=29),另选择80名同期健康体检者设为对照组。收集入组患者的一般资料,采用ELISA法检测各组的血清TAFI、GDF-15水平,采用Spearman等级相关分析探讨上消化道出血患者的血清TAFI、GDF-15水平与AIMS65评分的相关性,采用ROC曲线分析血清TAFI、GDF-15对上消化道出血患者诊断和预后评估的价值。结果 研究组与对照组中有消化道出血史的患者占比差异有统计学意义(P<0.05);研究组的血清TAFI水平显著低于对照组,而血清GDF-15水平显著高于对照组(P均<0.05)。预后不良组的血清TAFI水平显著低于预后良好组,而血清GDF-15水平显著高于预后良好组(P均<0.05)。Spearman等级相关分析结果显示,上消化道出血患者的血清TAFI水平与AIMS65评分呈显著负相关,而血清GDF-15水平与AIMS65评分呈显著正相关(r=-0.493,r=0.537,P均<0.001)。ROC曲线分析结果显示,血清TAFI、GDF-15诊断上消化道出血的曲线下面积(AUC)分别为0.734和0.776,两者联合诊断的AUC为0.842,两者联合诊断上消化道出血的效能优于单独诊断(P均<0.05)。血清TAFI、GDF-15水平预测上消化道出血患者预后不良的AUC分别为0.658和0.712,两者联合预测上消化道出血患者预后不良的AUC为0.820,两者联合预测预后的效能优于单独预测(P均<0.05)。结论 TAFI在上消化道出血患者血清中呈低表达,而GDF-15呈高表达,两者与AIMS65评分均有相关性,两者联合检测对上消化道出血患者具有一定的诊断和预后预测价值。

超声心动图联合血清cTnI、GDF-15检测对老年乳腺癌患者术后化疗心脏损伤的评估价值

目的探究超声心动图联合血清心肌肌钙蛋白I(cTnI)、生长分化因子-15(GDF-15)对老年乳腺癌(BC)患者术后化疗心脏损伤的评估价值。方法选取北京市大兴区人民医院2019年9月至2022年8月收治的112例老年BC术后应用表柔比星为主的化疗患者为研究对象,按照是否发生心脏损伤将其分为:心脏损伤组(40例)和心脏未损伤组(72例)。评估超声心动图对老年BC患者术后化疗心脏损伤的诊断价值;采用酶联免疫吸附法检测两组血清cTnI、GDF-15水平;采用受试者工作特征曲线评估血清cTnI、GDF-15对老年BC患者术后化疗心脏损伤的诊断价值;以心脏损伤判定标准为金标准,评价超声心动图、血清cTnI、GDF-15及三者联合对老年BC患者术后化疗心脏损伤的诊断价值。结果超声心动图诊断老年BC患者术后化疗心脏损伤的灵敏度、特异度、准确度分别为77.50%、88.89%、84.82%;心脏损伤组患者血清cTnI、GDF-15水平均明显高于心脏未损伤组(P<0.05);血清cTnI、GDF-15诊断老年BC患者术后化疗心脏损伤的曲线下面积分别为0.864、0.834,截断值分别为221.88 ng/L、8.06 ng/L,灵敏度分别为75.00%、80.00%,特异度分别为94.44%、87.50%,准确度分别为87.50%、84.82%;超声心动图联合血清cTnI、GDF-15诊断老年BC患者术后化疗心脏损伤的灵敏度、特异度、准确度分别为97.50%、86.11%、90.18%,优于单独诊断。结论超声心动图联合血清cTnI、GDF-15对老年BC患者术后化疗致心脏损伤有较高诊断价值,可有效提高灵敏度、准确度,具有较高特异度。

Identification of cytokines involved in hepatic differentiation of mBM-MSCs under liver-injury conditions

AIM: To identify the key cytokines involved in hepatic differentiation of mouse bone marrow mesenchymal stem cells (mBM-MSCs) under liver-injury conditions. METHODS: Abdominal injection of CCl4 was adopted to duplicate a mouse acute liver injury model. Global gene expression analysis was performed to evaluate the potential genes involved in hepatic commitment under liver-injury conditions. The cytokines involved in hepatic differentiation of mBM-MSCs was function-ally examined by depletion experiment using specifi c antibodies, followed by rescue experiment and direct inducing assay. The hepatic differentiation was characterized by the expression of hepatic lineage genes and proteins, as well as functional features. RESULTS: Cytokines potentially participating in hepatic fate commitment under liver-injury conditions were initially measured by microarray. Among the up-regulated genes determined, 18 cytokines known to closely relate to liver growth, repair and development, were selected for further identif ication. The f ibroblast growth factor-4 (FGF-4), hepatocyte growth factor (HGF) and oncostatin M (OSM) were fi nally found to be involved in hepatic differentiation of mBM-MSCs under liver-injury conditions. Hepatic differentiation could be dramatically decreased after removing FGF-4, HGF and OSM from the liver-injury conditioned medium, and could be rescued by supplementing these cytokines. The FGF-4, HGF and OSM play different roles in the hepatic differentiation of mBM-MSCs, in which FGF-4 and HGF are essential for the initiation of hepatic differentiation, while OSM is critical for the maturation of hepatocytes. CONCLUSION: FGF-4, HGF and OSM are the key cytokines involved in the liver-injury conditioned medium for the hepatic differentiation of mBM-MSCs.

血清H-FABP、GDF-15表达对STEMI患者PCI后不良心血管事件的预测价值

目的:探究血清心型脂肪酸结合蛋白(heart-type fatty acid binding protein,H-FABP)、生长分化因子-15(growth and differentiation factor-15,GDF-15)表达对ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)患者经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)后不良心血管事件发生的预测价值。方法:采用前瞻性研究,选择2020年6月—2023年6月于赣州市人民医院接受PCI的140例STEMI患者作为研究对象,术前检测患者血清H-FABP、GDF-15,行PCI,术后随访3个月,统计患者术后不良心血管事件发生情况,分析血清H-FABP、GDF-15与STEMI患者术后不良心血管事件发生的关系,同时绘制受试者工作特征(receiver operating characteristic,ROC)曲线,探究血清H-FABP、GDF-15对STEMI患者PCI后不良心血管事件发生的预测价值。结果:随访3个月期间,140例患者均无脱落病例;随访期间,140例STEMI患者PCI后发生不良心血管事件占比为23.57%(33/140),未发生不良心血管事件占比为76.43%(107/140)。两组心肌梗死面积、高血压、既往吸烟史比较,差异均有统计学意义(P<0.05);两组性别、年龄、病变支数、既往饮酒史、肌红蛋白(myoglobin,Myo)、心肌肌钙蛋白I(cardiac troponin I,cTnI)、肌酸激酶同工酶(creatine kinase-MB,CK-MB)、心室舒张末期内径(left ventricular end diastolic dimension,LVEDD)比较,差异均无统计学意义(P>0.05)。发生组血清H-FABP、GDF-15均高于未发生组,差异均有统计学意义(P<0.05)。点二列相关性分析显示,血清H-FABP、GDF-15与STEMI患者PCI后不良心血管事件发生呈正相关(r>0,P<0.05)。ROC曲线结果显示,血清H-FABP、GDF-15单独预测的AUC>0.7,联合预测的AUC>0.8,联合预测价值更高。结论:STEMI患者PCI前血清H-FABP、GDF-15水平越高,术后不良心血管事件发生风险越大,且临床可以将血清H-FABP、GDF-15作为STEMI患者PCI后不良心血管事件发生的有效预测指标。

脑组织GDF-15水平与脑梗死大鼠血管新生以及Th1/Th2免疫平衡轴的关系

目的:探讨脑组织GDF-15水平与脑梗死大鼠血管新生以及Th1/Th2免疫平衡轴的关系。方法:45只雄性SD大鼠随机分为脑梗死模型组、假手术组以及正常对照组,15只/组。模型组采用线栓法建立脑梗死模型,假手术组仅暴露颈内动脉后直接缝合皮肤,建模成功后1周评估大鼠改良神经功能缺损(mNSS)评分。采用HE染色检测脑组织病理学变化情况,Western blot法检测大鼠脑组织中组织生长分化因子-15(GDF-15)蛋白水平,RTPCR测定脑组织中GDF-15 mRNA水平。采用ELISA法检测脑组织INF-γ、IL-4表达情况,采用Spearman相关性分析大鼠脑组织中GDF-15蛋白、mRNA表达水平分别与mNSS评分、微血管密度(MVD)、INF-γ/IL-4水平之间的相关性。结果:模型组大鼠mNSS评分明显高于假手术组和正常对照组(P<0.001),模型组脑梗死面积比为(24.45±4.15)%,假手术组和正常对照组未发现脑梗死区域。模型组大鼠脑组织GDF-15蛋白、mRNA、MVD、INF-γ/IL-4水平均明显高于假手术组和正常对照组(P<0.05)。Spearman相关性分析显示,模型组大鼠脑组织中GDF-15蛋白、mRNA表达水平分别与mNSS评分、MVD、INF-γ/IL-4水平呈正相关关系(P<0.001)。结论:脑梗死大鼠脑组织中GDF-15处于高表达状态,且与神经功能密切关联,其作用机制可能与血管新生以及调控Th1/Th2免疫平衡轴有关。

BMP-4 induced proliferation and oriented differentiation of rat hepatic oval cells into hepatocytes

Objective:To explore the role of bone morphogenetic protein 4(BMP-4) in hepatic progenitor cells(HPCs).Methods:The effect of BMP-4 on rat hepatic oval cells was examined by using the WB-F344 rat hepatocytic epithelial stem-cell-like cell line.This hepatocytic cell line could exert various hepatocytc functions including the secretion of albumin and urea.Immunohistochemistry was used to examine the effects of BMP-4 and its antagonist,Noggin,on the proliferation and differentiation of these cells,cellular uptake and excretion of indocyanine green,the periodic acid-schiff(PAS) assay for glycogen storage and the expression of hepatic markers.Results:Our results showed for the first time that BMP-4 may acted as a potential inducer of hepatic differentiation in rat hepatic oval cells.Conclusions:This cell source offers a much-needed attractive and expandable source for future investigations of drug screening,stem cell technologies and cellular transplantation,in a society with increasing levels of liver disease and damage.

血清GDF-15、chemerin、PTX3水平与2型糖尿病患者肥胖、胰岛素抵抗及炎症的关系及其预测效能的构建与评价

目的探讨血清生长分化因子-15(GDF-15)、趋化素(chemerin)、正五聚蛋白3(PTX3)水平与2型糖尿病(T2DM)患者肥胖、胰岛素抵抗及炎症因子的关系,并进行预测效能的构建及评价。方法选取2020年2月至2022年9月该院收治的T2DM患者231例作为T2DM组。另选取同期来该院体检的健康者100例作为对照组。采用酶联免疫吸附试验法检测并比较两组血清GDF-15、chemerin、PTX3水平,收集两组临床资料并进行比较。采用Pearson相关性分析及多元线性回归分析血清GDF-15、chemerin、PTX3水平与肥胖、胰岛素抵抗及炎症指标的关系。采用多因素Logistic回归评估T2DM发生的独立危险因素,并构建血清GDF-15、chemerin、PTX3联合预测模型,绘制受试者工作特征(ROC)曲线评价其对T2DM发生的预测效能。结果与对照组比较,T2DM组体重指数(BMI)、腰臀比(WHR)、收缩压、总胆固醇、甘油三酯、空腹血糖、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、白细胞介素(IL)-1β、IL-6、GDF-15、chemerin、PTX3均升高,差异有统计学意义(P<0.05)。Pearson相关性分析显示,T2DM组血清GDF-15、chemerin、PTX3水平与BMI、WHR、FINS、HOMA-IR、IL-1β、IL-6呈正相关(P<0.05)。多元线性回归分析显示,BMI、FINS、HOMA-IR、IL-1β、IL-6与血清GDF-15、chemerin、PTX3水平呈正相关(P<0.05)。多因素Logistic回归分析结果发现,血清GDF-15、chemerin、PTX3水平升高是影响T2DM发生的独立危险因素(P<0.05)。ROC曲线分析结果显示,血清GDF-15、chemerin、PTX3联合预测模型预测效能较好,其曲线下面积及灵敏度、特异度、准确度均高于各指标单独应用。结论T2DM患者血清GDF-15、chemerin、PTX3水平升高,且其水平随着T2DM患者肥胖、胰岛素抵抗及炎症反应程度的加重而增加,该研究所构建的联合预测模型预测效能较好,对T2DM发生具有较高的预测价值。

慢性心力衰竭患者血清CA125 GDF15 sTREM-1水平及其与心功能的相关性分析

目的:探究血清糖类抗原125(CA125)、生长分化因子-15(GDF-15)、可溶性髓样细胞触发受体-1(sTREM-1)在慢性心力衰竭患者中的表达及其与心功能的相关性分析。方法:选取2022年6月至2023年6月本院收治的CHF患者96例临床资料开展回顾性分析,其中轻中度心力衰竭组46例(NYHA分级为Ⅰ~Ⅲ级)、重度心力衰竭组50例(NYHA分级为Ⅳ级),另按2∶1比例选取同期本院检查健康体检者48名为健康对照组。比较各组血清CA125、GDF15、sTREM-1水平与心功能指标的差异,并分析血清CA125、GDF15、sTREM-1水平与心功能指标的相关性。并通过ROC曲线分析血清CA125、GDF15、sTREM-1水平诊断慢性心力衰竭的效能。结果:研究组CA125、GDF15、sTREM-1水平均高于对照组(P<0.05)。研究组FS、EF均低于对照组,LAD、LVEDD均高于对照组(P<0.05)。Person相关性分析显示,CA125、GDF15、sTREM-1均与FS、EF呈负相关(r=-0.605/-0.617、-0.516/-0.512、-0.572/-0.613,P<0.05),均与LAD、LVEDD呈正相关(r=0.827/0.818、0.819/0.834、0.846/0.878,P<0.05)。重度心力衰竭组CA125、GDF15、sTREM-1水平均高于轻中度心力衰竭组(P<0.05)。二元Logistic回归分析显示,血清CA125、GDF15、sTREM-1为重度心力衰竭的危险因素(P<0.05)。采用ROC分析血清CA125、GDF15、sTREM-1评估慢性心力衰竭严重程度的AUC、敏感度、特异度,分别为0.761、0.695、0.822,以预测评分绘制ROC曲线评估慢性心力衰竭严重程度的AUC为0.848,敏感度为84.0%、特异性为82.6%。结论:血清CA125、GDF15、sTREM-1在CHF患者中高表达,与心功能相关密切,可作为评估心力衰竭严重程度的有效指标,联合评估效果更好。

心房颤动患者血清生长分化因子-15的表达差异和临床意义

目的:检测心房颤动(简称房颤)患者血清生长分化因子-15(growth differentiation factor-15,GDF-15)水平,分析其表达水平与临床因素、生化指标和心房结构的相关性,进一步分析GDF-15与房颤类型和结构重构的关系。方法:纳入2017年10月至2019年10月于北京大学第三医院心内科住院的房颤患者,选择同期住院无房颤病史的窦性心律者为对照组。收集患者的临床资料,采用酶联免疫吸附反应法检测血清GDF-15水平。采用SPSS 23.0软件进行统计学分析。结果:入组156例房颤患者,其中持续性房颤组64例,阵发性房颤组92例;对照组38例。房颤组血清GDF-15水平明显高于对照组[1 112 (723, 1 525) ng/L vs. 697 (499, 825) ng/L,P<0.001],持续性房颤组血清GDF-15水平明显高于阵发性房颤组[1 140 (858, 1 708) ng/L vs. 1 090 (662, 1 374) ng/L,P=0.047],差异具有统计学意义。血清GDF-15预测房颤的受试者工作特征曲线下面积为0.736(95%CI:0.651~0.822,P<0.001),最佳临界值843.2 ng/L,其敏感性为68.2%,特异性为78.9%。血清GDF-15预测持续性房颤的受试者工作特征曲线下面积为0.594(95%CI:0.504~0.684,P=0.047),最佳临界值771.5 ng/L,其敏感性为82.8%,特异性为35.9%。相关分析显示房颤患者血清GDF-15水平与年龄(r=0.480,P<0.001)、左心房压力(left atrial pressure, LAP,r=0.300,P<0.001)正相关,与左心耳血流速度(left atrial appendage flow velocity, LAAV,r=-0.252,P=0.002)负相关。多重线性回归显示年龄和LAP对血清GDF-15的影响差异具有统计学意义(P<0.05)。Logistic回归分析表明GDF-15(OR=1.002,95%CI:1.001~1.003,P=0.004)和左心房前后径(left atrial diameter, LAD,OR=1.400, 95%CI:1.214~1.616,P<0.001)是房颤发生的独立危险因素。结论:房颤患者血清GDF-15水平显著升高,且持续性房颤患者血清GDF-15水平高于阵发性房颤患者,血清GDF-15表达水平与房颤及心房结构重构具有一定相关性。

血清GDF-15、FGF-21水平对脓毒症患者病情评估及预后预测的临床价值

目的探讨血清生长分化因子15(GDF-15)、成纤维化生长因子21(FGF-21)水平对脓毒症患者病情评估及其对预后的预测价值。方法回顾性将2020年1月至2023年6月承德医学院附属医院ICU收治的脓毒症患者102例作为研究对象。按Sepsis-3脓毒症诊断标准,按病情不同将患者分为脓毒症组(n=46)与脓毒症休克组(n=56);并按28 d预后不同将患者分为存活组(n=75)与死亡组(n=27)。收集患者常规临床资料,包括性别、年龄、白细胞(WBC)计数、D-二聚体、淋巴细胞(LY)计数、入院24 h的急性生理学和慢性健康状况评价Ⅱ(APACHEⅡ)评分。比较不同组别临床资料及血清GDF-15、FGF-21水平差异,分析患者GDF-15、FGF-21与APACHEⅡ评分的关系,并使用受试者操作特征(ROC)曲线评价GDF-15、FGF-21对患者28 d死亡的预测价值。结果脓毒症组与脓毒症休克组的性别构成比、年龄、LY等比较,差异均无统计学意义(P>0.05);脓毒性休克组WBC、D-二聚体、APACHEⅡ评分、GDF-15、FGF-21水平均高于脓毒症组,且28 d病死率高于脓毒症组,差异均有统计学意义(P<0.05)。死亡组与存活组的性别构成比、年龄、LY比较,差异均无统计学意义(P>0.05);死亡组WBC、D-二聚体、APACHEⅡ评分、血清GDF-15、FGF-21水平均高于存活组,差异均有统计学意义(P<0.05)。经Pearson相关分析得出,脓毒症患者血清GDF-15、FGF-21水平与APACHEⅡ评分均呈正相关(r=0.378、0.394,P<0.001)。Logistic回归分析得出,血清GDF-15(OR=1.169,95%CI:1.041~1.312)、FGF-21水平(OR=1.406,95%CI:1.129~1.752)和APACHEⅡ评分(OR=1.346,95%CI:1.095~1.653)均是脓毒症患者28 d死亡的危险因素(P<0.05)。ROC曲线分析得出,血清GDF-15、FGF-21预测脓毒症患者28 d死亡的曲线下面积(AUC)分别为0.888、0.820,与APACHEⅡ评分(AUC为0.867)相比差异均无统计学意义(P>0.05)。结论血清GDF-15、FGF-21水平增高与脓毒症患者病情较重相关,且对患者预后有一定预测能力。

中性粒细胞明胶酶相关脂质运载蛋白和生长分化因子15在高血压肾损伤中的诊断价值

目的探讨血清中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、生长分化因子15(GDF-15)联合检测在老年H型高血压患者肾损伤中的诊断价值。方法选取2021年4月至2022年6月承德医学院附属医院神经内科及全科医疗科收治的H型高血压患者177例,依据估算肾小球滤过率分为肾功能损伤组81例和肾功能正常组96例。收集2组患者一般资料、实验室检查指标,受试者工作特征曲线(ROC)分析血清NGAL、GDF-15联合检测对老年H型高血压患者肾损伤的诊断价值,Pearson相关性分析血清NGAL、GDF-15水平与老年H型高血压患者肾损伤的相关性。结果肾功能损伤组收缩压水平高于肾功能正常组[(148.53±14.62)mm Hg(1 mm Hg=0.133 kPa)vs(138.75±13.36)mm Hg,P<0.01],2组舒张压比较差异无统计学意义(P>0.05);肾功能损伤组肌酐、尿素、β_2微球蛋白(β_2-MG)、胱抑素C(Cys C)、尿微量白蛋白(MA)、NGAL及GDF-15水平高于肾功能正常组(P<0.01);ROC曲线分析显示,NGAL、GDF-15联合检测显著高于NGAL、GDF-15单独检测(P<0.01)。Pearson相关性分析显示,血清NGAL、GDF-15水平与肌酐、尿素、β_2-MG、Cys C、MA水平均呈正相关(P<0.01)。结论老年H型高血压患者出现肾损伤后血清NGAL、GDF-15水平升高,血清NGAL、GDF-15联合检测在老年H型高血压患者肾损伤诊断中具有较高的诊断价值。