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.

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

BackgroundGrowth 区别因素(GDF )-15, 转变生长因素贝它总科的一个分叉的成员确实看起来响应试验性的压力超载和心失败(HF ) 的前进起来调整。HF 经常在心肌的梗塞(MI ) 以后发展，贡献更坏的结果。学习是在 HF.MethodsThe 学习的不同阶段估计在与骨胶原周转有关的 GDF-15 层次和标记之间的关联的这的目的由 179 个病人的一个队组成，包括稳定的心绞痛病人( AP 组， n = 50 )，没有 HF 的旧 MI 病人( OMI 组， n = 56 )，有 HF 的旧 MI 病人( OMI-HF 组， n = 38 )并且正常控制组( n = 35 )。包括 precollagen 反映骨胶原的合成和降级率的两指示物我N终端肽( PINP )，类型我骨胶原carboxy终端肽( ICTP )， precollagen III N终端肽( PIIINP )和 GDF-15 用连接酶的 inmunosorbent assay.ResultsThe 血浆 GDF-15 水平被测量在 OMI-HF 组是更高的( 1373.4 &#x000b1 ；275.4 ng/L ) 比 OMI 组(1036.1 &#x000b1；248.6 ng/L ) ， AP 组(784.6 &#x000b1；222.4 ng/L ) 并且控制组(483.8 &#x000b1；186.4 ng/L )(P &#x0003c；0.001 ) 。骨胶原周转的指示物(ICTP， PINP， PIIINP ) 与控制相比在 OMI-HF 组增加的所有组织(3.03 &#x000b1；1.02 &#x000b5； g/L 对 2.08 &#x000b1；0.95 &#x000b5； g/L， 22.2 &#x000b1；6.6 &#x000b5； g/L 对 16.7 &#x000b1；5.1 &#x000b5； g/L 和 13.2 &#x000b1；7.9 &#x000b5； g/L 对 6.4 &#x000b1；2.1 &#x000b5； g/L 分别地；P &#x0003c；0.01 ) 。GDF-15 断然与 ICTP 和 PIIINP 相关(r = 0.302， P &#x0003c；0.001 并且 r = 0.206， P = 0.006，分别地) 。GDF-15 断然相关到心脏舒张的指示物 E/Em 和左 atrial 迫使的 echocardiographic (r = 0.349 并且 r = 0.358 分别地；P &#x0003c；0.01 ) ，并且相反地相关到收缩指示物左室的喷射部分和山峰的一般水准收缩心肌的速度(Sm )(r =&#x02212； 0.623 并且 r =&#x02212； 0.365 分别地；P &#x0003c；0.01 ).ConclusionPlasma GDF-15 与类型的指示物被联系我和 III 骨胶原周转。

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.

Growth Differentiation Factor-15 Produces Analgesia by Inhibiting Tetrodotoxin-Resistant Nav1.8 Sodium Channel Activity in Rat Primary Sensory Neurons

Growth differentiation factor 15(GDF-15)is a member of the transforming growth factor-βsuperfamily.It is widely distributed in the central and peripheral nervous systems.Whether and how GDF-15 modulates nociceptive signaling remains unclear.Behaviorally,we found that peripheral GDF-15 significantly elevated nociceptive response thresholds to mechanical and thermal stimuli in naïve and arthritic rats.Electrophysiologically,we demonstrated that GDF-15 decreased the excitability of small-diameter dorsal root ganglia(DRG)neurons.Furthermore,GDF-15 concentration-dependently suppressed tetrodotoxin-resistant sodium channel Nav1.8 currents,and shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction.GDF-15 also reduced window currents and slowed down the recovery rate of Nav1.8 channels,suggesting that GDF-15 accelerated inactivation and slowed recovery of the channel.Immunohistochemistry results showed that activin receptor-like kinase-2(ALK2)was widely expressed in DRG medium-and small-diameter neurons,and some of them were Nav1.8-positive.Blockade of ALK2 prevented the GDF-15-induced inhibition of Nav1.8 currents and nociceptive behaviors.Inhibition of PKA and ERK,but not PKC,blocked the inhibitory effect of GDF-15 on Nav1.8 currents.These results suggest a functional link between GDF-15 and Nav1.8 in DRG neurons via ALK2 receptors and PKA associated with MEK/ERK,which mediate the peripheral analgesia of GDF-15.

Growth differentiation factor-15 combined with N-terminal prohormone of brain natriuretic peptide increase 1-year prognosis prediction value for patients with acute heart failure: a prospective cohort study

Background:Clinical assessment and treatment guidance for heart failure depends on a variety of biomarkers.The objective of this study was to investigate the prognostic predictive value of growth differentiation factor-15(GDF-15)and N-terminal prohormone of brain natriuretic peptide(NT-proBNP)in assessing hospitalized patients with acute heart failure(AHF).Methods:In total,260 patients who were admitted for AHF in the First Affiliated Hospital of Nanjing Medical University were enrolled from April 2012 to May 2016.Medical history and blood samples were collected within 24 h after the admission.The primary endpoint was the all-cause mortality within 1 year.The patients were divided into survival group and death group based on the endpoint.With established mortality risk factors and serum GDF-15 level,receiver-operator characteristic(ROC)analyses were performed.Cox regression analyses were used to further analyze the combination values of NT-proBNP and GDF-15.Results:Baseline GDF-15 and NT-proBNP were significantly higher amongst deceased than those in survivors(P<0.001).In ROC analyses,area under curve(AUC)for GDF-15 to predict 1-year mortality was 0.707(95%confidence interval[CI]:0.648–0.762,P<0.001),and for NT-proBNP was 0.682(95%CI:0.622–0.738,P<0.001).No statistically significant difference was found between the two markers(P=0.650).Based on the optimal cut-offs(GDF-15:4526.0 ng/L;NT-proBNP:1978.0 ng/L),the combination of GDF-15 and NT-proBNP increased AUC for 1-year mortality prediction(AUC=0.743,95%CI:0.685–0.795,P<0.001).Conclusions:GDF-15,as a prognostic marker in patients with AHF,is not inferior to NT-proBNP.Combining the two markers could provide an early recognition of high-risk patients and improve the prediction values of AHF long-term prognosis.Clinical trial registration:ChiCTR-ONC-12001944,http://www.chictr.org.cn.

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.

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。

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。

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。

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。

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。

出血性脑卒中患者血清PDGF-D GDF-15及D-二聚体水平与颅内血肿扩大的相关性

目的分析血清血小板源性生长因子-D(PDGF-D)、生长分化因子-15(GDF-15)及D-二聚体与出血性脑卒中患者血肿扩大的相关性。方法选取2021-01-2023-01厦门大学附属中山医院神经内科诊治的出血性脑卒中患者197例,根据颅内血肿是否扩大分为血肿未扩大组(119例)和血肿扩大组(78例),收集患者基线临床资料。利用酶联免疫吸附试验(ELISA)检测血清PDGF-D和GDF-15水平,采用凝血仪检测血清D-二聚体水平。比较2组患者入院时血肿量(V1)和复查时血肿量(V2),计算V2/V1比值。采用Logistic回归分析颅内血肿扩大的独立危险因素。结果与血肿未扩大组相比,血肿扩大组收缩压[(158.17±21.73)mmHg比(164.82±22.94)mmHg,P<0.05]、舒张压[(97.31±8.93)mmHg比(101.36±9.55)mmHg,P<0.05]、GCS评分[(13.52±1.31)分比(11.78±1.14)分,P<0.05]和血清PDGF-D[(498.73±40.32)ng/L比(596.91±45.82)ng/L,P<0.05]、GDF-15[(728.49±76.71)ng/L比(832.38±86.25)ng/L,P<0.05]、D-二聚体[(1.63±0.10)mg/L比(1.84±0.23)mg/L,P<0.05]水平及V2[(20.53±4.72)cm^(3)比(29.47±5.13)cm3,P<0.05]、V2/V1比值(1.04±0.31比1.42±0.43,P<0.05)均更高。Logistic回归分析显示,PDGF-D、GDF-15、D-二聚体、收缩压、舒张压及GCS评分均为出血性脑卒中患者发生颅内血肿扩大的独立危险因素(分别为OR=1.798、1.672、1.616、1.592、1.583、1.738,P<0.05)。结论血清PDGF-D、GDF-15及D-二聚体水平在发生颅内血肿扩大的出血性脑卒中患者中升高,均为血肿扩大的独立危险因素。

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。

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。

绝经后H型高血压合并骨质疏松症患者血清MCP-1、PTX3、GDF15的变化及其临床意义分析

目的分析绝经后H型高血压(HHT)合并骨质疏松症(OP)患者血清单核细胞趋化蛋白(MCP)-1、正五聚蛋白3(PTX3)、生长分化因子15(GDF15)的变化及其临床意义。方法选取2020年6月至2023年5月我院收治的127例绝经后HHT合并OP患者为研究组,另选取同期85例绝经后OP患者为OP组,62例绝经后单纯HHT患者为HHT组、60例体检健康的绝经后女性志愿者为健康组。比较4组血清MCP-1、PTX3、GDF15水平、股骨颈和腰椎(L_(1~4))骨密度、血清骨代谢指标[骨钙素(BGP)、Ⅰ型胶原羧基端肽β特殊序列(β-CTX)、Ⅰ型前胶原氨基端前肽(PINP)]及炎症因子[肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)]。采用Pearson相关性分析血清MCP-1、PTX3、GDF15水平与骨密度、血清骨代谢指标及炎症因子的相关性。采用受试者工作特征(ROC)曲线分析血清MCP-1、PTX3、GDF15对绝经后HHT合并OP的诊断价值。结果与健康组比较,OP组、HHT组及研究组血清MCP-1、PTX3、GDF15、BGP、β-CTX、PINP水平均较高,且OP组高于HHT组,研究组高于OP组和HHT组(P<0.05)。与健康组比较,OP组、HHT组及研究组血清TNF-α、IL-6水平均较高,且HHT组高于OP组,研究组高于OP组和HHT组(P<0.05)。与健康组比较,OP组、HHT组及研究组的股骨颈和腰椎(L_(1~4))骨密度均较低,且OP组低于HHT组,研究组低于OP组和HHT组(P<0.05)。Pearson相关性分析显示,血清MCP-1、PTX3、GDF15水平与股骨颈和腰椎(L_(1~4))骨密度呈负相关,与血清BGP、β-CTX、PINP、TNF-α、IL-6水平呈正相关(P<0.05)。ROC曲线分析显示,血清MCP-1、PTX3、GDF15联合诊断绝经后HHT合并OP的AUC值为0.945,高于单独指标诊断。结论绝经后HHT合并OP患者血清MCP-1、PTX3、GDF15水平升高,且与股骨颈和腰椎(L_(1~4))骨密度、血清骨代谢指标及炎症因子密切相关,三者联合检测对诊断绝经后HHT合并OP患者有较高价值。

GDF15、miR-122、AFP和PIVKA-Ⅱ联合评估在HBV感染肝硬化患者肝细胞癌发生风险中的预测价值

目的评估血清生长分化因子15(GDF15)、microRNA-122(miR-122)、甲胎蛋白(AFP)和异常凝血酶原(PIVKA-Ⅱ)联合检测在监测乙肝病毒(HBV)感染肝硬化患者中肝细胞癌(HCC)的风险预测价值。方法将2017年12月至2022年1月在首都医科大学附属北京友谊医院就诊的45例HBV相关肝硬化患者、50例HCC患者纳入横断面研究,设为肝硬化组和HCC组;另选22例监测期间新确诊HCC的HBV肝硬化患者纳入纵向研究队列,分别对肝硬化组和HCC组患者以及监测期间新确诊HCC的HBV肝硬化患者的系列血清标本[新确诊HCC前12~18个月(T_(1))、新确诊HCC前6~12个月(T_(2))以及HCC诊断时(T_(3))]进行检测,测定GDF15、miR-122、AFP和PIVKA-Ⅱ水平。比较各组患者每项标志物的检测水平,采用受试者工作特征(ROC)曲线分析GDF15、miR-122、AFP和PIVKA-Ⅱ单独或联合检测对HCC患者的诊断价值,评估标志物的组合预测HBV感染肝硬化患者的HCC风险。结果横断面研究中,HCC组患者血清GDF15、AFP和PIVKA-Ⅱ水平分别为1760.64 pg/mL、40.24 ng/mL、106.37 mAU/mL,均显著高于肝硬化组患者(1357.63 pg/mL、9.07 ng/mL、22.59 mAU/mL),miR-122水平为38.72,则显著低于肝硬化组患者(75.70),差异均有统计学意义(P<0.05)。GDF15、miR-122、AFP和PIVKA-Ⅱ单独诊断HCC时,曲线下面积(AUC)分别为0.734、0.644、0.776、0.823;AFP和GDF15两项联合,AUC为0.835;GDF15、AFP和PIVKA-Ⅱ三项联合,AUC为0.860;GDF15、miR-122、AFP和PIVKA-Ⅱ四项联合,AUC最佳为0.876。区分肝硬化和HCC时,PIVKA-Ⅱ具有较高的敏感度(72.5%);GDF15具有较高的特异度(83.2%);AFP和PIVKA-Ⅱ联合,特异度最高(92.0%);四项联合,敏感度增加(82.2%),约登指数最高(0.622)。纵向研究结果未观察到每种单一生物标志物随时间的变化,而GDF15、AFP和PIVKA-Ⅱ三项联合以及GDF15、miR-122、AFP和PIVKA-Ⅱ四项联合,在三个时间点的检测值差异有统计学意义(P<0.01)。肝硬化患者横截面和纵向(T_(1))之间观察到四项组合的差异有统计学意义(P<0.05),提示标志物的联合应用可有效区分即将发生HCC和不会发生HCC的肝硬化患者。结论GDF15、miR-122、AFP和PIVKA-Ⅱ联合检测可以提高对HBV相关肝硬化和HCC患者的分辨力,且在HBV相关的肝硬化中,GDF15、miR-122、AFP和PIVKA-Ⅱ的组合能够识别HCC发展风险较高的患者,具有临床价值。

血清脱嘌呤脱嘧啶核酸内切酶1自身抗体、生长分化因子15水平对结直肠癌患者术后复发转移的预测价值

目的分析血清脱嘌呤脱嘧啶核酸内切酶1自身抗体(APE1-AAbs)、生长分化因子15(GDF-15)水平及对结直肠癌患者术后复发转移的预测价值。方法选取52例结直肠癌患者为观察组,并根据预后情况分为术后复发转移组(n=15)和术后未复发转移组(n=37)。选取同期正常体检健康者52例为对照组。检测APE1-AAbs、GDF-15水平。采用Pearson相关性分析法分析APE1-AAbs、GDF-15与结直肠癌术后复发转移的相关性。绘制受试者工作特征(ROC)曲线分析APE1-AAbs、GDF-15对结直肠癌术后复发转移的预测价值。结果观察组的APE1-AAbs、GDF-15水平高于对照组,差异有统计学意义(P<0.05)。术后复发转移组的APE1-AAbs、GDF-15水平高于术后未复发转移组,差异有统计学意义(P<0.05)。APE1-AAbs、GDF-15水平与结直肠癌术后复发转移呈正相关(P<0.05)。APE1-AAbs、GDF-15联合预测结直肠癌术后复发转移的价值高于APE1-AAbs、GDF-15单独预测,差异有统计学意义(P<0.05)。结论APE1-AAbs、GDF-15在结直肠癌患者血清中呈高表达。APE1-AAbs、GDF-15或可作为结直肠癌术后复发转移的标志物。