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。

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。

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。

血清FGF19、GDF15对肝癌介入治疗患者预后的评估价值

目的探讨血清成纤维细胞生长因子19(FGF19)、生长分化因子15(GDF15)对肝癌介入治疗患者预后的评估价值。方法选取2019年5月至2022年5月期间在我中心接受介入治疗的78例原发性肝癌患者进行研究,根据患者行介入治疗后6个月内是否复发分为复发组(20例)和未复发组(58例),比较两组患者临床病理特征;Logistic回归分析影响肝癌介入治疗患者预后复发的相关因素;受试者工作特征(ROC)曲线分析FGF19和GDF15对肝癌介入治疗患者预后复发的预测价值。结果肝癌患者行介入治疗后血清FGF19和GDF15表达水平均降低(P<0.05);复发组患者血清FGF19和GDF15表达水平均显著高于未复发组(P<0.05);复发组分化程度为低分化的患者所占比例显著高于未复发组(P<0.05);低分化程度、FGF19和GDF15升高均为肝癌介入治疗患者复发的危险因素(P<0.05);血清FGF19、GDF15和AFP单独检测预测肝癌介入治疗患者预后复发的AUC分别为0.734、0.791和0.883,二者联合检测的AUC为0.886,二者联合检测优于血清FGF19和GDF15各自单独检测(Z二者联合-FGF19=2.294、Z二者联合-GDF15=1.946,P=0.022、0.048)。结论血清FGF19和GDF15表达水平的升高会促使肝癌患者行介入治疗后发生复发,二者联合检测对肝癌介入治疗患者的预后状态具有较好的预测价值。

Fibroblast growth factor 15,induced by elevated bile acids,mediates the improvement of hepatic glucose metabolism after sleeve gastrectomy

BACKGROUND Fibroblast growth factor(FGF)15/19,which is expressed in and secreted from the distal ileum,can regulate hepatic glucose metabolism in an endocrine manner.The levels of both bile acids(BAs)and FGF15/19 are elevated after bariatric surgery.However,it is unclear whether the increase in FGF15/19 is induced by BAs.Moreover,it remains to be understood whether FGF15/19 elevations contribute to improvements in hepatic glucose metabolism after bariatric surgery.AIM To investigate the mechanism of improvement of hepatic glucose metabolism by elevated BAs after sleeve gastrectomy(SG).METHODS By calculating and comparing the changes of body weight after SG with SHAM group,we examined the weight-loss effect of SG.The oral glucose tolerance test(OGTT)test and area under the curve of OGTT curves were used to assess the anti-diabetic effects of SG.By detecting the glycogen content,expression and activity of glycogen synthase as well as the glucose-6-phosphatase(G6Pase)and phosphoenolpyruvate carboxykinase(Pepck),we evaluated the hepatic glycogen content and gluconeogenesis activity.We examined the levels of total BA(TBA)together with the farnesoid X receptor(FXR)-agonistic BA subspecies in systemic serum and portal vein at week 12 post-surgery.Then the histological expression of ileal FXR and FGF15 and hepatic FGF receptor 4(FGFR4)with its corresponding signal pathways involved in glucose metabolism were detected.RESULTS After surgery,food intake and body weight gain of SG group was decreased compare with the SHAM group.The hepatic glycogen content and glycogen synthase activity was significantly stimulated after SG,while the expression of the key enzyme for hepatic gluconeogenesis:G6Pase and Pepck,were depressed.TBA levels in serum and portal vein were both elevated after SG,the FXR-agonistic BA subspecies:Chenodeoxycholic acid(CDCA),lithocholic acid(LCA)in serum and CDCA,DCA,LCA in portal vein were all higher in SG group than that in SHAM group.Consequently,the ileal expression of FXR and FGF15 were also advanced in SG group.Moreover,the hepatic expression of FGFR4 was stimulated in SG-operated rats.As a result,the activity of its corresponding pathway for glycogen synthesis:FGFR4-Ras-extracellular signal regulated kinase pathway was stimulated,while the corresponding pathway for hepatic gluconeogenesis:FGFR4-cAMP regulatory element-binding protein-peroxisome proliferator-activated receptorγcoactivator-1αpathway was suppressed.CONCLUSION Elevated BAs after SG induced FGF15 expression in distal ileum by activating their receptor FXR.Furthermore,the promoted FGF15 partly mediated the improving effects on hepatic glucose metabolism of SG.

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.

Effect and Mechanism of Epidermal Growth Factor on Proliferation of GL15 Gliomas Cell Line

The effects of epidermal growth factor （EGF） on proliferation of G15 glioma cells and the possible mechanisms were investigated. GFAP and EGFR expression was detected by immunohistochemical method. After the cells were treated with EGF at different concentrations, cell count method was used to determine the proliferation of glioma cells, cell cycle and apoptosis were analyzed by flow cytometry （FCM）, and laser scan confocal microscope （LSCM） was used to measure the cytoplasmic free calcium. The results showed that GFAP was diffusedly expressed in GLI5 cells and EGFR was over-expressed. EGF at doses of ≤ 1 ng/mL could significantly stimulate cell proliferation, cells in phase G0/G1 decreased, and those in phase S increased. EGF at doses of 10 and 100ng/ml could inhibit the cell proliferation significantly, and the apoptosis ratio in high dose of EGF group was higher than in control group. EGF could significantly induce a quick rise of intracellular free calcium, but the peak value of intracellular free calcium activated by high dose of EGF was higher than by low dose of EGF. It was suggested that EGF had a dual effect on gliomas： low dose of EGF could stimulate the cell proliferation of gliomas, but high dose of EGF could induce the cell apoptosis and inhibit the proliferation of gliomas, which might be contributed to the difference of intracellular free calcium.

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 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。

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。

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。

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。

血清生长分化因子15、细胞因子信号转导抑制因子3水平与原发性肝癌患者接受经导管动脉栓塞化疗预后的关系

目的探究血清生长分化因子15(growth differentiation factor 15,GDF15)、细胞因子信号转导抑制因子3(suppressor of cytokine signaling 3,SOCS3)水平与原发性肝癌患者接受经导管动脉栓塞化疗(transcatheter arterial chemoembolization,TACE)预后的关系。方法选取89例2018年9月至2020年5月在河北北方学院附属第一医院行TACE的原发性肝癌患者作为研究组,治疗3个周期后评估近期疗效,将研究组分为预后良好组(n=54)、预后不良组(n=35),另选取同期健康体检者89例作为对照组。血清GDF15、SOCS3表达水平用酶联免疫吸附法测定,并进行组间比较;用多因素Logistic回归分析患者接受TACE预后的影响因素;受试者操作特征曲线(receiver operating characteristic curve,ROC曲线)分析血清GDF15、SOCS3水平对预后的评估价值。结果与对照组相比,研究组血清GDF15水平升高,血清SOCS3水平下降(均P<0.05);与预后良好组相比,预后不良组血清GDF15水平升高,血清SOCS3水平降低(均P<0.05)。血清GDF15为原发性肝癌患者接受TACE预后的独立危险因素,而血清SOCS3为独立保护因素(均P<0.05)。血清GDF15、SOCS3二者联合评估原发性肝癌患者接受TACE预后的ROC曲线的曲线下面积为0.958,优于血清GDF15、SOCS3各自单独检测(Z_(二者联合-GDF15)=2.074、Z_(二者联合-SOCS3)=2.794,P=0.038、P=0.005)。结论血清GDF15表达水平较高和血清SOCS3表达水平较低的原发性肝癌患者接受TACE预后较差,血清GDF15、SOCS3为原发性肝癌患者接受TACE预后的影响因素,对患者预后情况有较好的评估价值。

脑反射联合普罗布考疗法对颈动脉斑块稳定度、血清GDF15、PON1指标水平的影响及相关性分析

目的 探究脑反射联合普罗布考对颈动脉斑块稳定性、血清生长分化因子15(GDF15)、血对氧磷酶1(PON1)的影响及相关性分析。方法 选取2019年6月至2022年6月入我院就诊的具备脑血管缺血表现症状且颈动脉可见斑块形成的患者共214例,依照干预治疗方案的不同将纳入患者分为联合治疗组(n=102)和对照组(n=112)。对照组采用普罗布考药物治疗方式,联合治疗组采用脑反射联合普罗布考疗法,观察两组治疗前后颈动脉状态等指标差异,对比两组治疗前后血清GDF15及PON1指标、血脂指标、神经功能评分(NIHSS)差异,采用Spearman相关系数分析分析患者颈动脉斑块稳定性与血清GDF15及PON1指标相关性。结果 治疗后联合治疗组斑块稳定患者例数明显高于对照组;治疗后两组IMT值、斑块数量及面积较治疗前均明显降低,且联合治疗组各指标水平较对照组显著降低(P<0.001);治疗后两组血清GDF15指标较治疗前均明显降低,且联合治疗组明显低于对照组,两组血清PON1较治疗前均明显升高,且联合治疗组明显高于对照组(均P<0.05);治疗后两组三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)指标水平较治疗前均明显降低,且联合治疗组各指标值明显低于对照组(均P<0.05);治疗后两组高密度脂蛋白胆固醇(HDL-C)指标水平较治疗前均明显升高,且联合治疗组指标值明显高于对照组(P<0.05);治疗后两组NIHSS评分结果较治疗前均明显降低,且联合治疗组评分结果明显低于对照组(P<0.05);采用Spearman相关系数分析显示患者颈动脉斑块稳定性与血清GDF15指标呈负相关,与PON1指标呈正相关(均P<0.05)。结论 脑反射联合普罗布考治疗方案对改善患者颈动脉斑块状态、血清GDF15、PON1指标及血脂等具有积极效用,亦可有效减轻患者神经功能缺损程度,值得临床推广应用。此外,本研究发现血清GDF15、PON1指标与缺血性脑血管病患者颈动脉斑块稳定性密切相关,提示后续针对该类患者可通过以上指标进行监测并针对性完善诊疗方案以改善患者预后。

血清HB-EGF、GDF15水平与卵巢癌手术治疗患者预后的相关性

目的探讨血清肝素结合性表皮生长因子(HB-EGF)、生长分化因子15(GDF15)水平与卵巢癌手术治疗患者预后的相关性。方法采用前瞻性随机试验方法,选取90例卵巢癌患者为研究对象,所有入选者术前均接受血清HB-EGF、GDF15水平检测,随访3年,观察患者预后情况,并分析血清HB-EGF、GDF15水平与卵巢癌手术治疗患者预后的相关性。结果90例卵巢癌患者预后不良14例,占15.56%;预后良好76例,占84.44%;预后不良组血清HB-EGF、GDF15水平均高于预后良好组,差异有统计学意义(P<0.05);经一般双变量Pearson相关性分析发现,血清HB-EGF、GDF15水平与预后不良发生呈正相关(r>0,P<0.05);绘制ROC曲线,结果显示,血清HB-EGF、GDF15水平预测预后不良发生的AUC均>0.8,具有一定预测价值。结论卵巢癌患者血清HB-EGF、GDF15水平与手术治疗后预后结局密切相关,在未来临床可通过检测血清HB-EGF、GDF15水平评癌症患者预后,为早期防治提供参考。

生长分化因子15在衰老、代谢和炎症相关疾病中的作用

生长分化因子15(GDF15)是TGF-β超家族的成员,在人体多种组织中表达。正常生理条件下GDF15在除胎盘和前列腺组织以外的其他组织中表达量均较低,随着衰老的发生、运动或压力的刺激,GDF15蛋白的表达水平明显增高。GDF15与其受体胶质细胞源性神经营养因子家族受体α样(GFRAL)蛋白结合后,可促进细胞内脂肪酸β氧化和脂质分解,从而缓解脂肪肝等的发展,同时也能降低机体的食物摄入量从而抑制肥胖。GDF15还可作为炎症因子调控衰老和纤维化相关疾病的发生。本文主要概述GDF15在衰老、代谢和炎症相关疾病中的调控作用,为开发以GDF15为靶点的疾病治疗策略提供思路。

血清GDF-15、TGF-β1及HbAc1与冠心病患者PCI围术期心肌损伤的相关性分析

目的 探究血清生长分化因子15(GDF-15)、转化生长因子-β1(TGF-β1)及糖化血红蛋白(HbA1c)与冠心病患者经皮冠状动脉介入治疗(PCI)围术期心肌损伤(PMI)的相关性。方法 以2020年1月至2023年1月108例冠心病患者及53例健康体检者为研究对象,根据PCI围术期PMI发生情况将冠心病患者分为PMI组及非PMI组。比较冠心病组、对照组及PMI组、非PMI组血清GDF-15、TGF-β1、HbA1c及肌钙蛋白T(cTnT)水平,分析血清指标与cTnT水平的相关性,并对血清GDF-15、TGF-β1及HbA1c水平联合检测对PMI的评估价值进行分析。结果 冠心病组的血清GDF-15、TGF-β1、HbA1c及cTnT水平均高于对照组(P<0.05)。PMI组手术前及手术后的血清GDF-15、TGF-β1、HbA1c水平均高于非PMI组,术后cTnT水平高于非PMI组(P<0.05);PMI组手术前后血清GDF-15、TGF-β1、HbA1c及cTnT水平差值均大于非PMI组(P<0.05)。血清GDF-15、TGF-β1及HbA1c水平与cTnT水平呈正相关(r=0.527、0.356、0.419,P<0.05)。血清指标联合检测评估PMI的AUC值(0.960)大于血清GDF-15、TGF-β1、HbA1c水平单独检测(0.814、0.848、0.889,P<0.05)。结论 冠心病PMI患者血清GDF-15、TGF-β1、HbA1c水平与PMI程度有关,且各指标联合检测对PMI具有评估价值。

老年冠心病病人血清MCP-1、GDF-15、GMP-140与冠状动脉狭窄程度的相关性

目的:分析老年冠心病病人血清单核细胞趋化蛋白-1(MCP-1)、生长分化因子-15(GDF-15)和血小板颗粒膜蛋白-140(GMP-140)与冠状动脉狭窄程度的相关性。方法:选取中国人民解放军西部战区总医院2022年3月—2023年3月收治的97例老年冠心病病人为冠心病组,并选取同期60名健康体检者为对照组,检测血清MCP-1、GDF-15、GMP-140水平。按照冠心病病人冠状动脉狭窄程度分为轻度狭窄组、严重狭窄组,比较轻度狭窄组、严重狭窄组血清MCP-1、GDF-15、GMP-140水平,采用Spearman相关性分析法分析血清MCP-1、GDF-15、GMP-140水平与冠状动脉狭窄程度的相关性,并使用受试者工作特征曲线(ROC)分析MCP-1、GDF-15、GMP-140评估冠状动脉狭窄程度的效能。结果:冠心病组血清MCP-1、GDF-15、GMP-140水平高于对照组,差异均有统计学意义(P<0.05)。严重狭窄组血清MCP-1、GDF-15、GMP-140水平高于轻度狭窄组,差异均有统计学意义(P<0.05)。Spearman相关性分析显示,冠心病病人血清MCP-1、GDF-15、GMP-140水平与冠状动脉狭窄程度呈正相关(P<0.05)。ROC曲线分析显示,MCP-1、GDF-15、GMP-140联合评估冠状动脉狭窄程度的曲线下面积为0.887,敏感度、特异度分别为88.89%、88.46%。结论:冠心病病人血清MCP-1、GDF-15、GMP-140水平显著升高,且与冠状动脉狭窄程度进展密切相关,联合检测血清MCP-1、GDF-15、GMP-140可有效评估冠状动脉狭窄程度。