Plasma Nogo-A and placental growth factor levels are associated with portal hypertension in patients with liver cirrhosis

BACKGROUND Clinically significant portal hypertension(CSPH) and severe portal hypertension(SPH) increase the risk for decompensation and life-threatening complications in liver cirrhosis. Pathologic angiogenesis might contribute to the formation of these conditions. Placental growth factor(PlGF) and Nogo-A protein are biomarkers of pathological angiogenesis, but data on their role in liver cirrhosis and portal hypertension is scarce.AIM To determine plasma levels of PlGF and Nogo-A in patients with liver cirrhosis,CSPH, SPH and potential to predict portal hypertension.METHODS A cohort of 122 patients with hepatitis C virus and/or alcohol-induced liver cirrhosis with characterized hepatic venous pressure gradient(HVPG) were included in the study. Demographic data, medical history, Child-Turcotte-Pugh and Model of End Stage liver disease score, clinical chemistry, liver stiffnessvalues were recorded on the day of the procedure prior HVPG measurement. The degree of portal hypertension was determined by the invasive HVPG measurement. Nogo-A and PlGF plasma levels were evaluated using enzyme linked immunosorbent assay. The control group consisted of 30 healthy age-and sex-matched individuals.RESULTS Peripheral PlGF levels were higher and Nogo-A levels were lower in patients with liver cirrhosis(23.20 vs 9.85;P < 0.0001 and 2.19 vs 3.12;P = 0.004 respectively). There was a positive linear correlation between peripheral levels of PlGF and HVPG(r = 0.338, P = 0.001) and negative linear correlation between the peripheral Nogo-A levels and HVPG(r =-0.267, P = 0.007). PlGF levels were higher in CSPH and SPH(P = 0.006;P < 0.0001) whereas Nogo-A levels were lower(P = 0.01;P < 0.033). Area under the curve for the diagnosis of CSPH for PlGF was 0.68(P = 0.003) and for Nogo-A-0.67(P = 0.01);for SPH 0.714(P <0.0001) and 0.65(P = 0.014) respectively. PlGF levels were higher and Nogo-A levels were lower in patients with esophageal varices(P < 0.05). PlGF cut-off value of 25 pg/mL distinguished patients with CSPH at 55.7% sensitivity and76.7% specificity;whereas Nogo-A cut-off value of 1.12 ng/mL was highly specific(93.1%) for the diagnosis of CSPH.CONCLUSION Plasma PlGF levels were higher while Nogo-A levels were lower in patients with liver cirrhosis and portal hypertension. Biomarkers showed moderate predictive value in determining CSPH and SPH.

Inhibitory effect on subretinal fibrosis by anti-placental growth factor treatment in a laser-induced choroidal neovascularization model in mice

AIM:To investigate whether anti-placental growth factor(PGF) can inhibit subretinal fibrosis and whether this effect is mediated by the inhibitory effect of PGF on epithelial-mesenchymal transition(EMT) of retinal pigment epithelial(RPE) cells.METHODS:Subretinal fibrosis model was established in laser induced choroidal neovascularization(CNV) mice on day 21 after laser photocoagulation.Immunofluorescence staining(IFS) of cryosections and enzyme-linked immunosorbent assay(ELISA) were used to detect the expression of PGF.IFS of whole choroidal flat-mounts was used to detect the degree of subretinal fibrosis.IFS of cryosections and ELISA were used to detect the expression of EMT related indicators in subretinal fibrosis lesions.RESULTS:The expression of PGF protein in subretinal fibrosis lesions was significantly up-regulated(P<0.05),and mainly co-stained with pan-cytokeratin labeled RPE cells.Intravitreal injection of anti-PGF neutralizing antibody reduced the area of subretinal fibrosis and the ratio of fibrotic/angiogenic area significantly at the concentrations of 0.25,0.5,1.0,and 2.0 μg/μL(all P<0.05).The expression of E-cadherin in the local RPE cells decreased,while α-SMA increased significantly in subretinal fibrosis lesions,and the application of anti-PGF neutralizing antibody could reverse these changes(P<0.05).CONCLUSION:The expression of PGF is up-regulated in the lesion site of subretinal fibrosis and mainly expressed in RPE cells.Intravitreal injection of anti-PGF neutralizing antibody can significantly inhibit the degree of subretinal fibrosis in CNV mice,and this effect may be mediated by the inhibition of PGF on EMT of RPE cells.

Analysis of Placental Growth Factor in Placentas of Normal Pregnant Women and Women with Hypertensive Disorders of Pregnancy

To investigate the expressions of placental growth factor （PLGF） in placenta with hypertensive disorders of pregnancy （ HDP）, 45 women with HDP and 20 normally pregnant women were studied. Among 45 women with HDP, there were 23 cases of severe preeclampsia and one case of eclampsia. The location and level of PLGF proteins was determined by immunohistochemistry and Western blot. The expression of PLGF mRNA in placenta was assessed by reverse transcriptionalpolymerase chain reaction （RT-PCR）. The results showed that： （1） The distribution of PLGF in placenta with HDP was similar to normal one, which was mainly in the cytoplasm of villous syncytiotrophoblast and villous stroma; （2） The expression of PLGF protein was significantly decreased in placentas with mild and severe preeclampsia compared to the normal ones （0.3±0.4 vs 0.6± 0.4, 0.2±0.5 vs 0. 6±0. 4, P〈0.01）. There were no differences between the gestational hypertension placenta and normal one （0.5±0.6 vs 0. 6±0. 4, P〉0.05） ; （3） The transcription levels of the PLGF mRNA in placentas with preeclampsia were significantly lower than in normal groups （3.33±0.39 vs 4.87±0. 60, 1.97±0.29 vs 4.87±0.60, P〈0.01）, and no differences were found between the gestational hypertension placenta and normal groups. These findings suggest that the abnormal expression of PLGF in placentas is related to the pathogenesis of HDP.

Effect of Compound Danshen Injection Combined with Labetalol on Liver Function and Placental Growth Factor in Patients with Eclampsia

Objective: To explore the effect of Compound Danshen Injection combined with Labetalol on liver function and placental growth factor in patients with eclampsia. Methods: Seventy patients with eclampsia who were treated in the Hospital from February 2017 to February 2019 were enrolled. The patients were divided into two groups according to the random number table, with 35 cases in each group. The Observation group was treated with Labetalol, and the combined therapy group was treated with Compound Danshen Injection combined with Labetalol. The liver function [alanine aminotransferase, aspartate aminotransferase, total protein, and albumin], hemorheology indicators, placental growth factor and serum insulin-like growth factor-1 and clinical indicators in the two groups were analyzed. Results: After treatment, the levels of alanine aminotransferase and aspartate aminotransferase in the combined therapy group were significantly lower than those in the Observation group. The levels of total protein and albumin in the combined therapy group were significantly higher than those in the Observation group (P<0.05). After treatment, the high-cut and low-cut whole blood viscosity, plasma viscosity and erythrocyte rigidity index in the combined therapy group were significantly lower than the Observation group, and the difference was statistically significant (P<0.05). After treatment, the levels of PLGF and IGF-1 in the combined therapy group were significantly higher than those in the Observation group, and the difference was statistically significant (P<0.05). After treatment, the gestational age, neonatal weight index, placental weight and neonatal 1 min Apgar score in the combined therapy group were significantly higher than the Observation group, and the difference was statistically significant (P<0.05). Conclusion: For patients with eclampsia, Compound Danshen Injection combined with Labetalol is with great safety, which can help stabilize their condition, and improve their liver function and placental growth factor status.

血清sFT-1、PIGF对子痫前期患者妊娠结局的预测价值

目的 探讨血清可溶性血管内皮生长因子受体1(sFlt-1)、胎盘生长因子(PIGF)水平对子痫前期(PE)患者妊娠结局的预测价值。方法 选取PE孕妇136例(其中轻度PE 94例,重度PE 42例)和健康孕妇100例(对照组),均行血清sFlt-1、PIGF检测,比较两组血清sFlt-1、PIGF水平差异。按是否发生不良妊娠结局,将PE产妇分为结局不良组(n=54)与结局良好组(n=82),比较不同妊娠结局组血清sFlt-1、PIGF水平差异,使用受试者工作特征(ROC)曲线评价sFlt-1、PIGF对不良妊娠结局的预测能力。结果 PE组与对照组比较,血清PIGF水平显著下降(P<0.05),sFlt-1增高(P<0.05);且重度PE组血清PIGF水平低于轻度PE组(P<0.05),sFlt-1高于轻度PE组(P<0.05)。与结局良好组比较,结局不良组收缩压、24 h尿蛋白定量及血清sFlt-1水平更高(P<0.05),PIGF水平更低(P<0.05)。Logistic回归模型分析得出,血清sFlt-1(OR=1.861)及PIGF(OR=0.654)均为PE产妇不良妊娠结局的独立影响因素(P<0.05)。ROC曲线分析显示,血清sFlt-1、PIGF预测不良妊娠结局的AUC分别为0.857、0.855。结论 血清sFlt-1、PIGF与PE的发生发展相关,且对PE孕妇不良妊娠结局有一定的预测价值。

Associations between Placental Insulin-Like Growth Factor-1 Gene Expression, DNA Methylation and Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) is a common fetal development disorder which has great impact on neonatal health. Insulin-like growth factor-1 (IGF1) has an important role in regulating fetal growth. Whether IGF1 DNA methylation was associated with IUGR has not been studied. Placenta samples from IUGR (n = 27) and normal delivery (n = 29) were collected whereas basic information of mothers and infants were also collected. RT-PCR was performed to examine IGF1 transcriptions and bisulfite sequencing PCR was used for DNA methylation analysis. Gene expression analysis found IUGR had significantly lower IGF1 transcription compared to control group (IUGR: 0.330 ± 0.351;control group: 1.001 ± 0.800, t = 3.995, P IGF1 were all highly methylated and there is no difference on DNA methylation rate between IUGR and control group (IUGR: 75%;control group: 81%;P = 0.09). Interestingly, in both IUGR and control groups, male fetus had significantly higher methylation rate than female fetus (IUGR: male: 87%;female: 74%, P = 0.016;control: male: 82%;female: 69%, P = 0.012). There was no correlation between IGF1gene expression and DNA methylation rate (r = 0.095, P = 0.063). Intrauterine fetal growth restriction placenta had significantly lower IGF1gene expression;however, IGF1 DNA methylation level was similar. A potential fetus gender difference was also found in IGF1 DNA methylation rate.

Effect of Bushen Yiqi Huoxue Recipe on Placental Vasculature in Pregnant Rats with Fetal Growth Restriction Induced by Passive Smoking

Interactions of vascular endothelial growth factor （VEGF） with receptors VEGFR1/Fltl and VEGFR2/Flk1, and those of angiopoietins （Ang-1, Ang-2） with receptor Tie2 play important roles in placental angiogenesis. This study investigated vascular morphology and expression of these angiogenic factors in rat placenta on the day 15, 18, 21 of gestation （D 15, D 18 and D21）. The rats were randomly assigned into 3 groups： normal group, model group [fetal growth restriction （FGR） model], and Bushen Tqi Huoxue （BYHR） recipe treatment group （BYHR group, the pregnant rats with FGR were treated with BYHR recipe）. Morphological analysis indicated that during initial villous formation, fetal nucle- ated erythrocytes （FNEs） appeared in maternal blood sinus （MBS）. Subsequently, FNEs were sur- rounded by endothelial cells to form fetal capillary （FC） and then by trophoblast cells to form villi. As pregnancy proceeded, FC density increased progressively with increasing endothelial identification staining （EIS） in normal and BYHR groups. Whereas, villous formation was suppressed, normal in- crease in FC density was impaired and EIS was weakened in model group. Quantitative PCR analysis showed that VEGF and Flkl mRNA increased over gestation in all groups, indicating that VEGF might play a pivotal role in FC growth during late gestation. VEGF mRNA was increased on D15, while de- creased on D21 in model group as compared with normal group and BYHR group. Immunohistochemi- cally, Ang-2 protein was highly expressed in FNEs, gradually disappeared as villi matured, and decreased over gestation in all groups, indicating that Ang-2 might play a pivotal role in villous formation, which was further supported by decreased Ang-2 mRNA and protein expression in model group on D 15. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio increased from D15 to D18 in all groups as placenta matured. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio were decreased on D18 in model group as compared with normal and BYHR groups, indicating delayed maturity of FGR placenta. Alterations in angiogenic factors may result in altered placental vasculature and cause placental insufficiency. BYHR recipe could balance the angiogenic factors to promote the formation and maturation of FGR placental vasculature.

IMMUNOHISTOCHEMICAL LOCALIZATION OF EPIDERMAL GROWTH FACTOR RECEPTOR AND C-erbB-2 ONCOGENE PRODUCT IN DEVELOPING HUMAN PLACENTA

Cytologic locailzation of epidermai growth factor receptor (EGF-R) and C-erbB2oncogene product in normal developing placenta ovas studied by avidin/biotin immunoperoxidase techniques.Both proteins were predominantly expressed in the villous syncytiotrophoblasts but not in the cytotrophoblasts.The immunoreactive intensity for EGF-R decreased with the development of pregnancy.Concerning the intermediate trophoblasts in cell islands and cell columns,both proteins were more easily detected in the cells distal to the villous stroma than in the juxtastromal cells.These findings suggest that EGF-R and C-erbB-2 may play a significant role in the induction and regulation of differentiated trophoblast function

血清PIGF、sFlt-1及PLGF水平对妊娠期高血压的预测效能及与子痫前期发病的关系

目的探讨血清促血管生成因子(PIGF)、可溶fms样酪氨酸激酶-1(sFlt-1)及胎盘生长因子(PLGF)对妊娠期高血压的预测效能及与子痫前期(PE)发病的相关性。方法回顾性分析接受检查的妊娠期高血压疾病患者共150例(观察组),另选取同期经检查的78例健康孕妇纳入对照组。对比两组血清中PIGF、sFlt-1及PLGF指标,采用受试者工作特征(ROC)曲线分析血清各指标对妊娠期高血压的预测效能,对比不同病情程度患者血清PIGF、sFlt-1及PLGF水平,采用Spearman相关系数分析血清PIGF、sFlt-1及PLGF与孕妇发生PE的相关性。结果观察组sFlt-1水平较对照组明显升高,PIGF、PLGF水平较对照组明显降低(均P<0.05);血清PIGF、sFlt、PLGF指标检测的ROC曲线下面积(AUC)均较高(AUC分别为0.878、0.795、0.890,均P<0.05)。随着病情程度的加重,血清PIGF、PLGF呈明显下降趋势,血清sFlt-1水平呈明显升高趋势(均P<0.05)。采用Spearman相关系数分析PE发生与血清sFlt-1呈正相关(r=0.764,P=0.013),与PIGF、PLGF水平呈负相关(r=-0.822、-0.645,P=0.007、0.016)。结论早期妊娠孕妇血清中PIGF、sFlt-1及PLGF对妊娠期高血压均具有较高预测效能,三项指标均与发生PE显著相关,各指标均可成为临床预测并诊断PE的有效依据,对制定有效的临床诊疗方案具有重要意义,具有较高的临床应用价值。

子宫动脉血流动力学指标联合PIGF和sFlt-1对妊娠期高血压患者不良妊娠结局的预测价值

目的探讨子宫动脉血流动力学指标联合胎盘生长因子(PLGF)和可溶性血管内皮生长因子受体-1(sFlt-1)在妊娠期高血压疾病(HDPs)患者发生不良妊娠结局中的预测价值。方法选择2020年1月至2021年12月在该院诊断为HDPs的患者106例纳入HDPs组,选择同期该院健康产检者56例纳入对照组。观察HDPs组和对照组子宫动脉搏动指数(PI)、阻力指数(RI)、收缩期峰值流速/舒张末期流速比值(S/D)、sFlt-1和PLGF水平变化,观察PI、RI、S/D、sFlt-1和PLGF水平与HDPs严重程度和妊娠结局的关系,以及以上指标预测不良妊娠结局的价值。结果HDPs组PI、RI、S/D和sFlt-1水平明显高于对照组(P<0.01),并且随着HDPs严重程度的升高而升高(P<0.01)。同时,不良妊娠结局者PI、RI、S/D和sFlt-1水平明显高于良好妊娠结局者(P<0.01)。HDPs组血清PLGF水平明显低于对照组(P<0.01),并且随着HDPs严重程度升高而降低(P<0.01),不良妊娠结局者血清PLGF水平明显低于良好妊娠结局者(P<0.01)。PI、RI、S/D、sFlt-1和PLGF预测HDPs患者发生不良妊娠结局具有更高的效能,5项指标联合检测的灵敏度为89.5%,特异度为86.3%,曲线下面积(AUC)为0.940,明显高于sFlt-1(Z=2.690,P<0.01)、PLGF(Z=2.961,P<0.01)和PI+RI+S/D(Z=3.533,P<0.01),而3项指标之间的AUC差异无统计学意义(P>0.05)。结论子宫动脉血流动力学指标、sFlt-1和PLGF水平与HDPs严重程度具有密切关系,子宫动脉血流动力学指标、sFlt-1和PLGF联合检测在预测不良妊娠结局中具有重要的临床价值。

Placenta Growth Factor and Soluble Fms-Like Tyrosine Kinase 1 in Preeclampsia and Normotensive Pregnant Nigerian Women

Background: Preeclampsia (PE) is still one of the leading causes of maternal/perinatal morbidity/mortality in Nigeria. Imbalance between placenta growth factor (PLGF) and soluble fms-like tyrosine kinase 1 (sFlt1) has been reportedly present both before and after the manifestation of PE;however, Nigerian data regarding these angiogenesis-related substances are lacking. We here attempted to determine the maternal serum level of PLGF and sFlt1 and sFlt1/PLGF ratio in PE vs. non-PE women in Lagos State University Teaching Hospital, Nigeria. Methods: An observational cross-sectional study was made on 75 women with PE and 75 age-gestational-age matched women without PE, as case and control, respectively. Levels of sFlt-1, PIGF and the sFlt-1: PIGF ratio was compared between the two. Results: Serum levels of Flt-1 and sFlt1/PIGF ratio were significantly higher in PE patients (6581.86 ± 865.75, and 146.42 ± 92.43) than in the normotensive control (4584.52 ± 1479.6 and 11.60 ± 6.42). PIGF was significantly lower in PE patients (70.14 ± 51.03) than the normotensives (494.06 ± 475.8). There were positive and negative correlations between the sFlt-1 and PLGF respectively and mean arterial blood pressure. Conclusion: Serum sFlt-1, sFlt1/PIGF ratio was significantly higher and PIGF levels were significantly lower in PE than normotensive control in Nigerian population.

基于血清ADMA、IL-18、PIGF、PCT水平构建B型链球菌感染孕妇不良妊娠结局的风险预测模型

目的分析基于血清非对称性二甲基精氨酸(ADMA)、白细胞介素-18(IL-18)、胎盘生长因子(PIGF)、降钙素原(PCT)水平构建B型链球菌(GBS)感染孕妇不良妊娠结局的风险预测模型,对GBS感染孕妇不良妊娠结局的预测价值。方法选取2021年5月—2022年5月80例GBS感染孕妇作为研究组,同期未发生GBS感染的健康孕妇作为对照组,比较2组血清ADMA、IL-18、PIGF、PCT水平。另对研究组孕妇随访至分娩,根据妊娠结局分为良好组与不良组,采用单因素、多因素Logistic回归分析探讨血清ADMA、IL-18、PIGF、PCT水平与GBS感染孕妇不良妊娠结局的关系。并采用受试者工作特征(ROC)曲线分析基于血清ADMA、IL-18、PIGF、PCT水平构建的风险预测模型对GBS感染孕妇不良妊娠结局的预测效能。结果研究组血清ADMA、IL-18、PCT水平显著高于对照组,血清PIGF水平显著低于对照组(P<0.01)。多因素Logistic回归分析结果显示,ADMA(高)、IL-18(高)、PCT(高)、PIGF(低)、IgA(低)、IgM(低)、IgG(低)、合并糖尿病、合并高血压是GBS感染孕妇发生不良妊娠结局的危险因素(P<0.05,P<0.01)。基于血清ADMA、IL-18、PIGF、PCT水平构建的风险预测模型预测GBS感染孕妇不良妊娠结局的敏感度、准确度、阳性预测值、曲线下面积分别为93.67%、91.12%、90.38%、0.933。结论基于血清ADMA、IL-18、PIGF、PCT水平构建的GBS感染孕妇不良妊娠结局风险预测模型,可较为准确地预测GBS感染孕妇的妊娠结局。

超声微血管成像联合血管内皮生长因子诊断胎儿生长受限

目的观察超声微血管成像(MV-Flow)联合孕妇血清血管内皮生长因子(VEGF)表达水平诊断胎儿生长受限(FGR)的价值。方法前瞻性纳入87例胎儿生长受限[FGR组,包括43例孕周<28周(<28周亚组)及44例孕周≥28周(≥28周亚组)]孕妇及112名正常孕妇[对照组,55名孕周<28周(对照组1)、57名孕周≥28周(对照组1)],以MV-Flow技术测量胎盘微血管指数(MVI),于同期检测孕妇血清VEGF表达水平,于分娩后即刻检测胎盘母体面VEGF表达水平;绘制受试者工作特征曲线,评价胎盘MVI、母体血清VEGF及二者联合诊断FGR的价值。结果FGR组2亚组胎盘MVI、孕妇血清VEGF表达水平及胎盘组织VEGF表达水平均明显低于对照组(P<0.01)。胎盘MVI、母体血清VEGF及二者联合诊断<28周FGR的曲线下面积(AUC)分别为0.981、0.870和0.997,诊断≥28周FGR的AUC分别为0.991、0.867和0.993。以单一孕妇血清VEGF诊断2亚组FGR的AUC均低于胎盘MVI及其联合孕妇血清VEGF(P均<0.05),而后二者AUC差异均无统计学意义(P均>0.05)。结论胎盘MVI和孕妇血清VEGF可用于筛查FGR,而前者更具价值。

超声测量胎儿静脉导管血流动力学参数联合血清胎盘生长因子预测妊娠期高血压疾病患者妊娠结局的价值

目的探讨超声测量胎儿静脉导管血流动力学参数联合血清胎盘生长因子(PLGF)预测妊娠期高血压疾病(HDP)患者妊娠结局的价值。方法回顾性分析2022年4月—2023年4月在承德市中心医院产检诊断为HDP的80例患者的临床资料,将其作为研究组。另取同期该院健康产检孕妇100例作为对照组。比较两组胎儿静脉导管血流动力学参数[搏动指数(PI)、阻力指数(RI)、血流速度峰谷比(S/D)、静脉导管分流率]、血清PLGF水平及不良妊娠结局发生率。根据HDP患者妊娠结局分为不良结局组(18例)、结局良好组(62例)。比较两组基线资料、胎儿静脉导管血流动力学参数、PLGF水平,绘制受试者工作特征(ROC)曲线分析胎儿静脉导管血流动力学参数及血清PLGF水平预测HDP患者不良妊娠结局的价值,采用多因素逐步Logistic回归模型分析HDP患者不良妊娠结局的危险因素。结果研究组胎儿静脉导管血流动力学参数(PI、RI、S/D、静脉导管分流率)均高于对照组(P<0.05),血清PLGF水平低于对照组(P<0.05)。研究组不良妊娠结局发生率高于对照组(P<0.05)。不良结局组年龄≥35岁占比、孕前BMI、PI、RI、S/D、静脉导管分流率均高于良好结局组(P<0.05),血清PLGF水平低于良好结局组(P<0.05)。ROC曲线分析结果显示,胎儿静脉导管血流动力学参数及血清PLGF水平均可用于预测HDP患者不良妊娠结局。孕前BMI、PI、RI、S/D、静脉导管分流率、血清PLGF水平及其联合预测HDP患者不良妊娠结局的敏感性分别为77.8%(95%CI:0.713,0.854)、83.3%(95%CI:0.682,0.951)、83.3%(95%CI:0.813,0.927)、94.4%(95%CI:0.847,0.952)、94.4%(95%CI:0.907,0.983)、72.2%(95%CI:0.682,0.841)、94.4%(95%CI:0.921,0.965),特异性分别为85.5%(95%CI:0.690,0.873)、54.8%(95%CI:0.522,0.764)、91.2%(95%CI:0.871,0.925)、75.8%(95%CI:0.723,0.862)、91.8%(95%CI:0.857,0.931)、93.6%(95%CI:0.748,0.964)、95.2%(95%CI:0.917,0.980)。多因素逐步Logistic回归分析结果显示,年龄[OR=1.357(95%CI:1.033,1.783)]、孕前BMI[OR=1.536(95%CI:1.118,2.110)]、PI[OR=1.797(95%CI:1.122,2.878)]、RI[OR=1.751(95%CI:1.121,2.735)]、S/D[OR=1.886(95%CI:1.075,3.309)]、静脉导管分流率[OR=1.967(95%CI:1.142,3.388)]、PLGF[OR=2.132(95%CI:1.176,3.865)]均为HDP患者不良妊娠结局的危险因素(P<0.05)。结论胎儿静脉导管血流动力学参数异常高表达、血清PLGF水平下降均与HDP发生、发展关系密切,以上指标可有效预测妊娠结局,且联合检测价值更高。

胎盘植入孕妇子宫动脉血流动力学参数与血管新生的关系及其相关指标诊断价值

目的 探究胎盘植入孕妇子宫动脉血流动力学参数与血管新生的关系及其相关指标的诊断价值。方法 收集2016年1月至2021年4月于丹阳市人民医院常规超声检查疑似胎盘植入的125例孕妇的临床资料,根据产后最终临床诊断及病理诊断结果分为观察组(n=35,胎盘植入)与对照组(n=90,非胎盘植入)。比较两组孕妇的临床特征、子宫动脉血流动力学参数[子宫动脉搏动指数(PI)、阻力指数(RI)、收缩期峰值血流速度与舒张末期血流速度的比值(S/D)]及血管新生指标[可溶性血管内皮生长因子受体-1(sFlt-1)、血管内皮生长因子(VEGF)]。分析子宫动脉血流动力学参数、血管新生指标与胎盘植入的关系,子宫动脉血流动力学参数对胎盘植入的诊断价值,以及子宫动脉血流动力学参数与血管新生指标的相关性。结果 观察组孕妇的流产次数、剖宫产次数均明显多于对照组孕妇,PI、RI及sFlt-1水平均明显低于对照组孕妇,S/D、VEGF水平均明显高于对照组孕妇,差异均有统计学意义(P<0.01)。多因素分析结果显示,调整混杂因素流产次数、剖宫产次数后,PI、RI、S/D、VEGF、sFlt-1均仍为胎盘植入的独立影响因素(P<0.05)。受试者工作特征(ROC)曲线分析结果显示,PI、RI、S/D、VEGF、sFlt-1诊断胎盘植入的曲线下面积(AUC)分别为0.716、0.717、0.626、0.797、0.793,各指标联合诊断胎盘植入的AUC为0.870。胎盘植入孕妇子宫动脉血流动力学参数PI、RI与VEGF呈负相关,与sFlt-1呈正相关(P<0.05);S/D与VEGF呈正相关,与sFlt-1呈负相关(P<0.05)。结论 胎盘植入孕妇彩色多普勒超声下的子宫动脉血流动力学参数与血管新生具有明显相关性,且临床监测子宫动脉血流动力学参数、血管新生指标对胎盘植入的诊断具有积极意义。

胎儿生长受限患者胎盘组织中VEGFA、HIF-1α表达及临床意义

目的:探究胎儿生长受限(FGR)患者胎盘组织中血管内皮生长因子A(VEGFA)、缺氧诱导因子(HIF)-1α表达及临床意义。方法:选择2020年5月-2022年9月在本院确诊FGR并住院分娩的孕妇116例(FGR组)、分娩正常孕妇(新生儿正常)116例为对照组临床资料。qRT-PCR检测胎盘组织中VEGFA、HIF-1α的mRNA表达情况,免疫组化法检测VEGFA、HIF-1α的蛋白表达情况。Pearson相关性分析VEGFA与HIF-1α的相关性以及与FGR患者临床资料相关性;多因素logistic回归分析影响FGR发生的因素。结果:FGR组VEGFA蛋白阳性表达率(25.9%)低于对照组(64.7%),HIF-1α蛋白阳性表达率(67.2%)高于对照组(24.1%);FGR组胎盘组织中VEGFA mRNA表达水平(0.75±0.20)低于对照组(1.00±0.23),HIF-1α mRNA表达水平(1.26±0.25)高于对照组(1.01±0.19)(均P<0.05)。FGR患者胎盘组织中VEGFA mRNA与HIF-1α mRNA呈负相关(P<0.05)。FGR患者新生儿出生1 min Apgar评分、胎盘重量、胎盘体积、新生儿体重与VEGFA表达水平呈正相关,与HIF-1α表达水平呈负相关;HIF-1α升高为影响FGR发生的危险因素,VEGFA升高为保护因素(均P<0.05)。结论:FGR患者胎盘组织中VEGFA低表达、HIF-1α高表达,二者影响FGR的发生及新生儿出生质量。

胎盘生长因子、可溶性fms样酪氨酸激酶-1及糖基化纤连蛋白在子痫前期预测中的应用价值

目的:探讨胎盘生长因子(placental growth factor,PLGF)、可溶性fms样酪氨酸激酶-1(soluble fms-like tyrosine kinase-1,SFLT-1)和糖基化纤连蛋白(glycosylated fibronectin,GLYFN)检测对子痫前期的预测价值。方法:选择在无锡市妇幼保健院就诊的188例孕妇,分154例正常孕妇(对照组)和34例子痫前期患者(子痫组),应用免疫荧光法分别检测其在孕16~18周血清中PLGF、SFLT-1和GLYFN的浓度,比较子痫前期组和对照组各标志物的水平,并使用受试者操作特征曲线(receiver operating characteristic,ROC)对3种标志物的预测价值进行效能评估。结果:在妊娠中期,子痫前期组血清PLGF浓度低于对照组,SFLT-1及GLYFN浓度均高于对照组,3种标志物的差异均有统计学意义(3指标P=0.000)。95%置信区间的ROC曲线下面积(areas under the ROC curve,AUC)为,PLGF为0.941(0.907~0.974),SFLT-1为0.881(0.800~0.962),GLYFN为0.951(0.918~0.985),联合指标SFLT-1和GLYFN、3项指标联合检测在ROC曲线下面积(areas under the ROC curve,AUC)分别为0.968、0.986。结论:PLGF、SFLT-1、GLYFN 3种标志物水平在对照组和子痫前期组均存在明显差异,对子痫前期的发病具有一定的预测价值,SFLT-1联合PLGF、SFLT-1联合GLYFN、3项指标联合检测对子痫前期的预测价值高于任一单项指标。

三维能量多普勒超声参数联合胎盘生长因子对早发型胎儿生长受限的预测价值

目的探讨三维能量多普勒超声参数联合胎盘生长因子(PLGF)对早发型胎儿生长受限(FGR)的预测价值。方法选取早发型FGR孕妇80例为FGR组,另选取同期产检健康孕妇50例为对照组。在孕11~13周+6对所有研究对象进行三维能量多普勒超声检查,收集胎盘容积(PV)、血管化指数(VI)、血流指数(FI)、血管化-血流指数(VFI)等指标。在孕14~16周+6检测所有研究对象血清PLGF水平。结果FGR组的PV、VI、FI、VFI以及血清PLGF水平均低于对照组,差异有统计学意义(P<0.05)。多元Logistic回归方程分析显示,PV、VI、FI、VFI以及血清PLGF水平过低是早发型FGR的危险因素(P<0.05)。受试者工作特征(ROC)曲线分析显示,PV、VI、VFI以及血清PLGF均对早发型FGR有一定的预测价值,曲线下面积分别为0.723(95%CI:0.629~0.817)、0.776(95%CI:0.693~0.860)、0746(95%CI:0.653~0.839)、0.799(95%CI:0.713~0.884),FI对早发型FGR的预测价值一般,曲线下面积为0.625(95%CI:0.524~0.725)。经分析显示,PLGF联合VI以及PLGF联合VFI对早发型FGR的预测价值较好,PLGF联合VI的敏感度、特异度和约登指数分别为86.25%、76.00%、0.623,PLGF联合VFI的敏感度、特异度和约登指数分别为81.25%、80.00%、0.613。结论三维能量多普勒超声参数联合PLGF对早发型FGR有一定的预测价值,可用于临床筛查早发型FGR高风险人群。

血清PLGF/sFlt-1联合胎盘3D-PDI对子痫前期的预测价值

目的探讨血清胎盘生长因子(PLGF)/可溶性血管内皮生长因子受体-1(sFlt-1)联合胎盘三维能量多普勒指数(3D-PDI)对子痫前期(PE)的预测价值。方法选取2021年1月至2022年12月于我院就诊且有PE高危因素的孕妇120例,随访至分娩后1周。于孕14~20周常规产检时检测血清PLGF和sFlt-1水平,并计算PLGF/sFlt-1比值,同时超声检测胎盘3D-PDI,包括血管化指数(VI)、血流指数(FI)、血管化-血流指数(VFI)。根据孕20周后是否发生PE,分为PE组(55例)和对照组(65例),根据病情轻重将PE组进一步分为非重度PE组(35例)和重度PE组(20例)。比较各组PLGF/sFlt-1及3D-PDI,并分析PLGF、sFlt-1与3D-PDI的相关性,绘制受试者操作特征(ROC)曲线,分析各指标单独或联合预测PE的价值。结果2组孕妇年龄、检测孕周、妊娠高血压史及生育史等均无差异(P>0.05)。PE组收缩压(SBP)、舒张压(DBP)、24 h尿蛋白水平、早产率、新生儿重症监护室入住率及孕前体质量指数均高于对照组(P<0.05),新生儿体质量低于对照组(P<0.05)。PE组血清PLGF/sFlt-1、3D-PDI均低于对照组,重度PE组血清PLGF/sFlt-1、3D-PDI均低于非重度PE组(均P<0.05)。PLGF与VFI呈显著正相关(P<0.01),sFlt-1与VFI呈显著负相关(P<0.01)。ROC曲线分析显示,PLGF/sFlt-1、VI、FI、VFI对PE均有预测价值,VI、FI、VFI联合预测PE的价值高于各参数指标[曲线下面积(AUC)=0.951],血清PLGF/sFlt-1、VI、FI、VFI四者联合预测价值最高(AUC=0.987)。结论PE患者孕早期血清PLGF、sFlt-1与胎盘VFI均具有显著相关性,且孕早期血清PLGF/sFlt-1及胎盘VI、FI、VFI均减低,4种指标联合应用预测PE的效能最高,可为临床早期筛查或预测PE提供参考。

自拟安胎饮联合黄体酮注射液治疗对黄体功能不足致复发性流产患者子宫动脉血流指标、血清PLGF和CTRP12表达的影响

目的探讨自拟安胎饮联合黄体酮注射液治疗对黄体功能不足致复发性流产(RSA)患者子宫动脉血流指标、血清胎盘生长因子(PLGF)和C1q肿瘤坏死因子相关蛋白12(CTRP12)表达的影响。方法选取2020年1月至2023年8月安徽医科大学附属巢湖医院收治的80例黄体功能不足致RSA患者作为研究对象,随机分为研究组和对照组,每组40例。对照组采用黄体酮注射液治疗,研究组在对照组基础上联合自拟安胎饮治疗,两组均治疗10周。比较两组临床疗效、治疗前后中医肾虚证候积分、子宫动脉血流指标、血清PLGF和CTRP12水平、不良发应发生率。结果研究组治疗总有效率高于对照组(P<0.05)。治疗后,两组各项中医肾虚证候积分均降低,且研究组低于对照组(P<0.05)。治疗后,两组血管指数(VI)降低,血流指数(FI)、血管化血流指数(VFI)升高,且研究组VI低于对照组,FI、VFI高于对照组(P<0.05)。治疗后,两组PLGF和CTRP12水平均升高,且研究组PLGF和CTRP12水平均高于对照组(P<0.05)。研究组不良反应总发生率低于对照组(P<0.05)。结论黄体功能不足致RSA患者采用自拟安胎饮联合黄体酮注射液治疗,可提高临床疗效,改善子宫动脉血流、血清PLGF和CTRP12表达水平。