Background and Aims:The results of basic research implicate the vascular endothelial growth factor(VEGF)family as a potential target of hepatopulmonary syndrome(HPS).However,the negative results of anti-angiogenetic t...Background and Aims:The results of basic research implicate the vascular endothelial growth factor(VEGF)family as a potential target of hepatopulmonary syndrome(HPS).However,the negative results of anti-angiogenetic therapy in clinical studies have highlighted the need for markers for HPS.Therefore,we aimed to determine whether VEGF family members and their receptors can be potential biomarkers for HPS through clinical and experimental studies.Methods:Clinically,patients with chronic liver disease from two medical centers were enrolled and examined for HPS.Patients were divided into HPS,intrapulmonary vascular dilation[positive contrast-enhanced echocardiography(CEE)and normal oxygenation]and CEE-negative groups.Baseline information and perioperative clinical data were compared between HPS and non-HPS patients.Serum levels of VEGF family members and their receptors were measured.In parallel,HPS rats were established by common bile duct ligation.Liver,lung and serum samples were collected for the evaluation of pathophysiologic changes,as well as the expression levels of the above factors.Results:In HPS rats,all VEGF family members and their receptors underwent significant changes;however,only soluble VEGFR1(sFlt-1)and the sFlt-1/placental growth factor(PLGF)ratio were changed in almost the same manner as those in HPS patients.Furthermore,through feature selection and internal and external validation,sFlt-1 and the sFlt-1/PLGF ratio were identified as the most important variables to distinguish HPS from non-HPS patients.Conclusions:Our results from animal and human studies indicate that sFlt-1 and the sFlt-1/PLGF ratio in serum are potential markers for HPS.展开更多
Objective:To investigate the correlation of urine sFlt-1/PLGF ratio with abnormal trophoblast invasion and apoptosis in pregnant women with preeclampsia.Methods:A total of 183 healthy second-trimester pregnant women w...Objective:To investigate the correlation of urine sFlt-1/PLGF ratio with abnormal trophoblast invasion and apoptosis in pregnant women with preeclampsia.Methods:A total of 183 healthy second-trimester pregnant women who received antenatal care in this hospital between December 2015 and December 2017 were selected as the normal control group, and 62 second-trimester pregnant women with preeclampsia who received antenatal care in this hospital during the same period were selected as the preeclampsia group. The difference of sFlt-1/PLGF ratio in the urine was compared between the two groups of pregnant women, and the expression levels of invasion-related genes and apoptosis-related genes in the placental tissues were detected. The Pearson test was adopted to further evaluate the correlation of urine sFlt-1/PLGF ratio with abnormal trophoblast invasion and apoptosis in pregnant women with preeclampsia.Results: Urine sFlt-1/PLGF ratio of preeclampsia group was significantly higher than that in normal control group;Rho, ROCK, Notch-1, MMP9 and LAMA4 mRNA expression in placental tissues of preeclampsia group were lower than those of normal control group whereas CDKN1C mRNA expression was higher than that of normal control group;Bcl-2 and Survivin mRNA expression in placental tissues of preeclampsia group were lower than those of normal control group whereas Bax, Caspase-3 and Caspase-8 mRNA expression were higher than those of normal control group. Correlation analysis showed that the urine sFlt-1/PLGF ratio of pregnant women with preeclampsia was directly correlated with the expression of placental trophoblast invasion-related genes and apoptosis-related genes in pregnant women with preeclampsia.Conclusion: The sFlt-1/PLGF ratio abnormally increases in the urine of pregnant women with preeclampsia, which can further aggravate the abnormal invasion and apoptosis of placental trophoblast cells.展开更多
Preeclampsia(PE),a multisystem disorder in pregnancy,is a main cause of perinatal mortality and is associated with long-term maternal complications.For a long time,PE was defined as the new onset hypertension and prot...Preeclampsia(PE),a multisystem disorder in pregnancy,is a main cause of perinatal mortality and is associated with long-term maternal complications.For a long time,PE was defined as the new onset hypertension and proteinuria after 20 weeks’gestation.It had been shown that this“gold standard definition”is not able to provide a sufficient prediction of PE-related fetal and/or maternal complications.In 2018 the International Society for the Study of Hypertension in Pregnancy recommended a broader definition of the disease.The new definition of the International Society for the Study of Hypertension in Pregnancy ruled out proteinuria as mandatory for the diagnosis of PE.This new definition increases the number of patients diagnosed as preeclamptic by nearly 21%,which is not accompanied by an increased severity of maternal outcomes.Including angiogenic biomarkers,however,has been shown to increase detection of adverse outcomes.The pathophysiology of PE is complex and not yet completely explained.Advances in prediction and diagnosis have been achieved by discovery and clinical evaluation of biomarkers,especially of placental origin.A broad spectrum of biomarkers has been tested,a few of them have been introduced into the clinical practice as of today.Especially angiogenic biomarkers that are rooted in the pathophysiology of PE have been demonstrated to be important in the prediction and diagnosis of adverse outcomes.At a cut-off value of the soluble fms-like tyrosine kinase-1(sFlt-1)/placental growth factor(PlGF)-ratio of 85,early-onset PE<34+0 weeks of gestation can accurately be diagnosed with a sensitivity of 89%and a specificity of 97%.The Prediction of short-term outcome in pregnant women with suspected preeclampsia(PROGNOSIS)study has shown that the high negative predictive value(99.3%)of the sFlt-1/PlGF-ratio below 38 in patients with suspected PE rules out the onset of the disease within one week.PROGNOSIS Asia,evaluating the sFlt-1/PlGF-ratio cut-off of 38 in an Asian population,confirmed the excellent a展开更多
目的檢測尿蛋白陽性孕婦血清可溶性血管内皮生長因子受體-1(sFlt-1)、胎盤生長因子(PlGF)水平,探討sFlt-1/PlGF比值預測子癇前期及其他不良妊娠結局的實用價值。方法收集2019年10月~2022年11月尿蛋白陽性孕婦80例為觀察組,同期尿蛋白陰...目的檢測尿蛋白陽性孕婦血清可溶性血管内皮生長因子受體-1(sFlt-1)、胎盤生長因子(PlGF)水平,探討sFlt-1/PlGF比值預測子癇前期及其他不良妊娠結局的實用價值。方法收集2019年10月~2022年11月尿蛋白陽性孕婦80例為觀察組,同期尿蛋白陰性的孕婦40例為對照組,檢測兩組孕婦血清中sFlt-1及PlGF水平,統計分析兩組sFlt-1/PlGF比值>38的差異性,受試者工作特徵曲線(Receiver Operating Characteristic curve,ROC)評估sFlt-1/PlGF比值預測不良妊娠結局及子癇前期的診斷價值。結果觀察組及對照組血清sFlt-1/PlGF比值中位數分别為14.66、5.06,觀察組高於對照組,兩組間差異有統計學意義(P<0.05);用sFlt-1/PlGF比值與不良妊娠結局及子癇前期作ROC曲線分析,曲線下面積(Area Under the Curve,AUC)分别為0.90、0.77。結論尿蛋白陽性孕婦血清sFlt-1/PlGF比值,能為子癎前期及其他不良妊娠結局的預測提供參考價值。展开更多
基金supported by National Science Foundation of China(No.82070630 from Bin Yi,82100658 from Yu-jie Li and 82170634 from Peng Li)National Key R&D Program of China(No.2018YFC0116702 from Bin Yi)+2 种基金Special support for Chongqing postdoctoral research project in 2020 from Yujie Li,Sichuan science and technology department research projects(2019YFS0221 from Peng Li)Chongqing Science and health joint medical research project(2020FYYX076,from Bin Yi)special support project for improving scientific and technological innovation ability of undergraduate(2021XBK19 from Xian-feng Wu).
文摘Background and Aims:The results of basic research implicate the vascular endothelial growth factor(VEGF)family as a potential target of hepatopulmonary syndrome(HPS).However,the negative results of anti-angiogenetic therapy in clinical studies have highlighted the need for markers for HPS.Therefore,we aimed to determine whether VEGF family members and their receptors can be potential biomarkers for HPS through clinical and experimental studies.Methods:Clinically,patients with chronic liver disease from two medical centers were enrolled and examined for HPS.Patients were divided into HPS,intrapulmonary vascular dilation[positive contrast-enhanced echocardiography(CEE)and normal oxygenation]and CEE-negative groups.Baseline information and perioperative clinical data were compared between HPS and non-HPS patients.Serum levels of VEGF family members and their receptors were measured.In parallel,HPS rats were established by common bile duct ligation.Liver,lung and serum samples were collected for the evaluation of pathophysiologic changes,as well as the expression levels of the above factors.Results:In HPS rats,all VEGF family members and their receptors underwent significant changes;however,only soluble VEGFR1(sFlt-1)and the sFlt-1/placental growth factor(PLGF)ratio were changed in almost the same manner as those in HPS patients.Furthermore,through feature selection and internal and external validation,sFlt-1 and the sFlt-1/PLGF ratio were identified as the most important variables to distinguish HPS from non-HPS patients.Conclusions:Our results from animal and human studies indicate that sFlt-1 and the sFlt-1/PLGF ratio in serum are potential markers for HPS.
文摘Objective:To investigate the correlation of urine sFlt-1/PLGF ratio with abnormal trophoblast invasion and apoptosis in pregnant women with preeclampsia.Methods:A total of 183 healthy second-trimester pregnant women who received antenatal care in this hospital between December 2015 and December 2017 were selected as the normal control group, and 62 second-trimester pregnant women with preeclampsia who received antenatal care in this hospital during the same period were selected as the preeclampsia group. The difference of sFlt-1/PLGF ratio in the urine was compared between the two groups of pregnant women, and the expression levels of invasion-related genes and apoptosis-related genes in the placental tissues were detected. The Pearson test was adopted to further evaluate the correlation of urine sFlt-1/PLGF ratio with abnormal trophoblast invasion and apoptosis in pregnant women with preeclampsia.Results: Urine sFlt-1/PLGF ratio of preeclampsia group was significantly higher than that in normal control group;Rho, ROCK, Notch-1, MMP9 and LAMA4 mRNA expression in placental tissues of preeclampsia group were lower than those of normal control group whereas CDKN1C mRNA expression was higher than that of normal control group;Bcl-2 and Survivin mRNA expression in placental tissues of preeclampsia group were lower than those of normal control group whereas Bax, Caspase-3 and Caspase-8 mRNA expression were higher than those of normal control group. Correlation analysis showed that the urine sFlt-1/PLGF ratio of pregnant women with preeclampsia was directly correlated with the expression of placental trophoblast invasion-related genes and apoptosis-related genes in pregnant women with preeclampsia.Conclusion: The sFlt-1/PLGF ratio abnormally increases in the urine of pregnant women with preeclampsia, which can further aggravate the abnormal invasion and apoptosis of placental trophoblast cells.
文摘Preeclampsia(PE),a multisystem disorder in pregnancy,is a main cause of perinatal mortality and is associated with long-term maternal complications.For a long time,PE was defined as the new onset hypertension and proteinuria after 20 weeks’gestation.It had been shown that this“gold standard definition”is not able to provide a sufficient prediction of PE-related fetal and/or maternal complications.In 2018 the International Society for the Study of Hypertension in Pregnancy recommended a broader definition of the disease.The new definition of the International Society for the Study of Hypertension in Pregnancy ruled out proteinuria as mandatory for the diagnosis of PE.This new definition increases the number of patients diagnosed as preeclamptic by nearly 21%,which is not accompanied by an increased severity of maternal outcomes.Including angiogenic biomarkers,however,has been shown to increase detection of adverse outcomes.The pathophysiology of PE is complex and not yet completely explained.Advances in prediction and diagnosis have been achieved by discovery and clinical evaluation of biomarkers,especially of placental origin.A broad spectrum of biomarkers has been tested,a few of them have been introduced into the clinical practice as of today.Especially angiogenic biomarkers that are rooted in the pathophysiology of PE have been demonstrated to be important in the prediction and diagnosis of adverse outcomes.At a cut-off value of the soluble fms-like tyrosine kinase-1(sFlt-1)/placental growth factor(PlGF)-ratio of 85,early-onset PE<34+0 weeks of gestation can accurately be diagnosed with a sensitivity of 89%and a specificity of 97%.The Prediction of short-term outcome in pregnant women with suspected preeclampsia(PROGNOSIS)study has shown that the high negative predictive value(99.3%)of the sFlt-1/PlGF-ratio below 38 in patients with suspected PE rules out the onset of the disease within one week.PROGNOSIS Asia,evaluating the sFlt-1/PlGF-ratio cut-off of 38 in an Asian population,confirmed the excellent a
文摘目的檢測尿蛋白陽性孕婦血清可溶性血管内皮生長因子受體-1(sFlt-1)、胎盤生長因子(PlGF)水平,探討sFlt-1/PlGF比值預測子癇前期及其他不良妊娠結局的實用價值。方法收集2019年10月~2022年11月尿蛋白陽性孕婦80例為觀察組,同期尿蛋白陰性的孕婦40例為對照組,檢測兩組孕婦血清中sFlt-1及PlGF水平,統計分析兩組sFlt-1/PlGF比值>38的差異性,受試者工作特徵曲線(Receiver Operating Characteristic curve,ROC)評估sFlt-1/PlGF比值預測不良妊娠結局及子癇前期的診斷價值。結果觀察組及對照組血清sFlt-1/PlGF比值中位數分别為14.66、5.06,觀察組高於對照組,兩組間差異有統計學意義(P<0.05);用sFlt-1/PlGF比值與不良妊娠結局及子癇前期作ROC曲線分析,曲線下面積(Area Under the Curve,AUC)分别為0.90、0.77。結論尿蛋白陽性孕婦血清sFlt-1/PlGF比值,能為子癎前期及其他不良妊娠結局的預測提供參考價值。
