Diagnosis and Management of Preeclampsia: Suggested Guidance on the Use of Biomarkers / Diagnóstico e tratamento da pré-eclâmpsia: Sugestão para o uso adequado dos biomarcadores

Abstract Objective It is a challenge to consider preeclampsia (PE) diagnosis and management in low and middle-income settings, where it represents a major public health concern. The placenta is the underlying cause of disease, and the plasma concentrations of proangiogenic and antiangiogenic factors released by the placenta can reflect the risks of disease progression. Antiangiogenic proteins, such as soluble fms-like tyrosine kinase 1 (sFlt-1), and proangiogenic, like placental growth factors (PlGF), are directly and inversely correlated with the disease onset, respectively. Methods Narrative review on the use of biomarkers (sFlt-1 to PlGF ratio) with a suggested guidance protocol. Results Key considerations on the use of biomarkers: the sFlt-1/PlGF ratio is mainly relevant to rule out PE between 20 and 36 6/7 weeks in cases of suspected PE; however, it should not replace the routine exams for the diagnosis of PE. The sFlt-1/PlGF ratio should not be performed after confirmed PE diagnosis (only in research settings). In women with suspected PE, sFlt-1/PlGF ratio < 38 can rule out the diagnosis of PE for 1 week (VPN = 99.3) and up to 4 weeks (VPN= 94.3); sFlt-1/PlGF ratio > 38 does not confirm the diagnosis of PE; however, it can assist clinical management. In cases of severe hypertension and/or symptoms (imminent eclampsia), hospitalization is imperative, regardless of the result of the sFlt-1/PlGF ratio. Conclusion The use of biomarkers can help support clinical decisions on the management of suspected PE cases, especially to rule out PE diagnosis, thus avoiding unnecessary interventions, especially hospitalizations and elective prematurity

Resumo Objetivo um desafio considerar o diagnóstico e o tratamento da pré-eclâmpsia (PE) em locais de baixa e média renda, onde a doença representa um grande problema de saúde pública. A placenta é a causa subjacente da doença, e as concentrações plasmáticas de fatores pró-angiogênicos e antiangiogênicos liberados pela placenta podem refletir os riscos de progressão da doença. Proteínas antiangiogênicas, como a tirosina quinase fms solúvel tipo 1 (sFlt-1), e pró-angiogênicas, como o fator de crescimento placentário (PlGF), estão direta e inversamente correlacionados com o início da doença, respectivamente. Métodos Revisão narrativa sobre o uso de biomarcadores (razão sFlt-1/PlGF) com sugestão de protocolo de orientação para uso clínico. Resultados Principais considerações sobre o uso de biomarcadores: a razão sFlt-1/PlGF é principalmente relevante para descartar PE entre 20 e 36 6/7 semanas em casos de suspeita de PE; entretanto, não deve substituir os exames de rotina para o diagnóstico de PE. A relação sFlt-1/PlGF não deve ser realizada após a confirmação do diagnóstico de PE (apenas em ambientes de pesquisa). Em mulheres com suspeita de PE, a razão sFlt-1/PlGF < 38 pode descartar o diagnóstico de PE por 1 semana (VPN = 99,3) e até 4 semanas (VPN = 94,3); A relação sFlt-1/PlGF > 38 pode auxiliar no manejo clínico. Em casos de hipertensão grave e/ou sintomas (eclâmpsia iminente), a hospitalização é imprescindível, independentemente do resultado da relação sFlt-1/PlGF. Conclusão O uso de biomarcadores pode auxiliar na tomada de decisões clínicas no manejo de casos suspeitos de PE, principalmente para afastar o diagnóstico da doença, evitando intervenções desnecessárias, tais como internações e prematuridade iatrogênica.

Intravitreal injection of Conbercept combined with PPV in the treatment of proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To observe the value of intravitreal injection of Conbercept in the treatment of proliferative diabetic retinopathy(PDR).<p>METHODS: Totally 64 patients(75 eyes)with PDR admitted to the hospital between January 2016 and October 2019 were recruited and divided into observation group(32 cases, 38 eyes)and control group(32 cases, 37 eyes)by random number table method. The observation group received vitrectomy and intravitreal injection of Conbercept, while the control group received simple vitrectomy. The best corrected visual acuity(BCVA)was detected before treatment, at 1wk, 1mo, and 3mo after operation. Changes in central macular thickness(CMT)before treatment and at 3mo after operation were determined. Aqueous humor or vitreous humor samples were collected before and after treatment to measure concentrations of vascular endothelial growth factor(VEGF), placental growth factor(PIGF)and basic fibroblast growth factor(bFGF)by enzyme-linked immunosorbent assay. The operation time, intraoperative blood loss and improvement time of symptoms(retinal edema, fundus hemorrhage, exudation)of the 2 groups were statistically analyzed. Incidences of complications in the 2 groups were recorded.<p>RESULTS: The observation group had better BCVA than the control group at 1wk, 1mo and 3mo after operation(<i>P</i><0.05), and had smaller CMT than the control group at 3mo after operation(<i>P</i><0.001). The concentrations of VEGF, PIGF and bFGF in observation group during operation were lower than those in the control group(<i>P</i><0.001). The operation time, absorption time of retinal edema, fundus hemorrhage and exudation, intraoperative blood loss, and the total incidence of complications in the observation group were shorter and lower than those in the control group(<i>P</i><0.05).<p>CONCLUSION: Intravitreal injection of Conbercept before vitrectomy can degrade new blood vessels, and shorten the operation time. It can not only help improve vision and relieve macular edema but also reduce surgical complications and promote postoperative recovery.

Importancia clínica y diagnóstica de la relación receptor de tirosin-quinasa tipo 1 en su forma soluble y el factor de crecimiento placentario / Clinical and diagnostic importance of the type 1 receptor tyrosine-kinase ratio in its soluble form and placental growth factor / Importância clínica e diagnóstica da relação receptor de tirosina-quinase tipo 1 em sua forma solúvel e o fator de crescimento placentário

El objetivo del trabajo fue evaluar la utilidad clínica de la relación factor de crecimiento placentario/receptor de tirosin-quinasa tipo 1 soluble (sFlt-1/ PlGF) para el diagnóstico de preeclampsia (PE) en embarazadas de alto riesgo y con diagnóstico clínico de PE en un centro de salud de Córdoba, Argentina. Se procesaron 135 muestras de embarazadas: 39 con diagnóstico clínico de PE (Grupo I), 72 con riesgo de PE (Grupo II), y 24 de grupo control (Grupo III). Se utilizó una técnica automatizada de electroquimioluminiscencia (Roche). Valores <38 se consideraron sin riesgo de PE, entre 38 y 85 (< semana 34) o 38 y 110 (> semana 34) con riesgo moderado o alto riesgo dentro de las 4 semanas posteriores a la realización de dichos marcadores y >85 en embarazadas con síntomas de aparición temprana o >110 en embarazadas con síntomas de aparición tardía, PE confirmada. En el Grupo I, 33 muestras dieron relación >38 y 6 fueron menores. De 72 muestras del Grupo II 69 dieron <38 y 3 >38. Todas las muestras del Grupo III dieron relación <38. La razón de verosimilitud positiva (LR+) fue de 20,31 y la razón negativa (LR-) fue de 0,16. La relación fue >38 en la mayoría de las embarazadas con diagnóstico de PE. La determinación es útil en aquellas mujeres embarazadas que son de alto riesgo, ya sea porque tienen hipertensión o proteinuria o algún antecedente previo, en las cuales puede ser fundamental para decidir el correcto diagnóstico.

The objective of this work was to evaluate the clinical usefulness of the relation placental growth factor/soluble tyrosine-kinase type 1 receptor (sFlt-1/PlGF) for the diagnosis of PE (preeclampsia) in pregnant women at high risk and with clinical diagnosis of PE in a health center of Córdoba, Argentina. A total of 135 samples of pregnant women were processed: 39 with clinical diagnosis of PE (Group I), 72 with risk of PE (Group II), and 24 of control group (Group III). An automated electrochemiluminescence technique (Roche) was used. Ratio sFlt-1/PlGF <38 was considered without risk of PE. Between 38 and 85 (< week 34) or 38 and 110 (> week 34), with moderate risk or high risk within 4 weeks after performing these markers. To confirm diagnosis, relationships >85 in pregnant women were considered with symptoms of early onset and >110 in pregnant women with symptoms of late onset. In Group I, 33 samples reported >38 and 6 were lower. Of 72 samples from Group II, 69 gave <38 and 3, >38. All samples from Group III gave a ratio <38. The positive likelihood ratio (LR+) was 20.31 and the negative likelihood ratio (LR-), 0.16. The ratio was >38 in the majority of women already diagnosed as PE. The test is useful in those pregnant women who are at high risk of PE, either because they have hypertension or proteinuria or a previous history. In those cases it can be fundamental to decide the correct diagnosis.

O objetivo do estudo é avaliar a utilidade clínica da relação fator de crescimento placentário/receptor de tirosina-quinase tipo 1 solúvel (sFlt-1/PIGF) para o diagnóstico de pré-eclâmpsia (PE) em grávidas de alto risco e com diagnóstico clínico de PE em um centro de saúde de Córdoba, Argentina. Foram processadas 135 amostras de gestantes, sendo 39 com diagnóstico clínico de PE (Grupo I), 72 com risco de PE (Grupo II) e 24 de grupo controle (Grupo III). Foi utilizada uma técnica automatizada de eletroquimioluminescência (Roche). Valores <38 foram considerados sem risco de PE, entre 38 e 85 (

Association of first trimester serum level of placental growth factor (PlGF) and cervical length with onset of preterm labour

Background: Preterm labour (PTL) or premature labour is defined as one where labour starts before the 37th completed week.  The incidence of preterm birth is around 5-10% and it is the leading cause of perinatal morbidity and mortality. Diagnosis and treatment of PTL is challenging. However, owing to the availability of effective strategies for prevention of preterm birth, risk identification and early prediction is even more essential. This may provide opportunity for intervention and better obstetric care. Various biochemical markers were studied for prediction of preterm labour, but the sensitivity and specificity were found to be low. This study focuses on determining whether serum level of PlGF and ultrasound measure of cervical length at 10 – 14 weeks period of gestation can be used for early prediction of preterm labour.Methods: 296 antenatal women participated in this prospective observational study carried out from Dec 2015 to Sep 2017 at a tertiary care hospital. Serum level of PlGF was determined at 10-14 weeks. In the same sitting, cervical length was measured by transvaginal sonography. All these patients were followed up in antenatal OPD for monitoring the onset of preterm labour.Results: Incidence of preterm labour was 6.76 %. Maternal characteristics and obstetric factors were comparable in cases and controls. Serum PlGF level and cervical length values were lower in preterm labour group than term deliveries. But this result was not statistically significant.Conclusions: Lower levels of PlGF and cervical length were seen in preterm labour group, although it was not found to be statistically significant.

Insulinorresistencia e hipertensión gestacional: Estudio preliminar en una muestra del Municipio de La Plata / Insulin resistance and gestational hypertension: A preliminary study in a small population of La Plata Municipality / Hipertensão gestacional e resistência à insulina: Estudo preliminar numa amostra do Município de La Plata

Las mujeres embarazadas con insulino-sensibilidad disminuida están en riesgo de desarrollar trastornos hipertensivos. Utilizando el corte HOMA-IR en 2,64 la población en estudio fue dividida en dos grupos: (n=154 mujeres embarazadas), las que arrojaron un HOMA-IR basal (HOMA-0) <2,64 (no-insulinorresistentes; n=113) y aquellas con HOMA-0>2,64 (insulinorresistentes, n=41). Se analizaron: a) las concentraciones circulantes de glucosa e insulina durante una prueba de tolerancia oral a 75 g de glucosa (PTOG), y b) las relaciones entre varios parámetros de insulino-sensibilidad y la predicción del desarrollo de trastornos hipertensivos. A las mujeres embarazadas (semana 24-28) se les cuantificaron las concentraciones plasmáticas de glucosa e insulina a ambos tiempos de la PTOG. Se calcularon los valores de HOMA-IR y las relaciones glucosa a insulina (G:I) y se registraron parámetros antropométricos y resultados del embarazo. Las mujeres con HOMA-0 >2,64, aunque con glucemias en ayunas normales, mostraron mayores niveles de insulinemia y de HOMA-IR, y menores valores G:I en ambos tiempos de la PTOG. Estas mujeres embarazadas fueron las que tuvieron un mayor riesgo de desarrollar trastornos hipertensivos y mayores parámetros de morbilidad durante el período estudiado al compararlas con aquellas cuyo HOMA-0 fue <2,64.

Pregnant women with impaired insulin sensitivity are at risk for developing hypertensive disorders. By using a cut-off at 2.64 of the homeostasis model assessment (HOMA-IR) in basal condition (HOMA-0), the population under study (n=154 pregnant women) was split into two groups: 1) with basal HOMA- 0 <2.64 (non-insulin resistant; n=113) and 2) with basal HOMA-0 >2.64 (insulin resistant; n=41). Glucose and insulin circulating levels were analyzed throughout a 2-h oral 75 g glucose tolerance test (OGTT). The relationship between several parameters related to insulin resistance and the prevalence of pregnancy-induced hypertensive disorders was analyzed. Pregnant women (on week 24-28) were submitted to an OGTT, and glucose and insulin plasma concentrations were measured throughout the test. These peripheral metabolites levels and the values of the HOMA-IR and the glucose to insulin ratio (G:I) were analyzed. Anthropometric parameters and pregnancy outcome were recorded. Women with HOMA-0 >2.64 but normal fasting glycemia showed higher insulinemias, G:I values and HOMA-IR values at both times of the OGTT. The latter were at greater risk for developing late pregnancy-induced hypertension compared to women with HOMA-0 ≤2.64.

As mulheres grávidas com diminuição da sensibilidade à insulina correm o risco de desenvolver distúrbios hipertensivos. Usando o corte HOMA-IR 2,64, a população em estudo foi dividida em dois grupos: (n=154 mulheres grávidas), que deram um HOMA-IR basal (HOMA-0) ≤2,64 (não resistentes à insulina; n=113) e aquelas com HOMA-0 >2,64 (resistentes à insulina, n=41). Foram analisadas: a) as concentrações circulantes de glicose e insulina durante uma prova de tolerância oral a 75 g. de glicose (PTOG), e b) as relações entre diversos parâmetros de sensibilidade à insulina e a predição de desenvolver distúrbios de hipertensão. Foram quantificadas nas mulheres grávidas (24-28 semanas) as concentrações plasmáticas de glicose e insulina a ambos os tempos da PTOG. Valores de HOMA-IR foram calculados e as relações glicose a insulina (G:I) e se registraram parâmetros antropométricos e os resultados da gravidez. Mulheres com HOMA-0 >2,64, mas com glicemias em jejuns normais, mostraram níveis mais elevados de insulinemia e de HOMA-IR, e menores valores G:I em ambos os tempos da PTOG. Essas mulheres grávidas foram aquelas que tiveram maior risco de desenvolver distúrbios de hipertensão e maiores parâmetros de morbidade durante o período estudado em comparação com as mulheres cujo HOMA-0 foi ≤2,64.

Evaluation of serum placental growth factor in predicting pregnancy outcomes in women with suspected pre-eclampsia

Background:Amount of Placental Growth Factor (PLGF) in the blood at 9 to 11 weeks before the onset of clinical signs of pre-eclampsia is reduced. So, diagnostic tests based on the pathophysiology of disease such as PLGF as an ideal marker for early screening in the diagnosis and management of women with preeclampsia, may be useful. The aim of this study was to investigate PLGF in predicting pregnancy outcome in women with suspected pre-eclampsia.Methods: A case - control study was conducted on 30 women with suspected pre-eclampsia and 101 healthy pregnant women which selected randomly among all pregnant women referred to clinic. Both groups were followed until pregnancy termination and in terms of pregnancy outcomes (Gestational age, Type of delivery and birth weight). Two groups were matched in terms of age, weight, education, substance abuse and socio-economic status. Placental growth factor assay was done by ELISA kit. Data collected by a checklist and analyzed by statistical methods in SPSS.19.Results:The mean PLGF level was lower for women who experienced preeclampsia compared with healthy women (71.5 pg/ml vs 272.1 pg/ml, p=0.001). Also, PLGF concentrations was very low in women with preeclampsia who had a preterm birth prematurity.Conclusions:Study findings identified PlGF as an ideal, simple and non-invasive marker for primary screening at prenatal care for women at risk of pre-eclampsia.

Evaluation of sFlt-1/PlGF Ratio for Predicting and Improving Clinical Management of Pre-eclampsia: Experience in a Specialized Perinatal Care Center

BACKGROUND: Management of pregnant women at high risk of pre-eclampsia (PE) requires frequent monitoring, with referral to specialized perinatal care centers. Reliable tests are necessary to improve prediction of PE and related complications and to assess disease severity and progression. An imbalance in two biomarkers, soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF), is involved in PE pathogenesis. The sFlt-1 to PlGF ratio is increased in pregnant women before the onset of PE. An elevated ratio is highly predictive of PE, whereas the diagnosis of PE can be ruled out within one week for low ratios. The main objective of this study was to assess whether a low sFlt-1/PlGF ratio, below a cutoff of 38, can predict the absence of PE within one week. METHODS: We performed a prospective, monocentric, observational study to evaluate serum sFlt-1/PlGF ratio (Roche Diagnostics Cobas e411 system) for predicting -PE in a group of 67 high-risk pregnant women (20–37 gestation weeks). RESULTS: Among the 67 patients included, 53 had a sFlt-1/PlGF ratio lower than 38; none developed subsequent PE leading to a negative predictive value of 100%. Eight patients developed clinical PE. The positive predictive value was 21% at one week and 18% at four weeks, in accordance with previous studies. CONCLUSIONS: The serum sFlt-1/PlGF ratio showed highly predictive performances for ruling out PE. Using these biomarkers in routine management of PE may improve clinical care and avoid inappropriate hospitalization, which has a significant economic impact.

Expression and purification of human placental growth factor 2 using the Pichia pastoris expression system / 中国药科大学学报

To prepare the human placental growth factor 2 (PIGF-2 ),human PIGF-2 gene was cloned into pPIC9K vector to construct the recombinant pPIC9K-PIGF-2 vector. Linearized recombinant pPIC9K-PIGF-2 was transformed into Pichia pastoris by electroporation. YPD-Geneticin plate was used to screen geneticin hyper-resistant colonies. The positive colonies were verified by PCR. Results of SDS-PAGE and Western blot showed that recom-binant human PIGF-2 was expressed after being induced by methanol. Using its characteristic heparin binding, recombinant human PIGF-2 was successfully purified by heparin affinity column chromatography.

Expressions of TGF-β1 and PLGF in tissue of patients with different types of gestational trophoblastic diseases and their significances / 吉林大学学报(医学版)

Objective; To detect the expressions of transforming growth factor-β1 (TGF-β1) and placental growth factor (PLGF) expressions in the tissue of the patients with different types of gestational trophoblastic diseases, and to clarfy the significances of their expressions in different types of gestational trophoblastic diseases. Methods: A total of 40 cases of hydatidiform mole tissue (hydatidiform mole group) and 26 cases of gestational trophoblastic tumour tissue (GTN group, including 22 cases of invasive hydatidiform mole and 4 cases of choriocarcinoma), and 40 cases of normal early pregnancy villi (normal control group) were collected. Immunohistochemical method was used to detect the positive expression rates of TGF-β1 and PLGF, the differences of TGF-β1 and PLGF expressions between normal group, hydatidiform mole group and GTN group were analyzed, and the associations between them and the clinical high risk factors (age>40 years old, the uterine volume> gestational age, and thecalutein ovarian cyst diameter>6 cm) were analyzed. Results: The positive expression rates of TGF-β1 in hydatidiform mole group (62. 5%) and GTN group (30. 8%) were lower than that in normal group (87. 5%) (P40 years old, the uterine volume>the gestational age, and the ovarian luteinized cyst diameter>6 cm were significantly decreased (P<0.05) and the positive expression rates of PLGF were significantly increased (P<0. 05) compared with normal control group. The positive expression rate of TGF-β1 of the patients in GTN group with the high risk factors was significantly decreased compared with those without the high risk factors (P<0. 05) and the positive expression rate of PLGF was significantly increased (P<0. 05). In hydatidiform mole group and GTN group, there were moderately negative correlations between the positive expression rates of TGF-β1 and PLGF (r= -0. 585, P<0. 05; r= -0. 479, P< 0. 05). Conclusion: The expression levels of TGF-β1 in hydatidiform mole and gestational trophoblastic tumor are gradually decreased, and the expression levels of PLGF are gradually increased, which may be related to the different types and prognosis of gestational trophoblastic diseases.

Clinical correlation analysis of placenta growth factor expression in human seminal plasma and oligoasthenospermia / 第二军医大学学报

Objective To explore the correlation between placental growth factor (P1GF) expression and sperm quality in seminal plasma, and to evaluate its clinical significance in patients with oligoasthenospermia and azoospermia. Methods A total of 88 patients undergoing seminal fluid detection were enrolled from the Department of Reproductive Medicine Center of Changhai Hospital of Second Military Medical University fromSep. 2014 to Nov. 2014. The patients were divided into three groups according to the test results: ten cases with normal semen (normal group), 68 cases with oligoasthenospermia (oligoasthenospermia group), and ten cases with azoospermia (azoospermia group). Semen samples from five patients with normal semen and 5 patients with oligoasthenospermiawere collected and assayed for cytokine-related proteinmicroarray. The contents of P1GF in seminal plasma were detected by ELISA. The correlations between P1GF concentration and the sperm concentration and activity in seminal plasma and the age of patients were analyzed by Pearson correlation analysis. Results The contents of P1GF in seminal plasma in the normal group were significantly higher than that in the oligoasthenospermia and azoospermia groups (P<0. 05). The level of P1GF in seminal plasma was related to the concentration and activity of sperm (r=0.362, 0.253; P<0.05), but not to the age of patients. Conclusion The levll of P1GF in seminal plasma is correlated with the sperm concentration, providing reference for diagnosis and treatment of oligoasthenospermia and azoospermia in clinic.

Risk assessment for preeclampsia by biochemical and biophisycal markers at first trimester / Монголын Анагаах Ухаан

Introduction@#Preeclampsia, which affects about 2-8% of pregnancies, is major cause of maternal and perinatal morbidity and mortality, particularly in developing countries. In Mongolia, preeclampsia and eclampsia occurred among pregnancy complications about 25% in recent years. There is a percentage for a cause of maternal death was 17.7% in preeclampsia and eclampsia between 2012 and 2015 in Mongolia.</br> Effective prediction of preeclampsia can be achieved at 11-13 week’s gestation by combination of maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtA PI), maternal serum placental growth factor (PlGF), and pregnancy-associated plasma protein-A (PAPP-A).@*Goal@#To investigate plasma concentration of PIGF and PAPP-A, in pregnant women at 11-13+6 of gestation for screening of preeclampsia, To examine the performance of first-trimester screening for preeclampsia based on maternal characteristics, MAP, and mUt.A-PI.@*Materials and Methods @#The study conducted among 393 single pregnant women at 11-13+6 weeks, who were visiting antenatal care services, between March, 2015 and June, 2017. The prospective Cohort research method was used for this study. Written informed consent was obtained from all participants. Maternal plasma PAPP-A, PlGF were determined using Perkin Elmer kits by fluoroimmunoassay.</br> Measurement of MAP was by validated automated devices (HEM-7120, Оmron, Japan). MAP was calculated from the formula DP + 1/3*(SP-DP), where DP represents diastolic blood pressure and SP- systolic blood pressure. Trans-abdominal ultrasound (Voluson E8, GE, USA) examination was carried out for Ut.A-PI.@*Results@#In the study population, there were 66 (16.8%) cases that experienced preeclampsia and 327 (83.2%) cases that were unaffected by preeclampsia. The result showed that the mean concentration of PlGF was 38.6±19.6 pg/ml in PE group whereas the mean was 45.1±24.0 pg/ml in normal pregnant women. Level of PAPP-A was 366.1±195.3 mU/L in group with PE, 633.6±496.9 mU/L in group without preeclampsia. </br> The best Youden’s index and area under the curve (AUC) for MAP and mUt.A-PI were as a predictor of PE. It can be shown that the cutoff point for MAP was 89.5 mmHg (sensitivity-71.2%; specificity-75.5% J-0.467; AUC-0.792; P<0.001). The cutoff point of mUt.A-PI was 2.34 (sensitivity-33.3%; specificity-77.7% J-0.12; AUC-0.577; P<0.001).@*Conclusions@#The concentration of PIGF and PAPP-A in pregnant women with preeclampsia at 11-13+6 of gestation was lower than normal pregnant women. The detection risk of PE by MAP is more accurate than the mUtA-PI measurement.

The Study on Maternal Plasma Placental Growth Factor Level and the Perinatal Outcome in Early-Onset Pre-Eclampsia Patients / 实用妇产科杂志

Objective:To investigate the relationship between plasma placental growth factor(PIGF) levels and perinatal outcomes in patients with early onset preeclampsia(EOPE).Methods:125 patients with EOPE undergoing cesarean section were enrolled in this study.Enzyme-linked immunosorbent assay(ELISA) was used to detect the level of maternal plasma PIGF.According to the plasma PIGF level,≤ 12 pg/ml was divided into PlGF≤12 pg/ml group(n =64) and PIGF ＞12 pg/ml was in PIGF ＞12 pg/ml group(n =61).The blood gas analysis and the level of lactic acid(LAC) were measured within 1 hour after fetal birth.The routine and biochemical indexes of two groups and their relation with perinatal outcomes were compared.Results:①In PIGF ≤ 12 pg/ml EOPE group,the Hb,HCT,24h urine protein level,BUN and Cr levels were higher than those in PIGF ＞ 12 pg/ml group (P ＜ 0.05).While the ALB level was lower than that of PIG F ＞ 12 pg/ml group (P ＜ 0.05).②The gestational age of PIGF≤12 pg/ml group was less than that of PIGF ＞ 12 pg/ml group,but the proportion of oligohydramnios,meconium stained amniotic fluid and less than gestational age infants(SGA) were all higher than those of PIGF ＞ 12 pg/ml group(P＜0.05).③In the PIGF≤12 pg/ml group,neonatal birth weight(BW),1 minute Apgar score,pH,serum Ca,BE were all lower than those in PIGF ＞12 pg/ml group.But the level of LAC and the NICU hospital stay were all higher than those in PIGF ＞ 12 pg/ml group (P ＜ 0.05).Conclusions:In EOPE patients,plasma PIGF level has certain clinical value in predicting perinatal outcome.If PIGF is ≤ 12 pg/ml,the maternal renal dysfunction may be more obviously,and there is higher incidence of oligohydramnios,meconium stained fluid,SGA and neonatal asphyxia,and the newborn is more susceptible to metabolic imbalance and acid-base disorders.Mother and child care should be strengthened.

Effects of combination of vascular endothelial growth factor and placental growth factor on angiogenesis and cardiac function after acute myocardial infarction in rats / 中国介入心脏病学杂志

Objective To evaluate the combined effects of vascular endothelial growth factor (VEGF) and placental growth factor (PLGF) on angiogenesis and cardiac function and compare with VEGF or PLGF only in acute myocardial infarction rats.Methods Seventy-five males Sprague-Dawley(SD) rats were randomly divided into five groups:sham group,NS group,VEGF group,PLGF group,and VEGF + PLGF group with 15 rats in each group.All the rats underwent LAD ligation and injection of NS,VEGF,PLGF,VEGF + PLGF,in the peri-infarct area,respectively,besides the sham group.Three weeks after coronary artery ligation and different agents injection,cardiac function,myocardial scar area,angiogenesis and arteriogenesis were studied.Cardiac structure and function,and infarct size were assessed by echocardiography.The number of new vessels and the number of new arterioles were evaluated by haematoxylin-eosin staining and immunohistochemistry staining.Results Three weeks after LAD ligation and different agents injection,the LVEDD and LVESD were significantly decreased (P ＜ 0.01)in NS group,VEGF group and PLGF group.While the LVEF and LVFS were higher in VEGF + PLGF group than that in other groups.Myocardial infarct size was reduced in VEGF group (P ＜ 0.05).Angiogenesis and arteriogenesis were higher in VEGF + PLGF group than that in VEGF group (P ＜ 0.01) and PLGF group (P ＜0.05).Angiogenesis and arteriogenesis were significantly higher in PLGF group than that in VEGF group (P＜0.01).The density of microvessels in VEGF group was higher than that in NS group (P ＜ 0.05),while arteriogenesis was of no statistical difference.Conclusion The combination of half VEGF and PLGF can increase angiogenesis and arteriogenesis in the ischemic marginal zone of myocardial infarction,decrease myocardial infarction area,and improve cardiac function.

Maternal serum placental growth factor and pregnancy-associated plasma protein A measured in the first trimester as parameters of subsequent pre-eclampsia and small-for-gestational-age infants: A prospective observational study

OBJECTIVE: To examine the first-trimester maternal serum placental growth factor (PlGF) and pregnancy-associated plasma protein A (PAPP-A) levels in pregnancies associated with pre-eclampsia (PE) or small-for-gestational-age (SGA) infants, and determine the predictive accuracy of PlGF and of PAPP-A for either PE or SGA infants. METHODS: This prospective, observational study included 175 pregnant women, and of these women, due to participant withdrawal or loss to follow-up, delivery data were collected from the medical records of 155 women, including 4 who had twin pregnancies. The women's maternal history was recorded, and the PlGF and PAPP-A levels at 11 to 13 gestational weeks were measured. During the second trimester, the maternal uterine artery's systolic/diastolic ratio was measured. Multiples of the median (MoM) of PlGF and PAPP-A were determined, and the associations of these values with the risk factors of SGA and PE were evaluated. Logistic regression analysis was used to determine whether PlGF and PAPP-A are useful markers for predicting SGA infants. RESULTS: The PAPP-A MoM level was significantly lower in women with advanced maternal age, multipara women, and women with gestational diabetes than in their counterparts. The PlGF and PAPP-A MoM levels were higher in women with a twin pregnancy than in those with a singleton pregnancy. There was a significant relationship between the maternal serum PAPP-A MoM level in the first trimester and the uterine artery systolic/diastolic ratio in the second trimester. Results of logistic regression analysis showed that low PlGF and PAPP-A MoM levels were predictors of SGA infants (odds ratio, 0.143; 95% confidence interval, 0.025 to 0.806; odds ratio, 0.191; 95% confidence interval, 0.051 to 0.718, respectively). CONCLUSION: PlGF and PAPP-A are potentially useful as first-trimester markers for SGA infants and some hypertensive disorders of pregnancy.

Progress in placental growth factor in ocular neovascular disease / 国际眼科杂志(Guoji Yanke Zazhi)

Neovascularization is the main cause of blindness, such as diabetic retinopathy, retinopathy of prematurity and age - related macular degeneration. Vascular endothelial growth factor( VEGF) plays an important role in the formation of angiogenesis, and is considered to be the most potent angiogenic growth factor. Placental Growth Factor(PlGF) is one of the VEGF family, which play a crucial role in endothelial cell proliferation and migration, angiogenesis, and immune - mediated inflammation. Meanwhile, PlGF is specifically expressed in pathological angiogenesis, but not in normal blood vessels. In recent years, there has been increasing attention to PlGF, therefore this article reviews the role of PlGF in neovascular ocular diseases.

Effect of placental growth factor gene silencing on migration and invasion of human pancreatic carcinoma cell line PANC1 / 中华胰腺病杂志

Objective To explore the effect of inhibiting placental growth factor ( PIGF ) by small interfering RNA ( siRNA) on migration, invasion and chemoresistance of human pancreatic cancer cell line PANC1.Methods Three specific siRNAs targeting PIGF (siRNA-PIGF) were designed.PANC1 cells were transfected with siRNA-PIGF by liposome transfection using untransfected cells as blank controls and nonspecific siRNA ( siRNA-NC) transfected cells as negative controls .The PIGF mRNA and protein expression was examined by real-time RT-PCR and ELISA.MTT method was used to assess the inhibition rate of chemotherapeutic reagents on cell proliferation .The abilities of migration and invasion were evaluated by Transwell assay.Results The inhibition rate of PIGF mRNA in PANC1 cells transfected by 3 siRNA-PIGF were (64.38 ±8.92)%, (70.48 ±7.72)% and (81.25 ±6.02)%, which was lowest in siRNA-PIGF-3 transfected cells.The expression of PIGF mRNA in PANC1 cells were decreased by (63.72 ±8.20)%at 24 h after siRNA-PIGF transfection compared with siRNA-NC transfected cells;and the level of PIGF protein in the supernatant of cultured PANC1 cells was lowered by (42.92 ±1.34)% compared with siRNA-NC transfected cells and by (46.25 ±3.64)% compared with untransfected cells at 48h after transfection, which all had significant difference .There was no statistical difference between untransfected and siRNA-NC transfected cells.After 3 ng/L gemicitabine treatment , the inhibition rate of cell proliferation in siRNA-PIGF group was even higher than that in siRNA-NC and untransfected group [(44.35 ±5.05)% vs(34.29 ±3.60)% and (31.01 ±1.08)%;both P<0.05], and no significant difference was not observed after 5-FU and adriamycin treatment.In migration and invasion assay , the number of transmembrane cells from siRNA-PIGF group was 38.1%and 28.2%of that from siRNA-NC group and 40.8% and 36.2% of that from untransfected group , which had statistical difference (all P<0.05).Conclusions PIGF silencing could significantly suppress the migration and invasion of PANC 1 cells and improve the sensitivity to gemicitabine .

Role of placental growth factor in neovascularage-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

? Choroidal neovascularization is the primary pathogenesis of neovascularage - related macular degeneration ( nAMD ) , and the role of vascular endothelial growth factor ( VEGF ) in neovascularization has been widely recognized. Currently, drugs target different targets of VEGF have been widely used in the treatment of nAMD. As a subtype of VEGF, placental growth factor ( PlGF) has synergistic effects with VEGF-A on promoting angiogenesis, stimulating the migration of endothelial cell proliferation and mediating immune inflammatory response. There is no expression of PlGF in mature blood vessels so PlGF hashigh specificity. ln this paper, the role of PlGF in the pathogenesis and treatment of nAMD is reviewed.

Relationship between serum level of placental growth factor and left ventricular structure and function in chronic kidney disease patients / 中华肾脏病杂志

Objective To investigate the serum level of placental growth factor (PLGF) and explore its relationship with left ventricular structure and function in chronic kidney disease (CKD) patients.Methods Seventy-two non-dialysis CKD patients and sixteen age-and sex-matched healthy controls were included in this study.Serum PLGF level was measured by ELISA.Cardiac structure and function were assessed by two dimensional echocardiography.Results (1)The serum level of PLGF in CKD patients[3.32(2.97,19.77) ng/L] was significantly higher compared to the healthy controls [2.33(2.27,2.49) ng/L] (P ＜ 0.01).It progressively increased with the decline of renal function (P＜ 0.05/6).(2)The interventricular septum (IVS),left ventricular posterior wall (LVPW) was significantly higher while the ejection fraction was significantly lower in CKD patients.(3)The serum PLGF level was higher in patients with left ventricular hypertrophy (LVH) than those without LVH [19.05(3.31,21.05) ng/L vs 2.99(2.60,3.32) ng/L,P ＜ 0.05].The prevalence of LVH in the group above median PLGF level was significantly higher than that in the group below the median PLGF level (70％ vs 18％,P ＜ 0.01).(4)PLGF level was positively correlated with left ventricular mass index (LVMI),systolic pressure,diastolic pressure,24 h urine protein,Scr,UA,BUN,iPTH,the history of high blood pressure and was negatively correlated with LVEF,hemoglobin,albumin,eGFR (P ＜ 0.05).Multiple regression results showed that UA,Scr,LVEF,Hb were associated with PLGF level independently (P ＜ 0.01).Conclusions CKD patients have elevated level of PLGF.It has a relationship with cardiac structure and function.It may participate in the occurrence of cardiovascular events.

Midtrimester maternal plasma concentrations of angiopoietin 1, angiopoietin 2, and placental growth factor in pregnant women who subsequently develop preeclampsia

OBJECTIVE: The aim of this study was to compare midtrimester maternal plasma concentrations of angiopoietin 1, angiopoietin 2, and placental growth factor between pregnant women who subsequently developed preeclampsia and those who did not. METHODS: Midtrimester maternal plasma was collected and stored at -70degrees C when genetic amniocentesis was performed. Cases included 37 samples of individual who subsequently developed preeclampsia, and matched controls were from individuals who did not develop preeclampsia. Angiopoietin 1, angiopoietin 2, and placental growth factor concentrations were measured by the enzyme-linked immunosorbent assay method and were compared using the Mann-Whitney U-test. A P-value <0.05 was considered significant. RESULTS: In pregnant women who subsequently developed preeclampsia, midtrimester maternal plasma concentrations of angiopoietin 1 and angiopoietin 2 were significantly higher and placental growth factor concentrations were significantly lower than in women who did not develop preeclampsia (angiopoietin 1: 10.6 [3.1-19.7] vs. 7.8 [0.9-24.4] ng/mL, P=0.031; angiopoietin 2: 31.0 [4.7-81.2] vs. 18.4 [4.2-49.7] ng/mL, P<0.001; placental growth factor: 87.1 [14.2-774.3] vs. 148.8 [57.2-425.6] pg/mL, P<0.001). Within the case group who subsequently developed preeclampsia, the placental growth factor was significantly lower in those who had fetal growth restrictions than in those who did not (placental growth factor: 72.5 [14.2-774.3] vs. 140.9 [44.2-257.5] pg/mL, P=0.003). CONCLUSION: Midtrimester maternal plasma concentrations of angiopoietin 1, angiopoietin 2, and placental growth factor may be associated with the subsequent development of preeclampsia.

Role of nitric oxide, angiogenic growth factors and biochemical analysis in preeclampsia.

Preeclampsia, a pregnancy-related hypertensive disorder, is one of the leading causes of fetal and maternal mortality and morbidity globally. Angiogenic growth factors, including vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are involved in the generation of new blood vessels required for placental development and physiological functions, while nitric oxide (NO) acts as vasodilator and also plays a role in angiogenesis. The objective of this study was to evaluate the role of NO, angiogenic growth factors (VEGF and PIGF) and other biochemical parameters in the development of preeclampsia among pregnant mothers. A complete clinical history, including anthropometric measurements and biochemical investigations, including renal function tests, liver function tests and lipid profile were performed among twenty preeclampsia patients aged 19 to 32 yrs. Results were compared with age-matched normotensive pregnant mothers. The body weight, body mass index (BMI), blood pressure, concentrations of urea, uric acid and triglyceride and activities of transaminase enzymes (aspartate transaminase, AST and alanine transaminase, ALT) in serum were significantly higher (p<0.05) than normotensive subjects. Serum concentrations of VEGF, PlGF and NO were significantly decreased (p<0.005) in preeclamptic patients. NO was found negatively correlated with body weight (r = -0.369, p<0.05), systolic blood pressure (r = -0.822, p<0.005), diastolic blood pressure (r = -0.714, p<0.005) and was positively correlated with VEGF (r = 0.464, p<0.005) and PlGF (r = 0.546, p<0.005). VEGF and PlGF showed significant (p<0.005) negative correlation with systolic and diastolic blood pressure and PlGF was significantly correlated with triglyceride (r = -0.379). However, no significant correlation was observed between the VEGF and PlGF. In conclusion, the results indicated that body weight, triglyceride, angiogenic growth factors and NO might associate with preeclampsia development.