Method for evaluating preeclampsia disease degree based on PLGF level

Abstract

The invention relates to the technical field of preeclampsia condition degree evaluation, and discloses a method for evaluating preeclampsia condition degree based on PLGF level, which comprises the following steps: dynamically monitoring plasma samples of a patient at 20 weeks of pregnancy and a plurality of time points after pregnancy to obtain data of PLGF level, sFlt-1 level, miR-3074-5p level and p27 protein expression level. Based on the data, the dynamic change rate of the PLGF level, the ratio of sFlt-1 to PLGF and the correlation coefficient of the miR-3074-5p level and the p27 protein expression level are calculated. The process ensures that the dynamic change of each biomarker is comprehensively known, and early abnormal signals can be captured.

Description

Technical Field

[0001] The present invention relates to the technical field of preeclampsia disease severity assessment, and in particular to a method for assessing the preeclampsia disease severity based on PLGF levels. Background Art

[0002] Pregnancy is a complex physiological process. The placenta regulates maternal and fetal circulation through nutrition, metabolism, exchange, endocrine and other functions. It is a bridge between mother and child and plays an important role in fetal growth and development and changes in maternal physiological functions. The normal development and good physiological function of the placenta are prerequisites for maintaining pregnancy and fetal growth and development. Abnormal placental formation and function are closely related to the occurrence of preeclampsia and fetal growth restriction (FGR). Placental growth factor (PLGF) is an important growth factor abundantly expressed in the placenta. It is a member of the vascular endothelial growth factor (VEGF) family. It is mainly secreted by syncytial trophoblasts and villous stromal endothelial cells. It plays an important role in the proliferation and activation of trophoblasts, the formation of fetal placental vascular network, and the establishment of an effective fetal placental vascular network.

[0003] Preeclampsia (PE) is a peculiar disease during pregnancy and an important cause of threat to the life safety of mother and baby. The pathogenesis of PE has not been fully elucidated, but the disorder of uterine spiral arteriole remodeling caused by various factors may be the initiating link of its occurrence. Subsequent placental ischemia and hypoxia, the secretion of multiple factors by the placenta into the maternal blood circulation, and the promotion of systemic inflammatory response will further aggravate endothelial damage, thus causing adverse perinatal outcomes. At present, there is no significant breakthrough in the treatment of preeclampsia. Early termination of pregnancy is a helpless and safe treatment option for patients with preeclampsia accompanied by severe clinical manifestations. The problem of iatrogenic premature birth is becoming increasingly prominent. Compared with iatrogenic premature birth caused by other factors, the gestational age and birth weight of premature infants in patients with preeclampsia are often smaller, and the proportion of perinatal asphyxia and small for gestational age (SGA) is higher. The prevalence of neonatal pulmonary dysplasia, cerebral palsy and long-term cardiovascular disease is also significantly increased, which brings a heavy burden to society and families. When faced with a disease like preeclampsia that affects multiple systems and organs, obstetrics often have to make a difficult choice between expectant treatment to prolong gestation as much as possible and active termination of pregnancy to prevent maternal harm. The overall assessment of maternal factors and placenta-fetal factors is the decisive factor in terminating pregnancy. The assessment of maternal factors includes laboratory auxiliary examinations of the involvement of multiple systems and organ functions such as the heart, liver, kidneys, and blood, which are more objective; electronic fetal heart monitoring and ultrasound are commonly used methods for assessing placenta-fetal factors, but there are many structural interference factors, and the doctor's subjective factors and the physical characteristics of the patient and his or her spouse can affect the assessment of placental function and fetal growth and development. Not only that, the impact of preeclampsia treatment plans on patients is also focused on the impact on the mother, and whether it has a positive impact on placenta-fetal factors cannot be assessed. Summary of the invention

[0004] In order to solve the above technical problems, the present invention provides a method for evaluating the severity of preeclampsia based on PLGF levels, comprising: Step 1, obtaining plasma samples from patients at multiple time points at and after 20 weeks of pregnancy; Step 2, obtaining the PLGF level, sFlt-1 level, miR-3074-5p level, and p27 protein expression level based on the plasma samples in step 1; Step 3, according to the PLGF level, the dynamic change rate of the PLGF level is obtained; according to the PLGF level and the sFlt-1 level, the ratio of sFlt-1 to PLGF is obtained; according to the miR-3074-5p level and the p27 protein expression level, the correlation coefficient is calculated; Step 4, obtaining the patient's historical PLGF level, historical sFlt-1 level, historical miR-3074-5p level, and historical p27 protein expression level at multiple historical time points before 20 weeks of pregnancy; calculating the average of the historical PLGF levels at multiple historical time points as the PLGF threshold; calculating the average of the historical sFlt-1 to historical PLGF ratios at multiple historical time points as the sFlt-1 to PLGF ratio threshold; calculating the average of the correlation coefficients between the historical miR-3074-5p levels and the historical p27 protein expression levels at multiple historical time points as the correlation coefficient threshold; Step 5, calculating the PLGF index according to the PLGF threshold, calculating the sFlt-1 to PLGF ratio index according to the sFlt-1 to PLGF ratio threshold, and calculating the correlation coefficient index according to the correlation coefficient threshold; Step 6, constructing a comprehensive evaluation function according to the PLGF index, the sFlt-1 to PLGF ratio index, and the correlation coefficient index, obtaining a comprehensive evaluation value, and obtaining the degree of preeclampsia according to the comprehensive evaluation value.

[0005] Furthermore, the historical PLGF levels of the patient at multiple historical time points before 20 weeks of pregnancy were arranged from high to low, and the median of the historical PLGF levels was used as the initial PLGF level; the patient's current PLGF level and the PLGF level at the previous moment were obtained, and the dynamic change rate of the PLGF level was calculated based on the initial PLGF level, the current PLGF level, and the PLGF level at the previous moment.

[0006] Furthermore, the PLGF index is calculated according to the PLGF threshold, including: When the dynamic change rate of PLGF level is less than the PLGF threshold, the PLGF index is the dynamic change rate of PLGF level; When the dynamic change rate of PLGF level is greater than or equal to the PLGF threshold: The standard deviation of historical PLGF levels was calculated using the patient's historical PLGF levels at multiple historical time points before 20 weeks of gestation; The PLGF index was calculated based on the historical PLGF level standard deviation, PLGF threshold, and PLGF level dynamic change rate.

[0007] Further, the sFlt-1 to PLGF ratio index is calculated according to the sFlt-1 to PLGF ratio threshold, including: When the sFlt-1 to PLGF ratio is less than the sFlt-1 to PLGF ratio threshold, the sFlt-1 to PLGF ratio index is the sFlt-1 to PLGF ratio; When the sFlt-1 to PLGF ratio is greater than or equal to the sFlt-1 to PLGF ratio threshold, the sFlt-1 to PLGF ratio index is calculated according to the sFlt-1 to PLGF ratio and the sFlt-1 to PLGF ratio threshold.

[0008] Furthermore, the correlation coefficient index is calculated according to the correlation coefficient threshold, including: When the correlation coefficient is less than the correlation coefficient threshold, the correlation coefficient indicator is the correlation coefficient; When the correlation coefficient is greater than or equal to the correlation coefficient threshold, the correlation coefficient index is calculated based on the correlation coefficient and the correlation coefficient threshold.

[0009] Furthermore, the severity of preeclampsia is determined based on comprehensive assessment, including: Obtain historical samples from patients at multiple historical time points at and after 20 weeks of gestation; Divide historical samples into positive samples and negative samples; calculate a positive sample comprehensive evaluation value based on the positive samples; calculate a negative sample comprehensive evaluation value based on the negative samples, use the positive sample comprehensive evaluation value as the first risk threshold, and use the negative sample comprehensive evaluation value as the second risk threshold; When the comprehensive assessment value is less than the first risk threshold, the patient's preeclampsia condition reaches a low risk level; When the comprehensive assessment is greater than or equal to the first risk threshold and less than the second risk threshold, the patient's preeclampsia condition reaches a medium risk level; When the comprehensive assessment value is greater than or equal to the second risk threshold, the patient's preeclampsia condition reaches a high-risk level.

[0010] Furthermore, the comprehensive evaluation function is: ; In the formula, F represents the comprehensive evaluation value, represents the PLGF index, Represents the ratio of sFlt-1 to PLGF. Represents the correlation coefficient indicator, , , Represent the weight coefficients respectively.

[0011] Furthermore, the calculation formula of the PLGF index is: ; In the formula, Represents the dynamic change rate of PLGF level, represents the patient's PLGF level at the current time t, represents the PLGF level of the patient at the previous time t-1, represents the initial PLGF level, represents the PLGF threshold, Represents the standard deviation of historical PLGF levels.

[0012] Furthermore, the calculation formula of the sFlt-1 to PLGF ratio index is: ; In the formula, represents the ratio of sFlt-1 to PLGF, represents the sFlt-1 level at the current time t, represents the patient's PLGF level at the current time t, Represents the threshold value of the ratio of sFlt-1 to PLGF.

[0013] Furthermore, the calculation formula of the correlation coefficient indicator is: ; In the formula, p represents the correlation coefficient, Represents the correlation coefficient threshold.

[0014] The embodiments of the present invention have the following technical effects: First, by dynamically monitoring the patient's plasma samples at 20 weeks of pregnancy and at multiple time points thereafter, data on PLGF levels, sFlt-1 levels, miR-3074-5p levels, and p27 protein expression levels were obtained. Based on these data, the dynamic change rate of PLGF levels, the ratio of sFlt-1 to PLGF, and the correlation coefficient between miR-3074-5p levels and p27 protein expression levels were calculated. This process ensures a comprehensive understanding of the dynamic changes of each biomarker and the ability to capture early abnormal signals.

[0015] Next, the specific values ​​of each indicator are calculated according to the threshold. For the PLGF indicator, when the dynamic change rate of the PLGF level is less than the PLGF threshold, the change rate is directly used as the indicator; when the change rate is greater than or equal to the threshold, it is further adjusted in combination with the standard deviation of the historical PLGF level to reflect its abnormality. Similarly, for the sFlt-1 to PLGF ratio indicator and the correlation coefficient indicator, corresponding calculations are performed based on whether they exceed the corresponding threshold. This segmented calculation method can not only distinguish between normal physiological fluctuations and pathological states, but also quantify the degree of abnormality, providing more refined data support for subsequent risk assessment.

[0016] Finally, the PLGF index, the sFlt-1 to PLGF ratio index and the correlation coefficient index are integrated into a comprehensive evaluation value. This comprehensive evaluation value can not only quantitatively reflect the severity of the patient's condition, but also divide the patient into three levels of low risk, medium risk and high risk according to the preset first risk threshold and second risk threshold. It not only relies on the changes of a single indicator, but also comprehensively considers the interactions between multiple biomarkers, thereby improving the accuracy and reliability of the evaluation. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0018] Figure 1 is a flow chart of a method for evaluating the severity of preeclampsia based on PLGF levels provided by an embodiment of the present invention; Figure 2 It is a comparative schematic diagram of the expression level of PLGF in the plasma of non-preeclampsia patients and in the plasma of preeclampsia patients provided by an embodiment of the present invention; Figure 3 It is a comparative schematic diagram of the expression level of sFlt-1 in the placenta of non-preeclampsia patients and the placenta of preeclampsia patients provided by an embodiment of the present invention; Figure 4 is a schematic diagram comparing the expression levels of miR-3074-5p in the placenta of non-preeclampsia patients and the placenta of preeclampsia patients provided by an embodiment of the present invention; Figure 5 It is a schematic diagram for comparing the expression levels of p27 protein in the plasma of non-preeclampsia patients and in the plasma of preeclampsia patients provided by an embodiment of the present invention. DETAILED DESCRIPTION

[0019] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work belong to the scope of protection of the present invention.

[0020] Figure 1 : is a flow chart of a method for evaluating the severity of preeclampsia based on PLGF levels provided by an embodiment of the present invention. Figure 1 , specifically including: Step 1: Obtain plasma samples from patients at multiple time points during and after 20 weeks of pregnancy.

[0021] Figure 2 FIG. 1 is a schematic diagram showing a comparison of the expression levels of PLGF in the plasma of non-preeclampsia patients and in the plasma of preeclampsia patients provided in an embodiment of the present invention, see Figure 2 , where the expression levels of preeclampsia patients and non-preeclampsia patients of the same gestational week were counted, the control group was the PLGF expression level of several non-preeclampsia patients after 20 weeks of gestation, and the PE group was the PLGF expression level of several preeclampsia patients after 20 weeks of gestation. Preeclampsia usually occurs after 20 weeks of gestation, especially in the late second trimester and early third trimester, the PLGF level in preeclampsia patients decreased significantly, see Table 1, which is the PLGF level measured in a patient who had symptoms of preeclampsia after 20 weeks of gestation and went to the clinic: Table 1 PLGF levels measured in a patient who presented with symptoms of preeclampsia after 20 weeks of pregnancy

[0022] See Table 1. The patient presented with symptoms of preeclampsia on the 5th day after 22 weeks of pregnancy, and the PLGF expression level was measured to be 11.87 pg / ml, which was far below the normal value. After medication treatment, the PLGF expression level increased (the 3rd day after 29 weeks of pregnancy - the PLGF expression level rebounded to 49.08 pg / ml), but continued to decline significantly over time until the 6th day after 33 weeks of pregnancy, when the PLGF expression level dropped again to 14.1, far below the normal value, indicating deterioration of placental function.

[0023] Figure 3 is a comparative schematic diagram of the expression levels of sFlt-1 in the placenta of non-preeclampsia patients and in the placenta of preeclampsia patients provided by an embodiment of the present invention, wherein the control group is the sFlt-1 expression level of several non-preeclampsia patients after 20 weeks of pregnancy, and the PE group is the sFlt-1 expression level of several preeclampsia patients after 20 weeks of pregnancy; see Figure 3 A large number of studies have shown that the level of sFlt-1 (Soluble fms-like tyrosine kinase-1) is significantly increased in the peripheral blood of patients with preeclampsia. At the same time, we also tested the placenta of patients with preeclampsia. The level of sFlt-1 in the placenta of patients with preeclampsia also showed a significant increasing trend, especially after 20 weeks of pregnancy. Figure 4is a schematic diagram of the comparison of the expression levels of miR-3074-5p in the placenta of non-preeclampsia patients and in the placenta of preeclampsia patients provided by an embodiment of the present invention, wherein the control group is the miR-3074-5p expression level of several non-preeclampsia patients after 20 weeks of pregnancy, and the PE group is the miR-3074-5p expression level of several preeclampsia patients after 20 weeks of pregnancy, see Figure 4 , miR-3074-5p was significantly reduced in the placenta of patients with preeclampsia. In addition, through literature retrieval, it was found that placental-derived miRNAs showed a dynamic change pattern in maternal peripheral blood circulation during pregnancy. These miRNAs can be released in trophoblast cells and stably exist in peripheral blood. We also found through experiments that miR-3074-5p (MicroRNA-3074-5p, microRNA-3074-5p) was differentially expressed in the placenta of patients with preeclampsia and non-preeclampsia. Given that placental tissue is not easy to obtain directly, and related studies have shown that abnormally expressed miRNAs are detected through peripheral blood, which is extremely important for the early diagnosis of PE, it can be inferred that miR-3074-5p will have a similar expression trend in the plasma of patients with preeclampsia and in the placenta, that is, miR-3074-5p will also have an abnormal change trend in the plasma of patients with preeclampsia. Figure 5 FIG. 1 is a schematic diagram showing a comparison of the expression levels of p27 protein in the plasma of non-preeclampsia patients and in the plasma of preeclampsia patients provided in an embodiment of the present invention. Figure 5 Among them, the control group was the p27 protein expression level of several non-preeclampsia patients after 20 weeks of pregnancy, and the PE group was the p27 protein expression level of several preeclampsia patients after 20 weeks of pregnancy; after experimental detection, the expression level of p27 protein in peripheral blood (p27 protein expression level) also showed abnormality in preeclampsia patients, with an obvious downward expression trend. The statistical results are shown in Table 2.

[0024] Table 2 Expression levels of p27 protein in patients with preeclampsia and non-preeclampsia

[0025] Among them, the t value represents the statistic of the difference in the mean values ​​of the two groups of data, reflecting the relationship between the amplitude of the difference between the two groups and the data variability (standard deviation). The negative sign indicates that the mean of the PE group is lower than that of the control group. The P value represents the probability of observing the current difference under the premise that the null hypothesis is established (i.e., "there is no difference between the two groups"). The P value in the table is 0.033, indicating that there is only a 3.3% probability that the difference in P27 concentration between the control group and the PE group is caused by random errors. Therefore, the null hypothesis is rejected, and it is believed that the trend of changes in the expression level of p27 protein is meaningful.

[0026] The changing trends of these indicators can serve as an important basis for early warning. Therefore, this embodiment collects relevant data of patients at 20 weeks of pregnancy and after 20 weeks for analysis.

[0027] At and after the 20th week of pregnancy, multiple key time points are selected for plasma sample collection. Exemplarily, the sampling time points in this embodiment include: 20th week of pregnancy, 24th week of pregnancy, 28th week of pregnancy, 32nd week of pregnancy, and 36th week of pregnancy. Plasma samples are collected from patients at the above time points.

[0028] Among them, the 20th week of gestation is the critical period for placental development, when placental dysfunction (such as spiral artery hypoperfusion) may begin to manifest, which is directly related to the pathological mechanism of preeclampsia (placental ischemia and hypoxia); 24 weeks of gestation is the fetal survival threshold, which is the critical point for the fetus to survive in vitro. About 50% of preeclampsia cases show changes in biomarkers of abnormal placental function (such as a significant decrease in PLGF and an increase in the sFlt-1 / PLGF ratio) at 24-28 weeks of gestation. The 28th week of pregnancy marks the beginning of the late pregnancy, when placental function ages faster. The risk of preeclampsia in high-risk pregnant women (such as those with diabetes or twin pregnancy) increases significantly, and preeclampsia may progress rapidly in the late pregnancy. Monitoring at 28 weeks can assess the dynamic trend of the disease (such as a continuous decrease in PLGF indicating worsening placental function). The 32nd week of pregnancy is the peak period for severe preeclampsia. About 30% of severe preeclampsia cases develop multiple organ damage (such as HELLP syndrome and renal dysfunction) after 32 weeks of pregnancy, requiring intensive monitoring. After 36 weeks of pregnancy, the fetus is close to full term, and some placental function indicators (such as PLGF) may decrease naturally. It is necessary to combine multiple other indicators to distinguish physiological changes from pathological progression.

[0029] Step 2, obtaining the PLGF level, sFlt-1 level, miR-3074-5p level, and p27 protein expression level based on the plasma samples in step 1.

[0030] Step 3, according to the PLGF level, the dynamic change rate of the PLGF level is obtained; according to the PLGF level and the sFlt-1 level, the ratio of sFlt-1 to PLGF is obtained; according to the miR-3074-5p level and the p27 protein expression level, the correlation coefficient is calculated.

[0031] The historical PLGF levels of the patient at multiple historical time points before 20 weeks of pregnancy are arranged from high to low, and the median of the historical PLGF levels is used as the initial PLGF level; the patient's current PLGF level and the PLGF level at the previous moment are obtained, and the dynamic change rate of the PLGF level is calculated based on the initial PLGF level, the current PLGF level, and the PLGF level at the previous moment: ; represents the patient's PLGF level at the current time t, represents the PLGF level of the patient at the previous time t-1, represents the initial PLGF level.

[0032] The miR-3074-5p level and the p27 protein expression level were normalized, and the normalized miR-3074-5p level and the p27 protein expression level were used in the correlation coefficient calculation to obtain the correlation coefficient between the miR-3074-5p level and the p27 protein expression level.

[0033] Step 4, obtaining the patient's historical PLGF level, historical sFlt-1 level, historical miR-3074-5p level, and historical p27 protein expression level at multiple historical time points before 20 weeks of pregnancy; calculating the average of the historical PLGF levels at multiple historical time points as the PLGF threshold; calculating the mean of the ratio of historical sFlt-1 to historical PLGF at multiple historical time points as the sFlt-1 to PLGF ratio threshold; calculating the mean of the correlation coefficient between the historical miR-3074-5p level and the historical p27 protein expression level at multiple historical time points as the correlation coefficient threshold.

[0034] Step 5, calculating the PLGF index according to the PLGF threshold, calculating the sFlt-1 to PLGF ratio index according to the sFlt-1 to PLGF ratio threshold, and calculating the correlation coefficient index according to the correlation coefficient threshold.

[0035] When the dynamic change rate of PLGF level is less than the PLGF threshold, the PLGF indicator is the dynamic change rate of PLGF level; when the dynamic change rate of PLGF level is greater than or equal to the PLGF threshold: The standard deviation of historical PLGF levels was calculated using the patient's historical PLGF levels at multiple historical time points before 20 weeks of gestation; The PLGF index was calculated based on the historical PLGF level standard deviation, PLGF threshold, and PLGF level dynamic change rate.

[0036] ; In the formula, Represents the dynamic change rate of PLGF level, represents the patient's PLGF level at the current time t, represents the PLGF level of the patient at the previous time t-1, represents the initial PLGF level, represents the PLGF threshold, Represents the standard deviation of historical PLGF levels.

[0037] The sFlt-1 to PLGF ratio index is calculated according to the sFlt-1 to PLGF ratio threshold, including: When the sFlt-1 to PLGF ratio is less than the sFlt-1 to PLGF ratio threshold, the sFlt-1 to PLGF ratio index is the sFlt-1 to PLGF ratio; when the sFlt-1 to PLGF ratio is greater than or equal to the sFlt-1 to PLGF ratio threshold, the sFlt-1 to PLGF ratio index is calculated based on the sFlt-1 to PLGF ratio and the sFlt-1 to PLGF ratio threshold.

[0038] ; In the formula, represents the ratio of sFlt-1 to PLGF, Represents the current time t sFlt-1 levels, represents the patient's PLGF level at the current time t, Represents the threshold value of the ratio of sFlt-1 to PLGF.

[0039] The correlation coefficient index is calculated according to the correlation coefficient threshold, including: when the correlation coefficient is less than the correlation coefficient threshold, the correlation coefficient index is the correlation coefficient between the miR-3074-5p level and the p27 protein expression level; when the correlation coefficient is greater than or equal to the correlation coefficient threshold, the correlation coefficient index is calculated according to the correlation coefficient and the correlation coefficient threshold: ; In the formula, p represents the correlation coefficient, Represents the correlation coefficient threshold.

[0040] Step 6, constructing a comprehensive evaluation function according to the PLGF index, the sFlt-1 to PLGF ratio index, and the correlation coefficient index, obtaining a comprehensive evaluation value, and obtaining the degree of preeclampsia according to the comprehensive evaluation value.

[0041] ; In the formula, F represents the comprehensive evaluation value, represents the PLGF index, Represents the ratio of sFlt-1 to PLGF. Represents the correlation coefficient indicator, , , Represent the weight coefficients respectively.

[0042] The weight coefficient can be determined by using historical clinical data (such as the correlation data between PLGF, sFlt-1, miR-3074-5p, p27 protein and the severity of preeclampsia), calculating the regression coefficient of each indicator through multivariate logistic regression, and normalizing it as the weight; or by using expert experience to score the importance of the indicator according to clinical experience (such as 1-10 points), summarizing it and normalizing it to assign weights, etc.; illustratively, It can be set to 0.5. It can be set to 0.3. Can be set to 0.2.

[0043] The severity of preeclampsia is determined based on a comprehensive assessment, including: Obtain historical samples from patients at multiple historical time points at and after 20 weeks of gestation; The historical samples are divided into positive samples and negative samples, where the positive samples are pregnant women diagnosed with preeclampsia, and the negative samples are healthy pregnant women; the ratio of positive samples to negative samples is preferably 1:1 or 1:2 to avoid data skew. If the sample size is insufficient, stratified sampling or oversampling methods can be used to balance the data; the positive sample comprehensive evaluation value is calculated based on the positive sample; the negative sample comprehensive evaluation value is calculated based on the negative sample, and the positive sample comprehensive evaluation value is used as the first risk threshold, and the negative sample comprehensive evaluation value is used as the second risk threshold; when the comprehensive evaluation value is less than the first risk threshold, the patient's preeclampsia condition reaches a low risk level; when the comprehensive evaluation value is greater than or equal to the first risk threshold and less than the second risk threshold, the patient's preeclampsia condition reaches a medium risk level; when the comprehensive evaluation value is greater than or equal to the second risk threshold, the patient's preeclampsia condition reaches a high risk level.

Claims

1. A method for evaluating the severity of preeclampsia based on PLGF levels, characterized in that: include: Step 1, obtaining plasma samples from patients at multiple time points at and after 20 weeks of pregnancy; Step 2, obtaining the PLGF level, sFlt-1 level, miR-3074-5p level, and p27 protein expression level based on the plasma samples in step 1; Step 3, according to the PLGF level, the dynamic change rate of the PLGF level is obtained; according to the PLGF level and the sFlt-1 level, the ratio of sFlt-1 to PLGF is obtained; according to the miR-3074-5p level and the p27 protein expression level, the correlation coefficient is calculated; Step 4, obtaining the patient's historical PLGF level, historical sFlt-1 level, historical miR-3074-5p level, and historical p27 protein expression level at multiple historical time points before 20 weeks of pregnancy; calculating the average of the historical PLGF levels at multiple historical time points as the PLGF threshold; calculating the average of the historical sFlt-1 to historical PLGF ratios at multiple historical time points as the sFlt-1 to PLGF ratio threshold; calculating the average of the correlation coefficients between the historical miR-3074-5p levels and the historical p27 protein expression levels at multiple historical time points as the correlation coefficient threshold; Step 5, calculating the PLGF index according to the PLGF threshold, calculating the sFlt-1 to PLGF ratio index according to the sFlt-1 to PLGF ratio threshold, and calculating the correlation coefficient index according to the correlation coefficient threshold; Step 6, constructing a comprehensive evaluation function according to the PLGF index, the sFlt-1 to PLGF ratio index, and the correlation coefficient index, obtaining a comprehensive evaluation value, and obtaining the degree of preeclampsia according to the comprehensive evaluation value.

2. A method for evaluating the severity of preeclampsia based on PLGF levels according to claim 1, characterized in that: The historical PLGF levels of the patient at multiple historical time points before 20 weeks of pregnancy were arranged from high to low, and the median of the historical PLGF levels was used as the initial PLGF level; the patient's current PLGF level and the PLGF level at the previous moment were obtained, and the dynamic change rate of the PLGF level was calculated based on the initial PLGF level, the current PLGF level, and the PLGF level at the previous moment.

3. A method for evaluating the severity of preeclampsia based on PLGF levels according to claim 1, characterized in that: The PLGF index is calculated according to the PLGF threshold, including: When the dynamic change rate of PLGF level is less than the PLGF threshold, the PLGF index is the dynamic change rate of PLGF level; When the dynamic change rate of PLGF level is greater than or equal to the PLGF threshold: The standard deviation of historical PLGF levels was calculated using the patient's historical PLGF levels at multiple historical time points before 20 weeks of gestation; The PLGF index was calculated based on the historical PLGF level standard deviation, PLGF threshold, and PLGF level dynamic change rate.

4. The method for evaluating the severity of preeclampsia based on PLGF levels according to claim 1, characterized in that: The sFlt-1 to PLGF ratio index is calculated according to the sFlt-1 to PLGF ratio threshold, including: When the sFlt-1 to PLGF ratio is less than the sFlt-1 to PLGF ratio threshold, the sFlt-1 to PLGF ratio index is the sFlt-1 to PLGF ratio; When the sFlt-1 to PLGF ratio is greater than or equal to the sFlt-1 to PLGF ratio threshold, the sFlt-1 to PLGF ratio index is calculated according to the sFlt-1 to PLGF ratio and the sFlt-1 to PLGF ratio threshold.

5. The method for evaluating the severity of preeclampsia based on PLGF levels according to claim 1, characterized in that: Calculate correlation coefficient indicators based on correlation coefficient thresholds, including: When the correlation coefficient is less than the correlation coefficient threshold, the correlation coefficient indicator is the correlation coefficient; When the correlation coefficient is greater than or equal to the correlation coefficient threshold, the correlation coefficient index is calculated based on the correlation coefficient and the correlation coefficient threshold.

6. The method for evaluating the severity of preeclampsia based on PLGF levels according to claim 1, characterized in that: The severity of preeclampsia is determined based on a comprehensive assessment, including: Obtain historical samples from patients at multiple historical time points at and after 20 weeks of gestation; Divide historical samples into positive samples and negative samples; calculate a positive sample comprehensive evaluation value based on the positive samples; calculate a negative sample comprehensive evaluation value based on the negative samples, use the positive sample comprehensive evaluation value as the first risk threshold, and use the negative sample comprehensive evaluation value as the second risk threshold; When the comprehensive assessment value is less than the first risk threshold, the patient's preeclampsia condition reaches a low risk level; When the comprehensive assessment is greater than or equal to the first risk threshold and less than the second risk threshold, the patient's preeclampsia condition reaches a medium risk level; When the comprehensive assessment value is greater than or equal to the second risk threshold, the patient's preeclampsia condition reaches a high-risk level.

7. The method for evaluating the severity of preeclampsia based on PLGF levels according to claim 1, characterized in that: The comprehensive evaluation function is: ； In the formula, F represents the comprehensive evaluation value, represents the PLGF indicator, Represents the ratio of sFlt-1 to PLGF. represents the correlation coefficient indicator, , , Represent the weight coefficients respectively.

8. A method for evaluating the severity of preeclampsia based on PLGF levels according to claim 7, characterized in that: The calculation formula of PLGF index is: ； In the formula, Represents the dynamic change rate of PLGF level, represents the patient's PLGF level at the current time t, represents the PLGF level of the patient at the previous time t-1, represents the initial PLGF level, represents the PLGF threshold, Represents the standard deviation of historical PLGF levels.

9. The method for evaluating the severity of preeclampsia based on PLGF levels according to claim 7, characterized in that: The calculation formula of the sFlt-1 to PLGF ratio index is: ； In the formula, represents the ratio of sFlt-1 to PLGF, represents the sFlt-1 level at the current time t, represents the patient's PLGF level at the current time t, Represents the threshold value of the ratio of sFlt-1 to PLGF.

10. The method for evaluating the severity of preeclampsia based on PLGF levels according to claim 7, characterized in that: The calculation formula of the correlation coefficient indicator is: ； In the formula, p represents the correlation coefficient, Represents the correlation coefficient threshold.

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