CN115166100A - Use of reagents for detecting FFA and/or MAG in the manufacture of a product for predicting the risk of onset of IPAH - Google Patents
Use of reagents for detecting FFA and/or MAG in the manufacture of a product for predicting the risk of onset of IPAH Download PDFInfo
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- CN115166100A CN115166100A CN202210929982.7A CN202210929982A CN115166100A CN 115166100 A CN115166100 A CN 115166100A CN 202210929982 A CN202210929982 A CN 202210929982A CN 115166100 A CN115166100 A CN 115166100A
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- G—PHYSICS
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- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
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Abstract
The invention provides application of an agent for detecting Free Fatty Acid (FFA) and/or Monoglyceride (MAG) in preparing a product for predicting the onset risk of Idiopathic Pulmonary Arterial Hypertension (IPAH), wherein the product comprises the agent for detecting the FFA and/or the MAG, and the higher the expression of the FFA and/or the MAG is, the higher the onset risk of the IPAH is. The invention verifies that the high expression of FFA and/or MAG in plasma indicates a high probability of occurrence of IPAH, which provides a basis for predicting the risk of the onset of IPAH of a subject, can help patients to screen early and improve the diagnosis rate.
Description
Technical Field
The invention relates to the technical field of molecular detection, in particular to application of a reagent for detecting Free Fatty Acid (FFA) and/or Monoglyceride (MAG) in preparation of a product for predicting the onset risk of idiopathic pulmonary hypertension (IPAH).
Background
Idiopathic pulmonary hypertension is a type of pulmonary vascular disease characterized by vascular remodeling of the pulmonary artery wall, with gradual increase in PVR, leading to remodeling of the pulmonary vessels and the right ventricle, and ultimately leading to right heart failure and even death. IPAH is good for women, the incidence rate is about 6/100 ten thousand, and the fatality rate is high. Statistically, 4 million people worldwide suffer from IPAH each year, with a mortality rate of up to 15%, and a 3-year survival rate of PAH patients, even with conventional treatment, of only 55% -65% 3%. The initial clinical presentation of IPAH is non-specific and difficult to diagnose, which often results in the patient missing the optimal treatment time, leading to later exacerbation and difficulty in targeted treatment. Although the current clinical targeted drugs aiming at PAH have obviously improved the survival time and the quality of life of part of patients, a large number of patients still cannot benefit from the clinical targeted drugs, wherein the prognosis of part of patients is poor, and the quality of life is not obviously improved. Therefore, more accurate and specific biomarkers are needed to improve the early screening and diagnosis rate of patients, and the method has important clinical significance for improving the prognosis of PAH patients.
Lipid molecules are important biomolecules, and it is estimated that there are tens of thousands of lipid substances in an organism. They are the most abundant species in plasma, with lipids on the cell membrane accounting for 50% of their weight, and large amounts of lipids being present in the endoplasmic reticulum, golgi, mitochondria, and lysosomes. The diversity of lipid structures also confers a variety of important biological functions that are involved in and regulate various vital activities such as cell growth and differentiation, apoptosis, energy conversion between cells and tissues, material transport, information recognition and signaling. Therefore, lipid metabolism and its functional changes have important effects on physiological functions of cells and pathological disorders of organisms. Abnormal lipid metabolism is often closely related to metabolic diseases, cardiovascular diseases, tumors and nervous system diseases. The study of lipid metabolism is of great biological importance in medicine. In recent years, with the gradual maturation and improvement of lipidomics technology, lipid metabolism has been extensively studied. With the extensive study of lipid metabolism in cardiovascular diseases, researchers have found that changes in lipid content can reveal changes in the levels, activities, and gene expression patterns of several enzymes simultaneously, playing an important role in disease progression. However, there are few reports on the relationship between lipid metabolism and IPAH.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides the application of the reagent for detecting FFA and/or MAG in the preparation of products for predicting the risk of the onset of IPAH.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides in a first aspect the use of an agent for detecting FFA and/or MAG in the manufacture of a product for predicting the risk of development of IPAH; the product comprises reagents for detecting FFA and/or MAG.
Further, the higher the FFA and/or MAG expression, the higher the risk of IPAH onset.
Further, the product is a kit.
Further, the kit is used based on a liquid chromatography-mass spectrometry technology.
Further, the FFA includes FFA (14: 0) and/or FFA (20: 5).
Further, the reagent for detecting FFA and/or MAG is a reagent for detecting the expression level of FFA and/or MAG in plasma.
A second aspect of the invention provides a product for predicting the risk of developing IPAH, which product comprises an agent for detecting FFA and/or MAG. Further, the use of the above products is based on the liquid chromatography-mass spectrometry technique.
Further, the reagent for detecting FFA and/or MAG is a reagent for detecting the expression level of FFA and/or MAG in plasma; the higher FFA and/or MAG expression in plasma, the higher the risk of IPAH onset.
Further, the FFA includes FFA (14: 0) and/or FFA (20: 5).
By adopting the technical scheme, compared with the prior art, the invention has the following technical effects:
the invention verifies that FFA and/or MAG with high expression in plasma suggest high possibility of occurrence of IPAH, provides basis for predicting the incidence risk of IPAH of a subject, can help patients to screen early and improve diagnosis rate.
Drawings
FIG. 1 is a BPC plot (positive ion mode) of quality control sample QC;
FIG. 2 is a BPC plot (negative ion mode) of quality control sample QC;
FIG. 3 shows the number of lipid species detected for each lipid subclass;
FIG. 4 shows the difference in expression of each lipid subclass between normal and patient; wherein panels a-n show the difference in expression of FFA, MAG, DAG, TAG, LPS, PA, PE, PG, PI, PS, SS, st, LPA and SM, respectively, between normal and patient; * P is less than 0.05; * P < 0.01; * P < 0.001; ns, P is more than or equal to 0.05;
FIG. 5 shows the difference in expression of FFA molecules between normal and patient; * P is less than 0.05; * P < 0.01; * P < 0.001; ns, P is more than or equal to 0.05;
FIG. 6 shows the results of a logistic regression analysis of lipids; OR represents odd ratio, odd ratio; 95% CI represents a 95% confidence interval;
FIG. 7 shows the results of logistic regression analysis of FFA molecules; OR represents odd ratio, odd ratio; 95% CI represents a 95% confidence interval;
FIG. 8 is a line graph of ROC analysis;
FIG. 9 shows the number of patients in a sample grouping based on the level of FFA and MAG expression; wherein Panel a is based on FFA expression levels, panel b is based on MAG expression levels, and Panel c is based on a combination of expression levels of both FFA and MAG; FFA & MAG, FFA and MAG joint group; * P is less than 0.05; * P < 0.01; * P < 0.001; ns, P is more than or equal to 0.05;
FIG. 10 shows the number of patients in a sample grouping of FFA and MAG joint prediction probabilities; FFA & MAG, and the FFA and the MAG jointly predict a probability group; * P is less than 0.05; * P < 0.01; * P < 0.001; ns, P is more than or equal to 0.05;
FIG. 11 is a line graph of ROC analysis of FFA molecules;
FIG. 12 shows the number of patients in a sample cohort based on the elevation of FFA (14: 0) to FFA (20: 5) expression; wherein panel a is based on FFA (14: 0) expression levels, panel b is based on FFA (20: 5) expression levels, and panel c is based on a combination of expression levels of both FFA (14: 0) and FFA (20: 5); & FFA (20: 5), FFA (14: 0) in combination with FFA (20: 5); * P is less than 0.05; * P < 0.01; * P < 0.001; ns, P is more than or equal to 0.05;
FIG. 13 shows the number of patients in a sample grouping of FFA (14: 0) and FFA (20: 5) joint prediction probabilities; FFA (14: 0) & FFA (20: 5), FFA (14: 0) and FFA (20: 5) jointly predicting a probability set; * P is less than 0.05; * P < 0.01; * P < 0.001; ns, P is more than or equal to 0.05.
Detailed Description
The invention provides application of an agent for detecting FFA and/or MAG in preparing a product for predicting the risk of developing IPAH. The present invention will now be described in detail and with reference to specific examples and figures to provide a better understanding of the invention, but the following examples do not limit the scope of the invention.
In the examples, conventional methods were used unless otherwise specified, and reagents used were, for example, conventional commercially available reagents or reagents prepared by conventional methods.
Example 1
In this example, lipid molecules that can be used as biomarkers to assess the risk of IPAH onset were screened, and the specific experimental procedures and results are as follows:
1. sample collection
Patient groups: 69 IPAH patients admitted to the pulmonarily department hospital in shanghai city in 2013 to 2019 in 5 months were selected, wherein 14 were male and 55 were female. Inclusion criteria were: the mean pulmonary artery pressure of the patient was measured by right-heart catheterization to be > 25mmHg, pulmonary capillary wedge pressure ≦ 15mmHg, and PVR > 3WoodUnits, as determined by the European Heart Association/European respiratory Association guidelines (ESC/ERC) 2015. Patients with PAH of definite etiology were excluded: portal hypertension, congenital left-to-right intracardiac shunts, human Immunodeficiency Virus (HIV) infection, and patients who have historically received hormones (thyroid hormones, anabolic steroids, corticosteroids) or drugs that significantly inhibit hormone production.
Control (Control) group: 30 healthy examiners matched with the age and the sex in the patient group are selected from the healthy examination center, wherein 6 healthy examiners are male, and 24 healthy examiners are female. And (3) inclusion standard: 1. no history of other lung diseases and related diseases; 2. family members have no history of relevant pulmonary diseases; 3. is healthy, and has no drug dependence or alcohol dependence. The baseline data for the study population of the above-mentioned patient group and control group are shown in table 1 below.
TABLE 1 study population baseline data
Note: data are presented as mean. + -. Standard deviation and median (interquartile range) (M [ P25, P75)]) (ii) form display; abbreviations: 6MWD,6-minute walking distance,6 minute walking distance; BMI, body mass index; CI, cardiac index; CO, cardiac output; CR, creatinine; DBIL, direct bilirubin; ERA, endothielin receptor antadonist, endothelin receptor antagonists; GLU, glucose; HDL, high-densety lipoprotein, high density lipoprotein; HGB, hemoglobin; LDL, low-density lipoprotein; mPAP, mean pulmonary artery pressure; mPAWP, mean pulmonary artery wedge pressure; mRAP, mean right atrial pressure; NT-proBNP, N-terminal pro-brain natruritic peptide precursor; PDE-5, phosphodiesterase 5, type 5 phosphodiesterase; PVR, pulmonary vascular resistance; RBCs, red blood cells, erythrocytes; saO 2 Mixed arterial oxygen saturation; svO 2 Mixed venous oxygen saturation; TBIL, total bilirubin; TC, total cholesterol; TG, trigyceride, triglycerides; UA, uric acid; WBC, white blood cell, white blood cells; WHO FC, world Health Organization functional classification, world Health Organization cardiac function classification.
All subjects collected venous blood during the morning after a night of fasting using an ethylenediaminetetraacetic acid anticoagulation tube. After standing for half an hour at room temperature (24 ℃), the blood sample is centrifuged for 5 minutes in a low-temperature (4 ℃) centrifuge at a centrifugal speed of 3500r/min, and the blood sample is divided into 3 layers after centrifugation, wherein the upper layer is clear and transparent (blood plasma), the middle layer is provided with a circle of white rings (white blood cells), and the lower layer is opaque and red (blood cells). The supernatant (blood plasma) was collected and dispensed into 1.5ml centrifuge tubes, frozen at-20 ℃ and stored at-80 ℃ until detected. During the test, samples were randomly arranged for testing and the laboratory technician was unaware of the identity, age and sex of the participants.
2. Sample processing and detection
2.1 sample treatment extraction of lipids from plasma by dichloromethane extraction
(1) The plasma samples to be treated were taken out of the-80 ℃ refrigerator and thawed in an ice box. After the plasma sample was completely thawed, it was vortexed in a vortex shaker for approximately 10 seconds. An internal standard solution is formulated which acts to correct for analyte extraction recovery and mass spectral response. And preparing an internal standard solvent by using isopropanol, acetonitrile and water as a mixed solvent. The solute of the internal standard solution is corticosterone-D8, and the internal standard solute is added to make the final concentration of the internal standard solution be 10 mug/ml.
(2) A sample of 50. Mu.l of plasma was taken, 50. Mu.l of the above internal standard solution and 0.75ml of methanol solution were added thereto, vortexed in a vortex shaker for 2 minutes to separate lipids bound to proteins while denaturing and precipitating the proteins, then 2.5ml of methylene chloride was added thereto to extract the lipids by vortexing again for 10 minutes, then 0.625ml of deionized water was added thereto to perform vortexing again for 5 minutes, and the mixture was centrifuged at 8000 g/minute in a high-speed centrifuge at 4 ℃ for 5 minutes to separate the organic phase and the aqueous phase, the lower layer was an organic phase containing lipids, and the upper layer was an aqueous phase.
(3) Transferring the lower organic phase into another glass tube, continuously adding 2ml dichloromethane into the upper aqueous phase for secondary extraction in order to prevent lipid in the sample from remaining in the aqueous phase, combining the organic phase solutions obtained by the two extractions, and volatilizing and concentrating in a vacuum centrifugal concentrator.
(4) And re-dissolving the volatilized and dried sample by using an acetonitrile solution with the volume fraction of 200vl 50% as a solvent, transferring the solution into a sample injection tubule, and waiting for liquid chromatography-mass spectrometry.
2.2 chromatography-Mass Spectrometry
The used instrument platform for liquid chromatography-mass spectrometry is EXION LC high performance liquid chromatography-tandem triple quadrupole mass spectrometry HPLC-tripleQuad of AB SCIEX company TM 6500 the system, the chromatographic mass spectrometry acquisition conditions adopted for detection are as follows:
(1) Setting chromatographic conditions:
positive and negative ion detection mode, wherein the chromatographic column is BEH amide HILIC chromatographic column (100 mm × 2.1mm i.d.,1.7 μm; waters);
mobile phase A is H 2 O/ACN (5: 95, v/v,10mM ammonium acetate), mobile phase B is H 2 O/ACN (50: 50, v/v,10mM ammonium acetate), the pH of both mobile phases A and B was adjusted to 8.2, and the elution procedure is as follows in Table 2 below.
The flow rate was 0.50mL/min, the amount of sample was 5. Mu.L, and the column temperature was 40 ℃.
Table 2 mobile phase elution procedure
(2) Setting mass spectrum conditions:
respectively adopting positive ions (ESI) for sample mass spectrum signal acquisition + ) And negative ion (ESI-) mode; the data acquisition mode adopts MRM scanning. The main parameters are as follows: the voltage of the electrospray capillary tube is 5500V (ESI) + )，-4500V(ESI - ) The ion source temperature is: the de-clustering voltage was 80V at 550 ℃, the atomization airflow was 55psi, the auxiliary heating airflow was 55psi, and the air curtain airflow was 35psi.
3. Data processing and statistical analysis
(1) To evaluate the stability of the assay system during the set-up procedure, a Quality Control sample (QC) was prepared during the experiment. The QC sample is formed by mixing all detection samples in equal volumes, one QC sample is inserted into every 20 analysis samples in the instrument analysis process, and the instrument stability in the whole analysis process can be inspected through the repeatability of the QC samples in the data analysis process, so that the reliability of results is ensured.
Analysis of sample Base Peak Chromatograms (BPC):
BPC profiles of quality control samples QC are shown in FIG. 1 and FIG. 2. The BPC spectrograms of the QC samples are superposed, so that the chromatographic peak intensity and the retention time of the QC samples are basically consistent, and the system stability and the experimental repeatability are very good.
(2) The basic data analysis includes data preprocessing and statistical analysis. In summary, raw data collected by mass spectrometry was subjected to MultiQuan (Sciex) TM ) And (4) preprocessing such as peak extraction, integration and the like is performed by software. And extracting lipid substances with the signal-to-noise ratio of more than 3 based on a self-built lipid standard substance spectrogram library to generate an identification list, and performing peak area normalization processing based on an internal standard substance. The resulting data matrix was analyzed by multivariate statistics including PCA and PLS-DA using SIMCA-P14.0. Finally, 588 lipid substances were detected in total, and classified according to classificationSubclass 14, which are respectively Free Fatty Acids (FFA), monoglycerides (monoacylglycerol, MAG), diglycerides (DAG), triglycerides (TAG), lysophosphatidic acids (lpa), lysophosphatidic serine (lps), phosphatidic Acid (PA), cephalin (PE), glycerophosphate (PG), phosphatidylinositol (PI), phosphatidylserine (PS), sphingomyelin, and sterols (sterol, st), as shown in fig. 3.
In terms of expression intensity, by comparing the expression of the 14 subclasses in IPAH patients with those in the control group, it was found that lipid expression of FFA, MAG, DAG, TAG, PA, PE, SS and St classes in IPAH patients all showed a tendency significantly higher than that in normal persons. The expression of LPS, PG, PI, PS also tended to increase in patients, whereas no significant statistical differences were seen for LPA and SM (fig. 4).
Obtaining variable weight values of various lipid molecules after OPLS-DA analysis, and screening out 24 important lipids in 588 lipid molecules by adopting the standard that the variable weight value is more than 1, wherein the lipids belong to FFA. Indicating that FFA expression is the strongest and most significant in human plasma compared to other classes of lipids. These FFA molecules are named according to the form FFA (A: B), where A represents the number of carbon atoms contained in the lipid molecule (i.e., the carbon chain length) and B represents the number of double bonds present in the molecule (i.e., the degree of unsaturation of the molecule).
As can be seen from FIG. 5, the expression levels of these FFA molecules, such as 18 molecules FFA (14: 0), FFA (14: 1), FFA (16: 1) and the like, in the plasma of patients are significantly higher than those of normal people, FFA (20: 5), FFA (22: 2) and FFA (30: 2) are also higher than those of normal people, and only FFA (16: 0), FFA (24: 0) and FFA (30: 4) have no significant statistical difference between patients and normal people.
(3) Single and multifactor logistic regression analysis
In the logistic regression analysis process, the lipid expression data of normal people and IPAH patients are included by taking the incidence of IPAH as a dependent variable, firstly, single-factor logistic regression analysis is carried out on different lipid subclasses, the influence of the lipid subclasses on the incidence risk of IPAH alone is evaluated, and then all indexes with statistical significance in the single-factor logistic regression analysis are included in multi-factor logistic regression analysis to select the index with the most independent prediction value.
As shown in FIG. 6, the results of one-way regression analysis showed that FFA, MAG, DAG, PE, sS predicted the onset of IPAH, in addition to LPS, PA, PG, PI, PS, and ST, had predictive value for the disease onset of IPAH, and that higher levels of these lipid subclasses suggested higher risk of the onset of IPAH, with MAG being the largest OR value (OR: 3.711, 95% CI. However, the metabolic mechanisms of the human body are complex and variable, and there may be some connection between various lipids. Therefore, we further performed multifactorial logistic regression, including age, gender and BMI corrected, and the final results showed that FFA (OR: 1.239, 95% CI.
The FFA molecules were subjected to one-way and multi-way logistic regression analysis in the same manner as shown in figure 7. Single-factor logistic regression results showed that higher levels of 21 FFA molecules, FFA (14: 0), FFA (14: 1), FFA (16: 1), etc., suggested a higher risk for IPAH development (P < 0.05). FFA (16: 0), FFA (24: 0), FFA (30: 4) had no significant predictive effect. In addition, CI and SvO 2 As in most studies, the risk of IPAH onset increases when these indices decrease. The final results show that FFA (14: 0) and FFA (20: 5) are indicators that independently predict the risk of IPAH development, suggesting an increased risk of IPAH development when FFA (14: 0) is elevated, or FFA (20: 5) is reduced.
(4) Lipid ROC analysis
To evaluate the predictive effect of FFA and MAG on IPAH events and facilitate subsequent statistical analysis, we performed Receiver Operator Characteristics (ROC) analysis on them and evaluated their predictive effect by area under the curve (AUC), the criteria for area under the ROC curve are shown in table 3. As shown in FIG. 8, AUC for FFA was 78.91% and AUC for MAG was 86.23%. ROC analysis is carried out according to the combined prediction probability of the FFA and the MAG, and the AUC is up to 90.53 percent, which shows that the combined prediction effect of the FFA and the MAG is better. Then, according to the highest john index, the cutoff values with the highest sensitivity and specificity of FFA, MAG and FFA & MAG are respectively selected to define the high and low levels of FFA, MAG and FFA & MAG.
TABLE 3 area under ROC Curve judgment standards
To further validate the actual effect of the two lipids on predicting the onset of IPAH, the lipid expression data of 69 IPAH patients and 30 normal persons were grouped according to FFA, MAG and FFA & MAG levels, defining high levels when FFA and MAG were above the respective cutoff values and low levels when FFA and MAG were below the respective cutoff values, and counting the number of normal and patients in each group, calculating the proportion of patients between each group. Results as shown in figure 9, first, the chi-square test results were very significant in each group (P < 0.001), and 85.94% of the high FFA population were IPAH patients in terms of lipid class alone, which accounted for 79.71% of the total number of patients (figure 9 a); in the high level MAG population, the probability of IPAH development is 93.33%. At the same time, 81.16% of all IPAH patients had higher levels of MAG, with slightly higher predicted efficacy and diagnostic levels than FFA (fig. 9 b). Furthermore, if both lipid binding groups were judged to be IPAH patients, the diagnosis rate reached 100% for both FFA and MAG high expression groups, and was the lowest, only 10.53% for both FFA and MAG low expression groups (fig. 9 c). After that, 99 samples were grouped again according to the prediction probability obtained by logistic regression by combining FFA and MAG expression data, and the results are shown in FIG. 10, the incidence rate of IPAH in the low-level group is reduced to 24.24%, the incidence rate in the high-level group is 92.42%, and 88.40% of patients are included, which shows that the results are more sensitive and accurate when FFA and MAG are combined to predict the incidence risk of IPAH.
We also performed ROC analysis on FFA (14: 0) and FFA (20: 5) finally obtained in multifactorial logistic regression on FFA molecules to evaluate their predictive effects. The result is shown in fig. 11, the prediction effect of single FFA (14: 0) is extremely excellent, and AUC reaches 92.87%, which shows that the FFA changes extremely remarkably in the pathogenesis process of IPAH patients, and the prediction accuracy can reach more than 90%, which suggests that the FFA may play an important role in the pathogenesis process of IPAH. FFA alone (20: 5) predicted not so well, with an AUC of only 70.53%. However, when the prediction probabilities of the FFA (14: 0) and the FFA (20: 5) are jointly analyzed, the FFA (20: 5) is used as an auxiliary factor to slightly improve the prediction effect of the FFA (14: 0), and the AUC reaches 93.86%.
FFA (14: 0) and FFA (20: 5) were classified into high and low levels based on the cutoff value with both sensitivity and specificity screened in ROC, and then into high and low expression groups in combination with the incidence of IPAH, with the results shown in FIG. 12. First, the chi-square test results were still very significant (P < 0.001), with a high percentage of IPAH patients accounting for up to 95.16% of the total number of patients in the high expression group of FFA (14: 0) in the single class of FFA molecule expression (fig. 12 a), and a low percentage of IPAH patients accounting for only 27.02% in the low expression group of FFA (14: 0). The expression level of FFA (14: 0) is used for predicting the IPAH disease or not, and the prediction effect is better than that of FFA and MAG alone. When prediction is carried out according to the expression level of FFA (20: 5), 88.47% of people in the high expression group are in an IPAH morbidity state, and the number of patients accounts for 55.07% of the total number of patients; in the underexpression group, 55.36% of the total number of patients in the underexpression group was found to be almost equal to that of normal persons, and thus the risk of development of IPAH was not well predicted when FFA (20: 5) was in an underexpression state (FIG. 12 b). Grouping of FFA alone (14: 0) and FFA alone (20: 5) at both high and low levels in 99 samples as shown in FIG. 12c, the incidence of IPAH was the lowest at only 20.00% when FFA (14: 0) was low and FFA (20: 5) was high, and the highest at 97.37% when both were high. Meanwhile, the incidence of IPAH in the two groups when FFA (14: 0) is highly expressed is more than 90%, which indicates that FFA (14: 0) has important significance for predicting whether IPAH is diseased or not.
Grouping based on the prediction probability of both FFA (14: 0) and FFA (20: 5) as shown in FIG. 13, although FFA (20: 5) alone is not ideal, it is a very good prediction model when combined with FFA (14: 0) as an auxiliary factor to make it more and more attractive, with high-level groups having an incidence as high as 98.36% and low-level groups having an incidence that is 23.68%.
In summary, in the context of lipid subclasses, FFA and MAG can be used as excellent indicators for predicting the risk of IPAH. At the lipid molecular level, the effect of FFA (14: 0) in predicting the risk of IPAH onset is also very significant. High expression of FFA and MAG in plasma suggests a high probability of IPAH occurrence, which may provide strong evidence that higher levels of FFA and MAG play an important role in contributing to the pathogenesis of IPAH.
The embodiments of the present invention have been described in detail, but the embodiments are merely examples, and the present invention is not limited to the embodiments described above. It will be appreciated by those skilled in the art that any equivalent modifications and substitutions are within the scope of the present invention. Accordingly, equivalent changes and modifications made without departing from the spirit and scope of the present invention should be covered by the present invention.
Claims (10)
1. Use of an agent for detecting FFA and/or MAG in the manufacture of a product for predicting the risk of developing IPAH, wherein the product comprises an agent for detecting FFA and/or MAG.
2. Use according to claim 1, wherein the higher the expression of FFA and/or MAG, the higher the risk of IPAH onset.
3. The use according to claim 1, wherein the product is a kit.
4. Use according to claim 3, wherein the use of the kit is based on the technique of liquid chromatography-mass spectrometry.
5. Use according to claim 1, wherein the FFA comprises FFA (14.
6. The use of claim 1, wherein the agent for detecting FFA and/or MAG is an agent for detecting the expression level of FFA and/or MAG in plasma.
7. A product for predicting the risk of development of IPAH comprising an agent for detecting FFA and/or MAG.
8. The product according to claim 7, characterized in that its use is based on the technique of liquid chromatography-mass spectrometry.
9. The product of claim 7, wherein the agent that detects FFA and/or MAG is an agent that detects the level of FFA and/or MAG expression in plasma; the higher FFA and/or MAG expression in plasma, the higher the risk of IPAH onset.
10. The product according to claim 7, characterized in that the FFA comprises FFA (14.
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| US20190113530A1 (en) * | 2016-03-09 | 2019-04-18 | Cbmed Gmbh Center For Biomarker Research In Medicine | Biomarker for the diagnosis of pulmonary hypertension (ph) |
| CN113533725A (en) * | 2021-06-23 | 2021-10-22 | 上海市肺科医院 | Marker for risk of onset and prognosis of pulmonary hypertension and application of marker |
| CN113884586A (en) * | 2021-06-17 | 2022-01-04 | 上海市肺科医院 | Prognostic marker for idiopathic pulmonary hypertension and application of prognostic marker |
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| US20190113530A1 (en) * | 2016-03-09 | 2019-04-18 | Cbmed Gmbh Center For Biomarker Research In Medicine | Biomarker for the diagnosis of pulmonary hypertension (ph) |
| CN113884586A (en) * | 2021-06-17 | 2022-01-04 | 上海市肺科医院 | Prognostic marker for idiopathic pulmonary hypertension and application of prognostic marker |
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