CN105758967B - The mark group of coronary atherosclerosis and stable angina cordis is distinguished in diagnosis - Google Patents
The mark group of coronary atherosclerosis and stable angina cordis is distinguished in diagnosis Download PDFInfo
- Publication number
- CN105758967B CN105758967B CN201610174022.9A CN201610174022A CN105758967B CN 105758967 B CN105758967 B CN 105758967B CN 201610174022 A CN201610174022 A CN 201610174022A CN 105758967 B CN105758967 B CN 105758967B
- Authority
- CN
- China
- Prior art keywords
- diagnosis
- stable angina
- coronary atherosclerosis
- coronary
- patients
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- 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
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/32—Cardiovascular disorders
- G01N2800/323—Arteriosclerosis, Stenosis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/32—Cardiovascular disorders
- G01N2800/324—Coronary artery diseases, e.g. angina pectoris, myocardial infarction
Abstract
One or more of the invention discloses the mark group that coronary atherosclerosis and stable angina cordis are distinguished in diagnosis, including glutathione, β hydroxybutyric acids, proline, fumaric acid, phenylalanine, lactic acid.It is single be used to diagnose distinguish patients with stable angina pectoris and during coronary atherosclerosis patients, area (AUC) is all higher than 0.7 under ROC curve, with clinical diagnosis meaning；Combine for when diagnosing, with the increase of joint number, AUC is further improved, highest during 6 whole joints, and AUC is up to 0.988, and under optimal cutoff values, sensitivity and specificity are respectively 98.5% and 98.3%.The metabolic markers group energy that the present invention is provided diagnoses differentiation coronary atherosclerosis and stable angina cordis exactly, and sensitivity is high, high specificity.
Description
Technical field
The invention belongs to biochemical field, it is related to the metabolic markers of diagnosis of coronary heart disease parting, and in particular to one group of use
The metabolic markers group of coronary atherosclerosis and stable angina cordis is distinguished in diagnosis.
Background technology
Coronary heart disease is also known as ischemic heart disease, and atherosis occurs for the artery for being related to supply myocardial blood, i.e., coronal dynamic
Pulse atherosclerosis lesion causes lumen of vessels narrow or patch formation even ruptures, completely plugged, causes myocardial ischemia, anoxic or bad
Extremely cause heart ischemia disease, so as to cause a series of clinically serious cardiovascular events such as angina pectoris, myocardial infarction.
Coronary heart disease is the primary killers of human health, the tool incidence of disease height, disability rate height, high recurrence rate, case fatality rate height, the spy such as more than complication
Point, has become the principal disease for threatening our people's health.
At present, based on pathophysiological mechanism, by coronary heart disease be divided into chronic stable coronary heart disease (i.e. stable angina cordis) and
Acute coronary syndrome；Acute coronary syndrome is further divided into unstable angina pectoris and acute myocardial infarction AMI.Coronary heart disease
From without to having, from gently to generally including following developing stage again：Coronary artery is normal → coronary atherosclerosis → stable type
Angina pectoris → unstable angina pectoris → acute myocardial infarction AMI.
Coronary atherosclerosis is the Etiological of coronary heart disease, is the early stage illness of coronary heart disease.Coronary artery is athero- hard
Change is a kind of common progressive arterial disease, and lesion mainly involves medium sized muscle layer artery, endarterium lipidosis,
Smooth muscle cell proliferation, forms limitation patch, arterial wall can be made to be hardened, plaque rupture causes thrombus, embolism, gone out when serious
Blood, involvement or is entirely shut at luminal part, and clinical manifestation is the generation of atherosclerotic blood vessel complication.Atherosclerosis
Early lesion can occur before 10 years old, and lesion causes arteriarctia to undergo for 20 to 30 years, in early days without clinical symptoms, no
Easily it is found and payes attention to, therefore early prevention to coronary atherosclerosis and diagnosis can effectively prevent the hair of coronary heart disease
It is raw.
Coronarography can make accurate judgement to stenosis coronarius, be the gold mark of diagnosis of coronary heart disease
Accurate [coronarography goldstandard and clinical routine diagnostics coronary heart disease otherness comparative studies, Shu Rongwen etc., naval medicine magazine
04 phase in 2015].As the goldstandard of diagnosis of coronary heart disease, coronary angiography can only find hemadostewnosis degree, and it or one
Intervention measurement means are planted, it is necessary to intervene operation, and diagnosis is expensive.On the other hand, doctor also need to according to the electrocardiogram of patient,
The inspection results such as cardiogram, Treadmill Exercise Test, CT make last diagnostic, because doctor's subjectivity judges, patient describes unclear
Situations such as appearance, larger mistaken diagnosis is still suffered to the diagnosis of coronary heart disease and is failed to pinpoint a disease in diagnosis, this influence prognosis to patient is very big.For
Improve the quality of life of patient, the life threat that reduction patient is subject to, we need badly, and development is a kind of to have that diagnosis is high, warp
Ji, the diagnostic method without the characteristic such as invasive, easy to operate.
Metabolism group is the science studied the entirety of organism endogenous metabolism material and its changed with internal cause and external cause, is
One important component of systems biology.It can be carried out quickly and without invasive point to body fluids such as blood and urine
Analysis, the metabolic markers of various biochemical reactions can be indicated by being obtained by the difference of metabolism spectrum.The analytical technology bag commonly used at present
Include nuclear magnetic resonance (NMR), mass spectrum (LC-MS/GC-MS) etc..LC-MS/GC-MS have to sample preparation require low, sensitivity it is high,
The features such as wide dynamic range, the metabolin differed greatly available for concentration in detection sample, thus in the research as metabolism group
Using increasing technology platform.Plasma analysis is a kind of clinically conventional methods for the diagnosis of diseases, because it is easy, it is quick,
The economic and advantage of relative noninvasive and be widely adopted.
Not yet someone carries out diagnosis typing using blood plasma metabolite level to coronary heart disease at present.Sought using blood plasma metabolism group
Look for the level error of coronary artery normal person and coronary atherosclerosis patients and different parting Patients Plasma with Coronary Heart Disease metabolins
It is different quickly to make a definite diagnosis coronary heart disease for clinical early stage and to carry out parting significant.
The content of the invention
In order to overcome the deficiencies in the prior art, an object of the present disclosure is that providing one group is used to diagnose differentiation coronary artery
The metabolic markers group of atherosis and stable angina cordis, this group of metabolic markers are present in blood plasma simultaneously, can the same time-division
Analysis is determined；The second object of the present invention is to provide a kind of method that can delicately analyze and detect the metabolic markers group；
The third object of the present invention is to provide a kind of detection kit based on metabolic markers group, coronal for diagnosing differentiation
Atherosclerosis and stable angina cordis, improve diagnosis convenience, promote diagnostic method standardization.
Above-mentioned purpose is achieved by following technical solution：
One group is used to diagnose the metabolic markers group for distinguishing coronary atherosclerosis and stable angina cordis, including one
Or multiple metabolic markers as described below：Glutathione, beta-hydroxy-butanoic acid, proline, fumaric acid, phenylalanine, lactic acid.
Further, the described metabolic markers for being used to diagnose differentiation coronary atherosclerosis and stable angina cordis
Group includes the metabolic markers described in any two.
Further, the described metabolic markers for being used to diagnose differentiation coronary atherosclerosis and stable angina cordis
Group includes the metabolic markers described in any three.
Further, the described metabolic markers for being used to diagnose differentiation coronary atherosclerosis and stable angina cordis
Group includes the metabolic markers described in any four.
Further, the described metabolic markers for being used to diagnose differentiation coronary atherosclerosis and stable angina cordis
Group includes the metabolic markers described in any five.
Further, the described metabolic markers for being used to diagnose differentiation coronary atherosclerosis and stable angina cordis
Group includes metabolic markers all described in six.
Further, the metabolic markers are blood plasma metabolic markers.
Being used for described in a kind of qualitative or quantitative analysis, which diagnoses, distinguishes coronary atherosclerosis and stable angina cordis
Metabolic markers group method be：Described metabolic markers are carried out using LC-MS and/or gas chromatography mass spectrometry qualitative or fixed
Amount analysis.The gentle quality detection of liquid matter limits that low, sensitivity is high, can delicately analyze metabolic markers in detection biological specimen and right
It is quantified.
It is a kind of to be used to diagnose the detection kit for distinguishing coronary atherosclerosis and stable angina cordis including described
The standard items of metabolic markers group, the standard items are the chemical monomer or mixture of each metabolic markers.Can using standard items
To carry out rapidly and accurately qualitative and quantitative analysis to the metabolic markers in biological specimen.Kit helps to realize detection mark
Standardization, improves detection convenience and reappearance.
Further, the detection kit also includes dissolving generation described in the solvent and/or Extraction and enrichment of the standard items
Thank to the solvent of mark.
Advantages of the present invention：
(1) the metabolic markers group energy that the present invention is provided diagnoses differentiation coronary atherosclerosis and the stable type heart exactly
Angina.In ROC curve evaluation method, area AUC is in the case of more than 0.5 under ROC curve, closer to 1, illustrates diagnosis effect
Fruit is better.AUC has relatively low accuracy at 0.5~0.7, and AUC has certain accuracy at 0.7~0.9, when AUC is more than 0.9
There is high accuracy.It is single athero- for diagnosing differentiation coronary artery in empirical tests, the metabolic markers group that the present invention is provided
When hardening and stable angina cordis, AUC is more than 0.7；During multiple use in conjunction, AUC is than single closer to 1, diagnosis effect
Fruit is more preferably；During six use in conjunction, AUC is closest to 1, and it is best that effect is distinguished in diagnosis.
(2) the method sensitivity for the analysis detection metabolic markers that the present invention is provided is high, as a result accurately and reliably.
(3) detection kit that the present invention is provided can be used for diagnosis differentiation coronary atherosclerosis and the stable type heart is twisted
Bitterly, diagnosis convenience is improved, promotes diagnostic method standardization.
Embodiment
Essentiality content of the present invention is further illustrated with reference to embodiment.The instrument or reagent used does not elaborate
Be conventional instrument and reagent；The experimental working technique not specifically described is routine known to a person of ordinary skill in the art
Operating method.
Embodiment 1：The sieve of blood plasma difference metabolin between coronary atherosclerosis patients and patients with stable angina pectoris
Choosing is characterized
First, object and method
1st, Specimen origin
After patient's agreement is obtained, Jiangsu Prov. People's Hospital in September, 2010~2015 year 480 coronary arteries in June are collected
The peripheric venous blood blood plasma of atherosis patient, 280 patients with stable angina pectoris and 350 Healthy Peoples, all patients or strong
Kang Renjun is confirmed through coronary angiography.Age, sex and the coronary atherosclerosis patients of Healthy People, patients with stable angina pectoris
Match.All coronary atherosclerosis patients, patients with stable angina pectoris and health have normal cardiopulmonary liver kidney and made per capita
Blood function.
Blood sampling time is early morning fasted conditions.
2nd, main agents
Acetonitrile and formic acid (UPLC is pure) are purchased from ROE companies of the U.S.；Chromatogram rank methanol and chloroform are purchased from Jiangsu Chinese nation science and technology
Co., Ltd；Chlorination methoxamine and N- methyl-N- (trimethyl silane) trifluoroacetamide (containing 1% trim,ethylchlorosilane) are purchased from U.S.
Sigma-Aldrich companies of state；Deionized water by U.S. Mi Libo (Millipore) company MIlli-Q ultrapure water system systems
It is standby；Standard items include glutathione, beta-hydroxy-butanoic acid, proline, fumaric acid, phenylalanine, lactic acid, are purchased from U.S. Sigma-
Aldrich。
3rd, the screening of blood plasma difference metabolin is characterized
3.1UPLC-Q/TOF-MS screenings are characterized
3.1.1 sample preparation
Extraction solvent optimization is carried out using response phase method：With the peak number and Zong Feng under mass spectrum ESI+ and ESI- detection pattern
Area is that factor investigates Extraction and enrichment efficiency of the different solvents (acetonitrile, methanol, ethanol, chloroform, water) to metabolin in blood plasma.Will
Test data measured and carry out multi-variables analysis, utilize (the variable importance to of importance factor in PLS models
Projection, VIP value) reflect the importance that variable is responded to model.Acetonitrile, methanol, ethanol, chloroform, water VIP values successively
For 1.503,0.802,0.651,0.688 and 0.987, the extraction efficiency highest of acetonitrile, therefore selection acetonitrile is used as plasma sample
Extraction solvent.
Sample treatment：100 μ L blood plasma are taken in 1.5mL centrifuge tubes, 400 μ L acetonitriles are added, mixed after being vortexed 30 seconds,
13000rpm × 10min centrifuges (4 DEG C), takes 200 μ L of supernatant in 1.5mL centrifuge tubes, is dried up at room temperature with nitrogen evaporator, gained
Residue 300 μ L 20% acetonitrile solution dissolves, and produces.
3.1.2 experimental condition and parameter
UPLC-Q/TOF-MS conditions：
Chromatographic isolation uses ultra performance liquid chromatography (UPLC, Agilent 1290, USA).Chromatographic column is Waters BEH
C18 posts (100mm × 2.1mm, 1.7 μm), 25 DEG C of column temperature, sample introduction room temperature is room temperature, the μ L of sample size 2.Positive and negative ion pattern stream
Dynamic phase composition is that A is the aqueous formic acid of volumetric concentration 0.1%, and B is the formic acid acetonitrile solution of volumetric concentration 0.1%.Gradient elution
Condition：0~1min is 0~30%B phases, and B is phase linear in 2min increases to 60%, 3~8min linear changes to 90%B phases, so
100%B phases are linearly increasing in 8~9min and keep 1min afterwards；Efflux is direct without shunting after flow velocity 0.3mL/min, post
Import mass spectrometer system detection.
Mass spectral analysis uses level Four bar-flight time mass spectrum (Agilent 6530Q-TOF/MS, USA).With electron spray from
Component (ESI) positive and negative ion mode detection；Dry gas stream speed is 7L/min, and it is 300 DEG C to dry temperature degree, dries gas and taper hole
Gas is high pure nitrogen；Capillary voltage is 3000V under 100 DEG C of ion source temperature, cation and negative ion mode, collision electricity
Press as 100V；Three data acquisitions, quality of scanning scope are carried out using full scan pattern is per second：M/z 100-1000 dalton.
3.2GC-Q/MS screenings are characterized
3.2.1 sample preparation
200 μ L blood plasma are taken in 1.5mL centrifuge tubes, 50 μ L 1mg/mL 2- isopropylmalate acid solution internal standards, whirlpool is added
Rotation is mixed for 20 seconds, the mixed solution (ratio is 2.5: 1: 1) of 400 μ L methanol, chloroform and water is added, then in 70 DEG C of metal bath
Upper shaking 30min (1200rpm), 16000g × 5min centrifugations (4 DEG C), takes 500 μ L of supernatant in 1.5mL centrifuge tubes, adds 500
μ L distilled water, is vortexed and mixes, and then 16000g × 5min centrifuges (4 DEG C), 500 μ L of supernatant is taken in 1.5mL centrifuge tubes, in room temperature
Lower to be dried up with nitrogen evaporator, the residue obtained methoxamine pyridine solution with 80 μ L dissolves, and the oximate 8h under the conditions of 50 DEG C adds 60 μ L
N- methyl-N- trimethyl silicon substrate trifluoroacetamides, derivatization 2h, is produced under the conditions of 70 DEG C.
3.2.2 experimental condition and parameter
GC-Q/MS conditions：U.S.'s Agilent 7890B-5977A gas chromatograph-mass spectrometer (GC-MS)s.HP-5MS maos of chromatographic column
Capillary column (30.0m × 0.25mm, 0.25 μm of capillary thickness)；Carrier gas is high-purity helium, flow velocity 1.0mL/min；The μ of sample size 2
L；Temperature programming：80 DEG C of constant temperature 2min, 80 DEG C -300 DEG C (5 DEG C/min) constant temperature 6min；Do not shunt, 300 DEG C of injector temperature；Interface
300 DEG C of temperature；200 DEG C of ion source temperature；Electron energy 50eV；Solvent delay 3min；Using full scan pattern, quality of scanning model
Enclose：M/z 30-600 dalton.
4th, data processing and analysis
The data that UPLC-Q/TOF-MS and GC-Q/MS are obtained import SIMCA softwares (version 13.0.2,
Umetrics multi-variate statistical analysis) is carried out.By setting up OPLS-DA (orthogonal ginsenoside) model, find
Metabolic profile contributes larger (VIP ＞ 1.0 and p ＜ 0.01) between coronary atherosclerosis patients and patients with stable angina pectoris
Metabolin.
Pass through HMDB (http：//www.hmdb.ca/) and Metline (http：//metlin.scripps.edu/) etc.
Database carries out the retrieval of the structure of matter, using at the beginning of the MS/MS collection of illustrative plates obtained by the accurate molecular weight and mass spectrum provided in database
The structure of the above-mentioned difference metabolin of step identification.Eventually through purchase standard items, with the molecular weight of standard items, chromatographic retention and
Corresponding multistage MS fragmentation patterns are compared, and confirm the structure of difference metabolin.
2nd, result
Screening symbolizes 6 difference metabolins, is respectively：Glutathione, beta-hydroxy-butanoic acid, proline, fumaric acid, phenylpropyl alcohol
Propylhomoserin, lactic acid.
Compared with coronary sclerosis patient, table of the above-mentioned 6 difference metabolins in patients with stable angina pectoris blood plasma
Raise or lower up to level.Quantitative by standard items, compared with coronary sclerosis patient, above-mentioned difference metabolin is in stable type
Expression in angina patients is：Fumaric acid lowers 0.7~0.8 times；Glutathione, beta-hydroxy-butanoic acid, proline,
Phenylalanine and lactic acid raise 0.7~0.8 times respectively.As can be seen here, above-mentioned 6 difference metabolins are in patients with stable angina pectoris
It is significantly different with expression in coronary sclerosis patients blood plasma, available for diagnosis differentiation coronary atherosclerosis and stably
Type angina pectoris.
Embodiment 2：Build ROC curve and verify that 6 difference metabolins are used to diagnose differentiation coronary atherosclerosis and steady
Shape anginal ability
Verified using receiver operating curves (ROC) method, it is athero- by patients with stable angina pectoris and coronary artery
The expression of difference metabolin judges that it is used to diagnose differentiation patients with stable angina pectoris and coronal dynamic in sclerosis patients' blood plasma
The ability of pulse atherosclerosis patient.As a result show, glutathione, beta-hydroxy-butanoic acid, proline, fumaric acid, phenylalanine, lactic acid
This 6 difference metabolins are single be used to diagnosing the ability for distinguishing patients with stable angina pectoris and coronary atherosclerosis patients compared with
By force, area (AUC) is all higher than 0.7 under ROC curve, with clinical diagnosis meaning；Combine for when diagnosing, with joint number
Increase, AUC further improves, 6 all joint when highest, AUC is up to 0.988, under optimal cutoff values, sensitivity and specifically
Property is respectively 98.5% and 98.3%.Single and any 2~5 Combining diagnosis the results are shown in Table 1~3.
Coronary atherosclerosis patients and patients with stable angina pectoris are distinguished in the single difference metabolin diagnosis of table 1
| Single difference metabolin | AUC | Sensitivity | Specificity |
| Glutathione | 0.878 | 87.7% | 88.9% |
| Beta-hydroxy-butanoic acid | 0.865 | 84.4% | 85.6% |
| Proline | 0.843 | 82.2% | 83.4% |
| Fumaric acid | 0.806 | 78.5% | 79.7% |
| Phenylalanine | 0.790 | 76.9% | 78.1% |
| Lactic acid | 0.769 | 74.8% | 76.0% |
2 two difference metabolin Combining diagnosis of table distinguish coronary atherosclerosis patients and patients with stable angina pectoris
3 any three~five difference metabolin Combining diagnosis of table distinguish coronary atherosclerosis patients and the stable type heart is twisted
Pain patient
| Joint number | AUC | Sensitivity | Specificity |
| Three | ≥0.918 | >=91.9% | >=91.3% |
| Four | ≥0.930 | >=92.4% | >=93.0% |
| Five | ≥0.934 | >=94.7% | >=94.5% |
It is used to diagnose differentiation coronary atherosclerosis patients and steady as it can be seen from table 1 this 6 difference metabolins are single
The ability of sizing patient with angina pectoris is stronger, and AUC is all higher than 0.7, and sensitivity is higher, specific relatively strong, with clinical diagnosis meaning；
From table 2 it can be seen that this 6 difference metabolins combine two-by-two for diagnose when, AUC than it is single be used for diagnose when it is higher, it is sensitive
Degree is high, specificity is higher, with clinical diagnosis meaning；From table 3 it can be seen that being joined with 3~5 in this 6 difference metabolins
Share when diagnosis, AUC is further improved, sensitivity is high, high specificity, with clinical diagnosis meaning.
Therefore, this 6 difference metabolins, which can be used as to be used to diagnose, distinguishes coronary atherosclerosis and stable type heart strand
The metabolic markers of pain.
Embodiment 3：The preparation of detection kit
The metabolic markers provided based on the present invention are prepared for detection kit, and the kit includes following composition：
The standard items of metabolic markers：Including glutathione, beta-hydroxy-butanoic acid, proline, fumaric acid, phenylalanine, breast
Acid, each standard items are encapsulated respectively；
Blood plasma metabolin Extraction solvent：100% acetonitrile and 20% acetonitrile solution (are used for UPLC-Q/TOF-MS sample systems
It is standby)；Mixed solution, methoxamine pyridine and the N- methyl-N- trimethyls silicon substrate three of methanol, chloroform and water that ratio is 2.5: 1: 1
Fluorakil 100 (is used for GC-Q/MS sample preparations)；During UPLC-Q/TOF-MS screenings are characterized, 20% acetonitrile solution may be used as
Dissolve the solvent of standard items；During GC-Q/MS screenings are characterized, prepared and marked by the method for sample preparation with blood plasma metabolin Extraction solvent
Quasi- product solution；
Internal standard：2- isopropylmolic acids.
Certainly, when designing detection kit, and the standard items of above-mentioned 6 metabolic markers need not be completely included, can be with
It is combined using only wherein several.These standard items can be encapsulated individually, and mixture encapsulation can also be made.
The kit is designed based on the metabolic markers that the present invention is provided, and be can be used for diagnosis and is distinguished coronary artery
Atherosis patient and patients with stable angina pectoris.
In summary, the present invention effectively overcomes deficiency of the prior art, and tool high industrial utilization.
The effect of above-described embodiment indicates that the essentiality content of the present invention, but the protection of the present invention is not limited with this
Scope.It will be understood by those within the art that, technical scheme can be modified or equivalent substitution,
Without departing from the essence and protection domain of technical solution of the present invention.
Claims (2)
1. one group of blood plasma metabolic indicator compositions distinguishes coronary atherosclerosis and stable angina cordis preparing diagnosis
Application in diagnostic reagent, it is characterised in that：The metabolic indicator compositions include beta-hydroxy-butanoic acid, proline, fumaric acid, benzene
Alanine and lactic acid.
2. application according to claim 1, it is characterised in that：The metabolic indicator compositions also include glutathione.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610174022.9A CN105758967B (en) | 2016-03-24 | 2016-03-24 | The mark group of coronary atherosclerosis and stable angina cordis is distinguished in diagnosis |
| PCT/CN2016/077606 WO2017161595A1 (en) | 2016-03-24 | 2016-03-29 | Marker group for making diagnosis to distinguish coronary arterial atherosclerosis from stable angina pectoris |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610174022.9A CN105758967B (en) | 2016-03-24 | 2016-03-24 | The mark group of coronary atherosclerosis and stable angina cordis is distinguished in diagnosis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105758967A CN105758967A (en) | 2016-07-13 |
| CN105758967B true CN105758967B (en) | 2017-10-27 |
Family
ID=56346271
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610174022.9A Active CN105758967B (en) | 2016-03-24 | 2016-03-24 | The mark group of coronary atherosclerosis and stable angina cordis is distinguished in diagnosis |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN105758967B (en) |
| WO (1) | WO2017161595A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107589263B (en) * | 2017-11-02 | 2019-01-25 | 武汉迈特维尔生物科技有限公司 | A kind of small molecule marker indicating lung cancer lymphatic metastasis and the application in terms of diagnosis |
| CN109406790B (en) * | 2018-09-19 | 2022-05-17 | 深圳市新产业生物医学工程股份有限公司 | Application of coenzyme Q10 and/or PCSK9 as marker for detecting atherosclerosis in preparation of reagent or kit |
| CN111458512A (en) * | 2019-01-21 | 2020-07-28 | 中国科学院分子细胞科学卓越创新中心 | Atherosclerosis biomarker and application thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GT199800127A (en) * | 1997-08-29 | 2000-02-01 | THERAPEUTIC COMBINATIONS. |
-
2016
- 2016-03-24 CN CN201610174022.9A patent/CN105758967B/en active Active
- 2016-03-29 WO PCT/CN2016/077606 patent/WO2017161595A1/en active Application Filing
Non-Patent Citations (2)
| Title |
|---|
| 冠心病心绞痛三种血瘀证的血浆代谢组学研究;华何与等;《热带医学杂志》;20100331;第10卷(第03期);第258-262页 * |
| 冠心病心绞痛患者的血清代谢组学分析;胡元会等;《2011年中华中医药学会心病分会学术年会暨北京中医药学会心血管病专业委员会年会论文集》;20111210;第56-63页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105758967A (en) | 2016-07-13 |
| WO2017161595A1 (en) | 2017-09-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105651923B (en) | The metabolic markers of unstable angina pectoris and acute myocardial infarction AMI are distinguished in diagnosis | |
| CN105445408B (en) | The metabolic markers of coronary atherosclerosis and stable angina cordis are distinguished in diagnosis | |
| CN105486799B (en) | Metabolic markers for diagnosing acute coronary syndrome | |
| Zhang et al. | Urinary metabolic profiling identifies a key role for glycocholic acid in human liver cancer by ultra-performance liquid-chromatography coupled with high-definition mass spectrometry | |
| De Paepe et al. | A validated multi-matrix platform for metabolomic fingerprinting of human urine, feces and plasma using ultra-high performance liquid-chromatography coupled to hybrid orbitrap high-resolution mass spectrometry | |
| Qiu et al. | Nontargeted metabolomic analysis and “commercial-homophyletic” comparison-induced biomarkers verification for the systematic chemical differentiation of five different parts of Panax ginseng | |
| Cao et al. | NMR-based metabolomic analysis of human bladder cancer | |
| Zhang et al. | Distinguishing pancreatic cancer from chronic pancreatitis and healthy individuals by 1H nuclear magnetic resonance-based metabonomic profiles | |
| CN105486778B (en) | The metabolic markers of stable angina cordis and acute coronary syndrome are distinguished in diagnosis | |
| CN105486773A (en) | Metabolic marker for diagnosing coronary heart disease | |
| CN107002113A (en) | The biomarker of fatty liver and its application method | |
| Legido‐Quigley et al. | Liquid chromatography–mass spectrometry methods for urinary biomarker detection in metabonomic studies with application to nutritional studies | |
| CN105758966B (en) | One group of metabolic markers group for being used for diagnosis of coronary heart disease | |
| Wang et al. | Metabolic profiling of urine in young obese men using ultra performance liquid chromatography and Q-TOF mass spectrometry (UPLC/Q-TOF MS) | |
| CN105758967B (en) | The mark group of coronary atherosclerosis and stable angina cordis is distinguished in diagnosis | |
| CN108693268A (en) | A kind of combination of metabolic marker object and its kit for predicting coronary heart disease prognosis | |
| Yu et al. | Discovery and validation of potential serum biomarkers for pediatric patients with congenital heart diseases by metabolomics | |
| CN105628809B (en) | The metabolic markers of coronary atherosclerosis and coronary heart disease are distinguished for diagnosing | |
| CN105424841B (en) | Metabolic markers for diagnosing coronary atherosclerosis | |
| CN106556656A (en) | A kind of blood plasma metabolism small molecule mark related to cholelithiasis and its application | |
| Goncharov et al. | Metabolomics: on the way to an integration of biochemistry, analytical chemistry, and informatics | |
| Misheva et al. | Recent advances and future directions in microbiome metabolomics | |
| CN105784873B (en) | High lithemia injury of kidney early diagnosis marker and its application based on metabolism group | |
| CN113325117B (en) | Application of a group of biomarkers in preparation of kit for predicting progression of intravenous smooth sarcomatosis | |
| LU et al. | Metabolomics approach to the biochemical differentiation of Traditional Chinese Medicine syndrome types of hypertension |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |