CN113564243B - Diagnostic marker for cerebral ischemic stroke - Google Patents

Diagnostic marker for cerebral ischemic stroke Download PDF

Info

Publication number
CN113564243B
CN113564243B CN202110872060.2A CN202110872060A CN113564243B CN 113564243 B CN113564243 B CN 113564243B CN 202110872060 A CN202110872060 A CN 202110872060A CN 113564243 B CN113564243 B CN 113564243B
Authority
CN
China
Prior art keywords
marker
pdcd1
cacna1e
usp14
ischemic stroke
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
Application number
CN202110872060.2A
Other languages
Chinese (zh)
Other versions
CN113564243A (en
Inventor
蔡学礼
谢慧蓉
舒小桓
孙景萍
黄慧芬
李威
兰卫明
吴骏
吴新校
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Lishui Central Hospital
Original Assignee
Lishui Central Hospital
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Lishui Central Hospital filed Critical Lishui Central Hospital
Priority to CN202110872060.2A priority Critical patent/CN113564243B/en
Publication of CN113564243A publication Critical patent/CN113564243A/en
Application granted granted Critical
Publication of CN113564243B publication Critical patent/CN113564243B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
    • G16H50/20—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
    • G01N2333/70521—CD28, CD152
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/914—Hydrolases (3)
    • G01N2333/948—Hydrolases (3) acting on peptide bonds (3.4)
    • G01N2333/95—Proteinases, i.e. endopeptidases (3.4.21-3.4.99)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/28—Neurological disorders
    • G01N2800/2871—Cerebrovascular disorders, e.g. stroke, cerebral infarct, cerebral haemorrhage, transient ischemic event

Abstract

The invention relates to the fields of biotechnology and biomedicine, in particular to a diagnostic marker for cerebral arterial thrombosis or a combination thereof, and also provides a kit and a system for detecting central nervous system diseases and application thereof. Preferably, the markers include CACNA1E, PDCD1, USP14; the central nervous system disease is stroke, more preferably, the central nervous system disease is ischemic stroke.

Description

Diagnostic marker for cerebral ischemic stroke
Technical Field
The invention relates to the fields of biotechnology and biomedicine, in particular to a diagnostic marker for ischemic stroke or a combination thereof.
Background
The cerebral apoplexy is a main clinical type of cerebrovascular disease, is a paroxysmal cerebral tissue blood circulation disorder disease, and is a group of diseases which are caused by arteriovenous stenosis, occlusion or rupture caused by various inducing factors to cause acute cerebral tissue blood circulation disorder and are clinically manifested as transient or permanent neurological impairment symptoms and physical signs. Stroke is one of three fatal diseases worldwide, and the high morbidity, high disability rate and high fatality rate of stroke cause heavy burden and pain to patients, families and society. The ischemic stroke is relatively common in clinic and is represented as clinical pathological processes of local cerebral tissue hypoxia, ischemia and neural necrosis, and the incidence rate of the ischemic stroke accounts for 60-80 percent of that of the cerebral stroke.
The clinical common diagnosis classification terms of ischemic stroke are more than one, and include cerebral infarction (or called cerebral infarction), cerebral thrombosis, cerebral embolism and the like. Patients with cerebral hemorrhage often show symptoms such as severe headache, frequent vomiting, hemiplegia, even coma and the like, and serious patients even die quickly. The most common cause of subarachnoid hemorrhage is rupture of intracranial aneurysm or rupture of cerebral vessel malformation, which is generally acute in onset and severe in headache, and is common to young and middle-aged people. The symptoms of ischemic stroke are mild, and most patients have clear consciousness and are manifested as hemiplegia or weakness, difficult speaking, numbness of limbs and the like.
Although the diagnosis of stroke is mostly clinical diagnosis, neuroimaging examination and bedside rapid blood glucose examination are still necessary. Within the first hours of the infarct, evidence on CT is minimal, even if the anterior circulation is extensive, including disappearance of striae or islet cortex banding, disappearance of gray-white borders, and high density images of the middle cerebral artery. In 6 to 12 hours of cerebral ischemia, medium to large infarcts begin to appear as CT-visible low density foci; small infarcts (e.g., lacunar infarcts) may only be found on MRI. Therefore, when ischemic stroke is suspected, diffusion weighted MRI (sensitive to early ischemic foci) can be examined immediately after the initial CT examination.
Stroke is a common acute cerebrovascular disease in the middle-aged and elderly people, and has a tendency to become younger. According to statistics, china died of nearly 300 million people with cerebrovascular diseases every year, which is 4 to 5 times higher than that of Europe and America, 3.5 times higher than that of Japan, and even higher than that of developing countries such as Thailand, india and the like; the incidence rate rises at a rate of 8.7% per year, the recurrence rate exceeds 30%, and the recurrence rate reaches 54% within 5 years; 75% of the survivors from stroke patients lose labor capacity to different degrees, and 40% are heavily disabled.
Disclosure of Invention
The inventor of the invention screens, verifies and provides a marker and a marker combination which can efficiently and accurately diagnose the central nervous system diseases by sequencing and analyzing collected patient samples and analyzing data of a data set. Also provides a kit and a system for detecting central nervous system diseases and application thereof.
In one aspect, the invention provides a marker combination for diagnosing central nervous system diseases, wherein the marker combination comprises any two or three of CACNA1E, PDCD1 and USP14.
Preferably, the central nervous system disease comprises stroke, epilepsy, alzheimer's disease, parkinson's disease, huntington's disease, amyotrophic lateral sclerosis, demyelinating disease, multiple sclerosis, schizophrenia, depression and central nerve injury.
Preferably, the stroke comprises ischemic stroke and hemorrhagic stroke.
Preferably, the central nervous system disease is ischemic stroke.
Preferably, the subject is a mammal. Such as bovine, equine, ovine, porcine, canine, feline, rodent, primate.
Preferably, the subject is a human.
Preferably, the CACNA1E is highly expressed in the patient.
Preferably, said PDCD1 is low expressed in the patient.
Preferably, said USP14 is low expressed in patients.
In another aspect, the invention provides a kit for detecting the expression level of at least any one of the aforementioned marker combinations.
Preferably, the at least any one includes two or three.
Preferably, the at least any one marker comprises the following markers or marker combinations CACNA1E, PDCD1, USP14, CACNA1E + PDCD1, PDCD1+ USP14, CACNA1E + PDCD1+ USP14; wherein "+" represents a combination, and "_" represents the same meaning in other portions of the text.
Preferably, the expression amount includes an mRNA expression amount and/or a protein expression amount.
Preferably, the kit comprises a reagent for detecting the mRNA expression amount.
Preferably, the kit comprises a reagent for detecting the expression amount of the protein.
Preferably, the reagent for detecting the expression amount of mRNA comprises a reagent used in the following method: PCR-based quantitative detection method, southern hybridization, northern hybridization, dot hybridization, fluorescence In Situ Hybridization (FISH), DNA microarray, ASO method, high throughput sequencing platform.
Preferably, the reagent for detecting the mRNA expression level comprises a specific primer and/or a probe.
Preferably, the probe may be DNA, RNA, DNA-RNA chimeras, PNA or other derivatives. The length of the probe is not limited, and any length may be used as long as specific hybridization and specific binding to the target nucleotide sequence are achieved. The length of the probe may be as short as 25, 20, 15, 13 or 10 bases in length. Also, the length of the probe can be as long as 60, 80, 100, 150, 300 base pairs or more, even for the entire gene. Since different probe lengths have different effects on hybridization efficiency and signal specificity, the length of the probe is usually at least 14 base pairs, and the longest is usually not more than 30 base pairs, and the length complementary to the nucleotide sequence of interest is optimally from 15 to 25 base pairs. The probe self-complementary sequence is preferably less than 4 base pairs so as not to affect hybridization efficiency.
Preferably, the reagent for detecting the expression level of the protein comprises reagents used in the following methods: western blotting (Western Blot), enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), sandwich assay, immunohistochemical staining, mass spectrometry, immunoprecipitation analysis, complement fixation analysis, flow cytofluorimetry, and protein chips.
Preferably, the reagent for detecting the expression level of the protein comprises a specific antibody.
Preferably, the antibody comprises a monoclonal antibody, a polyclonal antibody.
Preferably, the antibody comprises an intact antibody molecule, any fragment of an antibody or an antibody with modifications, in particular, the antibody comprises a chimeric antibody, scFv, fab, F (ab') 2, fv, or the like. As long as the fragment retains the ability to bind to the protein. The preparation of antibodies for detecting protein levels is well known to those skilled in the art, and any method can be used in the present invention to prepare the antibodies.
Preferably, the kit can also comprise an mRNA expression quantity auxiliary detection reagent, a protein expression quantity auxiliary detection reagent, an mRNA expression quantity auxiliary detection instrument and a protein expression quantity auxiliary detection instrument.
Preferably, the mRNA expression level auxiliary detection reagent includes, but is not limited to: a reaction reagent for visualizing the amplicon corresponding to the primer, for example, a reagent for visualizing the amplicon by an agarose gel electrophoresis method, an enzyme-linked gel method, a chemiluminescence method, an in situ hybridization method, a fluorescence detection method, or the like; an RNA extraction reagent; a reverse transcription reagent; a cDNA amplification reagent; preparing a standard substance for a standard curve; a positive control; and (5) a negative control product.
Preferably, the protein expression amount auxiliary detection reagent includes but is not limited to: blocking solution, antibody diluent, washing buffer solution, chromogenic stop solution and standard substance for preparing a standard curve.
In another aspect, the present invention provides a system for diagnosing central nervous system diseases, which comprises an input device for inputting the expression level of at least any one of the aforementioned combination of test markers, and an output device for outputting the diagnosis result.
Preferably, the system may further comprise a detection means for detecting the expression level of the combination of markers.
Preferably, the detection device comprises a real-time quantitative PCR instrument, a high-throughput sequencing platform, a detection chip and a chip signal reader.
Preferably, the chip comprises a probe for detecting the expression level of the marker.
Preferably, the chip further comprises an internal reference probe.
Preferably, the internal reference comprises GAPDH or β -Actin.
Preferably, the chip comprises a protein chip and/or a gene chip.
Preferably, the system further comprises an evaluation result transmission unit that can transmit the evaluation result of the subject to an information communication terminal device that can be referred to by the patient or medical staff.
In another aspect, the present invention provides a method for diagnosing a central nervous system disease, which comprises detecting the expression level of at least any one of the aforementioned marker combinations.
Preferably, the method further comprises the step of collecting the blood from the subject.
Preferably, the sample comprises: tissue, blood urine, saliva, semen, milk, cerebrospinal fluid, tears, sputum, mucus, lymph, cytosol, ascites, pleural effusion, amniotic fluid, bladder irrigation fluid and bronchoalveolar lavage fluid.
Preferably, the blood comprises: serum, plasma, whole blood.
Preferably, the blood is whole blood.
Preferably, the method further comprises a step of judging the diseased state of the subject by the detection result of the expression amount after the detection.
In another aspect, the invention provides a reagent for detecting the expression level of at least any one of the CACNA1E, PDCD1, USP14, a kit as described above, and use of the system as described above in preparing a product for diagnosing whether a subject has a central nervous system disease.
Drawings
FIG. 1 is a box plot of the difference of the differential genes, A is USP14, B is PDCD1, and C is CACNA1E.
FIG. 2 is a ROC curve chart of marker USP14 in diagnosing ischemic stroke; the ordinate is sensitivity and the abscissa is specificity.
FIG. 3 is a ROC curve graph of the marker PDCD1 in diagnosing ischemic stroke; the ordinate is sensitivity and the abscissa is specificity.
FIG. 4 is a ROC plot of marker CACNA1E in diagnosing ischemic stroke; the ordinate is sensitivity and the abscissa is specificity.
FIG. 5 is a ROC graph of marker combination PDCD1_ USP14 in diagnosing ischemic stroke; the ordinate is sensitivity and the abscissa is specificity.
FIG. 6 is a ROC plot of marker combination CACNA1E _ USP14 in diagnosing ischemic stroke; the ordinate is sensitivity and the abscissa is specificity.
FIG. 7 is a ROC plot of marker combination CACNA1E _ PDCD1 in diagnosing ischemic stroke; the ordinate is sensitivity and the abscissa is specificity.
FIG. 8 is a ROC plot of marker combination CACNA1E _ PDCD1_ USP14 in diagnosing ischemic stroke; the ordinate is sensitivity and the abscissa is specificity.
Detailed Description
The present invention will be further described with reference to the following examples, which are intended to be illustrative only and not to be limiting of the invention in any way, and any person skilled in the art can modify the present invention by applying the teachings disclosed above and applying them to equivalent embodiments with equivalent modifications. Any simple modification or equivalent changes made to the following embodiments according to the technical essence of the present invention, without departing from the technical spirit of the present invention, fall within the scope of the present invention.
Example 1 screening and validation of diagnostic Effect of marker combinations
Collecting blood samples of patients, wherein the information of the patients is shown in table 1, sequencing, and screening genes which are differentially expressed between healthy people and patients; differential expression analysis using software: ballgown (http:// cole-trapnell-la b. Githiub. Io/cufflinks/cuffdiff/index. Html). Screening is carried out by using differential expression screening standards to obtain 479 differential genes, wherein 346 genes with up-regulated expression are obtained, and 133 genes with down-regulated expression are obtained.
TABLE 1 sample information
Figure BDA0003189515450000061
Downloading a network database GSE22255 which is a blood genome expression profile of ischemic stroke, and carrying out the same difference analysis in the gene expression profile of the database; the markers with consistent changes detected in patient samples and databases are screened, the differential expression boxplot of the screened partial markers is shown in figure 1, and the expression changes in patients are shown in table 2.
TABLE 2 differentially expressed genes
Preliminary study GSE22255
CACNA1E up up
PDCD1 down down
USP14 down down
The data of the database is used for carrying out permutation and combination on the markers shown in the table 2, the AUC value of each marker or the combination of the markers in diagnosis is shown in the table 3, and the ROC curve is sequentially shown in the figures 2 to 8.
TABLE 3 AUC values for diagnosis
Marker/marker combination AUC Drawing (A)
USP14 0.757 2
PDCD1 0.71 3
CACNA1E 0.757 4
PDCD1_USP14 0.8175 5
CACNA1E_USP14 0.7775 6
CACNA1E_PDCD1 0.8525 7
CACNA1E_PDCD1_USP14 0.848 8
The AUC results in Table 3 show that each marker of CACNA1E, PDCD1 and USP14 can be independently used as a marker for diagnosing cerebral apoplexy, the AUC value after combination is further increased, higher diagnosis accuracy is obtained, any two markers have synergistic effect, and even if the AUC values of the independent markers are all about more than 0.7, the combination is obviously improved.
The above description of the embodiments is only intended to illustrate the method of the invention and its core idea. It should be noted that, for those skilled in the art, without departing from the principle of the present invention, several improvements and modifications can be made to the present invention, and these improvements and modifications will also fall into the protection scope of the claims of the present invention.

Claims (3)

1. The application of a reagent for detecting the mRNA expression quantity or the protein expression quantity of a marker in preparing a kit for diagnosing cerebral arterial thrombosis, wherein the marker comprises CACNA1E, PDCD1 and USP14.
2. The use according to claim 1, wherein the amount of mRNA expression or the amount of protein expression of the marker is detected in a patient sample selected from the group consisting of serum, plasma and whole blood.
3. The use of claim 1, wherein CACNA1E is highly expressed in the patient, PDCD1 is lowly expressed in the patient, and USP14 is lowly expressed in the patient.
CN202110872060.2A 2021-07-30 2021-07-30 Diagnostic marker for cerebral ischemic stroke Active CN113564243B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202110872060.2A CN113564243B (en) 2021-07-30 2021-07-30 Diagnostic marker for cerebral ischemic stroke

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110872060.2A CN113564243B (en) 2021-07-30 2021-07-30 Diagnostic marker for cerebral ischemic stroke

Publications (2)

Publication Number Publication Date
CN113564243A CN113564243A (en) 2021-10-29
CN113564243B true CN113564243B (en) 2023-02-07

Family

ID=78169492

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202110872060.2A Active CN113564243B (en) 2021-07-30 2021-07-30 Diagnostic marker for cerebral ischemic stroke

Country Status (1)

Country Link
CN (1) CN113564243B (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004113554A2 (en) * 2003-06-16 2004-12-29 Washington University Methods for determining susceptibility to psoriasis
JP2007143504A (en) * 2005-11-29 2007-06-14 Ehime Univ Gene marker of hypertension
WO2021114201A1 (en) * 2019-11-29 2021-06-17 中国科学院苏州生物医学工程技术研究所 Cancer biomarker and use

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9493834B2 (en) * 2009-07-29 2016-11-15 Pharnext Method for detecting a panel of biomarkers

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004113554A2 (en) * 2003-06-16 2004-12-29 Washington University Methods for determining susceptibility to psoriasis
JP2007143504A (en) * 2005-11-29 2007-06-14 Ehime Univ Gene marker of hypertension
WO2021114201A1 (en) * 2019-11-29 2021-06-17 中国科学院苏州生物医学工程技术研究所 Cancer biomarker and use

Also Published As

Publication number Publication date
CN113564243A (en) 2021-10-29

Similar Documents

Publication Publication Date Title
US10914745B2 (en) Biomarker-based methods for aiding the diagnosis of stroke
KR20190031072A (en) Method for diagnosing vascular dementia using lipocalin-2
JP6707181B2 (en) Kits or packages for identifying pregnant women at risk of preterm birth and use of such kits or packages
CN109891239B (en) Methods and kits for providing preeclampsia assessment and prediction of preterm labor
CN109196362A (en) For providing the method and composition of preeclampsia assessment
US20230220467A1 (en) Normal-pressure hydrocephalus diagnosis composition and diagnosis marker detection method, using level of expression of chi3l1 in blood
CN116519953A (en) Application of EDA2R protein and specific antibody thereof in preparation of syphilis diagnosis product
EP3545311B1 (en) Gfap derivatives for stroke diagnostics
CN113564243B (en) Diagnostic marker for cerebral ischemic stroke
KR101895767B1 (en) A biomarker composition for diagnosis of atherosclerosis
KR101995189B1 (en) Biomarker for non-invasive in vitro diagnosis of a Hepatocellular carcinoma and biokit for diagnosis thereof comprising the same
CN113667739B (en) Diagnostic marker combinations for coronary artery disease
CN113564244B (en) Application of molecular marker in diagnosis and treatment of ischemic stroke
KR20190038257A (en) Composition and kit for distinguishing between mild Alzheimer's disease and moderate Alzheimer's disease using nasal fluid
CN114164273A (en) Prognosis marker of squamous cell carcinoma, establishment method of prognosis risk evaluation model and application of prognosis marker
CN112816711A (en) Molecular marker for prenatal noninvasive diagnosis of neural tube malformation, congenital heart disease and cleft lip and palate and application thereof
KR101880554B1 (en) Method for screening stage of Alzheimer's disease progression using nasal fluid
KR20100070776A (en) Biomarkers for the diagnosis of recurrent pregnancy loss
KR102390827B1 (en) GDF15 gene marker for diagnosis or prediction of normal pressure hydrocephalus and uses thereof
CN116219017B (en) Application of biomarker in preparation of ovarian cancer diagnosis and/or prognosis products
KR102350228B1 (en) Urinary exosome-derived biomarkers for diagnosis or prognosis of T cell-mediated rejection in kidney allografts
US20230257819A1 (en) Application of biomarkers in preparing diagnostic tools for combined allergic rhinitis and asthma syndrome
KR102533728B1 (en) Markers specific for brain derived ectosome and non-invasive method for diagnosing dementia
CN116287208A (en) Method for noninvasively diagnosing coronary artery expansion disease
CN113528641A (en) Application of gene combination in diagnosis of diabetic nephropathy

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant