CN110484613A - A kind of ankylosing spondylitis early diagnosis marker - Google Patents
A kind of ankylosing spondylitis early diagnosis marker Download PDFInfo
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- ankylosing spondylitis
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Abstract
The invention discloses a kind of ankylosing spondylitis early diagnosis markers.Specifically, the application the invention discloses PDCD10 and miR-495 as diagnosis marker, therapeutic effect marker and/or drug screening marker.Utilize marker proposed by the present invention, only needing to detect the mRNA of PDCD10 or protein expression situation in peripheral blood mononuclear lymphocyte can be carried out the early diagnosis of ankylosing spondylitis, and the good high sensitivity of specificity is detected, provides a kind of very simple and effective way for the early diagnosis of ankylosing spondylitis;And its expression can change with therapeutic effect, utilize it as curative effect marker, can effectively monitor the validity of therapeutic scheme so that the treatment of ankylosing spondylitis more targetedly and purpose;Its target spot as treatment ankylosing spondylitis drug screening simultaneously can be screened effectively for treatment ankylosing spondylitis.
Description
Technical field
The present invention relates to field of biomedicine technology, early diagnose and indicate more particularly, to a kind of ankylosing spondylitis
Object.
Background technique
Ankylosing spondylitis (Ankylosing Spondylitis, AS) is a kind of common chronic auto-immune disease
Disease has the characteristics that disease time is early and pathogenesis is not known.The disease can be led by influencing articulatio sacroiliaca and axial bone
Cause the quality of life decline of patient.The early stage age of onset of AS is usually younger, and influence male is more than women, and ratio is about
2:1.Since symptom is fuzzy in early diagnosis, it is 8~11 years that the time interval between diagnosis, which occurs, for the symptom of AS.Although existing
Advanced imaging technique, anti-inflammatory drug and physical therapy, but this still proposes significant challenge to the early diagnosis and therapy of AS.
Although being reported in AS patient in the prior art, miR-21 and (the Progr ammed of apoptosis molecule 4
Cell death 4, PDCD4) mrna expression amount significantly increases, but inventor further tests and finds that it can not be as strong
The marker of straightforward rachitis early diagnosis and assessment treatment.
Apoptosis molecule 10 (Programmed cell death 10, PDCD10), initially in the cell of people
It is that clone obtains in TF-1, also referred to as TFAR15 (TF-1cellapoptosis related gene 15).The gene is dashed forward
Become the generation that can cause intracranial cavernous hemangioma (cerebralcavernous malformations, CCMs), causes patient
There are the symptoms such as epilepsy, bleeding and apoplexy.As the Disease-causing gene of the 3rd CCMs, PDCD10 is referred to alternatively as CCM3 again.PDCD10
It is NM_007217 that gene, which is 11235, GenBank number in the GeneID number of NCBI, and Protein Accession number is
NP_009148.The number Q9BUL8 in albumen database UniProtKB.Recent study discovery, it can with VEGFR2, CCM2,
The multiple proteins such as ERM combine and form interaction.By regulating and controlling MAPK/ERK- access, PDCD10 can enhance MST4/VEGFR2
Stability, and promote corresponding signal transduction.
Lack effective ankylosing spondylitis early diagnosis marker in the prior art.
Summary of the invention
The purpose of the invention is to overcome the shortcomings of that the early diagnosis of prior art ankylosing spondylitis is difficult, one kind is provided
Ankylosing spondylitis early diagnosis marker.
The first purpose of the invention is to provide PDCD10 genes and/or albumen as ankylosing spondylitis diagnosis marker
Application in preparation ankylosing spondylitis diagnostic reagent or kit.
A second object of the present invention is to provide PDCD10 genes and/or albumen as treating ankylosing spondylitis effect mark
Application of the will object in preparation ankylosing spondylitis therapeutic evaluation reagent or kit.
Third object of the present invention is to provide PDCD10 genes and/or albumen as ankylosing spondylitis drug screening mark
Will object is preparing the application in rigid spine drug selection agent or kit.
Fourth object of the present invention be to provide miR-495 as ankylosing spondylitis diagnosis marker prepare it is tatanic
Application in rachitis diagnostic reagent or kit.
It is strong in preparation as treating ankylosing spondylitis effect marker that fifth object of the present invention is to provide miR-495
Application in straightforward rachitis therapeutic evaluation reagent or kit.
It is strong in preparation as ankylosing spondylitis drug screening marker that sixth object of the present invention is to provide miR-495
Application in straightforward Spinal drug screening reagent or kit.
7th purpose of the invention is to provide a kind of diagnosis of ankylosing spondylitis, treating ankylosing spondylitis effect is commented
Valence, and/or ankylosing spondylitis drug screening kit.
To achieve the goals above, the present invention is achieved by the following technical programs:
PDCD10 can angiogenesis, oxidative stress, tumour occur in regulating cell proliferation, differentiation and apoptosis.Invention
People has found that up-regulated expression is presented in PDCD10 in AS by qPCR and Western blot;Further Mechanism Study shows to know
The not miR-495 of the gene is expressed in AS in downward, and the expression of PDCD10 and miR-495 is negatively correlated;Internal and body
Outer experiment shows that PDCD10 is an important target gene of miR-495;ROC curve analysis shows, PDCD10 be AS diagnosis
One potential molecular marker;And PDCD10 can indicate the treatment medication of AS, make in a line anti-inflammation drugs NSAIDs of AS
Under, PDCD10 occurs lowering expression.
Therefore claimed the following contents:
PDCD10 gene and/or albumen are tried as ankylosing spondylitis diagnosis marker in preparation ankylosing spondylitis diagnosis
Application in agent or kit.
PDCD10 gene and/or albumen are treated as treating ankylosing spondylitis effect marker in preparation ankylosing spondylitis
Application in effect evaluation reagent or kit.
PDCD10 gene and/or albumen are preparing rigid spine drug as ankylosing spondylitis drug screening marker
Application in screening reagent or kit.
MiR-495 is as ankylosing spondylitis diagnosis marker in preparation ankylosing spondylitis diagnostic reagent or kit
Application.
MiR-495 as treating ankylosing spondylitis effect marker preparation ankylosing spondylitis therapeutic evaluation reagent or
Application in kit.
MiR-495 is preparing rigid spine drug selection agent or examination as ankylosing spondylitis drug screening marker
Application in agent box.
A kind of diagnosis of ankylosing spondylitis, treating ankylosing spondylitis effect assessment, and/or ankylosing spondylitis drug sieve
Kit is selected, one of PDCD10 gene, PDCD10 albumen and/or miR-495 or a variety of detection reagents are contained.
Preferably, the PDCD10 gene detection reagent is the qPCR primer of PDCD10.
It is highly preferred that its nucleotide sequence of the qPCR primer of PDCD10 is as shown in NO:1~2 SEQ ID.
Preferably, the PDCD10 protein assay reagent is the detection antibody of PDCD10.
Preferably, the miR-495 detection reagent is the qPCR primer of miR-495.
It is highly preferred that the qPCR primer of miR-495 includes that nucleotide sequence miR-495 as shown in SEQ ID NO:3 is reversed
Primer and nucleotide sequence are recorded as shown in NO:4~5 SEQ ID.
A kind of ankylosing spondylitis diagnostic kit detects the monokaryon lymphocyte in peripheral blood, compared with Healthy People,
PDCD10 gene and/or protein expression rise or miR-495 expression decline then illustrates that patient has the wind with ankylosing spondylitis
Danger.
A kind for the treatment of ankylosing spondylitis effect assessment kit, detection is by the monokaryon in the peripheral blood of the patient treated
Lymphocyte, PDCD10 gene and/or protein expression decline or miR-495 expression, which rise, compared with not treating then illustrates to treat
It is effective;Otherwise illustrate that therapeutic effect is unobvious.
A kind of ankylosing spondylitis drug screening kit detects the tested material for using drug-treated to be measured to cross, if
Tested material after by drug-treated to be measured compared with before processing, PDCD10 gene and/or protein expression decline or miR-495 table
Then illustrate that the treatment of drug ankylosing spondylitis to be measured is effective up to rising.
Compared with prior art, the invention has the following beneficial effects:
The present invention only needs the mRNA or protein expression situation of PDCD10 in detection peripheral blood mononuclear lymphocyte
The early diagnosis of ankylosing spondylitis is carried out, and detects the good high sensitivity of specificity, is the early diagnosis of ankylosing spondylitis
Provide a kind of very simple and effective way;And its expression can change with therapeutic effect, utilize it as treatment
Valid flag object can effectively monitor the validity of quality scheme so that the treatment of ankylosing spondylitis more targetedly and mesh
Property;Its target spot as treatment ankylosing spondylitis drug screening simultaneously, can be effectively to treatment ankylosing spondylitis
It is screened.
Detailed description of the invention
Fig. 1 is detection of expression of the PDCD family gene in AS;(A) thermal map of PDCD family gene expression, HC
Control: normal healthy controls, AS:AS patient;(B) * * *: the column statistical chart of PDCD family gene expression indicates that conspicuousness is poor
It is different, and P < 0.01, HC: normal healthy controls, AS:AS patient;(C) Protein Detection of PDCD 10, HC-1, HC-2, HC-3: different
Normal healthy controls, AS-1, AS-2, AS-3: different AS patients, GADPH: reference gene;(D) PDCD10 Protein Detection is horizontal
* * *: column statistical chart indicates significant difference, and P < 0.01, HC: normal healthy controls, AS:AS patient.
Fig. 2 is the detection of miR-495 and miR-495 and PDCD10 expression correlation;(A) detection of miR-495, * * *:
Indicate significant difference, and P < 0.01, HC: normal healthy controls, AS:AS patient;(B) miR-495 and PDCD10 expression correlation
Detection, significant difference P < 0.01, coefficient R2=0.81.
Fig. 3 is the 3 ' UTR that in vitro and in vivo experimental verification miR-495 can identify PDCD10;(A) miR-495 is identified
The sequence of the 3 ' UTR regions of PDCD10, miR-495 and PDCD10 pairing base indicated using vertical line part, Mut-miR-
495: the miR-495 of mutation, wherein green portion indicate mutant nucleotide sequence, Mut-PDCD10: the PDCD10 of mutation, Green portion
Dividing indicates mutant nucleotide sequence;(B) external Dual-Luciferase is experiments have shown that miR-495 can identify PDCD10, Luciferase
Activity: Dual-Luciferase activity, the carrier of Vector PDCD10: the PDCD10 containing wild type 3 ' UTR, Vector Mut-
The carrier of PDCD10: the PDCD10 containing saltant type 3 ' UTR, MiR-495PDCD10: wild type miR-495 and wild type PDCD10
Expression vector, MiR-495Mut-PDCD10: wild type miR-495 with saltant type PDCD10 expression vector, Mut-MiR-
495PDCD10: saltant type miR-495 with wild type PDCD10 expression vector, Mut-MiR-495Mut-PDCD10: saltant type
MiR-495 and saltant type PDCD10 expression vector, * * *: P < 0.01;(C) miR-495 is overexpressed the rna level shadow to PDCD10
It rings;(D) miR-495, which is overexpressed, influences the protein level of PDCD10, Mock: Vector: untreated fish group is overexpressed empty carrier
Control: group is overexpressed control group, miR-495:miR-495 overexpression group.
Fig. 4 is NSAIDs effect front and back, the detection of expression of PDCD10 and miR-495;(A) NSAIDs effect front and back miR-
495 rna expression detection;(B) the rna level detection of NSAIDs effect front and back PDCD10;(C) NSAIDs effect front and back PDCD10
The detection of protein level, BN-1, BN-2, BN-3 indicate to take different AS patients before NSAIDs, AN-1, AN-2, AN-3 table
Show AS patient different after taking NSAIDs.
Fig. 5 is miR-495, the ROC curve and PDCD10 and AS disease assessment scale mSASSS of PDCD10, PDCD4,
The correlation of BASDAI;(A) ROC curve of miR-495;Specificity and sensitivity curves as AS medical diagnosis on disease assess table
Bright, in the case where the accuracy rate of 72.73% (Area=0.7273) of AS prediction, P value is 0.009851 (P value=
0.009851), 95% confidence interval be 0.5736 arrive 0.8810:(B) PDCD10 ROC curve;Spy as AS medical diagnosis on disease
Anisotropic and sensitivity curves, which are assessed, to be shown in the case where the accuracy rate of AS 84.09% (Area=0.8409) predicted, P value
For 0.0001089 (P value=0.0001089), 95% confidence interval is 0.7147 to arrive 0.9671:(C) ROC of PDCD4 is bent
Line;Specificity and sensitivity curves assessment as AS medical diagnosis on disease shows 52.27% (Area=0.5227) predicted in AS
Accuracy rate in the case where, P value be 0.7963 (P value=0.7963), 95% confidence interval be 0.3503 to 0.6951.
Sensitivity: sensibility, Specificity: specificity, 95%confidence interval:95% confidence interval, P
Value:P value;(E) correlation of PDCD10 and AS disease assessment scale mSASSS.(F) PDCD10 and AS disease assessment scale
The correlation of BSDAI.
Specific embodiment
The present invention is made with specific embodiment with reference to the accompanying drawings of the specification and further being elaborated, the embodiment
It is served only for explaining the present invention, be not intended to limit the scope of the present invention.Test method as used in the following examples is such as without spy
Different explanation, is conventional method;Used material, reagent etc., unless otherwise specified, for the reagent commercially obtained
And material.
The qPCR detection primer of PDCD10 and miR-495 used in the following embodiment:
1 patients with ankylosing spondylitis PDCD10 of embodiment expresses trend
One, experimental method
1, the extraction of RNA and qPCR
The whole blood 3ml that AS patient is obtained from clinical department, is collected using EDTA2Na anticoagulant tube.Normal healthy controls blood sample source
Outpatient service people taking physical examination.Subsequent experimental implementation is carried out immediately to the blood sample of acquisition.
(1) it is obtained in peripheral blood using Ficoll (TBDscience, Code No:LTS1077) and the separation of reference book
Monokaryon lymphocyte.
(2) RNAiso Plus (Takara, Code No:9108) is added and operates to specifications and extracts the total of cell
RNA is used for the quantitative detection of subsequent RNA.
(3) the synthesis PrimeScript of cDNATM RT reagent Kit with gDNA Eraser(Takara,Code
No:RR047A it) operates to specifications
Specific reaction system:
5×gDNA Eraser Buffer | 2μL |
gDNA Eraser | 1μL |
Total serum IgE | 500ng |
RNase-free H2O | Add to 10 μ L |
After reacting 2min at 42 DEG C, 4 DEG C are saved backup.
Following reagent is added into above-mentioned system:
Reagent | Usage amount |
Reverse transcription reaction liquid | 10μL |
PrimeScript RT Enzyme Mix I | 1.0μL |
RT Primer | 1.0μL |
5×PrimeScript Buffer 2(for ReaL Time) | 4.0μL |
RNase-free H2O | 4.0μL |
37℃ 30min;85℃ 5sec;4 DEG C of preservations.
(4) qPCR is detected, and using SYBR (Takara, Code No:RR420A), reference book is carried out
Amplification system is as follows:
QPCR amplified reaction program are as follows:
2, Western blot is detected
(1) it collects protein sample: being separated using protein lysate (referring to green skies RIPA lysate) processing Ficoll
The peripheral mononuclear cells arrived.Then the protein concentration of each protein sample is measured by BCA determination of protein concentration method.Finally to sample
Product are pre-processed: 5 × SDS-PAGE albumen sample-loading buffer being added in the protein sample of collection.100 DEG C of heating 10min,
It puts spare on ice.Albumen applied sample amount is 20ug.
(2) 10%SDS-PAGE electrophoresis: concentration glue uses 90V constant pressure electrophoresis 30min, makes when bromophenol blue enters separation gel
With 120V constant pressure electrophoresis 100min.
(3) transferring film: pvdf membrane, transferring film slot are placed in ice water, and transferring film electric current is 300mA, transferring film time 90min.
(4) it closes: after the completion of transferring film, using 5% skim milk immediately, room temperature shaker low speed closes 60~90min.Closing
After, film 3 times are washed using TBST, each 5min.
(5) primary antibody is incubated for: according to the specification of primary antibody, primary antibody is diluted using 5% skim milk, in 4 DEG C of slow refrigerator overnights.
Next day is cleaned film 3 times, each 5min using TBST.
(6) secondary antibody is incubated for: according to the specification of secondary antibody, diluting secondary antibody using TBST, low speed is incubated for 1h in room temperature shaker.
TBST is cleaned film 3 times, each 5min.
(7) Protein Detection: according to chemiluminescent method, expressing quantity is detected using ECL.
Two, experimental result
It can be seen that the rna level of PDCD10 expression significantly rises in AS from Figure 1A and 1B.Fig. 1 C and 1D can be seen
The protein level of PDCD10 expression significantly rises in AS out.It can be seen that PDCD10 is up-regulated expression in AS.
The detection of embodiment 2miR-495 and miR-495 and PDCD10 expression correlation
One, experimental method
The detection of expression of miR-495 is carried out to the RNA sample of AS patient and normal healthy controls.RNA extract and qPCR method and
Embodiment 1 is identical.The reverse transcriptase primer of miR-495 uses special primer, reverse transcription condition are as follows: 37 DEG C of 30min;85℃
5sec;4 DEG C of preservations.Other conditions are same as Example 1.When MiR-495 and PDCD10 expression correlation are analyzed, in same RNA sample
MiR-495 is that independent variable is placed on horizontal axis, and PDCD10 is dependent variable is placed in the longitudinal axis and is depicted as.
The extraction of RNA and qPCR, with embodiment 1.
Two, experimental result
It is expressed from can be seen that miR-495 is significantly lowered in AS in Fig. 2A.And its expression quantity and PDCD10 are in negative
Related (Fig. 2 B).
Identification of the embodiment 3miR-495 to the 3 ' UTR of PDCD10
One, experimental method
1, external Dual-Luciferase experiment
The RNA analogies (5 '-AAACAAACAUGGUGCACUUCUU-3 ') of MiR-495 and corresponding mutation (5 '-
CAAAAAAAAAUGGUGCACUUCUU-3 ') (Shanghai Genepharma) is synthesized by Shanghai Ji Ma.Used in the experiment
Skeleton carrier is psiCHECKTM-2 (Promega).The amplification of 3 ' UTR regions of the wild type and saltant type of PDCD10 and clone
It is completed by Wuhan Jin Kairui (GeneCreate).Dual-Luciferase detection kit from the green skies (article No. RG027,
beyotime institute of biotechnology).Detection is Glomax (Promega) using instrument.
Process letter is divided into:
(1) instrument Glomax is opened in advance, setting minute is 10 seconds, and the measuring interval time is 2 seconds,.
(2) after mixing well reporter gene cell pyrolysis liquid, 48 orifice plates are used in this research, every hole adds 150 μ L to report
Accuse gene cell lysate, abundant lytic cell.
(3) sufficiently after cracking, 10,000-15,000g is centrifuged 3 minutes, takes supernatant for measuring.
(4) melt Fluc detection reagent and Renilla luciferase detection buffer, and reach room temperature.Sea pansy
Luciferase detection substrate (100 ×) is placed in spare on ice.
(5) need 100 microlitres of amount according to each sample, take appropriate Renilla luciferase detection buffer, according to 1:100 plus
Enter Renilla luciferase detection substrate (100 ×) and is configured to Renilla luciferase detection working solution.
(6) 100 microlitres of sample are taken, 100 microlitres of Fluc detection reagents are added, beaten with rifle or is fitted with other
RLU (relative light unit) is measured after mode mixes.Using reporter gene cell pyrolysis liquid as blank control.
(7) after completing said determination Fluc step, 100 microlitres of Renilla luciferase detection work are added
Liquid is beaten with rifle or measures RLU (relative light unit) after being mixed with other appropriate ways.
(8) this research is using Renilla luciferase as internal reference, with the RLU value of obtained Fluc divided by sea pansy firefly
The RLU value of light element enzyme is relative luciferase activity.Carry out the activation degree of the different sample room reporter genes of comparison using the value.
2, cellular level adenovirus is overexpressed miR-495 expression experiment
(1) peripheral mononuclear cells in vitro culture:
It is obtained in peripheral blood using Ficoll (TBDscience, Code No:LTS1077) and the separation of reference book
Monokaryon lymphocyte;
Using 1640 culture mediums for containing 10% fetal calf serum, 1% dual anti-(penicillin and streptomysin), at 37 DEG C, 5%CO2
Cell incubator carries out cell culture.
(2) miR-495 is overexpressed the transfection with peripheral mononuclear cells
Building miR-495 is overexpressed building process: miRNA-495 being first cloned into p DC316-m CMV-EGFP carrier
In.Then carrier and Ad Easy are recombinated, packaging purifying has infective adenovirus miRNA-495.It is aobvious finally by fluorescence
Micro mirror observes the expression quantity of GFP and qPCR detection miR-495.Adenovirus is overexpressed miR-495 and control is triumphant by Shanghai Ji
((Shanghai Genechem) company completes.Transfection conditions: cell density 70~80% uses 6 orifice plates.After transfection 48 hours
It collects cell, carries out subsequent RNA and protein expression test experience (specific method is with embodiment 1).
Two, experimental result
External Dual-Luciferase experiment shows: miR-495 can identify the 3 ' UTR regions (Fig. 3 A and 3B) of PDCD10.Into
The internal overexpression experiment of one step shows: the rna level of PDCD10 is not influenced substantially by miR-495, and its protein water
It puts down but by the regulation of miR-495 (Fig. 3 C and 3D).This absolutely proves that PDCD10 is a target gene of miR-495.
Embodiment 4NSAIDs acts on the expression of lower PDCD10 and miR-495
One, experimental method
NSAIDs (non-steroidal anti-inflammatory drugs) is the first-line drug of AS treatment.Exist to assess PDCD10 and miR-495
NSAIDs treats the effect in AS, acts on NSAIDs the expression of PDCD10 and miR-495 in lower AS patient peripheral lymphocyte
It is detected.The application method of NSAIDs (national drug standard number: H41020415): 100mg (1), one time a day.The course for the treatment of is 16
Week, and place on record.By it is making a definite diagnosis and by signature Written informed consent AS Case treatment before and after blood sample into
The detection of expression of row PDCD10 and miR-495 are the same as embodiment 1 and embodiment 2.
Two, experimental result
The results show that under the first-line drug NSAIDs effect in AS treatment, the rna level expression up-regulation (figure of miR-495
4A), the RNA of PDCD10 and protein expression downward (Fig. 4 B and 4C).This also illustrates that PDCD10 may be advantageously employed in AS
The assessment of prognosis.
The correlation of embodiment 5PDCD10 and AS
One, experimental method
ROC (receiver operating characteristic, ROC) curve can objectively respond the excellent of diagnostic method
Bad, it includes sensitivity, specificity, accuracy rate index.It, will under column mode using Graphpad prism software
PDCD10 expression data are divided into A group (AS patient group) and B group (healthy control group).Carry out ROC curve analysis.In this way
It is primary to carry out miR-495, the ROC curve analysis of PDCD4.
Stoke ankylosing spondylitis backbone points-scoring system (modified stoke ankylosing spondylitis
Spine score, mSASSS): assessment AS patient spine structural damage.General comment score is higher, and vertebral column lesion is more serious.Bi Shi
Disease activity scoring (BASDIA) is used for assessment of ankylosing spondylitis morbid state, and assessment score is higher, and AS disease is tighter
Weight.
PDCD10 and mSASSS, PDCD10 and BASDAI analysis are analyzed using Graphpad prism software, and wherein AS suffers from
The expression quantity of PDCD10 is ordinate in person, and mSASSS and BASDAI are respectively abscissa.R is related coefficient, value < 0.001 P.
Two, experimental result
For research PDCD10 and miR-495 clinical diagnosis and context of detection application, using ROC curve have evaluated its
Sensitivity and specificity (Fig. 5) in AS medical diagnosis on disease.The result shows that: in 95% confidence interval, accuracy rate can be distinguished
Reach 84.09% (P=0.0001089) and 72.73% (P=0.009851), can be used as the molecular marker in AS diagnosis.
Under comparing, the PDCD4 relevant to ankylosing spondylitis having been reported that before is in 95% confidence interval, and accuracy rate is only
52.27% (P=0.7963) is only reached, is not used to AS diagnosis at all.
Claims (7)
1.PDCD10 gene and/or albumen are as ankylosing spondylitis diagnosis marker in preparation ankylosing spondylitis diagnostic reagent
Or the application in kit.
2.PDCD10 gene and/or albumen are as treating ankylosing spondylitis effect marker in preparation ankylosing spondylitis curative effect
Evaluate the application in reagent or kit.
3.PDCD10 gene and/or albumen are preparing rigid spine drug sieve as ankylosing spondylitis drug screening marker
Select the application in reagent or kit.
4.miR-495 is as ankylosing spondylitis diagnosis marker in preparation ankylosing spondylitis diagnostic reagent or kit
Using.
5.miR-495 is as treating ankylosing spondylitis effect marker in preparation ankylosing spondylitis therapeutic evaluation reagent or examination
Application in agent box.
6.miR-495 is preparing rigid spine drug selection agent or reagent as ankylosing spondylitis drug screening marker
Application in box.
7. a kind of ankylosing spondylitis diagnosis, treating ankylosing spondylitis effect assessment, and/or ankylosing spondylitis drug screening
Kit, which is characterized in that tried containing one of PDCD10 gene, PDCD10 albumen and/or miR-495 or a variety of detections
Agent.
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CN113621618A (en) * | 2020-05-25 | 2021-11-09 | 天津市环湖医院(天津市神经外科研究所、天津市脑系科中心医院) | Autosomal dominant CCM2 gene mutant and application thereof |
CN112266955A (en) * | 2020-10-26 | 2021-01-26 | 川北医学院附属医院 | Ankylosing spondylitis diagnosis marker and application thereof |
CN112266955B (en) * | 2020-10-26 | 2023-10-20 | 川北医学院附属医院 | Ankylosing spondylitis diagnostic marker and application thereof |
CN112210600A (en) * | 2020-11-15 | 2021-01-12 | 安徽中医药大学第一附属医院(安徽省中医院) | Application and detection method of circRNA0003307 gene |
CN114622008A (en) * | 2022-01-27 | 2022-06-14 | 赣南医学院 | Application of MST4 gene as ankylosing spondylitis diagnostic marker |
CN114622008B (en) * | 2022-01-27 | 2023-05-30 | 赣南医学院 | Application of MST4 gene as ankylosing spondylitis diagnostic marker |
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