CN105738631A - Autism serum polypeptide marker SERPINA5-A and application thereof - Google Patents
Autism serum polypeptide marker SERPINA5-A and application thereof Download PDFInfo
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Abstract
The invention discloses an autism serum polypeptide marker SERPINA5-A and the application thereof. The amino acid sequence of the marker is shown in SEQ.ID.NO.1. The molecule is called SERPINA5-A and is one fragment of SERPINA5, the exact molecular weight of the molecule is 3886 Daltons, SERPINA5-A is remarkably highly expressed in autism children sera diagnosis, and a method for detecting SERPINA5-A or ELISA by means of a matrix assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF-MS) is used for detecting the expression level of SERPINA5 and can be used as an autism serum detection method.
Description
Technical field
The invention belongs to autism detection technique field, relate to a kind of autism serum polypeptide mark
SERPINA5-A and application thereof.
Background technology
Autism, also referred to as autism-spectrum obstacle (Autism Spectrum Disorders, ASD),
It is a kind of abnormal with social function disappearance, speech and nonverbal communication, and behavior and the mechanical limitation of interest
For the extensive neurodevelopmental disorder of principal character, prevalence about 1%.Typically fall ill the child front in 3 years old
Phase, and even lifelong, boy's sickness rate is 4～6 times of girl.Research shows, the early stage of ASD examines
Disconnected and examination contributes to increasing the chance that autistic children belong benefits from early intervention.Raw yet with lacking
Thing mark, at present to the sieving and diagnosis of ASD mainly based on the behavior characteristics and developmental history of child,
Therefore there is dispute, need screening badly and can quantify biological diagnosis index.ASD sickness rate increases year by year,
Through causing the extensive concern of academia.The diagnosis of this disease initially originates from one group of patients clinical symptom
Observing, from having Autism Diagnostic so far, owing to lacking quantifiable index, diagnostic criteria was revised repeatedly.
The main contents of Autism Diagnostic standard are symptom and describe, and its symptom exists multiformity, educational circles pair
There is dispute in its diagnostic criteria based on evaluation.Therefore, examination ASD refers to quantifiable biology
Mark, the qualification of biomarker, not only contribute to its early screening and diagnosis, pathogenetic to this disease
The development of discussion, the formulation of diagnostic criteria and medicine also has great importance.
Summary of the invention
It is an object of the invention to provide a kind of autism serum polypeptide mark SERPINA5-A and answer
With, this serum polypeptide marker molecules is serpin suppression A5 (SERPINA5)
One fragment, is autism serum polypeptide mark.
The present invention is to be achieved through the following technical solutions:
A kind of autism serum polypeptide mark SERPINA5-A, its aminoacid sequence is such as
Shown in SEQ.ID.NO.1.
This serum polypeptide mark SERPINA5-A is serpin A5SERPINA5
A fragment, molecular weight is 3886 dalton.
Described autism serum polypeptide mark SERPINA5-A, the detection parameter in its serum is
2.81～5.11ng/mL.
The invention also discloses autism serum polypeptide mark SERPINA5-A to examine as autism serum
The application of the target spot of disconnected medicine.
The invention also discloses autism serum polypeptide mark SERPINA5-A at preparation autism serum
Application in diagnostic medicine.
Described autism serum diagnosis medicine is the medicine of ELISA detection autism serum polypeptide molecule.
The molecule combined with above-mentioned autism serum polypeptide mark SERPINA5-A is in preparation autism
Application in serum diagnosis medicine.
SERPINA5 albumen is as the application of the target spot of autism serum diagnosis medicine.
The molecule combined with SERPINA5 albumen application in preparation autism serum diagnosis medicine.
Compared with prior art, the present invention has a following useful technique effect:
The invention discloses blood serum designated object and the detection method thereof of a kind of Autism children.Its aminoacid sequence
Row are as shown in SEQ.ID.NO.1.This molecule is referred to as SERPINA5-A, for serpin
One fragment of suppression A5 (SERPINA5).Its accurate molecular weight is 3886 dalton, solitarily
Disease infant serum presents significantly high expression: and scope of expressing in serum in normal control population is:
2.08～3.28ng/mL；Scope of expressing in Autism children serum is: 2.81～5.11ng/mL, and
There is between group pole significant difference (p < 0.001).
In view of SERPINA5-A significantly high expression in autism serum, then SERPINA5-A just may be used
Using as autism serum diagnosis mark；And its parent protein SERPINA5 is at Autism children serum
In present specific high expressed, therefore, SERPINA5 can be applicable to Autism children serum diagnosis:
Detect with Matrix Assisted Laser Desorption ionization time of flight mass spectrometry technology (MALDI-TOF-MS)
SERPINA5-A or ELISA method survey the expression of detection SERPINA5, can suffer from as autism
The method of youngster's detection.And detecting autism serum diagnosis for ELISA, SERPINA5 can serve as
The new target spot of ELISA detection medicine.
Accompanying drawing explanation
Fig. 1 be three times of same Autism children serum sample repetitions protein polypeptide collection of illustrative plates (1KDa～
10KDa)；
Fig. 2 is protein polypeptide peak m/z:3886 protein polypeptide in Autism children and Normal group
Differential expression；
Fig. 3 is the MS/MS Mass Spectrometric Identification collection of illustrative plates of SERPINA5-A；
Fig. 4 is the expression of SERPINA5 albumen in autistic children belong and normal control serum of children.
Detailed description of the invention
The autism serum polypeptide molecule that the present invention provides, is the autism serum diagnosis mark of a kind of new screening
Will thing, its expression has specificity, can be applicable to Autism Diagnostic.Below in conjunction with specific embodiment pair
The present invention is described in further detail, and the explanation of the invention is not limited.
The screening of this concrete autism serum diagnosis mark is:
First application liquid protein chip technology separation and Extraction Autism children and normal control serum of children egg
White polypeptide, application MALDI-TOF-MS capture Autism children and normal control population's protein polypeptide figure
Spectrum, and use ClinProTools 2.1 software relative analysis Autism children and normal population serum albumin
Polypeptide spectrogram difference, finds out the protein polypeptide score value that between group, significant difference is expressed, at Autism children serum
In significantly high expression protein polypeptide peak value in sift out autism blood serum tumor markers.
For being verified as of the autism serum diagnosis mark that screened:
The protein polypeptide mixture that Autism children serum separates is divided into 20～30 groups by application HPLC
Point, it is being carried out the qualification of second order ms, and the protein polypeptide identified is being used euzymelinked immunosorbent assay (ELISA)
Carrying out serum regression analysis, result serum returns checking and proves its significantly high table in Autism children serum
Reach, there is specificity, can be as the biomarker of Autism children screening serum.
1, the collection of sample and process:
Gather from the 150 of attached children's hospital of Xi'an Communications University (in January, 2013 is in December, 2015)
Example (male 130 example；Women 20 example；3.5 years old mean age) Autism children and 150 of clinical definite
Example normal health comparison child's (male 130 example；Women 20 example；3.5 years old mean age).Sample is examined
Consider age, sex, acquisition time, condition of storage whether consistent, with or without factors such as underlying diseases.Adopted
Collection person plays on an empty stomach blood sampling morning, gathers whole blood 5mL, room temperature with vacuum test tube (yellow cap, have insulation rubber)
Stand 30min；Room temperature is centrifuged 5min (3000g), upper serum is distributed into 100 μ L/ pipes, immediately
It is stored in-80 DEG C, it is to avoid multigelation.
1.2 reagent and instrument
The magnetic bead kit " weak cation type " extracting Brooker company of employing Germany of serum albumin
(MB-WCX), and spectroscopic pure (HPLC level) acetonitrile, trifluoroacetic acid (Germany Merck company), α-
Cyano group-4-hydroxycinnamic acid (HCCA) (Sigma Co., USA).
Beads enrichment device, 600/384AnchorChip target plate and AutoFlex III ground substance assistant laser solution
Analysis ionization time of flight mass spectrometry MALDI-TOF-MS (Bruker Daltonics company of Germany).
2, the preparation of serum albumin sample
Using weak cation (MB-WCX) magnetic capture serum protein antioxidant peptide, concrete operation step is as follows:
1. bead suspension 1min is mixed completely with vortex mixer；
2. add 10 μ L MB-WCX and combine liquid and 10 μ L MB-WCX magnetic beads to PCR pipe, mixing
After add 5 μ L serum, mix at least 5 times, stand 5min；
3. PCR pipe is put into magnetic post separator, makes the adherent 1min of magnetic bead, after liquid is limpid, abandon supernatant；
4. 100 μ L MB-WCX flushing liquors are added, movable 10 PCR pipe on magnetic post separator,
Abandon supernatant after magnetic bead is adherent, repeat step 3., 4. twice；
5. the magnetic bead that 5 μ L MB-WCX eluent washings are adherent, and piping and druming 10 times, magnetic bead repeatedly are added
Adherent 2min, moves into clean centrifuge tube by supernatant；
6. adding 5 μ L MB-WCX stabilizing solutions to centrifuge tube and to mix, the protein polypeptide of extraction may be used for
Directly MALDI-TOF-MS detection or frozen mass spectral analysis within-20 DEG C of refrigerator 24h.
2.2 mass spectral analysis
Substrate alpha-cyano-4-the hydroxycinnamic acid separating and collecting the albumen sample 1 μ L obtained and 10 μ L is mixed
Even, take 1 μ L point (Bruker company of Germany) on Anchorchip target plate, each sample puts three respectively
Individual target spot repeats to make three times.After drying at room temperature, target plate is put into mass spectrograph to be analyzed, use
FlexControl 2.0 software starts pattern detection after carrying out standard substance correction, and each sample will be through altogether
Mass spectrum is generated, it is thus achieved that by not after 300 laser target shootings (5 some targets, every time practice shooting 2 × 30 times)
The protein polypeptide spectrogram that same karyoplasmic ratio (m/z) forms.ClinProTools2.1 software is used to combine heredity
The biostatisticss such as algorithm and bioinformatics method analyze the protein polypeptide collection of illustrative plates of two groups of serum samples.Enter
Row normalization smoothing processing total ion current figure, eliminates chemical and electric physical noise；Analyze group difference albumen
And calculate difference size, by the descending arrangement of difference size, find out expression between group and there is significant difference
Protein polypeptide peak value (P < 0.001).
After using Beads enrichment system to process Autism children group and Normal group serum sample, pass through
After MALDI-TOF-MS analyzes, each sample of Autism children group and Normal group is carried out egg
White many peptide mappings are drawn, and detect that 81 albumen are many altogether at molecular weight ranges 1000Da～10000Da
Peptide peak figure, and three repetition stability of each sample are higher, as shown in Figure 1.
Use ClinProTools 2.1 software Autism children that mass spectrum is captured and the blood of Normal group
Albumin polypeptide collection of illustrative plates is analyzed, and is compared with normal population by Autism children serum polypeptide spectrogram
Analyze, detect that molecular weight is that 3886 daltonian protein polypeptide peaks are significantly high in Autism children serum
Express (autistic children belong vs normal healthy controls child: 4.44 ± 1.07vs 2.53 ± 0.59, p < 0.001).Knot
Fruit is as in figure 2 it is shown, to M/Z:3886 at Autism children (red, peak value is at upper curve) and just
Often comparison (green, peak value under curve) in expression compare, find the egg of M/Z:3886
White polypeptide peak figure the most significantly high expression in Autism children serum, therefore carries out Sequence Identification to it and makees
First-selected for mark is identified further.
3, the Sequence Identification of the potential mark of autism serum
Concrete employing liquid chromatograph separates the technology with mass spectrometry to autism serum polypeptide mark M/Z:
3886 identify, use the Waters company Nano Acquity UPLC matter to collecting through Beads enrichment
The spectrum remaining serum protein antioxidant peptide of loading carries out two dimension gel chromatography separation, collects 15～30 parts of peptide fragments and evaporates
Part: in collecting liquid, destination protein detected；It is combined Thermo Fisher company LTQ Orbitrap XL again
Mass spectrometer system carries out sequence mirror to the protein polypeptide M/Z:3886 of up-regulated in Autism children serum
Fixed.
Concrete operating procedure is:
3.1 Sample pretreatment
Albumen sample after united extraction, 10 minutes, takes supernatant by 1300 turns, and freeze drier is dried,
Make final volume at 50ul, obtain liquid A, by Agilent ziptip extraction column, concentration liquid A.
Processing method: 1. ziptip pillar is blown and beaten 5 times with 100% acetonitrile, activates pillar；2. the ziptip activated
In liquid 1, pressure-vaccum 10 times repeatedly, avoid bubble to produce as far as possible；3. 50%ACN 0.1%TFA water
Solution, washs 3 ziptip pillars；4., ziptip pillar pressure-vaccum repeatedly in 0.1%TFA, make sample
This eluting, obtains eluent 2；5. repeat above 1-4 to walk, 30 times；6. the eluent 2 of 30 times is merged,
Lyophilization is to 10ul, for Mass Spectrometric Identification.
3.2 chromatographic isolation:
Primary sample adds 10ul mobile phase A, is transferred in sample injection bottle, altogether 20ul.
One-dimensional ultra high efficiency liquid phase systems: Waters company Nano Aquity UPLC (Waters Corporation,
Milford,USA).Chromatographic column:
Trapping column:C18,5μm,180μm×20mm,nanoAcquityTMColumn
Analytical column:C18,3.5μm,75μm×150mm,nanoAcquityTMColumn
Mobile phase A: 5% acetonitrile, 0.1% first aqueous acid
Mobile phase B: 95% acetonitrile, 0.1% first aqueous acid；All solution are HPLC level.
Trapping flow velocity 15 μ l/min, trap time 3min, analyze flow velocity 400nl/min；Analysis time 60min,
Chromatogram column temperature 35 DEG C；Partial Loop pattern sample introduction, sampling volume 18 μ l.
Gradient elution program:
| Time | Flow velocity | Mobile phase A % | Mobile phase B % |
| 40.0 | 0.400 | 95.0 | 5.0 |
| 41.0 | 0.400 | 55.0 | 45.0 |
| 45.0 | 0.400 | 20.0 | 80.0 |
| 45.50 | 0.400 | 95.0 | 5.0 |
| 60.00 | 0.400 | 95.0 | 5.0 |
Gel chromatography separation result is as shown in Figure 3.In chromatogram, abscissa represents the sample delivery time, vertical seat
Mark represents polypeptide relative abundance, and chromatograph sets the time as 60min, starts collection fraction from 10min,
Polypeptide moiety is mainly separated after 15min and is used gradient elution mode, makes elution efficiency improve, if
Determine trap time and collect fraction: collect 15～30 parts of peptide fragment fractions.
3.3LTQ-Orbitrap XL mass spectral analysis:
Use Thermo Fisher company LTQ Obitrap XL mass spectrometry system.Nano ion source
(Michrom Bioresources, Auburn, USA), spray voltage 1.8kV；Scanning of the mass spectrum time 60min；
Experiment model is data dependence (Data Dependent) and dynamically gets rid of (Dynamic Exclusion), 10
Join after parent ion being carried out 2 tandems in Miao in Exclude Lists 90 seconds；Sweep limits
400-2000m/z；One-level scanning (MS) uses Obitrap, and resolution setting is 100000；CID and two
Level scanning uses LTQ；The single isotope choosing 10 the strongest ions of intensity in MS spectrogram is made
MS/MS (single electric charge is got rid of, not as parent ion) is carried out for parent ion.Testing result is as shown in Figure 3.
Data analysis: use data analysis software Bioworks Browser 3.3.1SP1 to carry out SequestTM
Retrieval.Parent ion error is set as that 100ppm, fragment ion error are set to 1Da, and enzyme action mode is non-enzymatic
Cutting, variable to be modified to M (Methionine) methionine oxidized.Retrieval result parameter is set as deltacn >=
0.10.Retrieval result is: m/z:3886.84；IPI:IPI00007221.1；Gene Symbol=SERPINA5
Plasma serine protease inhibitor precursor；Sequence is
SARLNSQRLVFNRPFLMFIVDNNILFLGKVNRP。
The M/Z:3886 separated is referred to as SERPINA5-A, suppresses for serpin
One fragment of A5 (SERPINA5), its accurate molecular weight is 3886 dalton, its aminoacid sequence
SARLNSQRLVFNRPFLMFIVDNNILFLGKVNRP (as shown in SEQ.ID.NO.1).
Therefore, examine with Matrix Assisted Laser Desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS)
Survey SERPINA5-A or ELISA method surveys the expression detecting SERPINA5, can be as solitarily
The method of disease infant detection.
SERPINA5-A as a fragment of SERPINA5, prompting SERPINA5 is and autism
The albumen that specificity is relevant, is detected by ELISA further and verifies.
4, the ELISA serum checking that autism serum SERPINA5 expresses is analyzed:
1) serum sample: collect Autism children serum 48 example (male 40 example, women 8 example；Flat
All 3.5 years old ages), normal control serum of children 40 example (male 35 example；Women 5 example；Mean age
3.5 years old) carry out ELISA serum checking analyze.It is attached that all serum samples are all from Xi'an Communications University
Belong to children's hospital, acquisition time in January, 2014～in December, 2015.
2) detection method: use euzymelinked immunosorbent assay (ELISA) (ELISA) detection Autism children and normal control
The expression of the serum SERPINA5 of group, test kit is purchased from R&D company of the U.S..Test kit uses
Double antibody one step sandwich assay elisa (ELISA): toward being coated anti-human SERPINA5 in advance
Being coated in micropore of albumen (SERPINA5) antibody, is sequentially added into specimen, standard substance, HRP labelling
Detection antibody, through incubation and thoroughly wash.Developing the color with substrate TMB, TMB is at peroxidase
Change into blueness under catalysis, and change into final yellow under the action of an acid.The depth of color and sample
In SERPINA5 albumen be proportionate.Under 450nm wavelength, absorbance (OD is measured by microplate reader
Value), calculate sample concentration.Specific experiment step reference reagent box description, Positive judgement standards is according to examination
Agent box description defines.
3) statistical method: use GraphPad.Prism.v5.01 software to carry out one factor analysis of variance
(ANOVA) and independent sample T inspection.
4) interpretation of result: euzymelinked immunosorbent assay (ELISA) analysis result shows that SERPINA5 is in autism and the most right
It is autism vs Normal group according to the expression in detection group: 3.83 ± 0.47 (2.81～5.11) vs
2.42 ± 0.26 (2.08～3.28), p < 0.001, there is significant difference, concrete outcome such as Fig. 4 between group
Shown in.
SERPINA5 in normal control population and Autism children serum is carried out ELISA detection,
Result show the significantly high expression of SERPINA5 in Autism children serum (autism vs Normal group:
3.83 ± 0.47vs 2.42 ± 0.26): scope of expressing in normal control serum of children is: 2.08～3.28
ng/mL；In Autism children serum express scope be: 2.81～5.11ng/mL, and group between there is pole
Significant difference (p < 0.001).This shows: SERPINA5 is, with autism, closely-related albumen occurs,
Can be as preliminary autism Testing index.
Therefore can by ELISA experiment the SERPINA5 of serum sample to be checked expressed preliminary judgement its
The most also autism: Autism children (2.81～5.11ng/mL)；Normal population (2.08～3.28
ng/mL)。
In sum, the invention discloses a kind of new autism serum polypeptide molecule and detection method thereof and
Application.Its aminoacid sequence is as shown in SEQ.ID.NO.1.This molecule is referred to as SERPINA5-A, is silk
One fragment of serine protease inhibitor suppression A5 (SERPINA5), its accurate molecular weight is 3886
Dalton SERPINA5-A presents significantly high expression in Autism children Virus monitory, uses Matrix-assisted
MALDI-TOF-MS instrument (MALDI-TOF-MS) detection SERPINA5-A or
ELISA method surveys the expression of detection SERPINA5, can be as the detection method of autism serum.
Claims (9)
1. an autism serum polypeptide mark SERPINA5-A, it is characterised in that its aminoacid sequence
Row are as shown in SEQ.ID.NO.1.
2. autism serum polypeptide mark SERPINA5-A as claimed in claim 1, its feature exists
In, this serum polypeptide mark SERPINA5-A is serpin A5SERPINA5
A fragment, molecular weight is 3886 dalton.
3. autism serum polypeptide mark SERPINA5-A as claimed in claim 1, its feature exists
In, the detection parameter in its serum is 2.81～5.11ng/mL.
4. the autism serum polypeptide mark SERPINA5-A described in claim 1 is as autism
The application of the target spot of serum diagnosis medicine.
5. the autism serum polypeptide mark SERPINA5-A described in claim 1 is lonely in preparation
Application in disease serum diagnosis medicine.
Apply the most as claimed in claim 5, it is characterised in that described autism serum diagnosis medicine is
The medicine of ELISA detection autism serum polypeptide molecule.
7. combine with the autism serum polypeptide mark SERPINA5-A described in claim 1
Molecule application in preparation autism serum diagnosis medicine.
8.SERPINA5 albumen is as the application of the target spot of autism serum diagnosis medicine.
9. the molecule combined with SERPINA5 albumen answering in preparation autism serum diagnosis medicine
With.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110850086A (en) * | 2019-11-18 | 2020-02-28 | 西安交通大学 | Application of serum diagnosis marker ACLY for ischemic biliary tract lesion after liver transplantation |
| WO2020140425A1 (en) * | 2019-01-04 | 2020-07-09 | 深圳大学 | Application of group of serum differential protein combinations in preparing reagents for detecting autism |
| CN111471759A (en) * | 2020-05-08 | 2020-07-31 | 西安交通大学 | Application of autism serum neuron-derived exosome marker OSTC |
| WO2020230122A1 (en) | 2019-05-13 | 2020-11-19 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Peptides for the treatment of cancer |
| CN114280309A (en) * | 2021-11-29 | 2022-04-05 | 西安交通大学 | Application of serum polypeptide diagnostic marker C3 for primary depression |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102323365A (en) * | 2011-07-29 | 2012-01-18 | 毅新兴业（北京）科技有限公司 | Mass spectrum model for detecting type I diabetes characteristic protein and construction method |
| CN102558329A (en) * | 2010-12-10 | 2012-07-11 | 中国人民解放军军事医学科学院生物医学分析中心 | Group of specific polypeptides and application thereof in preparing reagents for early diagnosis of lung cancer |
| WO2012115885A1 (en) * | 2011-02-22 | 2012-08-30 | Caris Life Sciences Luxembourg Holdings, S.A.R.L. | Circulating biomarkers |
| CN103328501A (en) * | 2010-12-16 | 2013-09-25 | 奥蒂斯姆生物技术有限公司 | Novel biomarker and uses thereof in diagnosis, treatment of autism |
-
2016
- 2016-02-22 CN CN201610096309.4A patent/CN105738631B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102558329A (en) * | 2010-12-10 | 2012-07-11 | 中国人民解放军军事医学科学院生物医学分析中心 | Group of specific polypeptides and application thereof in preparing reagents for early diagnosis of lung cancer |
| CN103328501A (en) * | 2010-12-16 | 2013-09-25 | 奥蒂斯姆生物技术有限公司 | Novel biomarker and uses thereof in diagnosis, treatment of autism |
| WO2012115885A1 (en) * | 2011-02-22 | 2012-08-30 | Caris Life Sciences Luxembourg Holdings, S.A.R.L. | Circulating biomarkers |
| CN102323365A (en) * | 2011-07-29 | 2012-01-18 | 毅新兴业（北京）科技有限公司 | Mass spectrum model for detecting type I diabetes characteristic protein and construction method |
Non-Patent Citations (2)
| Title |
|---|
| ANTHONY J. RUSSO ET AL.: "Low Serum Alpha-1 Antitrypsin (AAT) in Family Members of Individuals with Autism Correlates with PiMZ Genotype", 《BIOMARKER INSIGHTS》 * |
| BA CORBETT ET AL.: "A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins", 《MOLECULAR PSYCHIATRY》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020140425A1 (en) * | 2019-01-04 | 2020-07-09 | 深圳大学 | Application of group of serum differential protein combinations in preparing reagents for detecting autism |
| WO2020230122A1 (en) | 2019-05-13 | 2020-11-19 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Peptides for the treatment of cancer |
| CN110850086A (en) * | 2019-11-18 | 2020-02-28 | 西安交通大学 | Application of serum diagnosis marker ACLY for ischemic biliary tract lesion after liver transplantation |
| CN110850086B (en) * | 2019-11-18 | 2023-05-02 | 西安交通大学 | Application of serum diagnostic marker ACLY for ischemic biliary tract lesions after liver transplantation |
| CN111471759A (en) * | 2020-05-08 | 2020-07-31 | 西安交通大学 | Application of autism serum neuron-derived exosome marker OSTC |
| CN111471759B (en) * | 2020-05-08 | 2021-11-19 | 西安交通大学 | Application of autism serum neuron-derived exosome marker OSTC |
| CN114280309A (en) * | 2021-11-29 | 2022-04-05 | 西安交通大学 | Application of serum polypeptide diagnostic marker C3 for primary depression |
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