CN108802379A - One group of molecular marker group for judging dissection of aorta prognosis - Google Patents
One group of molecular marker group for judging dissection of aorta prognosis Download PDFInfo
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Abstract
The present invention relates to one group of molecular marker group for judging dissection of aorta prognosis, the molecular marker is protein factor, and the protein factor is：TRAIL：TRAIL mRNA (TNF-related apoptosis inducing ligand)；OPG：Osteoprotegerin (osteoprotegerin)；D-dimer：D-dimer；The judgment method is：Pediatric risk of mortality score (LP)=- 5.2903+0.9318*Ln (OPG/TRAIL)+0.5227*Ln (D-dimer) in 1 year；Adverse reaction probability of happening (One-year risk of all-cause mortality)=1-0.947^exp { LP } in 1 year.
Description
Technical field
The invention belongs to technical field of pharmaceutical biotechnology, in particular to one group for judging dissection of aorta prognosis
Molecular marker group.
Background technology
Dissection of aorta (AD) is a kind of common cardiovascular critical illness, it is due to aorta wall part or diffusivity
Abnormal dilatation, oppress peripheral organs and cause corresponding symptom, be a kind of potentiality fatal disease.Dissection of aorta at present
It makes a definite diagnosis and depends on imageological examination, but it lacks simplicity.So diagnosed using effective laboratory examination project,
Prevent and prediction dissection of aorta have become a very active research field, it is often more important that monitoring and predictive disease with
The differentiation of time, clinical risk is assessed.
Dissection of aorta is the most dangerous one of arotic disease, however clinically preferably predict it at present
The biomarker of badness come-off.Biomarker may be implemented shorten Diagnostic Time, also can Expedite the application treatment, to urgency
Property artery dissection prognosis prompt significance.Previously research report, D-dimer, CRP and NT-proBNP can be predicted
It is dead in AAAD Hospital of Patients, but have certain limitation, long-range forecasting value is unknown.So finding that one kind can be with early prediction
The new reliable marker of badness come-off has important clinical significance.
Invention content
Present invention firstly relates to one group of serodiagnosis markers for judging dissection of aorta patient's prognosis, described
Blood serum designated object is protein factor, and the protein factor is：
TRAIL：TRAIL mRNA (TNF-related apoptosis inducing
ligand)；
OPG：Osteoprotegerin (osteoprotegerin)；
D-dimer：D-dimer；
Judgement dissection of aorta patient's prognosis refers to, and predicts the clinical adverse incidence in period certain time
Or mortality risk is classified, the adverse reaction includes but not limited to：It is dead, diffuse or local nerve ischemic injuries, acute
Renal failure, acute heart failure, aorta rupture, cerebral infarction or cerebral apoplexy postoperative open chest again.
Period certain time refers to：It detects in the certain time after the serodiagnosis marker, preferred one
In year；
The size that the described mortality risk classification passes through pediatric risk of mortality score (LP) value be low danger (<5 points), middle danger (5-15
Point), it is high-risk (>15 points) three-level；The calculation formula of the LP values is：
LP=-5.2903+0.9318*Ln (OPG/TRAIL)+0.5227*Ln (D-dimer)
Wherein, the unit of D-dimer is ng/ml；
The calculating of the adverse reaction probability of happening (One-year risk of all-cause mortality) is public
Formula is：
Adverse reaction probability of happening=1-0.947^exp { LP }.
The invention further relates to one group of serodiagnosis markers in the detection for preparing prediction dissection of aorta prognosis
Application in kit, the kit further include the content for OPG, TRAIL and D-dimer in quantitative patient's serum
Reagent.
It is using the method that the kit predicts dissection of aorta prognosis：
(1) serum sample of patient to be measured is collected；
(2) content of the serodiagnosis marker in ELISA method detection sample is used；
(3) it substitutes into following formula and calculates pediatric risk of mortality score and adverse reaction probability of happening in 1 year in 1 year
Pediatric risk of mortality score (LP)=- 5.2903+0.9318*Ln (OPG/TRAIL)+0.5227*Ln (D- in 1 year
dimer)
Wherein, the unit of D-dimer is ng/ml；
According to result of calculation by mortality risk in 1 year be divided into it is low danger (<5 points), middle danger (5-15 point), it is high-risk (>15 points) three
Grade.
Adverse reaction probability of happening (One-year risk of all-cause mortality)=1-0.947 in 1 year
^exp{LP}。
The diagnostic kit is the diagnostic kit diagnosed using ELISA principles.
The kit further includes sample diluting liquid, for the antibody of the diagnosis marker, color developing agent.
The invention further relates to the method for using the serodiagnosis marker to predict dissection of aorta prognosis, the methods
Include the following steps：
(1) serum sample of patient to be measured is collected；
(2) content of the serodiagnosis marker in ELISA method detection sample is used；
(3) it substitutes into following formula and calculates pediatric risk of mortality score and adverse reaction probability of happening in 1 year in 1 year
Pediatric risk of mortality score (LP)=- 5.2903+0.9318*Ln (OPG/TRAIL)+0.5227*Ln (D- in 1 year
dimer)
Adverse reaction probability of happening (One-year risk of all-cause mortality)=1-0.947 in 1 year
^exp{LP}。
Description of the drawings
(event includes for scatter plot that Fig. 1, serum OPG concentration compare in no event group and having in event group：Death diffuses
Or local nerve ischemic injuries, acute renal failure, acute heart failure, aorta rupture, cerebral infarction or cerebral apoplexy, postoperative chest is opened again).With impunity
Part group is compared, and OPG concentration in having event group is significantly raised.
Fig. 2, OPG often increase a SD (standard deviation), and the dead occurrence risk with adverse events in institute increases 3.153 respectively
(P is equal with 2.628 times<0.05), the computational methods of SD values：OPG data are done into ln conversions, according to average-standard deviation, averagely
Transformed numerical value is divided into 4 layers by number, average+standard deviation, calculates the HR values for often rising the layering of a standard deviation, dead and institute
The occurrence risk of interior adverse events increases 3.153 and 2.628 times respectively, and (P is equal<0.05)
Fig. 3, OPG are divided into four layers according to quartile from low to high, and two, three, four layers occur wind relative to first layer death
Danger increases 0.676 (P respectively>0.05),1.257(P>And 4.990 (P 0.05)<0.05) again.Two, three, four layers relative to first layer
Adverse events occurrence risk increases 2.023 (P respectively in institute>0.05),3.790(P<And 7.497 (P 0.05)<0.05) again.
Fig. 4, ROC curve：OPG differentiations have event group and are 0.718 (0.654- without area (AUC) under event suite line
0.783)。
Fig. 5, compare serum T RAIL concentration in no event group (no event) and have the difference of event group (event).With nothing
Event group is compared, and TRAIL concentration in having event group is substantially reduced.
Fig. 6, TRAIL often increase a SD (standard deviation), and the dead occurrence risk with adverse events in institute increases respectively
0.408 and 0.457 times (P is equal<0.05).
Fig. 7, TRAIL are divided into four layers according to quartile from low to high, and two, three, four layers relative to first layer death and institute
The occurrence risk of interior adverse events increases 0.278 (P respectively>0.05),0.278(P>And 0.098 (P 0.05)<0.05) again.Two,
Three, 0.298 (P is increased respectively relative to adverse events occurrence risk in first layer institute for four layers<0.05),0.366(P<0.05) and
0.094(P<0.05) again.
Fig. 8, TRAIL differentiation have event group and are 0.715 (0.650-0.781) without area (AUC) under event suite line.
Fig. 9, OPG/TRAIL and D-dimer are having event group and the scatter plot compared without event group (note：Ordinate is distinguished
Log10 conversions are done for OPG/TRAIL D-dimer detected values).
Figure 10, OPG/TRAIL and D-dimer predict the COX regression analyses of event in dead and institute (respectively to OPG/ respectively
TRAIL and Ddimer is done according to average-standard deviation after ln conversions, and average, average+standard difference is four layers, with COX wind
Dangerous regression model calculates separately the two indexs and often rises the risk that event risk in dead or institute occurs for a standard deviation, bracket
It is inside 95% confidence interval).
Figure 11, according to OTD models carry out it is low in high-risk layering K-M scheme.
The K-M of Figure 12, OTD model external certificate schemes.
Specific implementation mode
Embodiment 1, dissection of aorta Index for diagnosis molecular marked compound difference verification
Dissection of aorta patient 418 is selected, median time follow-up in 19.8 months is carried out, according to Follow-up results by patient
The ELISA experiments for being divided into no event group, having event group to carry out haemocyanin marker, use corresponding RayBiotech Human
ELISA Kit detect the expression of 9 kinds of protein factors, and can verify the histone factor be effectively predicted dissection of aorta trouble
Person's prognosis situation.
Experimental procedure：
1, reagent prepares
(1) by kit and Sample equilibration to room temperature (18-25 DEG C)；
(2) sample carries out the blood serum sample of personnel to be measured according to multiple shown in the following table 1 dilute according to preliminary result
It releases.
Extension rate when table 1, the different diagnostic marker objects of detection
| Detect target | Extension rate |
| TRAIL | 1.5 |
| FN1 | 20000 |
| LCN2 | 200 |
| PLG | 50000 |
| OPG | 5 |
| ANG | 30 |
| LOX-1 | 10 |
| SAA | 50 |
| PF4 | 4000 |
(3) Assay Diluent (Item E) are spare using 5 times of deionized water dilution；
(4) standard items prepare:
Item C tubules are centrifuged, are then added in 400 μ L Assay Diluent (Item E) to standard items tubule, are mixed
It is the standard stock liquid of 50ng/ml after uniformly；
Prepare 8 small centrifuge tubes of 1.5ml, 475 μ L Assay Diluent buffer solutions are added toward first pipe, then extract
The 25 μ L of standard stock liquid of 50ng/ml are added in first pipe, are after mixing 2500pg/ml, are labeled as STD1；
Toward remainder 7 pipes be separately added into 300 μ L Assay Diluent buffer solutions, later successively be labeled as STD2, STD3,
STD4,STD5,STD6,STD7；
Then the STD1 gradient dilution standard items for using 50ng/ml extract 200 μ L 50ng/ml standard solution (i.e. STD1) and add
Enter in STD2 tubules, mixing after 200 μ L solution in the pipe are added in STD3 tubules is extracted after mixing, method is until preparing successively
Good STD7, STD 8 are 300 μ L Assay Diluent, that is, standard items 0pg/ml；
(5) washing lotion dilutes：It is spare that 20 times of washing lotion dilution will be concentrated with deionized water；
(6) centrifugation detection antibody tubule (tem F) is added 100 μ L dilution 1x Assay Diluent (Item E) and fills
Divide dissolving, gently blown and beaten up and down with pipettor, is used after then diluting 80 times with dilution 1x Assay Diluent；
7) centrifugation HRP- Streptavidins (Item G), after then dilution 1x Assay Diluent being used to dilute 200 times
It uses；
2, operating procedure
(1) by kit and Sample equilibration to room temperature (18-25 DEG C)；Standard items and sample segment are examined using multiple holes
It surveys, the detection of sample segment single hole；
(2) the elisa plate of coated antibody is balanced to room temperature, and the 100 prepared standards of μ L are added in corresponding hole
Product and sample seal monoblock lath, 4 DEG C of overnight incubations with sealing plate film；
(3) prepared 1x washing lotions are added on board-washing machine, lath is cleaned 4 times with board-washing machine, 300 μ L are added per hole and wash
Liquid；
(4) after board-washing is clean, the prepared detection antibody (biotin labelled antibodies) of 100 μ L, incubation at room temperature are added per hole
1h；
(5) it cleans, step is the same as (3)；
(6) the prepared HRP- Streptavidins of 100 μ L are added per hole and are incubated at room temperature 45min；
(7) it cleans, step is the same as (3)；
(8) it is added in 100 μ L TMB developing solutions to every hole, room temperature, which is protected from light, is incubated 30min；
(9) it is added in 50 μ L terminate liquids to every hole, is read immediately in microplate reader 450nm；
(10) 12.0 softwares of sigmaplot are used to calculate concentration value.
3, statistical result：
(1) 9 protein factor expression differences see the table below 2 in test serum.
Table 2, ELISA explore the result that protein diversity is expressed in serum sample 9
LCN2：Lipocalin-2, lipocalin 2
LOX-1：Lectin-like oxidized LDL receptor-1
TRAIL：TRAIL mRNA, TNF-related apoptosis inducing
ligand
FN1：Fibronectin, fibronectin
PF4：Platlet factor 4, CXCL4, platelet factor 4
SAA：Serum Amyloid A, serum amyloid A protein
OPG：Osteoprotegerin, osteoprotegerin, tumor necrosis factor receptor super family, member 11b
(TNFRSF11B)
PLG：Plasminogen, plasminogen
ANG：Angiopoietin, angiogenesis factor.
OPG is increased in having event group patient, and TRAIL is reduced in having event group patient, the past document report OPG and
TRAIL plays a role on an access, so being selected in having event group and having 4 factors of differential expression without event group
OPG and TRAIL is as the subsequent authentication factor.It is divided by OPG and TRAIL to obtain ratio simultaneously, it is OTD models with Ddimer to combine
For predicting dissection of aorta patient's prognosis situation.
(2) OPG is there is event group and the scatter plot without event group differential expression is shown in Fig. 1.OPG is having event group expression raising.
(3) OPG often rise that the prediction of standard deviation is dead or institute in the risks of adverse events see Fig. 2.OPG is done
According to average-standard deviation after log10 conversions, average, average+standard difference is four layers, counts every with COX homing methods
Rise the multiple that event risk in dead or institute is respectively increased in standard deviation the two indexs, is 95% confidence area in bracket
Between, OPG often increases the dead occurrence risk with adverse events in institute of a SD (standard deviation) and increases 3.153 and 2.628 times respectively
(P is equal<0.05).
(4) OPG is shown in Fig. 3 according to the risk of event in the death of quartile hierarchical prediction or institute.OPG according to quartile from
Low to high to be divided into four layers, two, three, four layers increase 0.676 (P respectively relative to first layer death occurrence risk>0.05),1.257
(P>And 4.990 (P 0.05)<0.05) again.Two, it is increased respectively relative to adverse events occurrence risk in first layer institute for three, four layers
2.023(P>0.05),3.790(P<And 7.497 (P 0.05)<0.05) (it is divided into four layers according to OPG quartiles, most with numerical value again
The namely first layer of small one layer is respectively compared other three layers as reference, with COX homing methods and occurs extremely relative to first layer
Die or institute in the raised risk multiple of event).
(5) OPG, which distinguishes dissection of aorta patient, has event and the ROC curve without event to see Fig. 4.OPG differentiations have event group
It is 0.718 (0.654-0.783) with area (AUC) under no event suite line.
(6) TRAIL is there is event group and the scatter plot without event group differential expression is shown in Fig. 5.TRAIL is having event group expression to reduce.
(7) TRAIL often rise that the prediction of standard deviation is dead or institute in the risks of adverse events see Fig. 6.TRAIL is done
According to average-standard deviation after log10 conversions, average, average+standard difference is four layers, counts every with COX homing methods
Rise the multiple that event risk in dead or institute is respectively increased in standard deviation the two indexs, is 95% confidence area in bracket
Between, TRAIL often increases the dead occurrence risk with adverse events in institute of a SD (standard deviation) and increases 0.408 and 0.457 respectively
(P is equal again<0.05)
(8) TRAIL is shown in Fig. 7 according to the risk of event in the death of quartile hierarchical prediction or institute.TRAIL is according to quartile
Number is divided into four layers from low to high, and two, three, four layers increase 0.278 (P respectively relative to first layer death occurrence risk>0.05),
0.278(P>And 0.098 (P 0.05)<0.05) again.Two, distinguish relative to adverse events occurrence risk in first layer institute for three, four layers
Increase 0.298 (P<0.05),0.366(P<And 0.094 (P 0.05)<0.05) times (it is divided into four layers according to TRAIL quartiles, with
One layer of namely first layer of numerical value minimum is respectively compared other three layers relative to first layer as reference with COX homing methods
The raised risk multiple of event in dead or institute occurs).
(9) TRAIL, which distinguishes dissection of aorta patient, has event and the ROC curve without event to see Fig. 8.TRAIL distinguishes busy
Part group and without area (AUC) under event suite line be 0.715 (0.650-0.781).
(10) OPG/TRAIL and Ddimer in no event group and has the differential expression of event group to see Fig. 9.OPG/TRAIL and
Ddimer is increased in having event group, and difference is statistically significant, and (P is equal<0.05).
(11) OPG/TRAIL and D-dimer predicts that Figure 10 is shown in the COX regression analyses of event in dead and institute respectively.Respectively
OPG/TRAIL and Ddimer are done according to average-standard deviation after log10 conversions, average, average+standard difference is four
Layer often rises the HR that event risk in dead or institute is respectively increased in standard deviation the two indexs with COX homing methods statistics
Value and 95% confidence interval.As a result showing OPG/TRAIL and Ddimer has good prognostic value, OPG/TRAIL pre-
Value is surveyed compared with D-dimer highers.
(12) the K-M curves of 1 annual death rate of OTD model predictions dissection of aorta patient are shown in Figure 11.Joint OPG/TRAIL and
The two indexs of Ddimer are fitted OTD models, 1 year mortality risk of all patients are calculated by COX regression formulas, according to dead wind
Danger be divided into it is low danger (<5 points), middle danger (5-15 point), it is high-risk (>15 points) three groups, Kaplan-Meier survivorship curves are done by this grouping,
As a result find out, higher 1 annual death rate of grouping of scoring is higher.1 year mortality risk divides the LP calculation formula to be：
LP (linear predictor)=- 5.2903+0.9318*Ln (OPG/TRAIL)+0.5227*Ln (D-dimer)
Adverse reaction probability of happening (One-year risk of all-cause mortality)=1- in 1 year
0.947^exp{LP}
Embodiment 2, dissection of aorta Index for diagnosis molecular marked compound large sample verification
Outer court dissection of aorta patient 271 is selected, the ELISA experiments of haemocyanin marker are carried out, using corresponding
RayBiotech Human ELISA Kit, the expression for two protein factors of OPG and TRAIL that detection embodiment 1 is selected,
Can verification OTD models be effectively predicted dissection of aorta patient's prognosis situation.
Experimental procedure is as follows：
1, reagent prepares
(1) by kit and Sample equilibration to room temperature (18-25 DEG C)；
(2) sample is diluted the blood serum sample of personnel to be measured according to multiple shown in the following table 2 according to preliminary result.
Extension rate when table 2, the different diagnostic marker objects of detection
| Detect target | Extension rate |
| TRAIL | 1.5 |
| OPG | 5 |
(3) Assay Diluent (Item E) are spare using 5 times of deionized water dilution；
(4) standard items prepare:
Item C tubules are centrifuged, are then added in 400 μ L Assay Diluent (Item E) to standard items tubule, are mixed
It is the standard stock liquid of 50ng/ml after uniformly；
Prepare 8 small centrifuge tubes of 1.5ml, 475 μ L Assay Diluent buffer solutions are added toward first pipe, then extract
The 25 μ L of standard stock liquid of 50ng/ml are added in first pipe, are after mixing 2500pg/ml, are labeled as STD1；
Toward remainder 7 pipes be separately added into 300 μ L Assay Diluent buffer solutions, later successively be labeled as STD2, STD3,
STD4,STD5,STD6,STD7；
Then the STD1 gradient dilution standard items for using 50ng/ml extract 200 μ L 50ng/ml standard solution (i.e. STD1) and add
Enter in STD2 tubules, mixing after 200 μ L solution in the pipe are added in STD3 tubules is extracted after mixing, method is until preparing successively
Good STD7, STD 8 are 300 μ L Assay Diluent, that is, standard items 0pg/ml；
(5) washing lotion dilutes：It is spare that 20 times of washing lotion dilution will be concentrated with deionized water；
(6) centrifugation detection antibody tubule (tem F) is added 100 μ L dilution 1x Assay Diluent (Item E) and fills
Divide dissolving, gently blown and beaten up and down with pipettor, is used after then diluting 80 times with dilution 1x Assay Diluent；
(7) centrifugation HRP- Streptavidins (Item G), after then dilution 1x Assay Diluent being used to dilute 200 times
It uses；
2, operating procedure
(1) by kit and Sample equilibration to room temperature (18-25 DEG C)；Standard items and sample segment are examined using multiple holes
It surveys, the detection of sample segment single hole；
(2) the elisa plate of coated antibody is balanced to room temperature, and the 100 prepared standards of μ L are added in corresponding hole
Product and sample seal monoblock lath, 4 DEG C of overnight incubations with sealing plate film；
(3) prepared 1x washing lotions are added on board-washing machine, lath is cleaned 4 times with board-washing machine, 300 μ L washing lotions are added per hole；
(4) after board-washing is clean, the prepared detection antibody (biotin labelled antibodies) of 100 μ L are added per hole, are incubated at room temperature 1h；
(5) it cleans, step is the same as (3)；
(6) the prepared HRP- Streptavidins of 100 μ L are added per hole and are incubated at room temperature 45min；
(7) it cleans, step is the same as (3)；
(8) it is added in 100 μ L TMB developing solutions to every hole, room temperature, which is protected from light, is incubated 30min；
(9) it is added in 50 μ L terminate liquids to every hole, is read immediately in microplate reader 450nm.
(10) 12.0 softwares of sigmaplot are used to calculate concentration value.
Experimental result is as follows：
The Kaplan-Meier curves of 1 annual death rate of external certificate queue verification OTD model prediction dissection of aorta patient
See figure.
According to finding that 1 annual death rate calculation formula of queue brings 1 that OPG/TRAIL and D-dimer obtains each patient into
Year Mortality Prediction risk (being shown in Table 3), according to<5 points, 5-15 points,>15 points are divided into three groups basic, normal, high, and Kaplan- is according to this grouping
Meier curves.As a result it appear that, higher 1 annual death rate of grouping of scoring is higher, and is shown according to Follow-up results, finds queue
In, death toll is respectively in high, medium and low danger patient 1 year：25,10,5 people；It verifies in queue, high, medium and low danger patient 1 year is extremely
The number of dying is respectively：14,9,1 people illustrates that OTD models can be very good 1 annual death rate of prediction dissection of aorta patient.
Table 3, outer court dissection of aorta patient 271 mortality risk predicted value
Finally, it should be noted that above example only helps skilled in the art to understand the essence of the present invention, do not have to
Do limiting the scope of the present invention.
Claims (8)
1. one group of serodiagnosis marker group for judging dissection of aorta patient's prognosis, the blood serum designated object is egg
Bai Yinzi, the protein factor are：
TRAIL：TRAIL mRNA (TNF-related apoptosis inducing
ligand)；
OPG：Osteoprotegerin (osteoprotegerin)；
D-dimer：D-dimer.
2. one group is preparing the detection reagent for judging dissection of aorta prognosis by serodiagnosis marker described in claim 1
Application in box, the kit include the reagent for the blood serum designated object group content in quantitative patient's serum.
3. kit according to claim 2, which is characterized in that judgement dissection of aorta patient's prognosis refers to, in advance
The clinical adverse incidence surveyed in period certain time is classified mortality risk, and the adverse reaction includes but unlimited
In：It is dead, diffuse or local nerve ischemic injuries, acute renal failure, acute heart failure, aorta rupture, cerebral infarction or cerebral apoplexy, it is postoperative again
Open chest.
4. kit according to claim 2 or 3, which is characterized in that period certain time refers to：Detect the blood
In certain time after clear diagnosis marker group, in preferably 1 year.
5. kit according to claim 2 or 3, which is characterized in that the mortality risk classification passes through mortality risk
Score (LP) value size be it is low danger (<5 points), middle danger (5-15 point), it is high-risk (>15 points) three-level；The calculating of the LP values is public
Formula is：
LP=-5.2903+0.9318*Ln (OPG/TRAIL)+0.5227*Ln (D-dimer)
Wherein, the unit of D-dimer is ng/ml；
The calculation formula of the adverse reaction probability of happening (One-year risk of all-cause mortality) is：
Adverse reaction probability of happening=1-0.947^exp { LP }.
6. a kind of detection kit judging dissection of aorta prognosis, which is characterized in that the kit includes for quantitative
The reagent of the blood serum designated object group content in patients serum.
7. detection kit according to claim 6, which is characterized in that the diagnostic kit is to utilize ELISA originals
Manage the diagnostic kit diagnosed.
8. the detection kit described according to claim 6 or 7, which is characterized in that the kit further includes sample dilution
Liquid, for the antibody of the diagnosis marker group, color developing agent etc..
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810614415.6A CN108802379B (en) | 2018-06-14 | 2018-06-14 | Group of molecular markers for judging aortic dissection prognosis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810614415.6A CN108802379B (en) | 2018-06-14 | 2018-06-14 | Group of molecular markers for judging aortic dissection prognosis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108802379A true CN108802379A (en) | 2018-11-13 |
| CN108802379B CN108802379B (en) | 2021-04-16 |
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