CN117607432A - Application of MSR1 protein and specific antibody thereof in preparation of neural syphilis or neural injury diagnostic product - Google Patents
Application of MSR1 protein and specific antibody thereof in preparation of neural syphilis or neural injury diagnostic product Download PDFInfo
- Publication number
- CN117607432A CN117607432A CN202410066811.5A CN202410066811A CN117607432A CN 117607432 A CN117607432 A CN 117607432A CN 202410066811 A CN202410066811 A CN 202410066811A CN 117607432 A CN117607432 A CN 117607432A
- Authority
- CN
- China
- Prior art keywords
- msr1
- syphilis
- cerebrospinal fluid
- protein
- nerve
- 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.)
- Granted
Links
- 101001134216 Homo sapiens Macrophage scavenger receptor types I and II Proteins 0.000 title claims abstract description 126
- 102100034184 Macrophage scavenger receptor types I and II Human genes 0.000 title claims abstract description 126
- 208000006379 syphilis Diseases 0.000 title claims abstract description 123
- 230000001537 neural effect Effects 0.000 title claims description 24
- 230000006378 damage Effects 0.000 title description 14
- 208000027418 Wounds and injury Diseases 0.000 title description 4
- 239000012502 diagnostic product Substances 0.000 title description 4
- 208000014674 injury Diseases 0.000 title description 4
- 238000002360 preparation method Methods 0.000 title description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims abstract description 122
- 208000028389 Nerve injury Diseases 0.000 claims abstract description 49
- 230000008764 nerve damage Effects 0.000 claims abstract description 49
- 238000001514 detection method Methods 0.000 claims abstract description 45
- 210000005036 nerve Anatomy 0.000 claims abstract description 42
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 37
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 37
- 238000003745 diagnosis Methods 0.000 claims abstract description 36
- 238000013399 early diagnosis Methods 0.000 claims abstract description 17
- 210000000265 leukocyte Anatomy 0.000 claims abstract description 14
- 238000011156 evaluation Methods 0.000 claims abstract description 13
- 239000003550 marker Substances 0.000 claims abstract description 13
- 208000002040 neurosyphilis Diseases 0.000 claims description 108
- 210000002966 serum Anatomy 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 13
- 239000000523 sample Substances 0.000 claims description 11
- 238000004458 analytical method Methods 0.000 claims description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- 208000024891 symptom Diseases 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 5
- 238000012216 screening Methods 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 4
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 claims description 4
- 230000002490 cerebral effect Effects 0.000 claims description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 claims description 4
- 238000004820 blood count Methods 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 238000012360 testing method Methods 0.000 claims description 3
- 241000283707 Capra Species 0.000 claims description 2
- 238000008157 ELISA kit Methods 0.000 claims description 2
- 208000012902 Nervous system disease Diseases 0.000 claims description 2
- 102000003992 Peroxidases Human genes 0.000 claims description 2
- 239000011324 bead Substances 0.000 claims description 2
- 229960002685 biotin Drugs 0.000 claims description 2
- 235000020958 biotin Nutrition 0.000 claims description 2
- 239000011616 biotin Substances 0.000 claims description 2
- 210000000601 blood cell Anatomy 0.000 claims description 2
- 239000007979 citrate buffer Substances 0.000 claims description 2
- 230000002055 immunohistochemical effect Effects 0.000 claims description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 claims description 2
- 229920001184 polypeptide Polymers 0.000 claims description 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
- 229960005322 streptomycin Drugs 0.000 claims description 2
- 230000035945 sensitivity Effects 0.000 abstract description 18
- 238000011282 treatment Methods 0.000 abstract description 8
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 230000002349 favourable effect Effects 0.000 abstract 1
- 239000003147 molecular marker Substances 0.000 abstract 1
- 238000004393 prognosis Methods 0.000 abstract 1
- 201000000253 asymptomatic neurosyphilis Diseases 0.000 description 20
- 102000009265 Cerebrospinal Fluid Proteins Human genes 0.000 description 8
- 108010073496 Cerebrospinal Fluid Proteins Proteins 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
- 239000000090 biomarker Substances 0.000 description 5
- 230000002596 correlated effect Effects 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 231100000189 neurotoxic Toxicity 0.000 description 4
- 230000002887 neurotoxic effect Effects 0.000 description 4
- 241000589884 Treponema pallidum Species 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 238000009593 lumbar puncture Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 206010012289 Dementia Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 230000007658 neurological function Effects 0.000 description 2
- 230000001769 paralizing effect Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 1
- 208000008306 Latent Syphilis Diseases 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 206010061391 Tuberculosis of central nervous system Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000010219 correlation analysis Methods 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000002331 protein detection Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
Classifications
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/571—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses for venereal disease, e.g. syphilis, gonorrhoea
-
- 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
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- Physics & Mathematics (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention relates to the technical field of biological medicines, in particular to a cerebrospinal fluid molecular marker MSR1 serving as a marker for early diagnosis and typing detection and assessment of nerve injury severity of a patient with nerve syphilis. The invention can be used as indexes of early diagnosis, clinical typing, nerve injury degree evaluation and the like of the nerve syphilis by measuring the concentration of MSR1 protein in cerebrospinal fluid, and the indexes can be used as main reference indexes singly or in combination with other indexes to complete diagnosis, typing and nerve injury evaluation of the syphilis. Compared with the disclosed detection of the nerve syphilis marker protein and the detection of the white blood cell number, the marker has higher sensitivity to the early asymptomatic nerve syphilis, can accurately diagnose asymptomatic nerve syphilis and non-nerve syphilis patients, and is favorable for early diagnosis, treatment and prognosis management of the nerve syphilis.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to application of MSR1 protein and a specific antibody thereof in preparing a detection kit, a protein chip, a protein probe or a protein detector for diagnosing, typing detecting or evaluating nerve damage degree of nerve syphilis.
Background
Syphilis is a systemic infectious disease caused by invasion of treponema pallidum into the human body. Treponema pallidum spreads to the central nervous system within days after infection and can lead to asymptomatic meningitis and severe symptomatic neurosyphilis, i.e., the occurrence of neurosyphilis.
The neurosyphilis (neurophyisis) is a group of clinical syndromes of damage such as meninges, brains, blood vessels or spinal cords and the like caused by invasion of treponema pallidum into the nervous system, and has various manifestations, can have no clinical symptoms, and can also be represented as complex clinical manifestations caused by extensive involvement of the nervous system. Because of atypical clinical manifestations, the misdiagnosis rate is high and can reach 55.6%. For example, cerebral infarction caused by neuro-syphilis with unknown causes of young and young age, occurrence of epilepsy in young and young age, intelligent disorder and the like are frequently misdiagnosed. The neurosyphilis is classified into type 5 according to its clinical symptoms: asymptomatic, meningo-syphilis, meningo-vascular syphilis, tuberculosis of spinal cord and paralytic dementia. Although the asymptomatic neural syphilis patient has no obvious symptoms or signs, the cerebrospinal fluid is abnormally changed, and the probability of the asymptomatic neural syphilis patient developing into symptomatic neural syphilis is up to 87% when the cerebrospinal fluid abnormality lasts for more than 5 years. Because the asymptomatic neural syphilis patient has no obvious symptoms, the asymptomatic neural syphilis is detected as early as possible and is treated in time by the aid of the early and sensitive neural syphilis detection indexes, so that the asymptomatic neural syphilis is reduced to be developed into symptomatic neural syphilis, the disease development of nerve injury is delayed, the patient can be reasonably treated as early as possible, and the purpose of ensuring normal work and life of the syphilis patient is achieved, and pain and social burden of the patient are relieved.
Early diagnosis of neurosyphilis is very important, and finding sensitive biomarkers will help diagnosis of neurosyphilis, especially identifying patients with neurosyphilis including asymptomatic neurosyphilis, has great significance for preventing serious and irreversible nerve injury sequelae. Furthermore, neurosyphilis can occur at various stages of the syphilis course, not just in late stage syphilis, and thus all syphilis patients need to be subjected to strict screening for neurosyphilis. At present, the diagnosis of the neurosyphilis mainly depends on indexes such as neurological symptoms or signs, blood plasma, cerebrospinal fluid and the like to carry out comprehensive judgment. Cerebrospinal fluid indices include cerebrospinal fluid venereal disease research laboratory test (VDRL)/rapid serum reactive loop card test (RPR), cerebrospinal fluid white blood cell count and cerebrospinal fluid total protein levels. If VDRL/RPR is a negative result, it can also be diagnosed as a neurosyphilis if it is clinically symptomatic, serological positive and abnormal in cerebrospinal fluid cell count, but the patient has serious nerve damage at this stage of diagnosis. In addition, the sensitivity of VDRL/RPP is only 30% -70% found in the diagnosis process, the sensitivity is lower and the diagnosis of asymptomatic neurosyphilis is not sensitive, so that the development of a diagnostic reagent which is more sensitive to asymptomatic neurosyphilis, the accurate diagnosis in early stage of the disease and the provision of corresponding treatment are required.
In conclusion, the diagnosis and treatment of the neurosyphilis are mainly carried out on patients with the symptom of the neurosyphilis in the clinical diagnosis and treatment process at present, and sensitive and reliable biological markers for effectively distinguishing the neurosyphilis are lacked. The current judgment of the nerve injury degree only depends on the experience of doctors, and objective biological indexes for judging the nerve injury degree are lacked. The development of new markers for diagnosis of neurosyphilis is of great significance in diagnosis, typing and assessment of the degree of nerve damage.
Disclosure of Invention
First, the technical problem to be solved
In view of the problems that the existing neural syphilis diagnosis method is insensitive to early asymptomatic neural syphilis, the judgment of the degree of nerve injury needs to depend on the experience of a clinician, and the like, the invention provides a cerebrospinal fluid marker for early diagnosis, parting detection and nerve injury assessment of the neural syphilis, and the early diagnosis, parting detection and nerve injury degree assessment of the neural syphilis can be realized by utilizing the marker; compared with the prior art, the marker has higher sensitivity, and can accurately diagnose asymptomatic nervous syphilis and non-nervous syphilis patients, so that the corresponding patients can be timely given reasonable treatment and management.
(II) technical scheme
In order to achieve the above purpose, the main technical scheme adopted by the invention comprises the following steps:
in a first aspect, the invention relates to MSR1 as a marker of cerebrospinal fluid for early diagnosis, clinical typing and detection of nerve damage in patients with neurosyphilis.
In a second aspect, the invention provides the use of an MSR1 protein and its specific antibodies in the manufacture of a diagnostic product or an auxiliary diagnostic product for diagnosis, typing detection or assessment of the extent of neurological impairment; the method is characterized in that the diagnosis product or auxiliary diagnosis product is a detection kit, a protein chip, a protein probe or a protein detector which takes MSR1 protein or specific antibody thereof as target molecule.
According to the preferred embodiment of the invention, the detection kit takes MSR1 protein or the specific antibody thereof as a biomarker to detect the expression level of the MSR1 protein or the specific antibody thereof in cerebrospinal fluid.
According to a preferred embodiment of the invention, the detection kit is an MSR1 ELISA kit or an immunohistochemical kit.
According to a preferred embodiment of the invention, the kit comprises: primary antibody capable of specifically recognizing MSR1, polypeptide dye, magnetic bead and biotin labeled secondary antibody.
According to a preferred embodiment of the invention, the detection kit further comprises citrate buffer, PBS wash, peroxidase blocker, goat serum, streptomycin antibiotic-peroxidase, DAB solution and hematoxylin solution.
According to a preferred embodiment of the invention, the detection kit further comprises reagents, means or materials for separating cerebrospinal fluid from the patient.
It should be noted that, in detecting the expression level of the MSR1 protein in cerebrospinal fluid, an Olink ultra-high sensitivity protein detection platform can also be used to quantify the expression level of MSR 1.
In a third aspect, the present invention also relates to a product for early diagnosis, screening, typing detection or assessment of the extent of neurological damage in a patient suffering from a neuro-syphilis; the method is characterized in that the product can quantitatively detect the concentration of MSR1 in cerebrospinal fluid; the product is a detection kit, a protein chip, a protein probe or a protein detector which takes MSR1 protein or a specific antibody thereof as a target molecule; the product comprises an antibody that specifically recognizes MSR 1.
Preferably, the product comprises antibodies and other reagents that specifically bind MSR1 to quantitatively detect the concentration of MSR1 protein in serum and cerebrospinal fluid. The experimental method as used in the examples of the present application is Olink neurology panel (95801), which can be used to detect 92 protein biomarkers associated with neurological function, including MSR1 protein in this patent.
The syphilis type includes symptomatic nerve syphilis, asymptomatic nerve syphilis or non-nerve syphilis, i.e. recessive syphilis, etc.
In a fourth aspect, the present invention relates to a diagnostic system for neurosyphilis comprising:
comprises a first analysis unit and a second analysis unit;
the first analysis unit is a detection reagent composition, an antibody chip or an antibody probe for detecting the MSR1 protein level of cerebrospinal fluid; the second analysis unit is a blood cell counting plate/blood cell analyzer for detecting the level of white blood cells in cerebrospinal fluid or a detection reagent composition/biochemical analyzer for detecting the level of total protein in cerebrospinal fluid.
In the scheme, when diagnosing the neurosyphilis (including early diagnosis, typing and assessing nerve damage), two or even three indexes of the cerebrospinal fluid MSR1 protein level and the cerebrospinal fluid leucocyte and cerebrospinal fluid total protein level related to the nerve damage of the neurosyphilis patient can be combined for early diagnosis, typing and assessing the nerve damage of the neurosyphilis.
Wherein, MSR1 level in cerebrospinal fluid is detected by Olink precise proteomics, i.e. immunoassay of antibodies, combined with quantitative real-time PCR. The number of white blood cells in cerebrospinal fluid and the total protein content in cerebrospinal fluid can be detected by any known method.
In a fifth aspect, the present invention relates to an evaluation system for nerve damage degree or syphilis typing of a patient with a nerve syphilis, comprising a detection module and a judgment module; the detection module is used for acquiring the MSR1 concentration value of the cerebrospinal fluid of the patient; the judging module comprises a readable carrier storing judging rules; the judging rule is as follows:
when the concentration value of the cerebral spinal MSR1 obtained by the detection module is more than or equal to 2.66263NPX value, judging that the cerebral spinal MSR1 is at moderate nerve injury risk or nerve syphilis; otherwise, judging that the risk of nerve injury is low or the syphilis is non-neural;
and when the concentration value of the cerebrospinal fluid MSR1 obtained by the detection module is more than or equal to the 3.1681NPX value, judging that the risk of nerve injury is high or the symptom is caused by nerve syphilis.
The reference value is the Cut-off value of MSR1 obtained from a syphilis patient group; preferably, the cerebrospinal fluid Cut-off value for diagnosis of neurosyphilis is 2.66263NPX value; the Cut-off value of cerebrospinal fluid for symptomatic neurosyphilis diagnosis is 3.1681NPX value. The Cut-off value is a statistical analysis threshold for MSR1 obtained from 88 patients with syphilis.
(III) beneficial effects
The invention provides a novel cerebrospinal fluid marker MSR1 for early diagnosis, parting detection and nerve injury assessment of a nerve syphilis, and the quantitative assessment of the nerve injury degree of the nerve syphilis patient is realized by detecting the expression level of MSR1 in the cerebrospinal fluid of the patient; or diagnosis of the neurosyphilis, including early diagnosis and typing detection, is achieved by detecting the expression level of MSR1 in the cerebrospinal fluid of the patient. The marker can be used for accurately diagnosing asymptomatic nerve syphilis and non-nerve syphilis, and compared with the prior art, the marker has higher sensitivity (90.41) and stronger specificity (86.67).
Because the MSR1 expression level in the cerebrospinal fluid of a symptomatic nerve syphilis patient is highest in symptomatic nerve syphilis, asymptomatic nerve syphilis or non-nerve syphilis, the evaluation sensitivity of the MSR1 expression level to the symptomatic nerve syphilis is as high as 97.67, and therefore the MSR1 can be used as a marker to realize high-sensitivity and high-accuracy screening on the symptomatic nerve syphilis.
Drawings
FIG. 1 (a) shows the detection of MSR1 protein expression in cerebrospinal fluid of three different genotyping syphilis patients by the Olink method; FIG. 1 (b) shows protein indicators of a number of significant differences, even fold changes, in Olink screened asymptomatic neural syphilis versus occult syphilis cerebrospinal fluid.
Fig. 2 shows that cerebrospinal fluid of syphilis patients is positively correlated with MSR1 protein level in serum, correlation coefficient r= 0.3335.
Fig. 3 (a) and 3 (b) show that the expression of MSR1 in cerebrospinal fluid is significantly positively correlated with the indicators of neurosyphilis damage, cerebrospinal fluid proteins and leukocytes, respectively.
FIG. 4 (a) shows the possibility of different levels of MSR1 concentration in cerebrospinal fluid for the diagnosis of neurosyphilis, i.e. the area under ROC curve AUC, with diagnosis of neurosyphilis (both asymptomatic and symptomatic) as clinical outcome; FIG. 4 (b) shows the possibility of different levels of cerebrospinal fluid MSR1 concentrations for symptomatic neurosyphilis diagnosis, i.e. the area under ROC curve AUC, when diagnosed as clinical outcome with symptomatic neurosyphilis.
Fig. 5 (a) and 5 (b) show the differences between the two groups of patients with nerve damage index cerebrospinal fluid protein and leukocytes when all patients are divided into two groups of patients according to cut-off 2.66263NPX of cerebrospinal fluid MSR1, respectively.
Fig. 6 (a) and 6 (b) show differences between the two groups of patients with nerve injury index cerebrospinal fluid protein and leucocytes when the nerve syphilis is divided into two groups of patients according to the cut-off value 3.1681NPX of the cerebrospinal fluid MSR1, respectively.
Detailed Description
The present invention will now be described in detail for the purpose of better explaining the present invention.
Early diagnosis of neurosyphilis is very important, and finding sensitive biomarkers is helpful for diagnosis of neurosyphilis, and particularly needs to identify patients with neurosyphilis including asymptomatic neurosyphilis, and has important significance for early treatment, reduction of nerve injury and prevention of serious and irreversible sequelae of nerve injury. The inventor has studied with the aim of developing new markers for diagnosing and assessing nerve damage in a neurosyphilis, and distinguishing asymptomatic neurosyphilis from recessive syphilis (i.e., non-neurosyphilis), and screened 96 indexes related to nerve function in a neurosyphilis patient, and determined MSR1 proteins which are significantly different (in multiple) in cerebrospinal fluid, and have high sensitivity, so that the proteins have good diagnostic value on the neurosyphilis.
The inventor researches find that the MSR1 protein level of cerebrospinal fluid of patients with different types of syphilis is obviously different. The cerebrospinal fluid MSR1 protein level has a significant correlation with the typing of neurosyphilis, and there is a significant difference between the non-neurosyphilis (recessive syphilis) group and the asymptomatic neurosyphilis group, and the difference between symptomatic and asymptomatic neurosyphilis patients is also statistically significant. The above study demonstrates that MSR1 protein levels can be used as indicators for different clinically typed neurosyphilis patients and can effectively distinguish asymptomatic neurosyphilis from recessive syphilis, so that a treatment scheme can be given to asymptomatic neurosyphilis patients early, and the probability of the asymptomatic neurosyphilis patients developing into symptomatic neurosyphilis is reduced.
In the study, it was found that there was a certain correlation between the expression level of MSR1 in serum and the expression level in cerebrospinal fluid, but the correlation coefficient r= 0.3335, which means that the correlation was not high, and therefore the expression level of MSR1 in serum was not ideal in typing and assessing the occurrence of nerve damage, and then the correlation experiment was performed using only the expression level of MSR1 in cerebrospinal fluid. Further studies have found that the expression level of cerebrospinal fluid MSR1 shows a significant positive correlation with the total protein level of cerebrospinal fluid and leukocytes, which are the examination indicators for the evaluation of neurosyphilis damage, with correlation coefficients r= 0.8024 and 0.7122, and therefore the putative marker MSR1 can be used to evaluate the extent of damage to neurosyphilis.
To investigate the potential and efficacy of MSR1 in the diagnosis of neurosyphilis, 88 patients with syphilis, including neurosyphilis and recessive syphilis (also known as non-neurosyphilis), were studied in the following examples, and the potential of MSR1 for use in the diagnosis of neurosyphilis (including asymptomatic neurosyphilis) was assessed using the subject operating profile (ROC); the experimental result is that the AUC of the cerebrospinal fluid MSR1 is 0.9388, the P is less than 0.0001, the sensitivity is 90.41, and the specificity is 86.67, so that the evaluation of the diagnosis potential of the neurosyphilis by the MSR1 has statistical significance. Accordingly, the occurrence of the neurosyphilis including the asymptomatic neurosyphilis can be effectively estimated according to the level of MSR1 of a syphilis patient, and the neurosyphilis has strong specificity and high sensitivity.
Next, to clarify the diagnostic potential of MSR1 in patients with varying degrees of subtle neurosyphilis, 73 neurosyphilis patients including more severe symptomatic neurosyphilis and early asymptomatic neurosyphilis were studied in the following examples, and MSR1 was used to evaluate the potential of symptomatic neurosyphilis in neurosyphilis patients (both symptomatic and asymptomatic neurosyphilis patients); the experimental result shows that the AUC of the cerebrospinal fluid MSR1 is 0.9171, P is less than 0.0001, the sensitivity is 97.67, and the specificity is 76.67. The results show that the occurrence of severe symptomatic nerve syphilis can be well estimated according to the level of the cerebrospinal fluid MSR1 of the patient with the nerve syphilis, and the sensitivity is very high.
Further, the experiment further divided all patients with syphilis into two groups according to MSR1 Cut-Off value 2.66263 of diagnosis and prediction of the patients with the syphilis, and the cerebrospinal fluid damage related index of the patients with the syphilis above the value is obviously increased (P < 0.0001), and the leucocytes are obviously increased (P=0.0122) but no protein is obvious. As a result, it was found that the index related to cerebrospinal fluid damage increased significantly when MSR1 cerebrospinal fluid was higher than the 2.66263NPX value. Therefore, when MSR1 cerebrospinal fluid is lower than 2.66263NPX value, the risk of occurrence of nerve syphilis of syphilis patients is lower, and the risk of nerve injury is lower; above 2.66263NPX the risk of developing neurosyphilis increases in patients with syphilis and the risk of nerve damage increases. Next, all patients with neurosyphilis were divided into two groups based on the MSR1 Cut-Off value 3.1681 of the diagnostic prediction of symptomatic neurosyphilis in the cerebrospinal fluid of patients above which both the index cerebrospinal fluid protein and leukocytes associated with the damage to the cerebrospinal fluid were significantly increased (P < 0.0001). The risk of symptomatic neurosyphilis of the neurosyphilis patient is low when the MSR1 cerebrospinal fluid is lower than the 3.1681NPX value, and the risk of nerve injury is low; above this value, however, there is a higher risk of symptomatic syphilis and an increased risk of nerve damage. Therefore, the invention determines that the risk is Cut-Off value 2.66263NPX and the high risk Cut-Off value 3.1681NPX in the diagnosis of the neurosyphilis.
In summary, the present invention provides for the use of MSR1 in cerebrospinal fluid as a diagnostic, typing and assessment of neuro-syphilis, including asymptomatic neurosyphilis. In the actual use process, the MSR1 protein level in cerebrospinal fluid can be used as a unique index for early diagnosis, typing and nerve injury evaluation of syphilis, and also can be used as a main reference index or an auxiliary reference index. Since the ROC curves of MSR1 estimated and symptomatic syphilis are both greater than 0.9, MSR1 in cerebrospinal fluid has a high sensitivity to estimated and symptomatic syphilis.
Based on the findings, the invention realizes high-sensitivity detection typing of syphilis, especially neurosyphilis, and can accurately quantitatively evaluate the severity of nerve injury by designing a detection kit, a protein chip, a protein probe or a protein detector for detecting the expression level of MSR1 in cerebrospinal fluid.
In order that the above-described aspects may be better understood, exemplary embodiments of the present invention will be described in more detail below with reference to the accompanying drawings. While exemplary embodiments of the invention are shown in the drawings, it should be understood that the invention may be embodied in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.
The experimental methods in the following experimental examples are conventional methods unless otherwise specified. The raw materials and reagent materials used in the examples described below are commercially available products unless otherwise specified. The protocol and experimental results are as follows:
study object (one)
On the premise of informed consent and meeting inclusion conditions, 88 patients with hidden syphilis are selected, wherein 15 patients with asymptomatic neurotoxic 30 patients with paralytic dementia 43 patients are subjected to the treatment, and different neurotoxic queues with different degrees of severity are established. Diagnostic criteria were performed according to WS273-2007 syphilis diagnostic criteria.
(II) sample collection
According to the condition of the patient in the group, the lumbar puncture operation and the elbow vein puncture operation are carried out to collect cerebrospinal fluid and blood for routine examination, and cerebrospinal fluid and serum specimens are collected. Under the informed consent of the patient, 5mL of cerebrospinal fluid standard is collected by lumbar puncture, and 2mL of blood sample is collected by vein. After collecting cerebrospinal fluid by lumbar puncture, sub-packaging with a freezing tube, and coding and marking; after blood was collected by venipuncture, the mixture was centrifuged at 4℃for 10 minutes at 2000rpm and the supernatant serum was rapidly separated and placed in a freezing tube.
(III) detecting the concentration of MSR1 in cerebrospinal fluid by an Olink method
92 proteins associated with neurological function, including MSR1 protein, were detected using Olink neurology panel 95801. The Olink precision proteomics adopts PEA method, is suitable for a precision proteomics research tool of large-scale screening, and has good sensitivity, rapidness, high-throughput analysis and specificity on the level of multiple channels. Therefore, in the embodiment, the Olink is adopted to detect the markers in the cerebrospinal fluid of different types of patients with the neurosyphilis, and the MSR1 protein is found to have a significant difference in the cerebrospinal fluid. Detection of cerebrospinal fluid proteins and cerebrospinal fluid leukocytes was performed according to the standard methods described in WS 273-2007.
The following statistics and data analysis are performed on the Olink detection results:
(1) Significant increase of MSR1 protein in nerve syphilis cerebrospinal fluid
The difference of the expression of the nerve-related proteins in serum and cerebrospinal fluid is detected by using Olink precise proteomics, and MSR1 proteins with obvious difference in cerebrospinal fluid are screened. The Olink test results are shown in FIG. 1 and Table 1. Patients with symptomatic neurosyphilis (symptomatic) were found to have a significant increase in MSR1 over asymptomatic neurosyphilis (asymptomatic) and occult syphilis cerebrospinal fluid. Thus, cerebrospinal fluid MSR1 levels can be used to distinguish between syphilis types and are expected to indicate their severity.
In FIG. 1 (a), recessive syphilis represents non-neural syphilis, asymptomatic means asymptomatic neural syphilis, and symptomatic means symptomatic neural syphilis. As can be seen from fig. 1 (a), the concentration of MSR1 in the cerebrospinal fluid of symptomatic neurosyphilis patients > the concentration of MSR1 in the cerebrospinal fluid of asymptomatic neurosyphilis patients > the concentration of MSR1 in the cerebrospinal fluid of recessive syphilis patients; FIG. 1 (b) is a graph showing protein indicators of a significant or even fold change in the various differences between asymptomatic neural syphilis and occult syphilis cerebrospinal fluid screened in the experiment; it can be seen that the difference in the significance of the MSR1 protein in cerebrospinal fluid is most pronounced.
Table 1: differential statistics of the expression of cerebrospinal fluid MSR1 in three different syphilis types
Table 1 shows statistics of the concentration differences of MSR1 in cerebrospinal fluid of patients with three types of recessive syphilis, asymptomatic neurotoxic and symptomatic neurotoxic. The average difference is an average difference reflecting the difference between each flag value and the arithmetic average, the difference value may show whether there was a significant difference between the two groups before, and the fold difference may show a fold of such difference. As can be seen from the statistics of Table 1, there are significant differences in the levels of MSR1 protein in cerebrospinal fluid of patients with different types of syphilis, and the differences are statistically significant.
(2) Cerebrospinal fluid is positively correlated with MSR1 protein in serum
As shown in fig. 2, the MSR1 protein in serum has a certain positive correlation (r=0.3335, p=0.0015) with the protein in cerebrospinal fluid, but the correlation is not significant. Thus, the level of MSR1 protein in serum is insufficient as an indicator of an increase in cerebrospinal fluid, nor is the level of MSR1 protein in serum accurately diagnosed with neurosyphilis. Therefore, the subsequent experiments were conducted mainly using cerebrospinal fluid as an analysis sample.
(3) The expression level of the cerebrospinal fluid MSR1 is obviously and positively correlated with the index of the cerebrospinal fluid injury
Important diagnostic indicators of neurosyphilis are cerebrospinal fluid cell count and total protein levels. Patients with neurosyphilis are associated with abnormal cerebrospinal fluid cell counts and protein levels, and clinicians also recognize that these two indicators are indicative of the severity of the damage to neurosyphilis.
To verify the indicative effect of MSR1, experiments used correlation analysis of the MSR1 value of cerebrospinal fluid with cerebrospinal fluid protein and leukocyte values, and as can be seen in conjunction with fig. 3 (a) and 3 (b), the expression level of MSR1 protein in cerebrospinal fluid showed a significant positive correlation with protein in cerebrospinal fluid of the patient (correlation coefficient r=0.8024, p < 0.0001), and also showed a significant positive correlation with the number of leukocytes in cerebrospinal fluid (r=0.7122, p < 0.0001). Thus, MSR1 protein in cerebrospinal fluid may be indicative of abnormalities in proteins and leukocytes in cerebrospinal fluid.
(4) Cerebrospinal fluid MSR1 expression levels for diagnosis and typing of neurosyphilis
To clarify the relationship between cerebrospinal fluid MSR1 and the diagnosis of neurosyphilis, the present example conducted a study on 88 patients with syphilis, including patients with recessive syphilis, asymptomatic neurosyphilis and symptomatic neurosyphilis. The ROC curve was used to evaluate the potential of MSR1 for diagnosis of neurosyphilis (i.e., including asymptomatic neurosyphilis and symptomatic neurosyphilis). Referring to fig. 4 (a), the experimental results are: the area under the ROC curve AUC (0.9388[95%CI 0.8867-0.9909) of the cerebrospinal fluid MSR1, P <0.0001, sensitivity of 90.41 and specificity of 86.67, has statistical significance. To further clarify the relationship of cerebrospinal fluid MSR1 to symptomatic neurosyphilis, this example conducted an ROC curve evaluation study on 73 patients with neurosyphilis, including asymptomatic and symptomatic neurosyphilis patients. The potential of MSR1 levels in patients with neurosyphilis for symptomatic neurosyphilis diagnosis was studied using ROC. Referring to fig. 4 (b), the experimental results are: the area under the ROC curve AUC (0.9171[95%CI 0.8481-0.9860) of the cerebrospinal fluid MSR1, P <0.0001, sensitivity 97.67 and specificity 76.67, has statistical significance.
The results show that the recessive syphilis and the asymptomatic syphilis can be better distinguished according to the level of the cerebrospinal fluid MSR1 of the patients with the syphilis, and the symptomatic syphilis can be more accurately diagnosed. Therefore, the method can diagnose the nerve syphilis and symptomatic nerve syphilis with high sensitivity according to the level of the cerebrospinal fluid MSR1 of the syphilis patient.
(5) Cerebrospinal fluid MSR1 expression levels for assessing the extent of nerve damage
First, the 88 patients with syphilis were divided into two groups of high MSR1 concentration and low MSR1 concentration using Cut-Off value (threshold = 2.66263NPX value) according to the level of patient cerebrospinal fluid MSR 1. As shown in fig. 5, the cerebrospinal fluid protein related to the cerebrospinal fluid injury of patients with cerebrospinal fluid MSR1 higher than 2.66263NPX value was significantly increased, P <0.0001 (see fig. 5 (a)), the white blood cells were also significantly increased but the difference was less pronounced than the protein, p=0.0122 (see fig. 5 (b)). Therefore, patients with cerebrospinal fluid MSR1 below the 2.66263NPX value have low risk of neurosyphilis and low risk of nerve damage; above this value, however, the risk of neurosyphilis is higher and the risk of nerve damage is increased. Further, 73 patients with neurosyphilis were divided into two groups of high MSR1 concentration and low MSR1 concentration using threshold = 3.1681NPX. As shown in FIG. 6, the index of cerebrospinal fluid protein and leucocyte related to the damage of cerebrospinal fluid of patients with the MSR1 value higher than 3.1681NPX value are increased significantly, and P is less than 0.0001. Thus, patients with cerebrospinal fluid MSR1 below the 3.1681NPX value have a low risk of symptomatic neurosyphilis, with a relatively low risk of nerve damage; above this value, however, there is a higher risk of symptomatic syphilis and an increased risk of nerve damage.
In conclusion, the concentration of the MSR1 protein can be used as indexes of early diagnosis of the nerve syphilis, symptomatic nerve syphilis, typing detection of asymptomatic nerve syphilis and recessive syphilis, nerve injury degree evaluation and the like, and can be independently used for diagnosis, typing and nerve injury evaluation of the nerve syphilis, and can also be used as main reference indexes to finish diagnosis, typing and nerve injury evaluation of the nerve syphilis in combination with other indexes. It is particularly important that MSR1 distinguish asymptomatic from latent syphilis, that the AUC for the evaluation of the syphilis is >0.9, that the sensitivity is very high, and that asymptomatic syphilis can be accurately diagnosed from a syphilis patient by comparing the concentration of MSR1 protein in the cerebrospinal fluid of the patient with the Cut-Off value (threshold = 2.66263NPX value) in order to give a treatment regimen early on in the asymptomatic syphilis patient, reducing the chance of developing symptomatic syphilis.
Finally, it should be noted that the above embodiments are only for illustrating the technical solution of the present invention and are not limiting. Although the present invention has been described in detail with reference to the embodiments, it should be understood by those skilled in the art that modifications and equivalents may be made thereto without departing from the spirit and scope of the present invention, which is intended to be covered by the appended claims.
Claims (10)
- MSR1 is used as a cerebrospinal fluid marker for early diagnosis, clinical typing and nerve injury detection of patients with neurosyphilis.
- Application of MSR1 protein and specific antibody thereof in preparing diagnosis product or auxiliary diagnosis product for diagnosing nerve syphilis, parting detection or evaluating nerve damage degree; the method is characterized in that the diagnosis product or auxiliary diagnosis product is a detection kit, a protein chip, a protein probe or a protein detector which takes MSR1 protein or specific antibody thereof as target molecule.
- 3. The use according to claim 2, wherein the detection kit detects the expression level of the MSR1 protein or a specific antibody thereof in cerebrospinal fluid using the MSR1 protein or a specific antibody thereof as a target molecule.
- 4. The use according to claim 2, wherein the detection kit is an MSR1 enzyme-linked immunosorbent assay kit or an immunohistochemical kit.
- 5. The use according to claim 4, wherein the detection kit comprises: primary antibody capable of specifically recognizing MSR1, polypeptide dye, magnetic bead and biotin labeled secondary antibody.
- 6. The use according to claim 5, wherein the detection kit further comprises citrate buffer, PBS wash, peroxidase blocker, goat serum, streptomycin antibiotic-peroxidase, DAB solution and hematoxylin solution.
- 7. The use of claim 4, 5 or 6, wherein the test kit further comprises reagents, means or materials for separating cerebrospinal fluid from the patient.
- 8. Products for early diagnosis, screening, typing detection or assessment of the extent of neurological impairment in patients with neurosyphilis; the method is characterized in that the product can quantitatively detect the concentration of MSR1 in cerebrospinal fluid; the product is a detection kit, a protein chip, a protein probe or a protein detector which takes MSR1 protein or a specific antibody thereof as a target molecule; the product comprises an antibody that specifically recognizes MSR 1.
- 9. A neural syphilis diagnostic system, comprising:comprises a first analysis unit and a second analysis unit;the first analysis unit is a detection reagent composition, an antibody chip or an antibody probe for detecting the MSR1 protein level of cerebrospinal fluid;the second analysis unit is a blood cell counting plate/blood cell analyzer for detecting the level of white blood cells in cerebrospinal fluid or a detection reagent composition/biochemical analyzer for detecting the level of total protein in cerebrospinal fluid.
- 10. The evaluation system for the nerve injury degree or syphilis typing of the patients with the nerve syphilis is characterized by comprising a detection module and a judgment module; the detection module is used for acquiring the MSR1 concentration value of the cerebrospinal fluid of the patient; the judging module comprises a readable carrier storing judging rules;the judging rule is as follows:when the concentration value of the cerebral spinal MSR1 obtained by the detection module is more than or equal to 2.66263NPX value, judging that the cerebral spinal MSR1 is at moderate nerve injury risk or nerve syphilis; otherwise, judging that the risk of nerve injury is low or the syphilis is non-neural;and when the concentration value of the cerebrospinal fluid MSR1 obtained by the detection module is more than or equal to the 3.1681NPX value, judging that the risk of nerve injury is high or the symptom is caused by nerve syphilis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410066811.5A CN117607432B (en) | 2024-01-17 | 2024-01-17 | Application of MSR1 protein and specific antibody thereof in preparation of neural syphilis or neural injury diagnostic product |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410066811.5A CN117607432B (en) | 2024-01-17 | 2024-01-17 | Application of MSR1 protein and specific antibody thereof in preparation of neural syphilis or neural injury diagnostic product |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN117607432A true CN117607432A (en) | 2024-02-27 |
| CN117607432B CN117607432B (en) | 2024-04-09 |
Family
ID=89944608
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410066811.5A Active CN117607432B (en) | 2024-01-17 | 2024-01-17 | Application of MSR1 protein and specific antibody thereof in preparation of neural syphilis or neural injury diagnostic product |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117607432B (en) |
Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4740467A (en) * | 1982-05-26 | 1988-04-26 | Board Of Regents, The University Of Texas | Methods for diagnosing syphilis |
| US20060281130A1 (en) * | 2002-12-20 | 2006-12-14 | Elisabeth Bock | Metod of modulation of interaction between receptor and ligand |
| RU2473895C1 (en) * | 2011-11-14 | 2013-01-27 | Олег Владимирович Колоколов | Method for detecting neurosyphilis in patients infected by treponema pallidum |
| US20130287772A1 (en) * | 2010-03-01 | 2013-10-31 | Caris Life Sciences Luxembourg Holdings | Biomarkers for theranostics |
| CN108490176A (en) * | 2018-03-13 | 2018-09-04 | 首都医科大学附属北京地坛医院 | Application of the phosphorylated neurofilament ferritin heavy chain in Lues Assay |
| CN108490191A (en) * | 2018-03-13 | 2018-09-04 | 首都医科大学附属北京地坛医院 | Application of the neurofilament protein light chain in syphilis blood testing |
| CN110082542A (en) * | 2018-03-13 | 2019-08-02 | 首都医科大学附属北京地坛医院 | Application of the NF-L in the detection of neurolues cerebrospinal fluid |
| RU2699057C1 (en) * | 2018-08-30 | 2019-09-03 | Государственное бюджетное учреждение здравоохранения города Москвы "Московский научно-практический Центр дерматовенерологии и косметологии Департамента здравоохранения города Москвы" | Diagnostic neurosyphilis method |
| US20190328750A1 (en) * | 2018-01-11 | 2019-10-31 | Met P Pharma Ag | Treatment of demyelinating diseases |
| WO2020165405A1 (en) * | 2019-02-15 | 2020-08-20 | Rigshospitalet | Stem cell therapy for patients with salivary gland dysfunction |
| CN116042678A (en) * | 2023-02-08 | 2023-05-02 | 南方医科大学皮肤病医院（广东省皮肤病医院、广东省皮肤性病防治中心、中国麻风防治研究中心） | Fusion protein for detecting nerve syphilis and kit thereof |
| CN116519953A (en) * | 2023-06-26 | 2023-08-01 | 首都医科大学附属北京地坛医院 | Application of EDA2R protein and specific antibody thereof in preparation of syphilis diagnosis product |
-
2024
- 2024-01-17 CN CN202410066811.5A patent/CN117607432B/en active Active
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4740467A (en) * | 1982-05-26 | 1988-04-26 | Board Of Regents, The University Of Texas | Methods for diagnosing syphilis |
| US20060281130A1 (en) * | 2002-12-20 | 2006-12-14 | Elisabeth Bock | Metod of modulation of interaction between receptor and ligand |
| US20130287772A1 (en) * | 2010-03-01 | 2013-10-31 | Caris Life Sciences Luxembourg Holdings | Biomarkers for theranostics |
| RU2473895C1 (en) * | 2011-11-14 | 2013-01-27 | Олег Владимирович Колоколов | Method for detecting neurosyphilis in patients infected by treponema pallidum |
| US20190328750A1 (en) * | 2018-01-11 | 2019-10-31 | Met P Pharma Ag | Treatment of demyelinating diseases |
| CN108490176A (en) * | 2018-03-13 | 2018-09-04 | 首都医科大学附属北京地坛医院 | Application of the phosphorylated neurofilament ferritin heavy chain in Lues Assay |
| CN108490191A (en) * | 2018-03-13 | 2018-09-04 | 首都医科大学附属北京地坛医院 | Application of the neurofilament protein light chain in syphilis blood testing |
| CN110082542A (en) * | 2018-03-13 | 2019-08-02 | 首都医科大学附属北京地坛医院 | Application of the NF-L in the detection of neurolues cerebrospinal fluid |
| RU2699057C1 (en) * | 2018-08-30 | 2019-09-03 | Государственное бюджетное учреждение здравоохранения города Москвы "Московский научно-практический Центр дерматовенерологии и косметологии Департамента здравоохранения города Москвы" | Diagnostic neurosyphilis method |
| WO2020165405A1 (en) * | 2019-02-15 | 2020-08-20 | Rigshospitalet | Stem cell therapy for patients with salivary gland dysfunction |
| CN116042678A (en) * | 2023-02-08 | 2023-05-02 | 南方医科大学皮肤病医院（广东省皮肤病医院、广东省皮肤性病防治中心、中国麻风防治研究中心） | Fusion protein for detecting nerve syphilis and kit thereof |
| CN116519953A (en) * | 2023-06-26 | 2023-08-01 | 首都医科大学附属北京地坛医院 | Application of EDA2R protein and specific antibody thereof in preparation of syphilis diagnosis product |
Non-Patent Citations (10)
| Title |
|---|
| WILLIAM G. NELSON等: "The Role of Inflammation in the Pathogenesis of Prostate Cancer", THE JOURNAL OF UROLOGY, vol. 172, no. 5, 10 November 2005 (2005-11-10), pages 6 * |
| WURONG LI等: "Cerebrospinal Fluid Cytokines in Patients with Neurosyphilis: The Significance of Interleukin-10 for the Disease", BIOMED RESEARCH INTERNATIONAL, vol. 2020, 5 October 2020 (2020-10-05), pages 1 - 8 * |
| 于晓云等: "神经梅毒患者脑脊液中细胞因子的表达及诊断价值分析", 南京医科大学学报(自然科学版), vol. 42, no. 01, 31 January 2022 (2022-01-31), pages 63 - 70 * |
| 余伟等: "巨噬细胞清道夫受体1基因多态性与缺血性脑卒中遗传易感性的关系", 职业与健康, vol. 34, no. 06, 31 March 2018 (2018-03-31), pages 824 - 827 * |
| 张磊等: "以认知功能障碍及精神行为异常起病的神经梅毒治疗前后实验室指标的变化分析", 中国实用神经疾病杂志, vol. 25, no. 06, 30 June 2022 (2022-06-30), pages 729 - 735 * |
| 窦曼曼: "TSP-1/CD47信号通路调节动脉粥样硬化易损斑块的稳定性及其相关调控机制研究", 中国优秀硕士学位论文全文数据库, no. 01, 15 January 2022 (2022-01-15), pages 1 - 47 * |
| 许东梅等: "脑脊液寡克隆区带在神经梅毒诊断中的临床意义", 中华实验和临床感染病杂志, vol. 14, no. 03, 30 June 2020 (2020-06-30), pages 241 - 246 * |
| 陈莉等: "41例梅毒患者脑脊液检测结果分析", 临床输血与检验, vol. 20, no. 04, 20 August 2018 (2018-08-20), pages 434 - 436 * |
| 韩兴涛等: "miR-34a调控MSR1蛋白对前列腺癌细胞迁移和侵袭的影响", 中国免疫学杂志, vol. 34, no. 04, 20 April 2018 (2018-04-20), pages 544 - 548 * |
| 魏春波等: "有症状与无症状神经梅毒患者临床及实验室特征的比较", 中华实验和临床感染病杂志(电子版), vol. 07, no. 03, 15 June 2013 (2013-06-15), pages 59 - 62 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN117607432B (en) | 2024-04-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN116519953B (en) | Application of EDA2R protein and specific antibody thereof in preparation of syphilis diagnosis product | |
| CN103403549B (en) | The Forecasting Methodology of the prognosis of septicemia | |
| WO2011005893A9 (en) | Biomarkers and methods for detecting alzheimer's disease | |
| US11193946B2 (en) | Blood biomarker for discerning beta amyloid accumulation in brain | |
| Desplat-Jégo et al. | Quantification of immunoglobulin free light chains in cerebrospinal fluid by nephelometry | |
| US20170184611A1 (en) | Biomarker-based methods and biochips for aiding the diagnosis of stroke | |
| CN113192552B (en) | Active tuberculosis marker, kit, detection method and model construction method | |
| WO2012033999A2 (en) | Biomarkers for predicting kidney and glomerular pathologies | |
| Wang et al. | Serum amyloid a: A potential biomarker assessing disease activity in systemic lupus erythematosus | |
| Ghasemi et al. | Predictive accuracy of urinary neutrophil gelatinase associated lipocalin (NGAL) for renal parenchymal involvement in children with acute pyelonephritis | |
| CN112201318A (en) | Application method of laboratory index model in risk stratification of COVID-19 patients | |
| Rashwan et al. | Hematological indices in differentiation between iron deficiency anemia and beta-thalassemia trait | |
| CN117607432B (en) | Application of MSR1 protein and specific antibody thereof in preparation of neural syphilis or neural injury diagnostic product | |
| CN117741143B (en) | Application of Siglec-9 protein and specific antibody thereof in preparation of neural syphilis or neural injury diagnostic product | |
| Chen et al. | Soluble CD14 subtype (sCD14-ST) is a biomarker for neonatal sepsis | |
| CN113358881B (en) | Biomarker for NMOSD prediction or recurrence monitoring and application thereof | |
| Shiang Yui et al. | Microcytic to hypochromic ratio as a discriminant index of thalassaemia trait in subjects with hypochromic anaemia | |
| KR102254053B1 (en) | Biomarker for detecting amyloid beta accumulation in brain of subject with normal cognitive function or mild cognitive impairment using blood sample | |
| EP3514544A1 (en) | Method and device for differentially diagnosing encephalitis on basis of trail | |
| CN112285260B (en) | Application of a group of diagnostic markers in diagnosing asthenospermia caused by obesity | |
| CN115372625A (en) | Complement pathway-associated plasma protein marker and diagnostic kit | |
| US10088486B2 (en) | Method for detecting neurological disease accompanied by inflammation and/or demyelination | |
| CN117849341A (en) | Application of neopterin in asymptomatic neurosyphilis detection | |
| CN116087527A (en) | Application of blood difference protein combination in preparation of reagent for detecting ASD | |
| KR20220163839A (en) | Diagnostic composition of adult-onset Still’s disease and diagnosis method thereof |
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 |