Biomarker JAML protein of sepsis and application of biomarker JAML protein
By using JAML protein as a biomarker, the problems of early diagnosis and treatment of sepsis were solved, effective diagnosis and treatment monitoring of sepsis were achieved, and the treatment effect was improved.
Patent Information
- Application Number
- CN202411122228.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-15
- Publication Date
- 2024-12-20
AI Technical Summary
There are difficulties in the early diagnosis and treatment of sepsis. The existing technology relies on clinical scoring systems, microbiological testing and imaging examinations. It is difficult to treat antibiotic abuse and individualized treatment during the treatment process. It lacks effective biomarkers for early identification. and intervention.
Using ligation adhesion molecule-like protein (JAML protein) and its encoding genes as biomarkers, it is used to prepare diagnostic reagents and drugs to assist in diagnosis and monitoring of the presence and severity of sepsis by detecting their expression and activity, and as a Potential therapeutic targets.
JAML protein is involved in the occurrence and development of sepsis, which can distinguish between patients and normal people and distinguish severity. It is used for treatment plan selection and efficacy evaluation, significantly improving the diagnostic efficacy and therapeutic effect of sepsis.
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Figure CN119162298A_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the field of biotechnology, and in particular to a biomarker of sepsis, JAML protein, and an application thereof. Background Art
[0002] Sepsis, also known as sepsis or septicemia, is a systemic inflammatory response syndrome caused by infection. It is a life-threatening organ dysfunction caused by the host's dysregulated response to infection. It is caused by the interaction between pathogens and the host's immune system, inflammatory system, and coagulation response. It is common in patients with severe trauma or infectious diseases. Sepsis is the body's uncontrolled response to infection (usually caused by bacteria, viruses, fungi, or parasites). The main symptoms of sepsis include chills, fever, palpitations, shortness of breath, and changes in mental status. Sepsis can develop into severe sepsis and septic shock, which can lead to organ dysfunction and circulatory disorders, which are life-threatening. Although sepsis is not an infectious disease, its risk factors include age (young or old), impaired immune system, history of diabetes or cirrhosis, long-term treatment in the intensive care unit, trauma, invasive treatment, etc. Obviously, sepsis is not limited to the infection itself, but also includes organ dysfunction caused by excessive immune system response, which can lead to multiple organ failure and death in severe cases.
[0003] Sepsis is a common cause of in-hospital death in patients. In recent years, with the gradual aging of the population and the increase in awareness of the disease, the incidence of sepsis has been on the rise. In related technologies, the diagnosis of sepsis mainly relies on clinical scoring systems, biomarkers, microbiological tests, and imaging examinations. Even so, the diagnosis of sepsis still has defects such as difficulty in early identification of the disease, delayed microbiological testing, high cost and time consumption of imaging examinations. The prognosis of sepsis depends on multiple factors, including the patient's age, basic health status, severity of infection and timeliness of treatment. Even with timely treatment, sepsis patients still have a high mortality rate and long-term sequelae. Therefore, the current status of sepsis treatment is not optimistic. The current status of sepsis treatment mainly includes early identification, anti-infection treatment, fluid resuscitation and organ support. Although the current status of sepsis treatment has improved, the difficulties in sepsis treatment, such as abuse of antibiotics, many side effects and complications, and difficulty in individualized treatment, are still thorny.
[0004] Therefore, given the inherent complexity of sepsis, there is still an urgent need for a biomarker to identify and characterize clinical sepsis for early diagnosis, treatment, and intervention. Summary of the invention
[0005] In view of the above-mentioned shortcomings of the prior art, the present invention provides a biomarker of sepsis, JAML protein, and application thereof, so as to facilitate early diagnosis, treatment and intervention of sepsis patients.
[0006] To achieve the above objectives, the scheme of this application is as follows:
[0007] In a first aspect, the present invention provides the use of a junctional adhesion molecule-like protein (JAML protein for short) and / or a gene encoding the junctional adhesion molecule-like protein (i.e., junctional adhesion molecule-like gene, JAML gene for short) as a biomarker in the preparation of sepsis diagnosis, prognosis or evaluation, the junctional adhesion molecule-like protein and / or the gene encoding the junctional adhesion molecule-like protein as a biomarker for the preparation or screening of sepsis diagnostic reagents, and the reagents are used for the diagnosis and / or prognosis and / or treatment monitoring of sepsis.
[0008] Optionally, the reagent is used to determine the expression level of the junctional adhesion molecule-like protein and / or the activity of the gene in a biological sample of a subject.
[0009] Optionally, the biological sample is selected from at least one of whole blood, serum and plasma.
[0010] Optionally, the reagent uses at least one of chromatography, mass spectrometry, fluorescence, electrophoresis, immunoaffinity, immunochemistry, ultraviolet spectroscopy, fluorescence analysis, radiochemical analysis, near-infrared spectroscopy, nuclear magnetic resonance spectroscopy, light scattering analysis, turbidimetry, flow cytometry, polymerase chain reaction detection, protein immunoblotting, colloidal gold method, electrochemistry, microfluidics and high-throughput method to determine the expression level of connecting adhesion molecule-like protein and / or the activity of the gene in the subject's biological sample.
[0011] Optionally, the expression level of the junctional adhesion molecule-like protein in the biological sample of the subject is positively correlated with the severity of sepsis.
[0012] Optionally, the reagent is used to assist in diagnosing or monitoring the presence and / or course and / or severity and / or risk of death and / or prognosis of sepsis.
[0013] In a second aspect, the present invention also provides use of a connecting adhesion molecule-like protein and / or a gene encoding the connecting adhesion molecule-like protein in the preparation of a drug for preventing or treating sepsis.
[0014] Optionally, the active ingredient of the drug treats or alleviates sepsis by increasing the expression level of the junctional adhesion molecule-like protein and / or the activity of the gene in the biological sample of the subject.
[0015] Optionally, the drug further comprises a pharmaceutically acceptable excipient.
[0016] Optionally, the pharmaceutically acceptable excipients include at least one of a dispersant, an emulsifier, a solvent, a cosolvent, a solubilizer, a latent solvent, a carrier, a filler, a stabilizer, a wetting agent, a penetrant, an adhesive and a defoaming agent.
[0017] In the present application, the dispersant may include, for example, stearic acid dispersants, aliphatic amide dispersants, ester dispersants, paraffin dispersants, metal soap dispersants, low molecular weight wax dispersants, etc. Stearic acid dispersants may include, for example, stearic acid, linolenic acid, oleic acid, etc. Aliphatic amide dispersants may include, for example, vinyl bisstearamide, stearamide, hexenyl bisstearamide, etc. Ester dispersants may include, for example, stearic acid monoglyceride, tristearic acid glyceride, etc. Paraffin dispersants may include, for example, liquid paraffin, microcrystalline paraffin, etc. Metal soap dispersants may include, for example, stearates, etc. Low molecular weight wax dispersants may include, for example, polyethylene homopolymers, ethylene-acrylic acid copolymers, ethylene-vinyl acetate copolymers, low molecular weight ionomers, etc.
[0018] In the present application, emulsifiers include, but are not limited to, anionic emulsifiers, cationic emulsifiers, nonionic emulsifiers, etc. Examples of anionic emulsifiers include, for example, fatty acid soaps, alkyl sulfates, alkylbenzene sulfonates, phosphates, and the like. Examples of cationic emulsifiers include, for example, N-dodecyldimethylamine and its amine derivatives, quaternary ammonium salts, and the like. Examples of nonionic emulsifiers include, for example, polyoxyethylene ethers, polyoxypropylene ethers, ethylene oxide and propylene oxide block copolymers, polyol fatty acid esters, and the like.
[0019] In the present application, the solvent includes, but is not limited to, water, alcohols, and fatty oils. Examples of fatty oils include castor oil, soybean oil, peanut oil, olive oil, and the like.
[0020] In the present application, the cosolvent includes, but is not limited to, organic acids and their salts, amide compounds (such as urea, acetamide, etc.), etc. Examples of organic acid salts include sodium benzoate, sodium salicylate, and the like.
[0021] In the present application, the solubilizing agent may include, for example, polysorbate compounds, polyoxyethylene fatty acid ester compounds, and the like.
[0022] In the present application, the latent solvent may include, for example, ethanol, propylene glycol, glycerol and the like.
[0023] In the present application, carriers include but are not limited to micelles, microemulsions, gels, liquid crystals, vesicles, and the like.
[0024] In the present application, fillers may include, for example, starch, powdered sugar, dextrin, lactose, microcrystalline cellulose, inorganic salts, mannitol and the like.
[0025] In the present application, the stabilizer may include, for example, glycerol, syrup, gum arabic, sodium alginate, methylcellulose, sodium carboxymethylcellulose, polysorbates (i.e., Tweens), polyoxyethylene castor oil, acetates, phosphates and the like.
[0026] In the present application, the wetting agent may include, for example, water, ethanol, starch paste, syrup, gum arabic, gelatin, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, sodium alginate, magnesium aluminum silicate, bletilla striata gum, polyethylene glycol (PEG) 4000 and the like.
[0027] In the present application, examples of the penetrant include azone, propylene glycol, dimethyl sulfoxide (DMSO), dimethyl isosorbide (DMIS) and the like.
[0028] In the present application, the adhesive may include, for example, starch slurry, methyl cellulose (MC), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), sodium carboxymethyl cellulose (CMC-Na), ethyl cellulose (EC), polyvidone (PVP), gelatin, sodium alginate, magnesium aluminum silicate, bletilla striata gum, polyethylene glycol 4000, polyethylene glycol 6000, dextrin and the like.
[0029] In the present application, the defoaming agent may include, for example, vegetable oil, turpentine, polymethyl silicone, polyether fatty alcohol defoaming agent, polyether modified defoaming agent, silicone defoaming agent and the like.
[0030] Beneficial effects of the present invention:
[0031] Through a series of studies, the present invention found that JAML protein is involved in the occurrence and development of sepsis, and can be used as a biomarker for sepsis diagnosis, prognosis and treatment monitoring to distinguish sepsis patients from normal people, and can also distinguish the severity of sepsis patients to select treatment plans and evaluate the efficacy. JAML protein can also be used as a potential sepsis treatment target to provide new technical means for the treatment of sepsis and related diseases. BRIEF DESCRIPTION OF THE DRAWINGS
[0032] Figure 1 This is the result of JAML protein expression detection;
[0033] Figure 2 This is the ROC curve analysis result diagram;
[0034] Figure 3 This is the result of correlation analysis between the expression of JAML protein in the serum of patients with sepsis and SOFA score;
[0035] Figure 4 This is a graph showing the results of a comparative experiment on the expression of JAML protein in the serum of mice with sepsis model and mice in the sham operation group;
[0036] Figure 5 This is the result of the mouse survival rate experiment;
[0037] Figure 6 Figure 6A is a comparison of the bacterial load in the blood of sepsis model mice in the JAML protein treatment group and the PBS control group (i.e., PBS group). Figure 6 B is a comparison of bacterial loads in the lungs of sepsis model mice in the JAML protein treatment group and the PBS control group. Figure 6 C is a comparison of bacterial loads in the livers of sepsis model mice in the JAML protein treatment group and the PBS control group. DETAILED DESCRIPTION
[0038] The following will describe the embodiments of the present invention with reference to the accompanying drawings and preferred embodiments. Those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention. It should be understood that the preferred embodiments are only for illustrating the present invention, not for limiting the scope of protection of the present invention.
[0039] It should be noted that the illustrations provided in the following embodiments are only schematic illustrations of the basic concept of the present invention, and thus the drawings only show components related to the present invention rather than being drawn according to the number, shape and size of components in actual implementation. In actual implementation, the type, quantity and proportion of each component may be changed arbitrarily, and the component layout may also be more complicated.
[0040] In the following description, numerous details are discussed to provide a more thorough explanation of embodiments of the present invention; however, it is apparent to one skilled in the art that embodiments of the present invention may be practiced without these specific details.
[0041] (I) Sample statistics and detection of JAML expression in serum
[0042] Serum samples of 54 patients with sepsis treated in the First Affiliated Hospital of Chongqing Medical University from March 2022 to November 2023 were collected (all patients met the diagnostic criteria of Sepsis 3.0 for the disease in the International Sepsis Conference, excluding patients with malignant tumors, HIV infection, hemoglobin lower than 7g / mL or active bleeding, and requiring more than two units of red blood cells. All studies on the subjects were approved by the Science and Ethics Committee of the First Affiliated Hospital of Chongqing Medical University) and 30 serum samples of healthy physical examination subjects (i.e., healthy people) during the same period. The male / female ratio, age, white blood cell concentration, C-reactive protein (i.e., CRP) concentration, procalcitonin (i.e., PCT) concentration, sequential organ failure assessment score (i.e., SOFA score), acute physiology and chronic health score (i.e., APACHEII score), ICU days, number of shock / non-shock, death / non-death ratio, infection site and number were statistically analyzed. The results are shown in Table 1;
[0043] The collected serum samples were centrifuged at 4°C and 1400×g for 7 min, and the supernatant obtained by centrifugation was stored at -80°C. The expression of JAML protein was then detected using an ELISA kit (purchased from R&D Systems, DY3449). The operation steps were strictly carried out in accordance with the instructions attached to the kit. The test results were then statistically analyzed using SPSS20.0 software and graphed using GraphPad Prism9.5.0 software. The results are shown in Figure 2. Figure 1 shown.
[0044] Table 1 Sample statistics
[0045]
[0046]
[0047] Note: Infections in other parts refer to infections in other parts of the body except the respiratory system, urinary system, abdominal cavity and digestive system, skin and soft tissue.
[0048] like Figure 1 As shown in the results, compared with healthy people, the expression of JAML protein in the serum of patients with sepsis was significantly increased, and the difference was statistically significant (P<0.001). This result shows that JAML protein can be used as a biomarker for the clinical diagnosis of sepsis.
[0049] (II) ROC curve analysis
[0050] The detection results of JAML protein expression in the serum of healthy people and the serum of sepsis patients measured in (I) were statistically analyzed using the "pROC" package and "ggplot2" package of R language, and the ROC curve of JAML protein for diagnosing sepsis was drawn, and the optimal cutoff value, sensitivity, specificity and area under the ROC curve were calculated. The results are shown in Figure 2 shown.
[0051] Depend on Figure 2 It can be seen that the optimal cutoff value of JAML protein in serum for diagnosing sepsis is 2904.4 pg / mL, with a sensitivity of 0.52, a specificity of 0.90, and an area under the curve of 0.72. The results show that JAML protein has good diagnostic efficacy in the clinical diagnosis of sepsis.
[0052] (III) Correlation between JAML protein expression in serum of patients with sepsis and SOFA score
[0053] In the sepsis diagnostic standard Sepsis 3.0, the SOFA score is an important indicator for diagnosing sepsis. A large number of studies have shown that for patients with infection or suspected infection in the ICU, when the SOFA score is ≥ 2 points, they are diagnosed with sepsis; not only that, the SOFA score reflects the degree of dysfunction of multiple organs in patients with multiple organ dysfunction syndrome (MODS), and is closely related to the patient's in-hospital mortality rate. Therefore, this application conducted a correlation analysis on the JAML protein expression detection results in the serum of sepsis patients measured in (I) and the SOFA scores of the corresponding samples collected, used SPSS 20.0 software for statistical analysis, and used GraphPad Prism 9.5.0 software for drawing. The results are shown in the figure. Figure 3 shown.
[0054] like Figure 3 As shown in the figure, the expression of JAML protein in the serum of patients with sepsis was positively correlated with SOFA score. This result shows that JAML protein can be used to indicate the severity of sepsis.
[0055] (IV) Comparative experiment on the expression of JAML protein in the serum of sepsis model mice and sham operation group mice
[0056] Experimental animals: Wild type C57BL / 6J (WT) male mice, weighing 20-24 g, about 6-8 weeks old, were purchased from Beijing Sibeifu Biotechnology Co., Ltd. All mice used in this experiment were SPF-grade experimental animals, and the experimental animal license number was SCKK (Beijing) 2024-0001.
[0057] The cecal ligation and puncture (CLP) technique was used to construct septic mice. The specific steps were as follows: the above-mentioned wild type C57BL / 6J (Wild type, WT) male mice were selected, and 100 μL of 1.5% sodium pentobarbital was intraperitoneally injected to anesthetize the mice, and the mice were fixed on an operating board. The abdomen was shaved with a pet electric clipper, and the skin was disinfected. A 1 cm long incision was made in the middle of the abdomen, the cecum was ligated, and punctured with a 26-gauge syringe needle. Finally, the wound was sutured and the skin was disinfected (for specific experimental methods, refer to: Daniel Rittirsch, Peter AWard, et al. Immunodesign of experimental sepsis by cecal ligation and puncture. Nat Protoc. 2009; 4(1): 31-36).
[0058] Twenty-eight wild-type C57BL / 6J (WT) male mice were selected and randomly divided into four groups, namely, sham operation group, CLP6h group, CLP24h group and CLP48h group. The sepsis model was constructed in all four groups. The difference was that the cecum was not ligated and punctured in the sham operation group. The other steps were the same. The heart blood of mice was collected from the sham operation group 24 hours after the operation. The heart blood of mice was collected from the CLP6h group, CLP24h group and CLP48h group 6 hours, 24 hours and 48 hours after the model was constructed, respectively. The blood was centrifuged at 4°C and 1400×g for 7 minutes, and the serum was collected and the expression of JAML protein was measured using an ELISA kit (purchased from My BioSource, MBS7273874). The operation steps were strictly performed according to the instructions attached to the kit. Then the test results were statistically analyzed using SPSS20.0 software, and graphed using GraphPad Prism9.5.0 software. The results are shown in Figure 2 Figure 4 shown.
[0059] like Figure 4 As shown in the figure, compared with the sham operation group, 24 hours after the establishment of the sepsis model, the expression of JAML protein in the serum of wild-type mice was significantly increased, and the difference was statistically significant. This result shows that JAML protein can be used as a biomarker for the diagnosis of sepsis in mice.
[0060] (V) Mouse survival rate experiment
[0061] Thirty-one wild type C57BL / 6J (WT) male mice were selected and divided into two groups, one group was a protein treatment group (n=15) and the other group was a PBS control group (n=16). Then, the sepsis model was established according to the method in (IV), specifically: 100 μL of 1.5% sodium pentobarbital was intraperitoneally injected to anesthetize the mice, fixed on an operating board, the abdomen was shaved with a pet electric clipper, the skin was disinfected, a 1 cm long incision was made in the middle of the abdomen, the cecum was ligated, and punctured with a 26-gauge syringe needle, and finally the wound was sutured and the skin was disinfected;
[0062] Then, the protein treatment group was intraperitoneally injected with 100uL of 10ug mouse recombinant JAML protein (purchased from MedChemexpress, HY-P76464), and the PBS control group was intraperitoneally injected with the same volume of sterile PBS buffer. The survival of the mice was observed and recorded twice a day for 4 consecutive days. Each experiment was repeated at least twice. The results are shown in the figure. Figure 5 shown.
[0063] like Figure 5 As shown, after wild-type mice were supplemented with exogenous recombinant mouse JAML, their survival rate (i.e., survival probability) was 66.67% after CLP modeling for 4 days, while the survival rate of the PBS control group after CLP modeling was only 31.25%. This result shows that exogenous supplementation of JAML protein can protect septic mice and significantly improve the survival rate of septic mice.
[0064] (VI) Bacterial load test
[0065] Twelve wild type C57BL / 6J (WT) male mice weighing 21-22 g were selected and divided into a protein treatment group and a PBS control group. Both groups were modeled according to method (IV), namely: the mice were anesthetized by intraperitoneal injection of 100 μL of 1.5% sodium pentobarbital, fixed on an operating board, the abdomen was shaved with a pet electric clipper, the skin was disinfected, a 1 cm long incision was made in the middle of the abdomen, the cecum was ligated, and punctured with a 26-gauge syringe needle, and finally the wound was sutured and the skin was disinfected;
[0066] According to method (IV), the mice in the protein treatment group were injected with JAML recombinant protein, and the mice in the PBS control group were injected with the same volume of sterile PBS buffer. After 24 hours, heart blood, lungs and livers were collected, and the heart blood was diluted 100 times. The lungs and spleen were ground into a homogenate with 1 mL of sterile PBS buffer and then diluted 100 times. Then 15 μL of each was taken for plating. After 12 hours, the number of colonies on the blood agar plate was counted, and statistical analysis was performed using SPSS20.0 software, and graphing was performed using GraphPad Prism9.5.0 software. The results are shown in Figure 2. Figure 6As shown, 6A is a comparison of the bacterial load in the blood of sepsis model mice in the JAML protein treatment group and the PBS control group (i.e., PBS group), Figure 6 B is a comparison of bacterial loads in the lungs of sepsis model mice in the JAML protein treatment group and the PBS control group. Figure 6 C is a comparison of bacterial loads in the livers of sepsis model mice in the JAML protein treatment group and the PBS control group.
[0067] like Figure 6 As shown in the figure, compared with the control group, after wild-type mice were supplemented with mouse recombinant JAML protein, the bacterial load in the heart blood, lungs and liver of sepsis model mice was significantly increased, and the difference was statistically significant (P<0.001). This result shows that JAML protein enhances the bacterial clearance ability of mice.
[0068] In summary, the present invention used the ELISA method to detect the sera of several adult sepsis patients and healthy people. The results showed that the expression level of JAML protein in the sera of sepsis patients was significantly higher than that of healthy people, with statistical differences, suggesting that JAML protein can be used as a biomarker for the clinical diagnosis of sepsis.
[0069] The present invention found through ROC analysis that the optimal cutoff value of JAML protein in serum for diagnosing sepsis was 2904.4 pg / mL, the sensitivity was 0.52, the specificity was 0.90, and the area under the curve was 0.72, indicating that JAML protein has good diagnostic efficacy in the clinical diagnosis of sepsis.
[0070] The present invention found through correlation analysis that the JAML level was positively correlated with the sequential organ failure assessment (SOFA), indicating that the JAML protein can be used as a diagnostic indicator for sepsis and can reflect the severity of the disease.
[0071] The present invention also conducted a comparative experiment on the expression of JAML protein in the serum of mice with sepsis model and mice in the sham operation group. The results showed that compared with the sham operation group, 24 hours after the construction of the sepsis model, the expression of JAML protein in the serum of wild-type mice was significantly increased, and the difference was statistically significant, suggesting that JAML protein can be used as a biomarker for the diagnosis of sepsis mice.
[0072] The present invention also conducted a survival rate experiment, and the results showed that the survival rate of mice in the protein treatment group was significantly better than that of mice in the control group, and there was a statistical difference, indicating that exogenous supplementation of JAML protein can protect septic mice and thus significantly improve the survival rate of septic mice.
[0073] The present invention also conducted a bacterial load experiment, and the results showed that compared with the control group, the bacterial load in the heart blood, lungs and liver of septic mice given exogenous JAML protein was significantly increased, indicating that JAML protein can enhance the bacterial clearance function of septic mice.
[0074] The above embodiments are merely illustrative of the principles and effects of the present invention, and are not intended to limit the present invention. Anyone familiar with the technology may modify or change the above embodiments without violating the spirit and scope of the present invention. Therefore, all equivalent modifications or changes made by a person of ordinary skill in the art without departing from the spirit and technical ideas disclosed by the present invention shall still be covered by the claims of the present invention.
Claims
1. Use of a junctional adhesion molecule-like protein and / or a gene encoding the junctional adhesion molecule-like protein as a biomarker in the preparation of sepsis diagnosis, prognosis or assessment, It is characterized in that The junctional adhesion molecule-like protein and / or the gene are used as biomarkers for preparing or screening sepsis diagnostic reagents, and the reagents are used for diagnosis and / or prognosis and / or treatment monitoring of sepsis.
2. The use according to claim 1, It is characterized in that The reagent is used to determine the expression amount of the junctional adhesion molecule-like protein and / or the activity of the gene in a biological sample of a subject.
3. The use according to claim 2, It is characterized in that The biological sample is selected from at least one of whole blood, serum and plasma.
4. The use according to claim 2, It is characterized in that The reagent uses at least one of chromatography, mass spectrometry, fluorescence, electrophoresis, immunoaffinity, immunochemistry, ultraviolet spectroscopy, fluorescence analysis, radiochemical analysis, near-infrared spectroscopy, nuclear magnetic resonance spectroscopy, light scattering analysis, turbidimetry, flow cytometry, polymerase chain reaction detection, protein immunoblotting, colloidal gold method, electrochemistry, microfluidics and high-throughput method to determine the expression amount of the connecting adhesion molecule-like protein and / or the activity of the gene in the biological sample of the subject.
5. The use according to claim 2, It is characterized in that The expression level of the junctional adhesion molecule-like protein in the biological sample of the subject is positively correlated with the severity of sepsis.
6. The use according to claim 1, It is characterized in that The reagent is used to assist in diagnosing or monitoring the existence and / or course and / or severity and / or mortality risk and / or prognosis of sepsis.
7. Use of a connecting adhesion molecule-like protein and / or a gene encoding the connecting adhesion molecule-like protein in the preparation of a drug for preventing or treating sepsis.
8. The use according to claim 7, It is characterized in that The active ingredient of the drug treats or alleviates sepsis by increasing the expression level of the junctional adhesion molecule-like protein in the biological sample of the subject or enhancing the activity of the gene.
9. The use according to claim 8, It is characterized in that The drug also includes pharmaceutically acceptable excipients.
10. The use according to claim 9, It is characterized in that The pharmaceutically acceptable excipients include at least one of a dispersant, an emulsifier, a solvent, a cosolvent, a solubilizer, a latent solvent, a carrier, a filler, a stabilizer, a wetting agent, a penetrant, an adhesive and a defoaming agent.