Application of xylulose-5-phosphoric acid as inflammatory bowel disease biomarker with intestinal fibrosis characteristics

Abstract

The invention belongs to the technical field of biomedicine, and particularly relates to application of xylulose-5-phosphoric acid as an inflammatory bowel disease biomarker with intestinal fibrosis characteristics. It is found for the first time that xylulose-5-phosphoric acid is remarkably increased in a biological sample of a patient with the inflammatory bowel disease with the intestinal fibrosis characteristic, and the expression level of xylulose-5-phosphoric acid in the biological sample of the patient with the inflammatory bowel disease with the intestinal fibrosis characteristic is in a positive correlation relation with the occurrence degree of the intestinal fibrosis. The discovery provides an important therapeutic target for predicting or evaluating whether a subject suffers from the inflammatory bowel disease with the intestinal fibrosis characteristic by using the xylulose-5-phosphoric acid as the inflammatory bowel disease biomarker with the intestinal fibrosis characteristic.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical technology, and particularly relates to the application of xylulose-5-phosphate as a biomarker for inflammatory bowel disease with intestinal fibrosis characteristics. Background Art

[0002] Inflammatory bowel disease (IBD), as a gastrointestinal inflammatory disease widely existing globally, its complexity and intractability have always been the focus of the medical community. IBD not only brings great physical and mental pain to patients due to its recurrent characteristics, but also seriously affects the quality of life and life expectancy of patients due to its potential complications such as intestinal stricture and fistula. According to statistics, in some regions, the prevalence of IBD can be as high as 3.22‰.

[0003] The course of IBD often lingers and does not heal. As time goes by, patients face the risk of intestinal structural changes, among which intestinal stricture is one of the most representative complications. Intestinal stricture not only limits the intestinal function of patients, but may also trigger critical situations such as intestinal obstruction, forcing about 80% of IBD patients to finally have to undergo surgical treatment. And the surgery not only brings physical trauma, but also a series of subsequent problems such as postoperative recurrence and decreased quality of life, making the treatment of IBD a long-term and complex challenge.

[0004] Intestinal stricture and its related complications are the main reasons for IBD patients to receive surgical treatment, accounting for up to 40%. This data highlights the key position of intestinal stricture in the course of IBD, and also prompts us that finding effective prevention and treatment strategies is crucial for improving the clinical outcomes of IBD patients. The pathological basis of intestinal stricture lies in intestinal fibrosis, which is a complex process driven by chronic inflammatory responses and involving multiple cell types and molecular mechanisms. Once intestinal fibrosis forms, existing drug treatment means are often difficult to reduce its progression or achieve reversal, which makes early intervention the key to preventing intestinal stricture and improving the prognosis of patients.

[0005] However, currently there is a lack of biomarkers in clinical practice that can effectively predict the occurrence of intestinal fibrosis in IBD patients. This means that doctors cannot take targeted preventive measures before the occurrence of fibrosis, and can only intervene after patients show obvious stricture symptoms, which undoubtedly increases the difficulty and cost of treatment, and also reduces the treatment effect. Therefore, developing a biomarker that can early predict the risk of intestinal fibrosis in IBD patients is of great significance for achieving early prevention and treatment of intestinal fibrosis, reducing unnecessary surgical interventions, and improving the quality of life of patients. However, currently there is no biomarker for early predicting the occurrence of intestinal fibrosis in IBD patients in clinical practice, which greatly restricts the early prevention and treatment of IBD intestinal fibrosis.

[0006] In summary, given the high incidence and serious harm of intestinal stenosis in IBD and its complications, as well as the current lack of biomarkers for early prediction of intestinal fibrosis in clinical practice, the development of a new and reliable biomarker for early prediction and prevention of intestinal fibrosis in IBD not only has important clinical significance, but is also a key issue that needs to be urgently addressed in current medical research. Summary of the invention

[0007] In view of the high incidence, difficulty in treatment and serious impact on the quality of life of patients with existing inflammatory bowel disease and its serious complications, intestinal fibrosis or intestinal stenosis, and the lack of effective means to predict the risk of intestinal fibrosis in patients with inflammatory bowel disease, the present invention aims to provide the use of xylulose-5-phosphate as an inflammatory bowel disease biomarker with intestinal fibrosis characteristics. The biomarker can accurately and sensitively reflect the early changes of intestinal fibrosis in patients with inflammatory bowel disease, providing a reliable tool for clinical use so that fibrosis can be effectively identified when it has not yet formed or is in a reversible stage.

[0008] In order to achieve the above object, the present invention adopts the following technical solutions:

[0009] The first object of the present invention is to provide a use of xylulose-5-phosphate as a biomarker for inflammatory bowel disease with intestinal fibrosis characteristics.

[0010] The second object of the present invention is to provide the use of xylulose-5-phosphate as a biomarker for early diagnosis of inflammatory bowel disease with intestinal fibrosis characteristics.

[0011] The third object of the present invention is to provide the use of xylulose-5-phosphate in the preparation of an early diagnosis product for inflammatory bowel disease with intestinal fibrosis characteristics.

[0012] Preferably, the expression level of xylulose 5-phosphate in biological samples of patients with inflammatory bowel disease characterized by intestinal fibrosis is positively correlated with the degree of intestinal fibrosis; the biological samples include blood, serum, plasma and intestinal tissue samples.

[0013] Another object of the present invention is to provide an early diagnostic product for inflammatory bowel disease with intestinal fibrosis characteristics, which predicts or evaluates the degree of intestinal fibrosis in patients with inflammatory bowel disease with intestinal fibrosis characteristics by detecting the concentration or activity level of the xylulose-5-phosphate marker in the biological sample of the subject, and then determines whether the subject suffers from inflammatory bowel disease with intestinal fibrosis characteristics.

[0014] Preferably, the product is a detection kit, comprising reagents for quantitatively detecting the concentration or activity level of xylulose-5-phosphate in a biological sample of a subject and instructions for use.

[0015] Another object of the present invention is to provide a method for early diagnosis of inflammatory bowel disease with intestinal fibrosis characteristics, comprising the following steps:

[0016] a) Collecting a biological sample from a patient suspected of having inflammatory bowel disease with intestinal fibrosis characteristics;

[0017] b) Detecting the concentration or activity level of xylulose-5-phosphate in the biological sample;

[0018] c) Predicting or evaluating the degree of intestinal fibrosis in the patient based on the concentration or activity level of xylulose-5-phosphate, and further determining whether the subject has inflammatory bowel disease with intestinal fibrosis characteristics; wherein: the expression level of xylulose-5-phosphate in the biological sample of a patient with inflammatory bowel disease with intestinal fibrosis characteristics is positively correlated with the degree of intestinal fibrosis.

[0019] Preferably, the method for detecting the concentration or activity level of xylulose-5-phosphate in the biological sample in step b) includes chromatographic analysis, spectroscopic analysis, electrochemical analysis, immunological methods, nuclear magnetic resonance NMR or biosensor technology.

[0020] Preferably, the chromatographic analysis includes liquid chromatography-mass spectrometry; the spectroscopic analysis includes ultraviolet-visible spectroscopy and fluorescence spectroscopy; the immunological methods include enzyme-linked immunosorbent assay, immunoprecipitation and immunoblotting.

[0021] Another object of the present invention is to provide a system for early diagnosis of inflammatory bowel disease with intestinal fibrosis characteristics, comprising:

[0022] a) A blood collection device for collecting a biological sample from a patient suspected of having inflammatory bowel disease with intestinal fibrosis characteristics;

[0023] b) A xylulose-5-phosphate detection module for detecting the concentration or activity level of xylulose-5-phosphate in the biological sample;

[0024] c) A data processing module for predicting or evaluating the degree of intestinal fibrosis in the patient based on the concentration or activity level of xylulose-5-phosphate, and further determining whether the subject has inflammatory bowel disease with intestinal fibrosis characteristics; wherein: the expression level of xylulose-5-phosphate in the biological sample of a patient with inflammatory bowel disease with intestinal fibrosis characteristics is positively correlated with the degree of intestinal fibrosis;

[0025] d) An output module for displaying the prediction or evaluation result and treatment advice.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The present invention for the first time discovers that xylulose-5-phosphate is significantly elevated in biological samples of patients with inflammatory bowel disease characterized by intestinal fibrosis, and the expression level of xylulose-5-phosphate in biological samples of patients with inflammatory bowel disease characterized by intestinal fibrosis is positively correlated with the degree of intestinal fibrosis. This discovery provides an important therapeutic target for xylulose-5-phosphate to predict or evaluate the degree of intestinal fibrosis in patients with inflammatory bowel disease characterized by intestinal fibrosis, and further to determine whether a subject has inflammatory bowel disease characterized by intestinal fibrosis. Brief Description of the Drawings

[0028] Figure 1 It is the flow chart of the metabolomics of the present invention;

[0029] Figure 2 It is the mass spectrum of xylulose-5-phosphate;

[0030] Figure 3 It is the selected ion chromatogram XIC;

[0031] Figure 4 It is the result graph of the metabolomics data of human intestinal tissue;

[0032] Figure 5 It is the ROC curve graph for evaluating intestinal stricture with the level of xylulose-5-phosphate in human intestinal tissue;

[0033] Figure 6 It is the mass spectrum of xylulose-5-phosphate;

[0034] Figure 7 It is the standard curve graph;

[0035] Figure 8 It is the result graph of the metabolomics data of human serum;

[0036] Figure 9 It is the ROC curve graph for predicting the occurrence of intestinal stricture with the baseline level of xylulose-5-phosphate in human serum. Detailed Embodiments

[0037] The above content of the present invention is further described in detail below through specific embodiments in the form of examples. However, it should not be understood that the scope of the above subject matter of the present invention is limited to the following examples.

[0038] The experimental methods in the following examples of the present invention that are not specified under specific conditions are usually carried out under conventional conditions or according to the conditions recommended by the manufacturer. All kinds of commonly used chemical reagents used in the examples are commercially available products.

[0039] Unless otherwise defined, all technical and scientific terms used in this invention have the same meanings as commonly understood by those skilled in the technical field to which this invention belongs. The terms used in the description of this invention are only for the purpose of describing specific embodiments and are not intended to limit this invention.

[0040] To make the objectives, technical solutions and advantages of this invention clearer and more understandable, the following further details this invention in conjunction with specific embodiments. It should be understood that these descriptions are exemplary and not intended to limit the scope of this invention. In addition, in the following descriptions, the descriptions of well-known structures and technologies are omitted to avoid unnecessarily confusing the concepts of this invention.

[0041] The following embodiments further describe this invention, but these embodiments are not intended to limit the protection scope of this invention.

[0042] 1. Raw materials and reagents

[0043] Table 1

[0044]

[0045] 2. Equipment and instruments

[0046] Table 2

[0047]

[0048]

[0049] 3. Study population

[0050] All patients with inflammatory bowel disease featuring intestinal fibrosis in this invention are from the First Affiliated Hospital of Sun Yat-sen University and have obtained informed consent forms. The clinical ethics number is

[2025] 031.

[0051] 4. Experimental design and methods

[0052] This experiment uses LC-MS coupling technology to study the metabolites of intestinal tissues and serum samples of patients with inflammatory bowel disease featuring intestinal fibrosis, and uses a liquid chromatography-mass spectrometry instrument to conduct metabolomics screening and detection on the intestinal tissues and serum samples of patients with inflammatory bowel disease featuring intestinal fibrosis. The detection process diagram is as Figure 1 shown.

[0053] Example 1 Liquid chromatography-mass spectrometry analysis of metabolites in intestinal tissues of patients with inflammatory bowel disease featuring intestinal fibrosis

[0054] (1) Sample collection and pretreatment

[0055] Collection subjects: 30 patients aged between 18 and 65 years old, diagnosed with inflammatory bowel disease accompanied by intestinal fibrosis and stenosis requiring surgical treatment, and not receiving biological agent treatment in the past 3 months.

[0056] Collection sites: Tissue samples from the intestinal stenosis site and relatively normal site of each patient.

[0057] Sample processing: Take out 20 mg of the sample from the -80 °C refrigerator and thaw it on ice until it can be cut. Add steel beads to the centrifuge tube and homogenize it with a ball mill (30 HZ) for 20 s. Centrifuge at 3000 r / min for 30 s at 4 °C. Add 400 μL of 70% methanol-water internal standard extraction solution, oscillate at 1500 r / min for 5 min, and let it stand on ice for 15 min. Centrifuge at 12000 r / min for 10 min at 4 °C, transfer 300 μL of the supernatant to another centrifuge tube, and let it stand in the -20 °C refrigerator for 30 min. Centrifuge at 12000 r / min for 3 min at 4 °C again, and transfer 200 μL of the supernatant for machine analysis.

[0058] Quality control sample (QC): Prepared from the normal intestinal sites of each patient, and mixed from the sample extracts, used to analyze the repeatability of the samples under the same processing method. During the instrument analysis process, generally insert one quality control sample into every 10 test analysis samples to monitor the repeatability of the analysis process.

[0059] (2) Liquid chromatography-mass spectrometry analysis of intestinal tissue metabolites

[0060] 2.1 Instrument equipment Liquid chromatography: Vanquish ultra-high performance liquid chromatograph, Thermo Scientific, Massachusetts, USA; Mass spectrometry: Q Exactive HF-X mass spectrometer, Thermo Scientific, Massachusetts, USA;

[0061] Chromatographic column: Waters ACQUITY Premier HSS T3 Column 1.8 μm, 2.1 mm × 100 mm.

[0062] 2.2 Liquid chromatography conditions

[0063] Mobile phase: A is 0.1% formic acid / water, B is 0.1% formic acid / acetonitrile.

[0064] Column temperature: 40 °C, flow rate: 0.4 mL / min, injection volume: 4 μL.

[0065] The gradient elution program is shown in the following table:

[0066] Table 3 Gradient elution program

[0067] Time (min) A(％) B(％) 0.0 95 5 2.0 80 20 5.0 40 60 6.0 1 99 7.5 1 99 7.6 95 5 10.0 95 5

[0068] 2.3 Mass spectrometry conditions

[0069] Table 4

[0070] Item ESI+ ESI- Ionization Voltage (V) 3500 3200 Sheath Gas (Amb) 30 30 Auxiliary Gas (Arb) 5 5 Ion Transfer Tube Temperature (°C) 320 320 Atomization Temperature (°C) 300 300 MS1 Mass Scan Range (Da) 75～1000 75～1000 MS1 Resolution 35000 35000 MS1 Automatic Gain Control <![CDATA[1×10 6 > <![CDATA[1×10 6 > Collision Energy Step Size (V) 50 50 MS2 Mass Scan Range (Da) 75～1000 75～1000

[0071] (3) Analysis of characteristic differential metabolites in intestinal tissues

[0072] Data processing: The XCMS program was used for peak extraction, alignment, and retention time correction.

[0073] Metabolite identification: The corrected and screened peaks were used for metabolite identification by retrieving databases, integrating public libraries, prediction libraries, and the metDNA method. As Figure 2 and Figure 3 shown. Note: There are many samples in both groups. For XIC, two samples were taken from each group, and the corresponding sample numbers can be seen on the right side of the picture.

[0074] Screening conditions: Finally, substances with a comprehensive scoring of more than 0.5 points after extraction and identification and a CV value of less than 0.3 for QC samples were selected as characteristic differential metabolites. Among them, the CV value, that is, the coefficient of variation, is the ratio of the standard deviation of the original data to the average of the original data, which can reflect the degree of data dispersion. The empirical cumulative distribution function (ECDF) can be used to analyze the frequency of CVs of substances less than the reference value. The higher the proportion of substances with a lower CV value in QC samples, the more stable the experimental data: when the proportion of substances with a CV value less than 0.5 in QC samples is higher than 85%, it indicates that the experimental data is relatively stable; when the proportion of substances with a CV value less than 0.3 in QC samples is higher than 75%, it indicates that the experimental data is very stable.

[0075] Combination mode: Positive and negative mode combinations were carried out, and substances with the highest qualitative level and the smallest CV value were retained.

[0076] Data quality control: The repeatability of metabolite extraction and detection was evaluated by the overlap display of the total ion current chromatograms of quality control samples (QC). The absence of obvious peaks of internal standards in blank samples indicates less substance residue and controllable cross-contamination. The Pearson correlation analysis of QC samples shows high stability, and the small difference in the response of internal standards further proves the stability of the detection process. At the same time, the CV value distribution diagrams of all samples show that the proportion of substances with a CV value less than 0.5 in QC samples exceeds 85%, and the proportion of substances less than 0.3 exceeds 75%, comprehensively indicating that the experimental data is stable and of high quality.

[0077] (4) Evaluation of the diagnostic ability of biomarkers

[0078] The diagnostic ability of biomarkers was evaluated using receiver operating characteristic curve (ROC curve) analysis.

[0079] (5) Experimental results

[0080] As Figure 4 and Figure 5 shown, compared with the control group, the metabolomics data of intestinal tissues from inflammatory bowel disease patients with intestinal fibrosis characteristics detected a significant increase in the expression of D-Xylulose 5-phosphate at the intestinal stricture site. Moreover, through statistical analysis, it was found that the content of D-Xylulose 5-phosphate was closely related to whether inflammatory bowel disease patients had concurrent intestinal fibrosis (AUC = 0.742, 95% CI: 0.618 - 0.867, p < 0.001). This result indicates that D-Xylulose 5-phosphate may be a potential biomarker for intestinal fibrosis in inflammatory bowel disease, and changes in its expression level can reflect the progression of intestinal fibrosis.

[0081] Example 2 Liquid chromatography-mass spectrometry analysis of serum metabolites in inflammatory bowel disease patients with intestinal fibrosis characteristics

[0082] (1) Sample collection and pretreatment

[0083] Collection subjects: 45 inflammatory bowel disease patients aged between 18 and 65 years, naive treatment, without a history of intestinal stricture, penetration, or surgery. Whether the disease progressed to intestinal fibrosis and stricture was recorded through at least 1 year of follow-up.

[0084] Baseline serum samples: At the start of the study, the initial serum samples of each patient were collected as the baseline and stored in a -80°C refrigerator.

[0085] Sample processing: After thawing the samples, 50 μL was taken and added to a centrifuge tube, 250 μL of 20% acetonitrile methanol extraction solution was added, vortexed for 3 min, and then centrifuged at 12000 r / min for 10 min at 4°C. After centrifugation, 250 μL of the supernatant was aspirated into a centrifuge tube, left to stand in a -20°C refrigerator for 30 min, and then centrifuged again at 12000 r / min for 10 min at 4°C. 180 μL of the supernatant was passed through a protein precipitation plate and used for on-machine analysis.

[0086] Using the mixed solution as the QC sample, during the instrument analysis process, generally, one quality control sample was inserted every 10 detected analysis samples. By performing overlapping display analysis on the total ion current chromatogram (TIC) of the same quality control sample for mass spectrometry detection and analysis, the stability of the instrument during the project detection period could be judged.

[0087] (2) Liquid chromatography-mass spectrometry analysis of serum metabolites

[0088] 2.1 Instrumentation

[0089] Liquid chromatography: Ultra Performance Liquid Chromatography (UPLC) (Waters ACQUITY H-Class D);

[0090] Mass spectrometry: Tandem mass spectrometry (MS / MS) ( 6500+);

[0091] Chromatographic column: ACQUITY UPLC BEH Amide column (1.7 μm, 100 mm × 2.1 mm i.d.).

[0092] 2.2 Liquid chromatography conditions

[0093] Mobile phase: Phase A, ultrapure water (10 mM ammonium acetate, 0.3% ammonia water); Phase B, 90% acetonitrile / water (V / V); Flow rate 0.4 mL / min.

[0094] Column temperature: 40 °C.

[0095] Injection volume: 2 μL.

[0096] Mobile phase gradient: 0 - 1.2 min, A / B is 5:95 (V / V), 8 min, A / B is 30:70 (V / V), 9.0 - 11 min, A / B is 50:50 (V / V), 11.1 - 15 min, A / B is 5:95 (V / V).

[0097] 2.3 Mass spectrometry conditions

[0098] Mass spectrometry conditions: Electrospray Ionization (ESI) source temperature 550 °C, mass spectrometry voltage 5500 V in positive ion mode, mass spectrometry voltage -4500 V in negative ion mode, Curtain Gas (CUR) 35 psi.

[0099] Scan detection: In Q-Trap 6500+, each ion pair is scanned and detected according to the optimized declustering potential (DP) and collision energy (CE).

[0100] (3) Analysis of serum characteristic differential metabolites

[0101] Data processing: Use the XCMS program for peak extraction, alignment, and retention time correction.

[0102] Metabolite Identification: The calibrated and screened peaks were used for metabolite identification by retrieving databases, integrating public libraries, prediction libraries, and the metDNA method. An MWDB (Metware Database) was constructed based on standards for qualitative analysis of the mass spectrometry data. Quantification was performed using the multiple reaction monitoring (MRM) mode of triple quadrupole mass spectrometry (as shown below Figure 6 ). In the MRM mode, the quadrupole first screens the precursor ions (parent ions) of the target substance to exclude ions corresponding to other molecular weight substances for preliminary interference elimination. The precursor ions are fragmented after being induced to ionize in the collision cell and then multiple fragment ions are formed. The fragment ions are then filtered through the triple quadrupole to select the required characteristic fragment ions, excluding non-target ion interference, making the quantification more accurate and the repeatability better. After obtaining the mass spectrometry data of different samples, the chromatographic peaks of all target substances are integrated and quantitative analysis is performed through a standard curve, as shown in Figure 7 .

[0103] Screening Criteria: Finally, substances with a comprehensive identification score of more than 0.5 and a CV value of less than 0.3 in the QC samples were extracted as characteristic differential metabolites. Among them, the CV value, i.e., the coefficient of variation, is the ratio of the standard deviation of the original data to the average of the original data, which can reflect the degree of data dispersion. The empirical cumulative distribution function (ECDF) can be used to analyze the frequency of CVs of substances less than the reference value. The higher the proportion of substances with a lower CV value in the QC samples, the more stable the experimental data. When the proportion of substances with a CV value less than 0.3 in the QC samples is higher than 80%, it indicates that the experimental data is stable. When the proportion of substances with a CV value less than 0.2 in the QC samples is higher than 80%, it indicates that the experimental data is very stable.

[0104] Mode Merging: Positive and negative mode merging was performed (retaining the substance with the highest qualitative level and the smallest CV value).

[0105] Data Quality Control: A mixed solution was used as the QC sample and inserted regularly during the instrument analysis process to evaluate the instrument stability. Through methods such as total ion current chromatogram overlay display, Pearson correlation analysis, and CV value (coefficient of variation) distribution diagram (analyzed using the empirical cumulative distribution function), the stability of the detection process and the data quality were comprehensively judged. The results showed that the instrument had high stability, strong correlation of the QC samples, and the proportion of substances with a CV value less than 0.3 exceeded 80%, and the proportion of those less than 0.2 also exceeded 80%, indicating that the experimental data was stable and very reliable.

[0106] (4) Evaluation of the Diagnostic Ability of Biomarkers

[0107] The diagnostic ability of biomarkers was evaluated using receiver operating characteristic (ROC) curve analysis.

[0108] (5) Experimental results

[0109] As Figure 8 and Figure 9 shown, metabolomic analysis of baseline serum from patients with inflammatory bowel disease focused on the expression of xylulose-5-phosphate. The research results showed that in patients with inflammatory bowel disease who developed intestinal fibrosis or intestinal stricture after follow-up (follow-up time: median, IQR: 49.0 months, 42.0 - 53.0 months), the level of xylulose-5-phosphate at baseline (i.e., at the start of the study) was significantly higher compared to those without intestinal fibrosis or intestinal stricture. This finding suggests that the baseline level of xylulose-5-phosphate may be associated with the risk of future intestinal stricture in patients with inflammatory bowel disease.

[0110] Furthermore, the receiver operating characteristic curve was used to evaluate the efficacy of the baseline value of xylulose-5-phosphate in predicting the occurrence of intestinal fibrosis in patients with inflammatory bowel disease. The results showed that among the entire metabolome, the baseline value of xylulose-5-phosphate had the best predictive ability, with an area under the curve (AUC) of 0.744 (95% CI: 0.589 - 0.899, p = 0.005). Therefore, the baseline level of xylulose-5-phosphate can be used as an effective indicator for predicting the occurrence of intestinal fibrosis in patients with inflammatory bowel disease.

[0111] In summary, the present invention verified through liquid chromatography-mass spectrometry experiments that xylulose-5-phosphate can be used as a biomarker for inflammatory bowel disease with intestinal fibrosis characteristics to predict or evaluate the degree of intestinal fibrosis in patients with inflammatory bowel disease, and further to determine whether the subject has inflammatory bowel disease with intestinal fibrosis characteristics, thus providing an important therapeutic target for inflammatory bowel disease with intestinal fibrosis characteristics.

[0112] The above embodiments merely illustrate the principles and effects of the present invention and are not intended to limit the present invention. Any person familiar with this technology can modify or change the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or changes completed by those with ordinary knowledge in the technical field without departing from the spirit and technical ideas disclosed by the present invention should still be covered by the claims of the present invention.

Claims

1. Application of xylulose 5-phosphate as a biomarker for inflammatory bowel disease with intestinal fibrosis characteristics.

2. Application of xylulose 5-phosphate as a biomarker for early diagnosis of inflammatory bowel disease with intestinal fibrosis characteristics.

3. Application of xylulose 5-phosphate in the preparation of early diagnostic products for inflammatory bowel disease with intestinal fibrosis characteristics.

4. The use according to any one of claims 1 to 3, characterized in that: The expression level of xylulose-5-phosphate in biological samples of patients with inflammatory bowel disease with intestinal fibrosis characteristics is positively correlated with the degree of intestinal fibrosis; the biological samples include blood, serum, plasma and intestinal tissue samples.

5. An early diagnosis product for inflammatory bowel disease with intestinal fibrosis characteristics, characterized in that: By detecting the concentration or activity level of xylulose-5-phosphate markers in the biological samples of the subjects, the degree of intestinal fibrosis in patients with inflammatory bowel disease with intestinal fibrosis characteristics can be predicted or evaluated, thereby determining whether the subjects suffer from inflammatory bowel disease with intestinal fibrosis characteristics.

6. The early diagnosis product for inflammatory bowel disease with intestinal fibrosis characteristics according to claim 5, characterized in that: The product is a detection kit, including reagents for quantitatively detecting the concentration or activity level of xylulose-5-phosphate in a biological sample of a subject and instructions for use.

7. A method for early diagnosis of inflammatory bowel disease with intestinal fibrosis characteristics, characterized in that: The following steps are involved: a) Collect biological samples from patients with suspected inflammatory bowel disease with features of intestinal fibrosis; b) detecting the concentration or activity level of xylulose 5-phosphate in a biological sample; c) predicting or evaluating the degree of intestinal fibrosis in patients according to the concentration or activity level of xylulose 5-phosphate, and then determining whether the subject suffers from inflammatory bowel disease with intestinal fibrosis characteristics; wherein: the expression level of xylulose 5-phosphate in biological samples of patients with inflammatory bowel disease with intestinal fibrosis characteristics is positively correlated with the degree of intestinal fibrosis.

8. The method according to claim 7, characterized in that The method for detecting the concentration or activity level of xylulose 5-phosphate in the biological sample in step b) includes chromatography, spectral analysis, electrochemical analysis, immunological method, nuclear magnetic resonance NMR or biosensor technology.

9. The method according to claim 8, characterized in that The chromatographic analysis includes liquid chromatography-mass spectrometry; the spectral analysis includes ultraviolet-visible spectroscopy and fluorescence spectroscopy; the immunological method includes enzyme-linked immunosorbent assay, immunoprecipitation and immunoblotting.

10. A system for early diagnosis of inflammatory bowel disease with intestinal fibrosis characteristics, characterized in that: include: a) a blood collection device for collecting biological samples from patients with inflammatory bowel disease suspected of having intestinal fibrosis features; b) a xylulose 5-phosphate detection module, which detects the concentration or activity level of xylulose 5-phosphate in a biological sample; c) a data processing module, predicting or evaluating the degree of intestinal fibrosis in patients according to the concentration or activity level of xylulose 5-phosphate, and then determining whether the subject suffers from inflammatory bowel disease with intestinal fibrosis characteristics; wherein: the expression level of xylulose 5-phosphate in the biological sample of patients with inflammatory bowel disease with intestinal fibrosis characteristics is positively correlated with the degree of intestinal fibrosis; d) Output module, which displays the prediction or evaluation results and treatment recommendations.

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