Application of MK and NLR combined as osteoarthritis diagnosis and treatment marker

Abstract

The invention discloses an application of MK combined with NLR as a diagnosis and treatment marker for osteoarthritis, and research finds that a serum midkine (MK) combined with a blood neutrophil lymphocyte ratio (Neutrophil to Lymphocyte ratio) not only shows relatively high diagnosis efficiency in the diagnosis of osteoarthritis, but also shows relatively high diagnosis efficiency in the diagnosis of osteoarthritis. The potential prediction value is realized in the aspect of predicting the curative effect of the osteoarthritis patient on the treatment of the bone fracture No.1 prescription. The discovery provides a new biomarker for diagnosis and personalized treatment of osteoarthritis, and possibly contributes to optimization of a treatment scheme and improvement of a treatment effect.

Description

Technical Field

[0001] The present invention relates to the technical field of nutritional management of cancer patients, and specifically to the application of MK combined with NLR as markers for the diagnosis and treatment of osteoarthritis, and also to the application of serum midkine combined with neutrophil-to-lymphocyte ratio as markers for the diagnosis and treatment of osteoarthritis. Background Art

[0002] Osteoarthritis (OA), a chronic degenerative disease characterized by joint cartilage degeneration and bone hyperplasia, affects hundreds of millions of people worldwide and is particularly prevalent among the elderly. With the accelerating aging of the global population, the prevalence of OA is increasing, severely impacting patients' quality of life. Research on OA is crucial for improving diagnostic accuracy, guiding treatment, and improving patient outcomes.

[0003] Currently, OA is diagnosed clinically based on a combination of patient symptoms, imaging studies, and exclusionary testing. Clinical manifestations of OA primarily include joint pain, stiffness, dysfunction, swelling, deformity, and joint crepitus. Imaging studies demonstrate joint space narrowing, subchondral bone sclerosis, and marginal osteophyte formation. Laboratory tests often lack specific findings but can be used to exclude other conditions. Joint fluid analysis can reveal abnormal white blood cell counts and decreased viscosity in patients with significant joint effusions. The gold standard for diagnosing OA is arthroscopy, which accurately reflects the extent and type of joint damage. However, this procedure is invasive and expensive, and is not widely accepted by most patients, hindering its widespread clinical application. Hematological tests are simple, convenient, and well-accepted by patients, making them more useful for clinical diagnosis and treatment response assessment. However, hematological test results are often lacking specificity and cannot be directly used to confirm OA. For example, while inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) may be slightly elevated in OA, such elevations can also be seen in a variety of other inflammatory conditions or diseases. In addition, although current hematological inflammatory markers can provide some information about the inflammatory state, their value in monitoring the treatment effect of patients is limited. Therefore, there is a need to find more sensitive and specific blood markers that can be used to evaluate the progression and outcome of OA. In recent years, the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII) as comprehensive indicators reflecting the body's inflammatory state have attracted widespread attention due to their simplicity, convenience, and cost-effectiveness. They have also shown good predictive value in the prognosis assessment of various inflammatory diseases.

[0004] Current clinical treatments for OA primarily utilize traditional Chinese medicine (TCM), Western medications for anti-inflammatory and analgesic effects, and limb function exercises. Surgical treatments, including arthroscopic surgery and joint replacement, are also available. These treatments can effectively stabilize patients' moods, improve joint mobility, alleviate inflammatory stimulation, and reduce joint dysfunction and pain. From a Traditional Chinese Medicine (TCM) perspective, treatment focuses on unblocking Qi and blood throughout the joints and the entire body, achieving therapeutic goals through promoting meridian circulation, activating collaterals, relaxing tendons, promoting Qi circulation, and removing dampness. Traditional Chinese medicine formulas, due to their multi-target regulatory effects and minimal side effects, have shown potential in the treatment of OA. Summary of the Invention

[0005] To address the current challenges of OA research in improving diagnostic accuracy, guiding treatment, and improving patient prognosis, this study provides the use of MK combined with NLR as markers for the diagnosis and treatment of osteoarthritis. The study found that serum midkine (MK) combined with the neutrophil-to-lymphocyte ratio (NLR) not only demonstrated high diagnostic efficacy in the diagnosis of osteoarthritis, but also had potential predictive value in predicting the efficacy of osteoarthritis patients receiving Bone Injury Prescription No. 1. This discovery provides a new biomarker for the diagnosis and personalized treatment of osteoarthritis, and may help optimize treatment plans and improve treatment outcomes.

[0006] The purpose of the present invention is achieved through the following technical solutions:

[0007] Application of serum midkine (MK) combined with neutrophil-to-lymphocyte ratio (NLR) as markers for the diagnosis and treatment of osteoarthritis.

[0008] The application of MK combined with NLR as markers for the diagnosis and treatment of osteoarthritis, including the application of MK combined with NLR in the diagnosis of osteoarthritis and the prediction of the therapeutic efficacy of Bone Injury Prescription No. 1.

[0009] The inventors' previous studies found that compared with healthy people (Negative Control, NC), OA patients had significantly increased neutrophils, while lymphocytes, basophils, red blood cells, and hemoglobin were significantly decreased; OA patients also showed significantly increased NLR, PLR, and SII.

[0010] Further analysis showed that the AUC values ​​of NLR, PLR, and SII for OA patient classification were 0.682, 0.665, and 0.647, respectively, suggesting that NLR, PLR, and SII have a certain diagnostic ability for OA. The specificity of NLR and SII for OA classification was as high as 0.9390, but their sensitivities were relatively low (0.4417 and 0.3542, respectively). Therefore, combining NLR and SII with other biomarkers to improve the diagnostic sensitivity of OA has important clinical significance.

[0011] Serum midkine (MK) is a growth factor that is highly expressed during inflammation and tissue damage repair, and has been shown to play an important role in the pathological process of various diseases. Studies have shown that MK is significantly elevated in the serum of OA patients and is associated with the severity of OA. Recombinant human midkine (rhMK) has a significant repair effect on cartilage damage animal models, suggesting that MK may play a key role in the development of OA. It also suggests the possibility of MK as a diagnostic marker for OA and predicting OA disease outcomes. The inventors' previous test results also showed that MK is highly expressed in the serum of OA patients. The AUC value of MK for the classification of OA patients was 0.8621, with a specificity of 0.8293 and a sensitivity of 0.7875, indicating the potential value of MK as a biomarker for diagnosing OA.

[0012] Based on previous findings of the high specificity of NLR and SII for OA patient classification, and the high sensitivity of MK, the inventors attempted to construct a diagnostic model combining NLR, SII, and MK. Multivariate logistic regression analysis showed that the p-values ​​for MK and NLR were less than 0.05 (0.000 and 0.001, respectively), while the p-value for SII was greater than 0.05 (0.361).

[0013] Therefore, the inventors selected MK and NLR to construct a regression model. AUC analysis of the Logreg_1 model showed that its AUC value for OA classification was 0.8965, with a sensitivity and specificity of 0.8625 and 0.8293, respectively.

[0014] Based on the above results, the combined detection of MK in serum and NLR in blood showed high diagnostic efficacy and specificity in the diagnosis of OA.

[0015] Compared with the prior art, the present invention has the following advantages:

[0016] The application of MK combined with NLR as a marker for the diagnosis and treatment of osteoarthritis described in the present invention has the following innovative features:

[0017] 1. Combined use of different blood biomarkers:

[0018] For the first time, a model constructed based on the two indicators of MK and NLR was used for the diagnosis and efficacy prediction of OA, providing new ideas for the personalized treatment of osteoarthritis.

[0019] 2. Efficacy prediction model:

[0020] A therapeutic efficacy prediction model based on MK and NLR levels was developed to provide personalized treatment recommendations for OA patients and help improve treatment outcomes.

[0021] 3. Personalized treatment plan:

[0022] By evaluating different treatment groups, we provide OA patients with personalized treatment plans based on biomarkers, which helps to improve the targeting and effectiveness of treatment and reduce unnecessary treatment measures for patients.

[0023] 4. Clinical transformation:

[0024] By conducting prospective clinical validation studies in multiple medical institutions, we promote the practical application of research results and improve the diagnosis and treatment of OA.

[0025] 5. Model Validation

[0026] Through internal and external validation, the reliability and practicality of the model are ensured, providing a solid scientific basis for clinical practice.

[0027] Through these technical features and innovations, this project provides new biomarkers and highly accessible support tools for the early diagnosis, efficacy prediction and personalized treatment of osteoarthritis, ultimately improving patients' treatment outcomes and quality of life. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is a graph showing the hematological index levels of healthy people and osteoarthritis patients using MK combined with NLR as a marker for the diagnosis and treatment of osteoarthritis according to an embodiment of the present invention;

[0029] Figure 2 This is a ROC curve diagram of neutrophils, NLR, PLR and SII for the classification of osteoarthritis, which shows the application of MK combined with NLR as a marker for the diagnosis and treatment of osteoarthritis according to an embodiment of the present invention;

[0030] Figure 3 This is a ROC curve diagram of Midkine for osteoarthritis classification based on the application of MK combined with NLR as a marker for the diagnosis and treatment of osteoarthritis according to an embodiment of the present invention;

[0031] Figure 4 This is a ROC curve diagram of the Logreg_1 model constructed based on NLR and MK for the classification of osteoarthritis, which shows the application of MK combined with NLR as a marker for the diagnosis and treatment of osteoarthritis as described in an embodiment of the present invention;

[0032] Figure 5 This is a graph showing the NLR and MK levels of osteoarthritis patients in different efficacy groups using MK combined with NLR as markers for the diagnosis and treatment of osteoarthritis according to an embodiment of the present invention;

[0033] Figure 6This is a ROC curve diagram of the application of MK combined with NLR as a marker for the diagnosis and treatment of osteoarthritis in an embodiment of the present invention, and the classification of effectiveness / ineffectiveness of NLR combined with MK detection in osteoarthritis patients after treatment with Bone Injury No. 1 prescription. DETAILED DESCRIPTION

[0034] The present invention will be further described in detail below with reference to specific examples, but the examples do not limit the present invention in any form. In addition, after reading the present invention, those skilled in the art may make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0035] Example:

[0036] The application of MK combined with NLR as a marker for the diagnosis and treatment of osteoarthritis includes the following:

[0037] 1. Development and validation: Develop and validate a combined detection method and model based on serum midkine (MK) and neutrophil-lymphocyte ratio (NLR) for the early diagnosis and efficacy prediction of OA.

[0038] 2. Personalized treatment plan: Through this detection method and model, personalized treatment plans are provided for OA patients, especially those patient groups who may benefit most from the treatment of Bone Injury Prescription No. 1.

[0039] 3. Optimize treatment effects: By identifying the patient groups that respond best to Bone Injury Prescription No. 1, optimize the treatment plan and improve the overall treatment effect.

[0040] 4. Improve diagnostic accuracy: Combined detection of MK and NLR can improve the diagnostic accuracy of OA, helping clinicians identify the disease earlier and take appropriate intervention measures.

[0041] 5. Promote clinical translation: Promote the transformation of research results into clinical practice, provide new tools and technical support for the diagnosis and treatment of OA, and ultimately improve patients' prognosis and quality of life.

[0042] By achieving these goals, the inventors hope to provide new directions for the diagnosis and prediction of treatment effects of OA, improve clinical diagnosis and treatment, and bring more effective treatment options to patients.

[0043] To achieve the above goals, this embodiment will focus on the following core research contents:

[0044] 1. Development of a combined detection method and model for serum midkine (MK) and neutrophil-lymphocyte ratio (NLR):

[0045] Objective: To develop a combined detection method based on MK and NLR and construct a model for early diagnosis and efficacy prediction of OA.

[0046] content:

[0047] Design and optimize the experimental process for the combined detection of MK and NLR.

[0048] Collect and process blood samples from patients with osteoarthritis.

[0049] Test and validate the diagnostic efficacy of the combined detection method.

[0050] 2. Evaluation of the diagnostic efficacy of combined MK and NLR detection for OA:

[0051] Objective: To evaluate the sensitivity, specificity and other diagnostic indicators of the model constructed by MK combined with NLR in the diagnosis of OA.

[0052] content:

[0053] Blood samples were collected from healthy people and OA patients

[0054] Analyze and compare the levels of MK and NLR in the blood of different populations

[0055] The relationship between MK and NLR levels and the severity of OA was analyzed.

[0056] The optimal threshold for combined detection of MK and NLR was determined by ROC analysis.

[0057] The performance of combined MK and NLR detection was compared with existing diagnostic methods.

[0058] Internal Validation: Cross-validation techniques are used to assess the stability and generalization ability of the model.

[0059] Inclusion criteria for OA patients: patients diagnosed with osteoarthritis and aged 60 years or older; informed consent from patients and their families. Exclusion criteria: (1) patients with concurrent liver, kidney, hematopoietic system, cardiovascular and cerebrovascular diseases; (2) patients with other inflammatory diseases such as Sjögren's syndrome, systemic lupus erythematosus, psoriatic arthritis, gouty arthritis, reactive arthritis, ankylosing spondylitis, rheumatoid arthritis, etc.; (3) patients with various acute and chronic infectious diseases; (4) patients with congenital diseases; (5) patients with cognitive expression disorders; (6) patients with drug allergies.

[0060] Inclusion criteria for healthy physical examination population (control group): age over 60 years old.

[0061] Clinical staging standards for osteoarthritis include: four-level staging based on clinical characteristics, Kellgren & Lawrence classification based on X-ray changes, and Outbridge classification based on articular cartilage damage under arthroscopic examination.

[0062] 3. Application of the model constructed by MK combined with NLR in predicting the therapeutic effect of Bone Injury Prescription No. 1:

[0063] Objective: To evaluate the value of MK combined with NLR detection in predicting the therapeutic effect of Bone Injury No. 1 prescription in patients with osteoarthritis.

[0064] content:

[0065] MK and NLR level data were collected in OA patients who were about to receive Bone Injury Prescription No. 1 treatment.

[0066] Treatment Method: Based on TCM syndrome differentiation and treatment, administer Orthopedic Prescription No. 1 with modifications for internal use. The ingredients are as follows: Astragalus 30g, Salvia miltiorrhiza 30g, Rehmannia glutinosa 15g, Chuanxiong 15g, Cornus officinalis 15g, Lycium barbarum 15g, Rehmannia glutinosa 15g, Cistanche deserticola 15g, Drynaria fortunei 15g, White Peony 15g, Eucommia ulmoides 15g, Carthamus tinctorius 10g, Dipsacus asper 15g, Alisma orientalis 15g, Licorice root 6g, Angelica sinensis 15g, and Epimedium 15g. Six doses total, one daily, taken with 150ml of warm water, half an hour after meals, morning and evening.

[0067] Observation indicators:

[0068] a. Efficacy: Efficacy is evaluated on a three-level scale: markedly effective, effective, and ineffective. Markedly effective refers to restoration of joint function, disappearance of symptoms, and unrestricted mobility; effective refers to improvement of symptoms and joint function with some restriction of mobility; and ineffective refers to no change in clinical symptoms with inability to move normally. Total effective rate = (markedly effective + effective) / total number of cases × 100%.

[0069] b. Clinical efficacy indicators: Clinical efficacy indicators include the Visual Analog Scale (VAS) score and the Japanese Orthopedic Association Assessment Score (JOA score). The maximum score is 10 and 100, respectively. Higher VAS scores indicate more severe pain, and higher JOA scores indicate better joint function.

[0070] c. Quality of Life Score: The Quality of Life Scale (QoL) is used to assess quality of life across physical, physiological, mental, and social dimensions. The maximum score is 100; higher scores indicate higher quality of life.

[0071] The relationship between MK and NLR levels and treatment effects was analyzed.

[0072] Develop a therapeutic efficacy prediction model based on MK and NLR levels.

[0073] Internal validation: Use the training set and validation set for model building and preliminary validation.

[0074] 4. Optimize personalized OA treatment plans:

[0075] Objective: To provide personalized treatment plans for OA patients using a prediction model constructed by combining MK and NLR.

[0076] content:

[0077] Patients were divided into different treatment groups based on MK and NLR levels: a. The experimental group received Traditional Chinese Medicine treatment: moxibustion to warm the meridians and replenish qi combined with internal administration of Bone Injury Formula No. 1; b. The control group received Western medicine treatment, including diclofenac sodium sustained-release tablets, taken orally twice daily. This was combined with 2 mL of sodium hyaluronate, injected into the joint via syringe once daily. Patients in the chronic sustained-release phase should not receive medication.

[0078] To evaluate the therapeutic effects of different treatment groups.

[0079] Develop personalized treatment plans based on efficacy prediction models.

[0080] Internal validation: Use hold-out or other cross-validation techniques to evaluate the performance of the model on different datasets.

[0081] 5. Clinical application and translational research:

[0082] Objective: To promote the application of the diagnostic and predictive model of MK combined with NLR indicators in the clinical diagnosis and treatment of OA.

[0083] content:

[0084] A prospective clinical validation study was conducted in multiple medical institutions.

[0085] To evaluate the practicality and operability of the constructed model in clinical settings.

[0086] Promote the application of the combined detection model of MK and NLR to improve the diagnosis and treatment of OA.

[0087] External validation: Use independent datasets from other institutions or regions to verify the generalization and practicality of the model.

[0088] Experimental results:

[0089] Table 1. Basic clinical and hematological characteristics of healthy subjects (NC) and patients with osteoarthritis (OA) (mean ± standard error)

[0090]

[0091] Figure 1 This is a graph showing the hematological index levels of healthy people and osteoarthritis patients using MK combined with NLR as a marker for the diagnosis and treatment of osteoarthritis as described in the Examples;

[0092] Table 2. ROC analysis of neutrophil counts, NLR, PLR, and SII for the classification of osteoarthritis

[0093]

[0094] Figure 2 The figure is a ROC curve diagram of neutrophils, NLR, PLR and SII for the classification of osteoarthritis, which shows the application of MK combined with NLR as a marker for the diagnosis and treatment of osteoarthritis as described in the examples;

[0095] Figure 3 The figure is a ROC curve diagram of Midkine for the classification of osteoarthritis based on the application of MK combined with NLR as a marker for the diagnosis and treatment of osteoarthritis as described in the examples;

[0096] Table 3. Multivariate Logistic Regression Analysis (Including NLR, SII, and MK)

[0097]

[0098] Table 4. Multivariate Logistic Regression Analysis (Including NLR and MK)

[0099]

[0100] Table 5. ROC analysis of the Logreg_1 model based on NLR and MK for the classification of osteoarthritis

[0101]

[0102] Figure 4 This is a ROC curve diagram of the Logreg_1 model constructed based on NLR and MK for the classification of osteoarthritis, which shows the application of MK combined with NLR as a marker for the diagnosis and treatment of osteoarthritis as described in the Examples;

[0103] Table 6. NLR and MK levels in osteoarthritis patients with different efficacy groups after treatment with Gushang No. 1 prescription (mean ± standard error)

[0104]

[0105] Figure 5 This is a graph showing the NLR and MK levels of osteoarthritis patients in different efficacy groups using MK combined with NLR as markers for the diagnosis and treatment of osteoarthritis as described in the Examples;

[0106] Table 7. ROC analysis of the effectiveness / ineffectiveness of NLR and MK in patients with osteoarthritis treated with Bone Injury No. 1 prescription

[0107]

[0108] Figure 6 This is a ROC curve diagram of the application of MK combined with NLR as a marker for the diagnosis and treatment of osteoarthritis described in the examples, and the classification of effective / ineffectiveness of NLR combined with MK detection in osteoarthritis patients after treatment with Bone Injury No. 1 prescription.

[0109] Through the implementation of these research components, this project aims to provide new biomarkers and supporting tools for early diagnosis, efficacy prediction, and personalized treatment of OA, ultimately improving patient outcomes and quality of life. At the same time, internal and external validation will be used to ensure the reliability and practicality of the model.

[0110] Results and Discussion

[0111] The inventors' previous studies found that compared with the healthy control group (NC), the neutrophil count of OA patients was significantly increased, while the lymphocyte, basophil, red blood cell, and hemoglobin count were significantly decreased; similarly, the NLR, PLR, and SII of OA patients were significantly increased (Table 1 and Figure 1 Further analysis showed that the AUC values ​​of NLR, PLR and SII for the classification of OA patients were 0.682, 0.665 and 0.647, respectively, suggesting that NLR, PLR and SII have certain diagnostic capabilities for OA (Table 2 and Figure 2 The specificity of NLR and SII for OA classification was as high as 0.9390, but their sensitivities were relatively low (0.4417 and 0.3542, respectively). Therefore, combining them with other biomarkers to improve the diagnostic sensitivity of NLR and SII for OA has important clinical significance.

[0112] Serum midkine (MK) is a growth factor that is highly expressed during inflammation and tissue damage repair, and has been shown to play an important role in the pathological process of many diseases. Studies have shown that MK is significantly elevated in the serum of OA patients and is associated with the severity of OA. Recombinant human midkine (rhMK) has a significant repair effect on cartilage damage animal models, suggesting that MK may play a key role in the development of OA. It also suggests the possibility of MK as a diagnostic marker for OA and predicting OA disease outcomes. The research team's early test results also showed that MK is highly expressed in the serum of OA patients. The AUC value of MK for the classification of OA patients was 0.8621, with a specificity of 0.8293 and a sensitivity of 0.7875 ( Table 2 and Figure 3 ), indicating the potential value of MK as a biomarker for diagnosing OA.

[0113] Based on the previous findings of the high specificity of NLR and SII in classifying OA patients and the high sensitivity of MK, we attempted to construct a diagnostic model by combining NLR, SII, and MK. Multivariate logistic regression analysis showed that the p-values ​​of MK and NLR were less than 0.05 (0.000 and 0.001, respectively), while the p-value of SII was greater than 0.05 (0.361) (Table 3). Therefore, we selected MK and NLR to construct a regression model ( Table 4, Logreg_1=-9.113+0.903*NLR+0.024*MK The AUC analysis of the Logreg_1 model showed that its AUC value for OA classification was 0.8965, with a sensitivity and specificity of 0.8625 and 0.8293, respectively (Table 5 and Figure 4 ). Based on the above results, the combined detection of serum MK and blood NLR showed high diagnostic efficacy and specificity in the diagnosis of OA.

[0114] Bone Injury Prescription No. 1 is a traditional Chinese medicine formula independently developed by our hospital. Its formula has been optimized through years of clinical practice and scientific research. It is designed to comprehensively regulate the symptoms of patients with osteoarthritis. It contains herbs such as Astragalus, Salvia miltiorrhiza, Rehmannia root, Chuanxiong, Cornus officinalis, Lycium barbarum, Rehmannia root, Cistanche deserticola, Drynaria fortunei, White Peony root, Eucommia bark, Carthamus tinctorius, Dipsacus root, Alisma orientalis, Licorice root, Chinese Angelica sinensis, and Epimedium. These ingredients have different pharmacological effects. In this prescription, peach kernel relieves stagnation and relieves numbness, while salvia miltiorrhiza promotes menstruation and relieves pain as the main herb. Astragalus membranaceus replenishes qi, Chuanxiong promotes blood circulation and relieves pain, angelica replenishes blood and activates blood circulation, Rehmannia root nourishes essence and replenishes marrow, raw Rehmannia root clears heat and cools blood, Cornus officinalis and Lycium barbarum nourish the liver and kidneys, Cistanche deserticola replenishes kidney yang and strengthens essence and blood, Drynaria fortunei, Eucommia barbata, and Dipsacus root promote blood circulation, heal injuries and relieve pain, and strengthen the kidneys and bones. Epimedium nourishes the kidneys and strengthens yang and tendons as the assistant herb. White peony root softens the liver and relieves pain, safflower promotes blood circulation, relieves blood stasis and relieves pain, and Alisma orientalis, combined with Cornus officinalis and Rehmannia root, treats kidney yin deficiency as the adjuvant. Licorice root harmonizes the various herbs as the guiding herb. The different ingredients of Bone Injury Recipe No. 1 act synergistically on multiple pathological aspects of OA, offering promising therapeutic prospects. Although Bone Injury Recipe No. 1 has demonstrated some efficacy in the treatment of osteoarthritis, not all patients experience the same benefits. In order to improve the treatment effect and achieve individualized treatment, the research team has previously explored MK and NLR as biomarkers to predict the response of OA patients to Bone Injury No. 1 prescription. The efficacy of patients treated with Bone Injury No. 1 prescription was evaluated as a markedly effective group, an effective group, and an ineffective group. Our previous experiments found that the levels of NLR and MK in the markedly effective group and the effective group were significantly higher than those in the ineffective group (Table 6 and Figure 5 The classification AUC values ​​of NLR and MK for patients who were effective in the treatment of Bone Injury No. 1 Recipe (significantly effective group + effective group) were 0.774 and 0.878 respectively ( Table 7The prediction model constructed by combining NLR and MK (Logreg_2=13.745-0.444*NLR-0.034*MK) had an AUC value of 0.8686 for the classification of effective and ineffective patients, with a sensitivity of 0.96 ( Table 7 and Figure 6 ).

[0115] Technical features of the embodiment:

[0116] 1. Construction of joint detection model:

[0117] A diagnostic and predictive model based on serum midkine (MK) and neutrophil-lymphocyte ratio (NLR) was constructed for the early diagnosis and therapeutic effect prediction of osteoarthritis.

[0118] By optimizing the experimental process, the accuracy and reliability of the detection were improved.

[0119] 2. Diagnostic efficacy evaluation:

[0120] ROC analysis was used to determine the optimal threshold for combined detection of MK and NLR, which improved the diagnostic sensitivity and specificity.

[0121] The stability and generalization ability of the model were evaluated through internal validation techniques to ensure the reliability of the model.

[0122] 3. Development of efficacy prediction model:

[0123] A therapeutic effect prediction model was developed based on MK and NLR levels to provide a predictive basis for the effect of Bone Injury Prescription No. 1 on the treatment of osteoarthritis patients.

[0124] The preliminary performance of the model was assessed through internal validation.

[0125] 4. Personalized treatment plan:

[0126] Patients were divided into different treatment groups according to MK and NLR levels, realizing personalized treatment plans based on biomarkers.

[0127] The therapeutic effects of different treatment groups were evaluated to provide support for clinicians in treatment decision-making.

[0128] 5. Clinical application and transformation:

[0129] Subsequently, prospective clinical validation studies will be conducted in multiple medical institutions to evaluate the practicality and operability of combined MK and NLR detection in clinical settings.

[0130] The generalization ability and practicality of the model were verified through external validation, which promoted the transformation of research results into clinical practice.

[0131] In summary, our preliminary research and analysis revealed that serum midkine (MK) combined with the neutrophil-to-lymphocyte ratio (NLR) not only demonstrated high diagnostic efficacy for osteoarthritis but also had potential predictive value in predicting the efficacy of Bone Injury Formula No. 1 in osteoarthritis patients. This discovery provides a new biomarker for the diagnosis and personalized treatment of osteoarthritis and may help optimize treatment plans and improve treatment outcomes.

[0132] To enhance the universality and reliability of our findings, the research team plans to expand the sample size and, whenever possible, recruit a broadly representative patient population through multicenter collaboration. Advanced statistical methods and machine learning techniques will be used to construct a more accurate prediction model, and rigorous internal and external validation will be conducted to ensure the model's stability and generalizability. Furthermore, we will consider a variety of clinical factors for multivariate analysis and conduct long-term follow-up studies to evaluate the model's effectiveness in predicting long-term treatment response and disease progression. At the same time, we will conduct a cost-effectiveness analysis to assess the economic value of the model and collaborate with clinical experts to develop guidelines for the diagnosis of osteoarthritis and the evaluation of traditional Chinese medicine treatments based on MK and NLR, in order to provide scientific and precise guidance for diagnosis and treatment in clinical practice.

[0133] In summary, the application of MK combined with NLR testing in the early diagnosis, efficacy prediction, and personalized treatment of osteoarthritis has broad market prospects and significant social value. With the continuous advancement and improvement of technology, this new technology will provide a theoretical basis for revolutionary changes in the diagnosis and treatment of osteoarthritis, and is expected to bring better treatment outcomes and quality of life to patients.

[0134] The above description is a detailed description of the preferred embodiments of the present invention, but the embodiments are not intended to limit the scope of the patent application of the present invention. Any equivalent changes or modifications completed under the technical spirit suggested by the present invention should fall within the patent scope covered by the present invention.

Claims

1. Application of serum midkine combined with neutrophil-to-lymphocyte ratio as a marker for the diagnosis and treatment of osteoarthritis.

2. The use of serum midkine combined with neutrophil-to-lymphocyte ratio as a marker for the diagnosis and treatment of osteoarthritis according to claim 1, characterized in that: The application of serum midkine combined with neutrophil-to-lymphocyte ratio in the diagnosis of osteoarthritis and prediction of the therapeutic efficacy of Bone Injury Prescription No. 1.

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