A marker combination for alleviating the hypercoagulable state of lung cancer, a method for establishing and applying a therapeutic efficacy discrimination model, and a Chinese medicine combination

Abstract

The present invention discloses a marker combination for alleviating the hypercoagulable state of lung cancer, a method for establishing and applying a therapeutic discrimination model, and a Chinese medicine combination. The marker combination is D-D and FIB. Based on real clinical diagnosis and treatment data, two specific indicators D-D and FIB are obtained after screening, and a logistic regression model is established after multi-factor analysis to discriminate the therapeutic effect of intervening in the hypercoagulable state, which has better accuracy and feasibility than traditional indicator detection. Further based on the clinical efficacy, the Chinese medicine prescription used is analyzed by association rules according to the Chinese medicine syndrome type, and the corresponding Chinese medicine combination is obtained, which has better specificity and applicability than the traditional syndrome differentiation prescription. Then guide the clinical treatment of traditional Chinese medicine and integrated Chinese and Western medicine and provide a Chinese medicine combination suitable for specific syndromes, provide a more accurate solution for clinical intervention of advanced lung cancer hypercoagulable state with integrated Chinese and Western medicine, and provide a research basis for transformation application.

Description

Technical Field

[0001] The present invention belongs to the field of clinical medicine, laboratory medicine, traditional Chinese medicine or integrated Chinese and Western medicine. Specifically, it is a marker combination for alleviating the hypercoagulable state of lung cancer, a method for establishing and applying an efficacy discrimination model and a traditional Chinese medicine combination. Background Art

[0002] Tumor hypercoagulability can induce tumor infiltration, invasion and distant metastasis, and is closely related to surgery, chemoradiotherapy, targeted therapy and tumor progression. It is a common complication of advanced lung cancer. Its clinical manifestations include abnormal coagulation and anticoagulation related indicators, but the independence of each indicator of "coagulation function and dimer" is strong, lacking specific indicators and prompting effects; treatment is mainly based on anticoagulants such as low molecular weight heparin and rivaroxaban, which are prone to adverse events such as venous thromboembolism and bleeding, and even life-threatening. If the existing clinical indicators can be innovated, a feasible method for distinguishing efficacy can be established, and the treatment plan can be optimized, this problem that plagues clinical diagnosis and treatment can be effectively solved. To this end, the applicant used traditional Chinese medicine and the combination of traditional Chinese and Western medicine to conduct clinical intervention and research, monitored relevant clinical indicators before and after the intervention, and screened out specific indicators with predictive efficacy of tumor hypercoagulable state from "coagulation function, dimer" through analytical methods based on clinical efficacy, and established a logistic model with efficacy discrimination; further, the prescription association rule analysis method was used to obtain a stable and definite combination of Chinese medicines that synergistically intervene in the hypercoagulable state of advanced lung cancer, thereby establishing a method and Chinese medicine combination for discriminating the efficacy of hypercoagulable state of advanced lung cancer. Summary of the invention

[0003] The present invention aims at the current situation of the difficulty in diagnosing and treating the hypercoagulable state of advanced lung cancer. After research, the present invention proposes a marker combination for alleviating the hypercoagulable state of lung cancer, a method for establishing and using a therapeutic discrimination model, and a Chinese medicine combination. It is a method for intervening in the hypercoagulable state of advanced lung cancer and discriminating the therapeutic effect through traditional Chinese medicine. 176 patients with hypercoagulable state of advanced lung cancer were collected clinically, and their main syndromes were qi and yin deficiency syndrome and qi deficiency and phlegm dampness syndrome. Under the premise of not affecting the standard treatment, one of the methods of traditional Chinese medicine, conventional anticoagulation of western medicine, traditional Chinese medicine combined with conventional anticoagulation of western medicine, and clinical observation was selected for intervention according to the actual situation, and the indicators such as coagulation function were tested before and after the intervention. The study found that the effective rates of TCM group and TCM combined with conventional anticoagulation were 93.65% and 80.56%, respectively, the effective rate of Western medicine conventional anticoagulation group was 75%, and the effective rate of observation group was 56.76%. The clinical manifestations were that DD (D-dimer) and FIB (fibrinogen) indicators were significantly reduced, and they were confirmed as specific indicators after inter-group comparison, LASSO regression and multivariate analysis. Further logistic multivariate analysis was used to establish an efficacy discrimination model, and its AUC value was 0.873. The TCM prescriptions were analyzed by the association rule method to obtain the applicable intervention The core combination of "Pseudostellariae Radix-Angelicae Sinensis-Glycyrrhizae Radix-Pielliae Rhizoma-Cinnamon Twig-Salviae Miltiorrhizae" for preventing and treating the hypercoagulable state of qi deficiency and phlegm-dampness syndrome in advanced lung cancer is obtained, and "Pseudostellariae Radix-Angelicae Sinensis-Glycyrrhizae Radix Ophiopogonis-Cinnamon Twig-Rhubarb" suitable for intervening in the hypercoagulable state of qi deficiency and phlegm-dampness syndrome in advanced lung cancer is obtained, thereby establishing a method for Chinese medicine to intervene in the hypercoagulable state of advanced lung cancer and distinguish the efficacy, and providing specific indicators, methods for distinguishing efficacy and intervention plans for clinical promotion. This logistic discriminant model and Chinese medicine combination established based on specific indicators and their reasonable variations in this field are all within the content to be protected by the technical scheme of the present invention.

[0004] The present invention is achieved through the following technical solutions:

[0005] A marker combination is used in preparing a product for alleviating the hypercoagulable state of lung cancer, wherein the marker combination is DD (D-dimer) and FIB (fibrinogen).

[0006] A method for establishing a therapeutic efficacy discrimination model for alleviating the hypercoagulable state of advanced lung cancer uses two specific markers, D-dimer difference and FIB difference, as independent variables to establish a logistic regression model:

[0007]

[0008] e is the natural logarithm, Y is the calculated value of the logistic regression, the AUC value of the model is 0.873, and the AUC value of the validation set is 0.931. After specificity and sensitivity calculations, the threshold is set to 0.5.

[0009] A method for applying a therapeutic efficacy discrimination model for alleviating the hypercoagulable state of advanced lung cancer, substituting the values ​​of two specific indicators, the D-dimer difference and the FIB difference, into the established model to obtain the Y value. If the Y value is <0.5, it indicates that the patient can benefit from a treatment regimen containing traditional Chinese medicine; if the Y value is >0.5, it indicates that the patient will benefit relatively less from the treatment regimen containing traditional Chinese medicine.

[0010] A traditional Chinese medicine composition for alleviating a hypercoagulable state of lung cancer. The traditional Chinese medicine composition has the effect of alleviating a hypercoagulable state of advanced lung cancer after clinical efficacy judgment. When intervening in a hypercoagulable state of advanced lung cancer with qi deficiency and phlegm-dampness syndrome, the traditional Chinese medicine composition comprises: pseudoginseng, angelica, liquorice, pinellia, cassia twig, and salvia miltiorrhiza; when intervening in a hypercoagulable state of advanced lung cancer with qi and yin deficiency syndrome, the traditional Chinese medicine composition comprises: pseudoginseng, angelica, liquorice, ophiopogon, cassia twig, and rhubarb.

[0011] The beneficial effects of the present invention are as follows:

[0012] The present invention is based on real clinical diagnosis and treatment data, and after screening, two specific indicators DD and FIB are obtained, and after multi-factor analysis, a logistic regression model is established to discriminate the efficacy of intervention in hypercoagulable state, which has better accuracy and feasibility than traditional indicator detection. Further based on the clinical efficacy, the Chinese medicine prescription used is analyzed according to the TCM syndrome type, and the corresponding Chinese medicine combination is obtained, which has better specificity and applicability than the traditional syndrome differentiation prescription. When used in clinical practice, the discriminant efficacy results can be obtained by importing the test data, thereby guiding the clinical treatment of traditional Chinese medicine and integrated Chinese and Western medicine, and providing a Chinese medicine combination suitable for specific syndromes, providing a more accurate solution for clinical intervention of advanced lung cancer hypercoagulable state with integrated Chinese and Western medicine, and providing a research basis for transformation application.

[0013] The present invention has established a discriminant tool that assists physicians in dynamically monitoring the hypercoagulable state of advanced lung cancer, which has the characteristics of universality, accuracy and specificity, and provides a research basis and core parameters for subsequent development of test kits and other transformations. At the same time, it provides a combination of Chinese medicines for intervening in the hypercoagulable state of advanced lung cancer, improves the preparedness and effectiveness of traditional Chinese medicine treatment, and promotes the improvement of the level of treatment of advanced lung cancer by traditional Chinese medicine and integrated traditional Chinese and Western medicine. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 Analysis chart of clinical test indicators;

[0015] Figure 2 It is the risk factor screening of LASSO regression model in patients with advanced lung cancer and hypercoagulable state;

[0016] Figure 3 It is the nomogram efficacy prediction model line for patients with advanced lung cancer and hypercoagulable state;

[0017] Figure 4 This is a diagram showing the validation of the prediction model for patients with advanced lung cancer who are in a hypercoagulable state;

[0018] Figure 5 It is a combination of traditional Chinese medicines for the hypercoagulable state of Qi deficiency and phlegm-dampness syndrome in advanced lung cancer;

[0019] Figure 6 It is a combination of traditional Chinese medicines for the hypercoagulable state of Qi and Yin deficiency syndrome in advanced lung cancer. DETAILED DESCRIPTION

[0020] A marker combination for alleviating the hypercoagulable state of lung cancer, a method for establishing and applying a therapeutic efficacy discrimination model, and a Chinese medicine combination

[0021] 1) Collect cases of hypercoagulable state in advanced lung cancer

[0022] Collect cases of advanced lung cancer with clear pathological diagnosis that meet the "Chinese Primary Lung Cancer Diagnosis and Treatment Guidelines" (2022 edition) and the 8th edition of the International Association for the Study of Lung Cancer staging criteria (IASLC 2015);

[0023] The diagnostic criteria for hypercoagulable state of malignant tumors refer to the pre-DIC diagnostic criteria in the "Several Diagnostic Reference Standards Designated by the Seventh National Academic Conference on Thrombosis and Hemostasis", which specifically include: ① Plasma prothrombin time (Prothrombin time, PT) shortened> 3s; ② Activated partial thromboplastin time (Activated partial thromboplastin time, APTT) shortened> 3s; ③ Fibrinogen (Fibrinogen, FIB)> 4.0g / L; ④ D-dimer (D-dimer, DD) ≥ 300ug / L; ⑤ Platelet count (platelet, PLT)> 300×10^9 / L. A diagnosis can be made if two or more of the above conditions are met at the same time.

[0024] The TCM syndrome differentiation standards were based on the Guidelines for TCM Treatment of Tumors (Implementation) (2008 edition) and Guidelines for TCM Diagnosis and Treatment of Malignant Tumors (2014 edition) for syndrome differentiation and diagnosis.

[0025] According to the above Western medicine diagnostic standards and TCM syndrome differentiation standards, 176 patients with hypercoagulable state of advanced lung cancer who visited Zhejiang Provincial Tongde Hospital from January 2017 to December 2021 were selected (see Table 1).

[0026] Table 1 Baseline status of cases

[0027]

[0028]

[0029] 2) Conduct clinical treatment

[0030] According to the actual clinical situation, without affecting the implementation of standard treatment, one of the following methods is selected: traditional Chinese medicine, conventional anticoagulation of Western medicine, traditional Chinese medicine combined with conventional anticoagulation of Western medicine, and clinical observation. Standard Western medicine treatment refers to the pre-DIC diagnostic criteria, and selects conventional anticoagulation treatments such as subcutaneous injection of low molecular weight heparin calcium and rivaroxaban according to the patient's coagulation function indicators, blood routine indicators, venous blood vessels and other specific conditions; Traditional Chinese Medicine syndrome differentiation treatment is based on the Qi and Yin deficiency syndrome and Qi deficiency and phlegm dampness syndrome. Each dose of prescription has 12-14 ingredients, 1 dose per day, decocted in 200ml of water, taken warm in 3-4 times, re-examined every 2 weeks, and the medication is adjusted according to the syndrome.

[0031] 3) Evaluation of efficacy after intervention

[0032] After treatment, the effective rates of the TCM group and the TCM combined with conventional Western medicine anticoagulation group were 93.65% and 80.56%, respectively, the effective rate of the conventional Western medicine anticoagulation group was 75%, and the effective rate of the observation group was 56.76% (see Table 2). There were significant differences between the groups (P<0.01, X 2 =27.325). The effective rate of Chinese medicine treatment for Qi deficiency and phlegm dampness syndrome was 91.07% (51 / 56), the effective rate of Qi and Yin deficiency syndrome was 88.24% (30 / 34), and the effective rate of other syndromes was 85.71% (6 / 7).

[0033] Table 2 Comparison of clinical efficacy of four groups

[0034]

[0035]

[0036] After treatment, the D-dimer (DD) (P < 0.01) and fibrinogen (FIB) in the TCM group and the TCM combined with Western medicine conventional anticoagulation group before and after treatment were significantly reduced (P < 0.01) (see Table 3); and the difference between the four groups was also statistically significant (see Appendix Figure 1 ).

[0037] Table 3 Comparison of clinical test indicators before and after treatment

[0038]

[0039] Note: Compared with before treatment, *p<0.05

[0040] 4) Statistical analysis

[0041] Frequency statistics: basic information, blood indexes, TCM syndrome types, prescription drugs and their dosages (unit: g) are included in the table;

[0042] Evaluation of therapeutic efficacy: Effective rate = number of markedly effective cases + number of cured cases / total cases; Cure rate = number of cured cases / total cases;

[0043] Data analysis: Statistical analysis was performed using SPSS (v.25.0) and R (v.4.2.3) software. Quantitative data were expressed as median (interquartile range), and the Man-Whitney U test was used for analysis; count data were expressed as [cases (%)], and the chi-square test was used for intergroup comparison of indicators and differences before and after treatment. The difference was considered statistically significant when P < 0.05. The LASSO regression model was used to obtain the risk factors (non-zero coefficients) of hypercoagulable state in advanced lung cancer; the multivariate logistic regression method was used to further screen independent risk factors and establish a nomogram prediction model for individualized clinical efficacy prediction; the area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, and decision curve were suitable for internal and external validation of the nomogram prediction model to determine its discrimination, calibration, and clinical practicality.

[0044] Gender, age, pathology, smoking history, metastatic sites (lung, liver, bone, brain, other), anti-tumor treatment regimen (chemotherapy, targeted therapy, immunotherapy, radiotherapy), conventional anticoagulation therapy, Chinese medicine treatment, and the difference before and after treatment of blood indicators (DD, PT, APTT, FIB, PLT) were used as independent variables and numbered 1-20 in sequence. Through LASSO regression analysis, a total of 4 risk factors (non-zero coefficients) were obtained, namely targeted therapy, Chinese medicine treatment, D-dimer difference, FIB difference (see Appendix Figure 2 The above factors were analyzed by Logistic multivariate regression method. The results showed that the difference in D-dimer and FIB were independent influencing factors for predicting the efficacy of hypercoagulable state in patients with advanced lung cancer (see Table 4).

[0045] Table 4 Multifactorial analysis of improvement of hypercoagulable state

[0046]

[0047] 5) Establishing a model for predicting efficacy

[0048] The D-dimer difference and FIB difference obtained from the above screening were used as the core, and a Logistic regression model was used to establish a therapeutic effect prediction model:

[0049]

[0050] e is the natural logarithm, Y is the logistic calculation value, and the AUC value of the model is 0.873.

[0051] In addition, an individualized nomogram efficacy prediction model for hypercoagulable state in patients with advanced lung cancer was established (see Appendix Figure 3). Through the scale above the model, the individual scores corresponding to the four independent risk factors can be obtained. The sum of the individual scores is the total score. The predicted probability corresponding to the total score is the cure rate of hypercoagulable state in patients with advanced lung cancer.

[0052] After testing, the AUC value of the experimental group model was 0.873 (95% CI: 0.804-0.942), indicating that the prediction model has good discrimination (see Appendix Figure 4 -a); The calibration curve results show that the mean absolute error (MAE) of the modeled population is 0.03, and the mean square error (MMSE) is 0.00139 (the smaller the MAE and MSE values, the higher the calibration), indicating that the prediction model has a high degree of calibration (see Appendix). Figure 4 -b). When the threshold probability value in the decision curve of the modeled population is in the range of 3% to 79%, the net benefit of using the nomogram to predict the clinical effective rate is high, indicating that the prediction model has good clinical practicality (see Appendix Figure 4 -c). Its threshold value was set to 0.5 after empirical calculation, at which point its sensitivity and specificity were at their best. Its Y value < 0.5 indicated that the patient benefited significantly from the regimen containing TCM treatment, while its Y value > 0.5 indicated that the patient benefited relatively little from the regimen containing TCM treatment (see Table 5).

[0053] Table 5 Threshold verification table of test group

[0054]

[0055] External validation work: According to the above-mentioned standards, 30 patients with hypercoagulable state of advanced lung cancer who visited Zhejiang Provincial Tongde Hospital from January 2022 to August 2023 were collected (see Table 6), with an average age of 65.30±12.052 years old, including 22 males (73.33%) and 8 females (26.67%). The differences before and after DD and FIB treatment (see Table 7) were substituted into the formula for calculation. After testing, the AUC value of the validation group model was 0.931 (95% CI: 0.811-1.000), which has good diagnostic efficacy and stability.

[0056] Table 6 Basic information of the validation group

[0057]

[0058]

[0059] Table 7 Comparison of clinical test indicators before and after treatment in the validation group

[0060]

[0061] 6) Screening for Chinese medicine combination

[0062] Combined with clinical efficacy and syndrome distribution, 411 prescriptions were included, and Qi deficiency and phlegm dampness syndrome and Qi and Yin deficiency syndrome were selected as the dominant syndromes for "syndrome-drug" relationship analysis based on association rules (confidence 0.9, support 50%), which was displayed in a network diagram. The Chinese medicine combination suitable for the hypercoagulable state of Qi deficiency and phlegm dampness syndrome in advanced lung cancer was obtained: "Pseudostellariae Radix-Danggui-Glycyrrhizae Radix-Pinelliae Rhizoma-Cinnamomum Cassiae Twig-Salvia Miltiorrhizae" (see Appendix Figure 5 ) and obtained the Chinese medicine combination of "Pseudostellariae Radix-Angelicae Sinensis-Glycyrrhizae Radix-Ophiopogonis-Cinnamon Twig-Rhubarb" suitable for the hypercoagulable state of Qi and Yin deficiency syndrome in advanced lung cancer (see Appendix Figure 6 ).

[0063] According to the above steps, the present invention discloses a method for distinguishing the clinical efficacy of hypercoagulable state in advanced lung cancer, that is, based on specific indicators DD and FIB, a logistic regression model for distinguishing clinical efficacy is established.

[0064] The invention also discloses a Chinese medicine combination for intervening in the hypercoagulable state of advanced lung cancer.

[0065] The technical solution of the present invention is further described below through specific embodiments in conjunction with the accompanying drawings:

[0066] The present invention discloses a method and use for discriminating the clinical efficacy of intervention in the hypercoagulable state of advanced lung cancer. Specifically, the specific indicators are DD and FIB, and the independent influencing factors of the efficacy of the hypercoagulable state of advanced lung cancer patients are further clarified as the D-dimer difference and the FIB difference, and a logistic regression model for discriminating the clinical efficacy is established.

[0067] The present invention also discloses a Chinese medicine combination for intervening in the hypercoagulable state of advanced lung cancer, namely, a Chinese medicine combination suitable for the hypercoagulable state of advanced lung cancer with qi deficiency and phlegm dampness syndrome: "Pseudostellariae Radix-Angelicae Sinensis-Glycyrrhizae Radix-Pinelliae Rhizoma-Cinnamomum Twig-Salviae Miltiorrhizae"; a Chinese medicine combination suitable for the hypercoagulable state of advanced lung cancer with qi and yin deficiency syndrome "Pseudostellariae Radix-Angelicae Sinensis-Glycyrrhizae Radix-Ophiopogon Japonicus-Cinnamomum Twig-Rhubarb" is obtained. Specifically, the following steps are included:

[0068] 1) Establish a logistic regression model

[0069] After verification, a therapeutic effect prediction model was established by using the Logistic regression model with DD difference and FIB difference as the core:

[0070]

[0071] Y is the calculated value of the logistic model, and the AUC value of the model is 0.873. The AUC value is an industry standard for evaluating markers. The closer the AUC value is to 1, the stronger the marker's discriminatory power is. The value of A determines whether to select the molecular marker. The higher the AUC value of the logistic model, the more accurate the calculation result of the model. The threshold is set to 0.5 after empirical calculation. If the Y value is <0.5, it indicates that the patient can benefit from the treatment plan containing traditional Chinese medicine.

[0072] 2) Traditional Chinese medicine intervention

[0073] According to the Y value results and combined with the clinical TCM syndrome types, the Chinese medicine combination suitable for the hypercoagulable state of qi deficiency and phlegm-dampness syndrome in advanced lung cancer was selected as "Pseudostellaria baicalensis - Angelica sinensis - Licorice - Pinellia ternata - Cinnamon twig - Salvia miltiorrhiza"; or the Chinese medicine combination suitable for the hypercoagulable state of qi and yin deficiency syndrome in advanced lung cancer "Pseudostellaria baicalensis - Angelica sinensis - Licorice - Ophiopogon japonicus - Cinnamon twig - Rhubarb" was selected for 2 weeks of intervention.

[0074] Based on the above steps, here is an example:

[0075] 1. Mr. Liu, male, 83 years old. In 2010, the patient underwent a puncture of the right lung mass in a hospital, and pathology showed lung adenocarcinoma. The reexamination in November 2022 indicated that the disease had progressed to advanced lung cancer. For treatment, pemetrexed 0.9g + nedaplatin 140mg + bevacizumab 0.4g chemotherapy was given for 2 cycles, and then adjusted to targeted therapy with 80mg qd of vometinib. Coagulation function related indicators were checked: D-dimer 10.52mg / L, PT 9.90s, APTT 18.9s, FIB4.57g / L, PLT 186*10^9 / L. Western medicine diagnosis: lung malignant tumor (TxNxM1, stage IV), secondary malignant tumor of bone, secondary malignant tumor of brain, and hypercoagulable state.

[0076] The patient was tired and weak, with occasional chest tightness and shortness of breath, paroxysmal cough and sputum, one bowel movement per day, yellow urine, pale purple tongue, white and greasy fur, and deep and stringy pulse. The TCM diagnosis was Qi deficiency and phlegm dampness syndrome. The treatment was based on a combination of traditional Chinese medicine (Pseudostellariae Radix-Angelicae Sinensis-Glycyrrhizae Radix-Pinelliae Rhizoma-Cinnamomum Cassiae Twig-Salvia Miltiorrhizae) suitable for the hypercoagulable state of Qi deficiency and phlegm dampness syndrome in advanced lung cancer. The coagulation function related indicators were re-examined 1 week later: D-dimer 1.38mg / L, PT 9.90s, APTT 20.2s, FIB2.46g / L, PLT 185*10^9 / L.

[0077] The difference in DD before and after the intervention was 9.14, and the difference in FIB was 2.11. Substituting the difference in DD and FIB into the formula, the result showed that Y = 0.003210669, with a value of < 0.5. The results showed that intervention of hypercoagulable state by traditional Chinese medicine was effective. Therefore, the above-mentioned traditional Chinese medicine or traditional Chinese medicine combined with anticoagulation scheme was continued for intervention.

[0078] 2. Ye, female, 76 years old. In 2016, the patient underwent a right upper lung puncture in a hospital, and pathology showed lung adenocarcinoma. In March 2018, due to disease progression, osimertinib targeted therapy was adjusted. Coagulation function related indicators: D-dimer 8.04mg / L, PT 10s, APTT 29s, FIB8.42g / L, PLT 249*10^9 / L. Western medicine diagnosis: lung malignant tumor (T4N3M1, stage IV), with lung and bone metastasis, hypercoagulable state.

[0079] The patient was tired and weak, had occasional cough, numbness of the right lower limb, hot flashes, constipation, one bowel movement every 2-3 days, regular urination, pale tongue, thin fur, and deep and fine pulse. The syndrome of qi and yin deficiency was diagnosed by TCM. The treatment was based on the combination of traditional Chinese medicine (Pseudostellariae Radix-Angelicae Sinensis-Glycyrrhizae Radix-Ophiopogonis-Cinnamomum Cassiae-Rhubarb) suitable for the hypercoagulable state of qi and yin deficiency in advanced lung cancer. The coagulation function related indicators were re-examined 1 week later: D-dimer 0.43mg / L, PT 11.5s, APTT 26.5s, FIB6.6g / L, PLT 244*10^9 / L.

[0080] The difference in DD before and after the intervention was 7.61, and the difference in FIB was 1.82. Substituting the difference in DD and FIB into the formula, the result showed that Y = 0.0083035, with a value of < 0.5. The results showed that intervention of hypercoagulable state by traditional Chinese medicine was effective. Therefore, the above-mentioned traditional Chinese medicine or traditional Chinese medicine combined with anticoagulation scheme was continued for intervention.

[0081] 3. Zhou, female, 69 years old. In 2022, the patient underwent a left clavicle puncture biopsy in a hospital, and pathology showed metastatic lung adenocarcinoma. In January 2023, due to disease progression, osimertinib was discontinued and pemetrexed 0.8g + carboplatin 0.6 + bevacizumab 500mg chemotherapy combined with targeted therapy was adjusted. Coagulation function related indicators: D-dimer 8.41mg / L, PT 11.4s, APTT25.2s, FIB4.10g / L, PLT 187*10^9 / L. Western medicine diagnosis: lung malignant tumor (T2N2M1, stage IV), secondary bone malignant tumor, hypercoagulable state.

[0082] The patient was weak, had pain in the right chest wall and waist and back, poor appetite, normal bowel movements, dark tongue, thin white fur, and stringy pulse. TCM syndrome differentiation was qi stagnation and blood stasis. No intervention was given with the TCM medicine involved in the present invention. One week later, the coagulation function related indicators were: D-dimer 12.6mg / L, PT 11.5s, APTT 25.5s, FIB3.53g / L, PLT 161*10^9 / L.

[0083] The DD difference before and after the intervention was -4.19, and the FIB difference was 0.57. Substituting the DD and FIB differences into the formula for calculation, the result showed Y=0.816072269, and the value was >0.5. The results indicated that the effect of intervention in hypercoagulable state was poor and the intervention plan needed to be adjusted.

[0084] The above are preferred embodiments of the present invention. The present invention is not limited to the above contents. Other improvements and changes directly derived or associated by those skilled in the art without departing from the spirit and concept of the present invention should be considered to be included in the protection scope of the present invention.

Claims

1. A method for establishing a therapeutic efficacy discrimination model for alleviating the hypercoagulable state of advanced lung cancer, characterized in that: Using the difference of two specific markers, D-dimer and FIB fibrinogen, as independent variables, a logistic regression model was established: ； e is the natural logarithm, Y is the calculated value of the logistic regression, the AUC value of the model is 0.873, and the AUC value of the validation set is 0.

931. After specificity and sensitivity calculations, the threshold is set to 0.

5.

2. A method for using a therapeutic efficacy discrimination model for alleviating the hypercoagulable state of advanced lung cancer, characterized in that: Substitute the values ​​of the two specific indicators, D-dimer difference and FIB difference, into the model to obtain the Y value. If the Y value is <0.5, it indicates that the patient can benefit from the treatment plan containing traditional Chinese medicine; if the Y value is >0.5, it indicates that the patient will benefit relatively less from the treatment plan containing traditional Chinese medicine; wherein the model is the model established by the method as claimed in claim 1.

3. A Chinese medicine composition for alleviating the hypercoagulable state of lung cancer, characterized in that: The Chinese medicine composition is obtained after clinical efficacy determination, wherein the clinical efficacy determination includes: substituting the values ​​of two specific indicators, the D-dimer difference and the FIB difference, into the model to obtain the Y value, if the Y value <0.5, it indicates that the patient can benefit from the treatment plan containing traditional Chinese medicine; if the Y value>0.5, it indicates that the patient benefits relatively less from the treatment plan containing traditional Chinese medicine; wherein the model is a model established by the method according to claim 1; when intervening in the hypercoagulable state of qi deficiency and phlegm dampness syndrome of advanced lung cancer, the Chinese medicine combination is: Pseudostellaria baicalensis, Angelica sinensis, Licorice, Pinellia ternata, Cinnamon twig, Salvia miltiorrhiza; when intervening in the hypercoagulable state of qi and yin deficiency syndrome of advanced lung cancer, the Chinese medicine combination is: Pseudostellaria baicalensis, Angelica sinensis, Licorice, Ophiopogon japonicus, Cinnamon twig, Rhubarb.

Images