A TCM syndrome differentiation system for early breast cancer during chemotherapy and its construction method and application

Abstract

The invention discloses a TCM syndrome differentiation system for early breast cancer during chemotherapy, including four syndrome types, namely: liver depression and yin deficiency syndrome, corresponding syndrome items are: irritability, thin white tongue coating, forgetfulness, chest and flank distension and pain, dry mouth, hot flashes, chest and abdominal pain, bone pain, abdominal distension, chest tightness; qi and yin deficiency syndrome, corresponding syndrome items are: deep pulse, thin white tongue coating, red tongue, hot flashes, forgetfulness, dry mouth, pale complexion, sore waist and knees, spontaneous sweating, ruddy complexion; spleen deficiency and blood deficiency syndrome, corresponding syndrome items are: pale tongue color, white and greasy tongue coating, pale complexion, dry mouth, poor appetite, thin pulse, fat tongue; qi stagnation and blood stasis syndrome, corresponding syndrome items are: ecchymosis on tongue, blue lips, varicose veins under tongue, stringy pulse, dark complexion, numbness of limbs, oral ulcers. The invention also discloses a construction method and application of the system. The invention provides a theoretical basis for the standardized TCM treatment of patients in the chemotherapy period of early breast cancer, and has broad application prospects.

Description

Technical Field

[0001] The present invention belongs to the field of traditional Chinese medicine, and specifically relates to a traditional Chinese medicine syndrome differentiation system for early breast cancer during chemotherapy, and a construction method and application thereof. Background Art

[0002] Breast cancer is the most common malignant tumor in women, and its incidence in my country is increasing year by year. At present, the comprehensive treatment of breast cancer has formed a relatively standardized and reasonable treatment model. Adjuvant chemotherapy, as a major treatment method, can enable patients to obtain better benefits and survival time, reduce the recurrence and metastasis rate, and increase disease-free survival. However, chemotherapy side effects such as leukopenia, liver damage, hair loss, and oral ulcers often daunt patients. Long-term clinical application has found that the combined treatment of traditional Chinese medicine can effectively improve the patient's immune status, improve the quality of life, and increase the completion rate of adjuvant chemotherapy. However, due to the use of chemotherapy drugs, the symptoms of patients at this stage are significantly different from those at other stages, so the distribution characteristics and laws of syndrome differentiation are also inconsistent with those of patients at other stages.

[0003] In 2010, the Breast Disease Prevention and Treatment Cooperation Working Committee of the Chinese Association of Traditional Chinese Medicine formulated the "Stage Diagnosis and Syndrome Differentiation Standard for Breast Cancer" based on the experience of national experts through the expert questionnaire method. The TCM staging and syndrome differentiation of breast cancer is divided into four stages, including the perioperative period, including preoperative: liver depression and phlegm stagnation, Chong and Ren disorders, deficiency of body qi and toxicity, phlegm and blood stasis; postoperative: spleen and stomach disharmony, qi and blood (yin) deficiency; peri-chemotherapy period: spleen and stomach disharmony, liver and kidney deficiency, qi and blood (yin) deficiency, spleen and kidney deficiency; peri-radiotherapy period: qi and yin deficiency, yin deficiency and fire toxicity, yin deficiency and body fluid deficiency; consolidation period: qi and blood deficiency, Chong and Ren disorders, spleen and kidney deficiency. The establishment of this standard has played a guiding role in clinical practice for a long time. In recent years, some scholars have used statistical methods to conduct relevant syndrome type research. However, a literature review found that there are large-scale clinical research reports with high evidence level in the consolidation period, perioperative period, and advanced stage of breast cancer staging differentiation. However, the syndrome differentiation research in the chemotherapy period is still mostly based on medical experience. For example, Professor Lin Yi mainly differentiates breast cancer chemotherapy patients as Qi and Yin deficiency, Qi and blood deficiency, spleen and stomach disharmony, and liver and kidney deficiency; Professor Li Tong believes that chemotherapy patients are mostly Qi and Yin deficiency, Yin deficiency and fire excess. There are few macroscopic syndrome differentiation law studies based on large samples. At the same time, in most studies, the use of traditional Chinese medicine is mostly based on the experience of each research group, lacking the basis for syndrome differentiation and treatment. Although traditional Chinese medicine is widely used in the chemotherapy period of breast cancer and has achieved certain clinical efficacy, it has not been widely recognized and promoted in the clinic due to the lack of more scientific and objective syndrome differentiation basis support. Therefore, it is particularly important to use scientific research methods to explore and analyze the syndrome characteristics and laws of patients in the chemotherapy stage of breast cancer in the current era, so as to better guide the treatment of traditional Chinese medicine. Summary of the invention

[0004] In order to better guide the traditional Chinese medicine treatment of breast cancer, the present invention provides a traditional Chinese medicine syndrome differentiation system for early breast cancer chemotherapy, including four syndrome types, namely:

[0005] Liver depression and Yin deficiency syndrome, the corresponding syndrome items are: irritability, thin white tongue coating, forgetfulness, chest and flank pain, dry mouth, hot flashes, chest and abdominal pain, bone pain, abdominal distension, chest tightness;

[0006] Qi and Yin deficiency syndrome, corresponding to the following syndrome items: deep pulse, thin white tongue coating, red tongue, hot flashes, forgetfulness, dry mouth, pale complexion, sore waist and knees, spontaneous sweating, ruddy complexion;

[0007] The corresponding syndrome items for spleen deficiency and blood deficiency are: pale tongue, greasy white tongue coating, pale complexion, dry mouth, poor appetite, thin pulse, and enlarged tongue;

[0008] The corresponding symptom items for Qi stagnation and blood stasis syndrome are: ecchymosis on the tongue, bluish lips, varicose veins under the tongue, stringy pulse, dull complexion, numbness of limbs, and oral ulcers.

[0009] Furthermore, for the syndrome of liver depression and yin deficiency, the corresponding syndrome items and the weight coefficients of the syndrome items are: irritability and its weight coefficient is 11, thin white tongue coating and its weight coefficient is 6, forgetfulness and its weight coefficient is 6, chest and flank distension and its weight coefficient is 5, dry mouth and its weight coefficient is 5, hot flashes and its weight coefficient is 4, chest and abdominal pain and its weight coefficient is 4, bone pain and its weight coefficient is 3, abdominal distension and its weight coefficient is 3, chest tightness and its weight coefficient is 3;

[0010] Qi and Yin deficiency syndrome, the corresponding syndrome items and the weight coefficients of the syndrome items are: deep pulse and its weight coefficient is 18, thin white tongue coating and its weight coefficient is 11, red tongue and its weight coefficient is 11, hot flashes and its weight coefficient is 4, forgetfulness and its weight coefficient is 1, dry mouth and its weight coefficient is 1, pale complexion and its weight coefficient is 1, soreness of waist and knees and its weight coefficient is 1, spontaneous sweating and its weight coefficient is 1, ruddy complexion and its weight coefficient is 1;

[0011] For the syndrome of spleen deficiency and blood deficiency, the corresponding syndrome items and their weight coefficients are as follows: pale tongue and its weight coefficient is 13, greasy white tongue coating and its weight coefficient is 12, pale complexion and its weight coefficient is 7, dry mouth and its weight coefficient is 6, poor appetite and its weight coefficient is 5, thin pulse and its weight coefficient is 4, and enlarged tongue and its weight coefficient is 3;

[0012] For Qi stagnation and blood stasis syndrome, the corresponding symptom items and their weight coefficients are: ecchymosis on the tongue and its weight coefficient is 21, cyanosis of the lips and its weight coefficient is 13, varicose sublingual venous tract and its weight coefficient is 6, stringy pulse and its weight coefficient is 6, dull complexion and its weight coefficient is 2, numbness of limbs and its weight coefficient is 1, and oral ulcers and their weight coefficient is 1.

[0013] The present invention also provides a method for constructing the above-mentioned TCM syndrome differentiation system for early breast cancer during chemotherapy, comprising:

[0014] Step 1: Enrollment of patients undergoing chemotherapy for breast cancer: Patients undergoing chemotherapy for breast cancer who meet the inclusion criteria and are not within the scope of the exclusion criteria are enrolled;

[0015] Step 2, collect and input information, and establish a database of traditional Chinese medicine syndromes during breast cancer chemotherapy: collect information of patients during breast cancer chemotherapy using the questionnaire of traditional Chinese medicine syndromes during breast cancer chemotherapy; the information includes syndrome item information; use binary classification to count and input each syndrome item, and establish a database of traditional Chinese medicine syndromes during breast cancer chemotherapy;

[0016] Step 3: Cluster analysis was used to establish a candidate system for TCM syndrome differentiation during chemotherapy for early breast cancer;

[0017] Step 4: Screen and determine the TCM syndrome differentiation and analysis system for breast cancer during chemotherapy.

[0018] Further, step 3 includes:

[0019] Step 3-1, screening of syndrome items in TCM syndrome differentiation during breast cancer chemotherapy: frequency analysis was used to sort TCM syndrome items, and TCM syndrome items with a frequency of <2% were eliminated. The remaining syndrome items were used as initial syndrome items for cluster analysis;

[0020] Step 3-2, initial clustering results under K-means clustering analysis: After K-means clustering analysis, the syndrome items were clustered into three categories, four categories, five categories, and six categories, which are the initial clustering results;

[0021] Step 3-3, obtain the candidate system of TCM syndrome differentiation and typing for early breast cancer during chemotherapy by Logistic regression analysis: perform secondary screening on the syndrome items under the initial clustering results of step 3-2 by logistic regression analysis; assign weights to the top 20 syndrome items as the main diagnostic information of TCM syndrome differentiation and typing for breast cancer during chemotherapy, and only retain the TCM syndrome items with original weight coefficients > 0, and include them as diagnostic indicators of the candidate system of TCM syndrome differentiation and typing for early breast cancer during chemotherapy, thus obtaining the candidate system of TCM syndrome differentiation and typing for early breast cancer during chemotherapy.

[0022] Furthermore, the original weight coefficient was obtained by retrieving the binary information in the TCM syndrome database of breast cancer during chemotherapy and performing logistic regression analysis using SPSS software.

[0023] Furthermore, step 3 also includes step 3-4, determining the weight coefficient of the syndrome item:

[0024] i. Retrieve binary information from the database of traditional Chinese medicine syndromes during breast cancer chemotherapy, and perform logistic regression analysis using SPSS software to obtain the original weight coefficient of each syndrome item;

[0025] ii. The total score of each syndrome type in the candidate system of TCM syndrome differentiation and classification for early breast cancer during chemotherapy obtained in step 3-3 is set to M, and the weight coefficient of the syndrome item corresponding to each syndrome type and the adjustment coefficient F of the original weight coefficient are calculated by formula 1; and the weight coefficient of the syndrome item corresponding to each syndrome type is obtained by formula 2; M is 25 to 55;

[0026] Formula 1 The sum of the original weight coefficients of the syndrome items corresponding to the syndrome type × F = M

[0027] Formula 2: The weight coefficient of the syndrome item corresponding to the syndrome type = the original weight coefficient of the syndrome item corresponding to the syndrome type × F.

[0028] Further, M=50.

[0029] Furthermore, step 4, screening and determining the TCM syndrome differentiation classification system for early breast cancer during chemotherapy; screening criteria: when the weight coefficient of a syndrome item in a syndrome type is ≥25, it means that the syndrome type is overly dependent on this single syndrome item, and the syndrome differentiation classification is eliminated; the TCM syndrome differentiation classification system for early breast cancer during chemotherapy is obtained by screening in the syndrome differentiation classifications of cluster three, cluster four, cluster five, and cluster six.

[0030] In one or more specific embodiments, the Chinese medicine syndrome questionnaire for breast cancer during chemotherapy includes an investigation of general symptoms, tongue image, and pulse image; general symptoms include fatigue, pale nails, frequent urination, chest tightness, swelling of the limbs, difficult urination, irritability, dry mouth, loose stools, forgetfulness, insomnia, dry stools, anxiety, poor appetite, bluish lips, hot flashes, bone pain, ruddy complexion, spontaneous sweating, numbness of the limbs, sallow complexion, tinnitus, dizziness, dark complexion, dry eyes, abdominal distension, pale complexion, chest and flank pain, oral ulcers, soreness of the waist and knees, nausea and vomiting, chest and abdominal pain, and chills.

[0031] Furthermore, tongue image includes tongue color, tongue shape and tongue coating.

[0032] Further, tongue colors include pale red, pale white, red, purple and dark.

[0033] Further, tongue shapes include tooth marks, enlargement, cracks, thinness, prickles, varicose veins under the tongue and ecchymosis.

[0034] Furthermore, the tongue coating includes thin white, thin yellow, white and greasy, yellow and greasy, and light and peeled.

[0035] Furthermore, pulse conditions include deep, thin, stringy, slippery, astringent, rapid and weak.

[0036] In another one or more specific embodiments, the Chinese medicine syndrome questionnaire for breast cancer chemotherapy includes investigation of the following syndrome items: irritability, thin white tongue coating, forgetfulness, chest and flank pain, dry mouth, hot flashes, chest and abdominal pain, bone pain, abdominal distension, chest tightness, deep pulse, red tongue, pale complexion, soreness of waist and knees, spontaneous sweating, ruddy complexion, pale tongue, greasy white tongue coating, poor appetite, thin pulse, fat tongue, ecchymosis on tongue, blue lips, varicose veins under the tongue, stringy pulse, dull complexion, numbness of limbs and oral ulcers.

[0037] The present invention also provides a computer-readable storage medium having a computer program stored thereon, and when the computer program is executed by a processor, the steps of the construction method described above are implemented.

[0038] The present invention also provides an application of the above-mentioned TCM syndrome differentiation system for early breast cancer during chemotherapy in TCM treatment of breast cancer, TNM staging (tumor node metastasis classification), molecular typing and chemotherapy regimen grouping.

[0039] The present invention establishes a TCM syndrome differentiation system for early breast cancer during chemotherapy, and analyzes the correlation between the syndrome differentiation and clinical factors, providing a theoretical basis for the standardized TCM treatment of patients with early breast cancer during chemotherapy, and has broad application prospects. At the same time, the classification system has a great correlation with the TNM staging, molecular typing and chemotherapy regimen grouping of breast cancer, and can be used to assist in the analysis of the TNM staging, molecular typing and chemotherapy regimen grouping of breast cancer.

[0040] The concept, specific structure and technical effects of the present invention will be further described below in conjunction with the accompanying drawings to fully understand the purpose, characteristics and effects of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 The present invention is a flow chart of a method for constructing TCM syndrome differentiation classification for early breast cancer during chemotherapy in a specific implementation manner.

[0042] Figure 2 The present invention is a flowchart of correlation analysis between TCM syndrome differentiation and clinical factors during chemotherapy of early breast cancer in a specific implementation manner.

[0043] Figure 3 The invention relates to a TCM syndrome questionnaire for breast cancer during chemotherapy in a specific implementation manner. DETAILED DESCRIPTION

[0044] In order to make the technical means, creative features, objectives and effects of the invention easier to understand, the invention is further described below with reference to specific diagrams. However, the invention is not limited to the following implementation cases.

[0045] It should be noted that the structures, proportions, sizes, etc. illustrated in the drawings in this specification are only used to match the contents disclosed in the specification so as to facilitate understanding and reading by persons familiar with this technology. They are not used to limit the conditions under which the present invention can be implemented, and therefore have no substantive technical significance. Any structural modification, change in proportion or adjustment of size, without affecting the effects and purposes that can be achieved by the present invention, should still fall within the scope of the technical contents disclosed by the present invention.

[0046] The process of constructing the TCM syndrome differentiation method for early breast cancer during chemotherapy is as follows. Figure 1 :

[0047] Among patients with early breast cancer undergoing chemotherapy, 400 patients who met the inclusion criteria and were not within the exclusion criteria were enrolled;

[0048] A questionnaire survey was conducted according to the TCM syndrome questionnaire for breast cancer, and information was collected and entered to establish a TCM syndrome database for breast cancer during chemotherapy.

[0049] Cluster analysis and logistic regression analysis were used to establish a candidate system for TCM syndrome differentiation in early breast cancer during chemotherapy;

[0050] Screen and determine the TCM syndrome differentiation system for early breast cancer during chemotherapy.

[0051] Example 1 Collection and entry of TCM syndrome information of breast cancer patients during chemotherapy

[0052] 1) Case source: A total of 400 patients with breast malignant tumors who received chemotherapy at the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine and the Shanghai Cancer Hospital Affiliated to Fudan University from December 2019 to January 2021 were collected.

[0053] 2) Diagnostic criteria: refer to "Surgery" (Editor: Chen Xiaoping, Beijing: People's Medical Publishing House, 2nd edition, August 2010). Combined with the patient's clinical manifestations, physical examination, imaging examination, and pathological examination, the diagnosis of breast malignancy was made. Postoperative TNM staging was based on the American Joint Committee on Cancer (AJCC 2010 edition); molecular typing of breast cancer was based on the "St. Gallen Consensus".

[0054] 3) Inclusion criteria: ① Female; ② Breast cancer patients with a clear pathological diagnosis; ③ Breast cancer-related surgical resection has been performed; ④ Currently receiving adjuvant chemotherapy for breast cancer; ⑤ Complete medical history and examination data; ⑥ Informed consent has been signed.

[0055] 4) Exclusion criteria: ① Those who cannot cooperate with the questionnaire survey, including those with language difficulties, mental illness, etc.; ② Those with advanced breast cancer who have undergone multiple lines of chemotherapy; ③ Patients undergoing neoadjuvant chemotherapy.

[0056] 5) Collect and enter information to establish a database of TCM syndromes during breast cancer chemotherapy: The data were collected in the second week after the patients received adjuvant chemotherapy, according to the TCM syndrome questionnaire for breast cancer chemotherapy (see Figure 3 ), record the general clinical information and TCM syndrome information of the patients. Each syndrome element was classified into two categories (0 = no, 1 = yes) for statistics, and the corresponding entry program was established through EpiData database software. The database was tested and data entry was completed to establish a TCM syndrome database for breast cancer chemotherapy period dedicated to this study. This study used fixed personnel to collect data, and paid attention to avoiding inductive language. The tongue and pulse were collected by two physicians; the data was entered by two people twice, and the results of the two entries were checked to reduce the entry error.

[0057] The frequency statistics method was used to sort the syndrome items from high to low. The top 10 syndrome items were: thin white tongue coating 221 times (55.25%), forgetfulness 219 times (54.75%), dark tongue 214 times (53.50%), dry mouth 214 times (53.50%), fatigue 207 times (51.75%), insomnia 198 times (49.50%), purple tongue 185 times (46.25%), pale complexion 172 times (43.00%), hot flashes 162 times (40.50%), and poor appetite 157 times (39.25%), see Table 1.

[0058] Table 1. Distribution of syndrome items in 400 patients with breast cancer during chemotherapy

[0059]

[0060]

[0061] Example 2 Cluster analysis method to establish a candidate system for TCM syndrome differentiation during chemotherapy of early breast cancer

[0062] ① Screening of syndrome items in TCM syndrome differentiation during chemotherapy for breast cancer: The syndrome items were sorted by frequency analysis, and the syndrome items with a frequency of <2% were eliminated. The remaining 52 syndrome items were included in the cluster analysis as initial syndrome items; ② Initial clustering results under K-means cluster analysis: The syndrome items were clustered into three, four, five, and six categories by K-means cluster analysis, which were the initial clustering results; ③ Logistic regression analysis was used to obtain the candidate system for TCM syndrome differentiation during chemotherapy for early breast cancer: The syndrome items under the above initial clustering results were screened again by logistic regression analysis. The top 20 syndrome items were used as the main diagnostic information of the TCM syndrome differentiation during chemotherapy for early breast cancer, and weights were assigned. Only TCM syndrome items with original weight coefficients > 0 were retained and included as diagnostic indicators for the candidate system for TCM syndrome differentiation during chemotherapy for early breast cancer. i. Retrieve the binary information in the TCM syndrome database for breast cancer chemotherapy, and perform logistic regression analysis using SPSS software to obtain the original weight coefficient of each syndrome item;

[0063] ii. The total score of each syndrome type in the candidate system of TCM syndrome differentiation for early breast cancer during chemotherapy obtained in step 3-3 is set to M, and the weight coefficient of the syndrome item corresponding to each syndrome type and the adjustment coefficient F of the original weight coefficient are calculated by formula 1; and the weight coefficient of the syndrome item corresponding to each syndrome type is obtained by formula 2; M is 50 (in other embodiments, M can take any value between 25 and 55);

[0064] Formula 1 The sum of the original weight coefficients of the syndrome items corresponding to the syndrome type × F = M

[0065] Formula 2: The weight coefficient of the syndrome item corresponding to the syndrome type = the original weight coefficient of the syndrome item corresponding to the syndrome type × F.

[0066] The final results are shown in Table 2-5.

[0067] Table 2. Clustering of three types

[0068]

[0069]

[0070] Table 3. Clustering of four categories

[0071]

[0072] Table 4. Clustering of five categories

[0073]

[0074]

[0075] Table 5. Six types of clusters

[0076]

[0077]

[0078] Example 3 Screening and determination of TCM syndrome differentiation system for early breast cancer chemotherapy period

[0079] According to the cluster analysis results recorded in Table 2-5, screening was performed according to the screening criteria. The results were as follows: Scheme 1 (cluster 3) had a dark tongue weight coefficient of 40 in Class II, so this scheme was eliminated; Scheme 3 (cluster 5) had a purple tongue weight coefficient of 50 in Class I, so this scheme was eliminated; Scheme 4 (cluster 6) had a pulse depth weight coefficient of 31 in Class I, a pulse depth weight coefficient of 48 in Class II, a dark tongue weight coefficient of 27 in Class V, and a thin pulse weight coefficient of 37 in Class VI, so this scheme was eliminated. Finally, Scheme 2 (cluster 4) was retained.

[0080] Example 4 General conditions of included cases:

[0081] A total of 400 patients with breast cancer undergoing chemotherapy were included in this study, and general clinical information of the patients was collected, including age, clinical stage, molecular classification, and chemotherapy regimen (see Table 6 for details).

[0082] Table 6. General information included

[0083]

[0084]

[0085] Example 5: Distribution of TCM syndrome differentiation of included cases:

[0086] According to the scheme 2 (four categories) TCM syndrome differentiation system for early breast cancer during chemotherapy determined in Example 3, the distribution of TCM syndrome differentiation of 400 breast cancer patients during chemotherapy was as follows: Liver depression and Yin deficiency syndrome: 79 cases, accounting for 19.75%; Qi and Yin deficiency syndrome: 173 cases, accounting for 43.25%; Spleen deficiency and blood deficiency syndrome: 101 cases, accounting for 25.25%; Qi stagnation and blood stasis syndrome: 47 cases, accounting for 11.75%, as shown in Table 7 for details.

[0087] Table 7. Distribution of TCM syndrome differentiation of included cases

[0088]

[0089] Example 6 Correlation analysis between TCM syndrome differentiation and clinical factors of included cases

[0090] Patients with breast cancer during chemotherapy who met the inclusion criteria and were not within the scope of the exclusion criteria (400) were divided into two groups according to the TCM syndrome differentiation system for early breast cancer during chemotherapy determined in Example 3. After data entry, a study was conducted on the relationship between the TCM syndrome differentiation system for early breast cancer during chemotherapy and age grouping, TNM stage grouping, molecular typing grouping, and chemotherapy regimen grouping (see Figure 2 ).

[0091] ① Correlation analysis between TCM syndrome differentiation system and age in early breast cancer during chemotherapy

[0092] A total of 400 patients with breast cancer undergoing chemotherapy were included in this study. The age range was 28-76 years old, with a median age of 53 years old. Among them, 48 patients were 20-39 years old, accounting for 12.00%; 231 patients were 40-59 years old, accounting for 57.75%; and 121 patients were 60-79 years old, accounting for 30.25%. See Table 8 for details.

[0093] Table 8. Distribution of TCM syndrome types in patients of different age groups

[0094]

[0095] ② Correlation analysis between TCM syndrome differentiation system and TNM staging during chemotherapy for early breast cancer

[0096] According to the 2010 AJCC TNM staging system, 400 patients with breast cancer undergoing chemotherapy were divided into stage I, stage II, and stage III. The specific distribution was as follows: 98 patients in stage I, accounting for 24.50%; 177 patients in stage II, accounting for 44.25%; and 125 patients in stage III, accounting for 31.25%. See Table 9 for details.

[0097] Table 9. Distribution of TCM syndrome types in patients at different clinical stages

[0098]

[0099] ③Correlation analysis between TCM syndrome differentiation system and molecular typing in early breast cancer during chemotherapy

[0100] According to the "St. Gallen Consensus" (2017 edition), breast cancer is divided into Luminal A, Luminal B, Her-2 positive, and TNBC types. The specific distribution is: Luminal A: 79 cases, accounting for 19.75%; Luminal B: 164 cases, accounting for 41.00%; Her-2 positive: 55 cases, accounting for 13.75%; TNBC: 102 cases, accounting for 25.50%, see Table 10 for details.

[0101] Table 10. Distribution of TCM syndrome types among patients with different molecular classifications

[0102]

[0103] ④ Correlation analysis between TCM syndrome differentiation system and chemotherapy regimen in early breast cancer during chemotherapy

[0104] The chemotherapy regimens received by the 400 cases in this study included anthracycline sequential taxane, taxane alone, and other chemotherapy regimens. The drugs in the regimens included anthracyclines, taxanes, and other types. The data were entered based on the chemotherapy regimen that the patient was receiving when the symptoms were collected. Each patient was only entered once for each regimen, and no duplication was made. The specific distribution was as follows: 140 patients received anthracycline chemotherapy, accounting for 35.00%; 216 patients received taxane chemotherapy, accounting for 54.00%; and 44 patients received other types of chemotherapy drugs, accounting for 11.00%. See Table 11 for details.

[0105] Table 11. Distribution of TCM syndrome types in patients with different chemotherapy regimens

[0106]

[0107] Example 7 Obtaining the Weight Coefficient

[0108] 1) SPSS 21.0 software was used to perform statistical analysis on the data in the TCM syndrome database of breast cancer during chemotherapy. TCM syndrome differentiation was performed based on the four syndrome types of liver depression and yin deficiency, qi and yin deficiency, spleen deficiency and blood deficiency, and qi stagnation and blood stasis. The original weight coefficient corresponding to each syndrome item in the syndrome differentiation relationship of breast cancer during chemotherapy (see Tables 12-15) was used as the score ratio. Tables 1-4 are the results of the logistic regression analysis of the clustered four categories (retaining the syndrome items with the original weight coefficient > 0), where B represents the standard value and p represents the probability.

[0109] Table 12. Logistic regression analysis results of liver depression and Yin deficiency type

[0110] Syndrome Items B Standard error Wald Degrees of Freedom p Original weight coefficient Thin white tongue coating 1.512 0.466 10.523 1 0.001 4.534 forgetful 1.6 0.504 10.064 1 0.002 4.954 Dry mouth 1.374 0.477 8.301 1 0.004 3.952 Hot flashes 1.147 0.453 6.404 1 0.011 3.149 Bone pain 0.909 0.451 4.058 1 0.044 2.481 Abdominal bloating 0.874 0.429 4.164 1 0.041 2.398 Chest tightness 0.997 0.417 5.715 1 0.017 2.71 Irritability 2.151 0.48 20.116 1 0 8.596 Chest and abdominal pain 1.231 0.473 6.778 1 0.009 3.423 Chest and flank pain 1.467 0.462 10.083 1 0.001 4.335

[0111] Table 13. Logistic regression analysis results of Qi and Yin deficiency type

[0112] Syndrome Items B Standard error Wald Degrees of Freedom p Original weight coefficient Thin white tongue coating 1.673 0.375 19.86 1 0 5.326 forgetful -1.118 0.344 10.576 1 0.001 0.327 Dry mouth -1.295 0.336 14.852 1 0 0.274 Pale complexion -0.948 0.382 6.166 1 0.013 0.387 Hot flashes 0.754 0.358 4.437 1 0.035 2.125 Weak waist and knees -1.419 0.371 14.617 1 0 0.242 Spontaneous sweating -1.083 0.364 8.852 1 0.003 0.339 Deep pulse 2.18 0.458 22.666 1 0 8.85 Ruddy complexion -1.238 0.49 6.392 1 0.011 0.29 Red tongue 1.695 0.483 12.296 1 0 5.444

[0113] Table 14. Logistic regression analysis results of spleen deficiency and blood deficiency type

[0114] Syndrome Items B Standard error Wald Degrees of Freedom p Original weight coefficient Dry mouth 1.318 0.344 14.661 1 0 3.735 Pale complexion 1.488 0.331 20.199 1 0 4.43 Thin pulse 1.046 0.333 9.848 1 0.002 2.847 Naturopathic 1.185 0.346 11.74 1 0.001 3.271 Pale tongue 2.162 0.345 39.194 1 0 8.687 Fat tongue 0.79 0.349 5.141 1 0.023 2.204 Greasy white tongue coating 2.092 0.437 22.907 1 0 8.104

[0115] Table 15. Logistic regression analysis results of Qi stagnation and blood stasis type

[0116] Syndrome Items B Standard error Wald Degrees of Freedom p Original weight coefficient Limb numbness 4.387 2.054 4.56 1 0.033 80.415 Mouth ulcers 3.906 1.747 4.997 1 0.025 49.684 Bluish lips 7.332 2.379 9.501 1 0.002 1528.374 Dark complexion 5.355 2.617 4.186 1 0.041 211.647 Bruise on tongue 7.817 2.962 6.965 1 0.008 2483.437 Sublingual varicose veins 6.677 2.635 6.42 1 0.011 793.749 Pulse 6.551 3.067 4.564 1 0.033 700.253

[0117] 2) For the convenience of calculation and comparison, the sum of the weight coefficients of all syndrome items corresponding to each syndrome type is set to 50, and the weight coefficients of the corresponding syndrome items are calculated by the original weight coefficients in Tables 12-15. Taking liver depression and Yin deficiency syndrome as an example, the calculation method is: (4.534+4.954+3.952+3.149+2.481+2.398+2.71+8.596+3.423+4.335)×F 1 =50. Calculate F 1 =1.23, F is the adjustment coefficient between the weight coefficient of the syndrome item corresponding to the syndrome type and the original weight coefficient, F 1 It is the adjustment coefficient of the weight coefficient of the syndrome item corresponding to liver depression and Yin deficiency syndrome and the original weight coefficient. The weight coefficient of the syndrome item = the original weight coefficient of the syndrome item × F. Substitute the value of F and round it off to the integer to obtain the weight coefficient of the syndrome item (see the values ​​in the brackets of the syndrome items in Table 3).

[0118] The preferred specific embodiments of the present invention are described in detail above. It should be understood that ordinary technicians in the field can make many modifications and changes based on the concept of the present invention without creative work. Therefore, all technical solutions that can be obtained by technicians in the technical field based on the concept of the present invention through logical analysis, reasoning or limited experiments on the basis of the prior art should be within the scope of protection determined by the claims.

Claims

1. A TCM syndrome differentiation system for early breast cancer during chemotherapy, characterized in that: There are four types of syndromes: Liver depression and Yin deficiency syndrome, the corresponding syndrome items are: irritability, thin white tongue coating, forgetfulness, chest and flank pain, dry mouth, hot flashes, chest and abdominal pain, bone pain, abdominal distension, chest tightness; Qi and Yin deficiency syndrome, corresponding to the following syndrome items: deep pulse, thin white tongue coating, red tongue, hot flashes, forgetfulness, dry mouth, pale complexion, sore waist and knees, spontaneous sweating, ruddy complexion; The corresponding syndrome items for spleen deficiency and blood deficiency are: pale tongue, greasy white tongue coating, pale complexion, dry mouth, poor appetite, thin pulse, and enlarged tongue; Qi stagnation and blood stasis syndrome, the corresponding syndrome items are: ecchymosis on the tongue, bluish lips, varicose veins under the tongue, stringy pulse, dull complexion, numbness of limbs, and oral ulcers; The syndrome of liver depression and yin deficiency, the corresponding syndrome items and the weight coefficients of the syndrome items are: irritability and its weight coefficient is 11, thin white tongue coating and its weight coefficient is 6, forgetfulness and its weight coefficient is 6, chest and flank distension and its weight coefficient is 5, dry mouth and its weight coefficient is 5, hot flashes and its weight coefficient is 4, chest and abdominal pain and its weight coefficient is 4, bone pain and its weight coefficient is 3, abdominal distension and its weight coefficient is 3, chest tightness and its weight coefficient is 3; The syndrome of Qi and Yin deficiency, the corresponding syndrome items and the weight coefficients of the syndrome items are: deep pulse and its weight coefficient is 18, thin white tongue coating and its weight coefficient is 11, red tongue and its weight coefficient is 11, hot flashes and its weight coefficient is 4, forgetfulness and its weight coefficient is 1, dry mouth and its weight coefficient is 1, pale complexion and its weight coefficient is 1, soreness of waist and knees and its weight coefficient is 1, spontaneous sweating and its weight coefficient is 1, ruddy complexion and its weight coefficient is 1; The syndrome of spleen deficiency and blood deficiency, the corresponding syndrome items and the weight coefficients of the syndrome items are: pale tongue and its weight coefficient is 13, white and greasy tongue coating and its weight coefficient is 12, pale complexion and its weight coefficient is 7, dry mouth and its weight coefficient is 6, poor appetite and its weight coefficient is 5, thin pulse and its weight coefficient is 4, fat tongue and its weight coefficient is 3; The corresponding symptom items and weight coefficients of the symptom items for the Qi stagnation and blood stasis syndrome are: ecchymosis on the tongue and its weight coefficient is 21, cyanosis of the lips and its weight coefficient is 13, varicose veins under the tongue and its weight coefficient is 6, stringy pulse and its weight coefficient is 6, dull complexion and its weight coefficient is 2, numbness of limbs and its weight coefficient is 1, and oral ulcers and their weight coefficient are 1.

2. A method for constructing a TCM syndrome differentiation system for early breast cancer during chemotherapy as claimed in claim 1, characterized in that: include: Step 1. Enrollment of patients undergoing chemotherapy for breast cancer: Patients undergoing chemotherapy for breast cancer who meet the inclusion criteria and are not within the scope of the exclusion criteria are enrolled; Step 2, collect and input information, and establish a database of traditional Chinese medicine syndromes during breast cancer chemotherapy: collect information of patients during breast cancer chemotherapy using a questionnaire on traditional Chinese medicine syndromes during breast cancer chemotherapy; the information includes syndrome item information; each syndrome item is counted and input using binary classification to establish a database of traditional Chinese medicine syndromes during breast cancer chemotherapy; Step 3: Establish a candidate system for TCM syndrome differentiation during chemotherapy for early breast cancer using cluster analysis; Step 4: Screening and determining the TCM syndrome differentiation system for early breast cancer during chemotherapy; Step 3 includes: Step 3-1, screening of syndrome items in TCM syndrome differentiation during breast cancer chemotherapy: frequency analysis was used to sort TCM syndrome items, and TCM syndrome items with a frequency of <2% were eliminated. The remaining syndrome items were used as initial syndrome items for cluster analysis; Step 3-2, initial clustering results under K-means clustering analysis: After K-means clustering analysis, the syndrome items were clustered into three categories, four categories, five categories, and six categories, which are the initial clustering results; Step 3-3, obtain the candidate system of TCM syndrome differentiation and typing for early breast cancer during chemotherapy by Logistic regression analysis: perform secondary screening on the syndrome items under the initial clustering results of step 3-2 by logistic regression analysis; assign weights to the top 20 syndrome items as the main diagnostic information of the TCM syndrome differentiation and typing scheme for breast cancer during chemotherapy, and only retain the TCM syndrome items with original weight coefficients>0, and include them as diagnostic indicators of the candidate system of TCM syndrome differentiation and typing for early breast cancer during chemotherapy, so as to obtain the candidate system of TCM syndrome differentiation and typing for early breast cancer during chemotherapy; the step 3 also includes step 3-4, determining the weight coefficients of the syndrome items: i. Retrieving the binary classification information in the TCM syndrome database of breast cancer during chemotherapy, and performing logistic regression analysis using SPSS software to obtain the original weight coefficient of each syndrome item; ii. The total score of each syndrome type in the candidate system of TCM syndrome differentiation for early breast cancer during chemotherapy obtained in step 3-3 is set to M, and the weight coefficient of the syndrome item corresponding to each syndrome type and the adjustment coefficient F of the original weight coefficient are calculated by formula 1; and the weight coefficient of the syndrome item corresponding to each syndrome type is obtained by formula 2; M is 25 to 55; The sum of the original weight coefficients of the syndrome items corresponding to the syndrome type in formula 1×F=M; M=50; Formula 2: The weight coefficient of the syndrome item corresponding to the syndrome type = the original weight coefficient of the syndrome item corresponding to the syndrome type × F; The step 4, screening and determining the TCM syndrome differentiation system for early breast cancer during chemotherapy; screening criteria: when a certain syndrome item weight coefficient ≥ 25 appears in a certain syndrome, it means that the syndrome is overly dependent on this single syndrome item, and the syndrome differentiation is eliminated; the TCM syndrome differentiation system for early breast cancer during chemotherapy is obtained by screening in the syndrome differentiation of cluster three, cluster four, cluster five, and cluster six; The Chinese medicine syndrome questionnaire for breast cancer during chemotherapy includes investigations on general symptoms, tongue image, and pulse image; the general symptoms include fatigue, pale nails, frequent urination, chest tightness, swollen limbs, difficult urination, irritability, dry mouth, loose stools, forgetfulness, insomnia, dry stools, anxiety, poor appetite, bluish lips, hot flashes, bone pain, ruddy complexion, spontaneous sweating, numbness of limbs, sallow complexion, tinnitus, dizziness, dull complexion, dry eyes, abdominal distension, pale complexion, chest and flank pain, oral ulcers, soreness of waist and knees, nausea and vomiting, chest and abdominal pain, and chills.

3. A computer-readable storage medium, characterized in that: The computer-readable storage medium stores a computer program, and when the computer program is executed by a processor, the steps of the construction method according to claim 2 are implemented.

4. An application of the TCM syndrome differentiation and classification system for early breast cancer during chemotherapy as claimed in claim 1 in the preparation of products for TCM syndrome differentiation and classification for early breast cancer during chemotherapy, and in products for auxiliary analysis of TCM treatment, TNM staging, molecular typing and chemotherapy regimen grouping for breast cancer.

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