A method, system, and apparatus for evaluating the therapeutic effect of empagliflozin on atherosclerosis

Abstract

The application discloses a kind of method, system and equipment for evaluating the therapeutic effect of empagliflozin on atherosclerosis.The application first finds that empagliflozin treats atherosclerosis by promoting endothelial cell mitochondrial autophagy, and finds that the expression of mitochondrial autophagy-related proteins Pink1, Parkin and LC3-II / LC3-I is up-regulated after empagliflozin treatment, and the protective effect of empagliflozin is weakened after using methyladenine to inhibit mitochondrial autophagy, therefore, the method, system and equipment for evaluating the therapeutic effect of empagliflozin on atherosclerosis provided by the application can assist doctors in evaluating the therapeutic effect on atherosclerosis patients, and guide clinicians to develop personalized treatment plans for patients.

Description

Technical Field

[0001] This invention belongs to the field of bioinformatics, specifically relating to a method, system, and device for evaluating the therapeutic effect of empagliflozin on atherosclerosis. Background Technology

[0002] Atherosclerosis (AS) is a lipid-driven chronic inflammatory vascular disease and the pathological basis for cardiovascular diseases such as coronary heart disease and myocardial infarction. Its pathogenesis involves multiple factors, including endothelial damage, immune response, inflammatory response, and lipid metabolism. With changing lifestyles and an accelerating aging of the global population, the incidence of atherosclerosis continues to rise and is increasingly affecting younger populations.

[0003] Empagliflozin (EMPZ) is a specific inhibitor of sodium-glucose co-transporter 2 (SGLT-2). It lowers blood glucose levels by preventing glucose reabsorption in the proximal tubules of the kidney and promoting its excretion in urine. In addition to lowering blood glucose, empagliflozin has shown protective effects against atherosclerotic heart disease. Furthermore, empagliflozin can reduce ferroptosis in vascular endothelial cells by regulating the NRF2 / HO-1 signaling pathway, thereby enhancing endothelial function and inhibiting the progression of atherosclerosis. Despite these findings, the exact mechanism by which empagliflozin alleviates atherosclerosis remains not fully understood. Summary of the Invention

[0004] To overcome the shortcomings of the prior art, the purpose of this invention is to provide a method, system, and device for evaluating the therapeutic effect of empagliflozin on atherosclerosis.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: The first aspect of the present invention provides a method for evaluating the therapeutic effect of empagliflozin on atherosclerosis.

[0006] Furthermore, the method is performed by a computer, and the method includes the following steps: Data Acquisition: Acquire expression data of mitochondrial autophagy-related proteins in atherosclerotic patient samples after empagliflozin treatment, wherein the mitochondrial autophagy-related proteins include one or more of the following: Pink1, Parkin, LC3-II, LC3-I; Data processing: The expression data of mitophagy-related proteins were input into the constructed empagliflozin evaluation model, which evaluated the therapeutic effect of empagliflozin on atherosclerosis based on the expression data of mitophagy-related proteins. Output results.

[0007] Furthermore, the expression data of the mitophagy-related proteins include, but are not limited to, data obtained by immunoblotting, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and mass spectrometry.

[0008] Furthermore, the construction steps of the aforementioned empagliflozin evaluation model are as follows: Expression data of mitophagy-related proteins were obtained, including one or more of the following: Pink1, Parkin, LC3-II, and LC3-I; the expression data of mitophagy-related proteins were obtained from untreated atherosclerotic patients and atherosclerotic patients treated with empagliflozin; the expression data of mitophagy-related proteins were input into a machine learning algorithm to construct an empagliflozin evaluation model.

[0009] Furthermore, the empagliflozin evaluation model obtains results using the following criteria: when the expression levels of any one or more of the mitophagy-related proteins Pink1, Parkin, and LC3-II / LC3-I are above a threshold, a classification result indicating that empagliflozin is effective in treating patients with atherosclerosis is obtained; when the expression levels of any one or more of the mitophagy-related proteins Pink1, Parkin, and LC3-II / LC3-I are below a threshold, a classification result indicating that empagliflozin is ineffective in treating patients with atherosclerosis is obtained.

[0010] In some embodiments of the present invention, the preset threshold is a representative value of normal samples in an atherosclerotic population, including but not limited to the maximum value, the third quartile, and the mean. In some preferred embodiments of the present invention, the population sample includes 20 or more samples, such as 30, 50, 80, 100, 150, 200, 300, 500, or more.

[0011] Furthermore, the machine learning algorithm includes algorithmic models developed using various development tools.

[0012] Furthermore, the development tools include, but are not limited to, TensorFlow, Scikit-Learn, PyTorch, OpenNN, RapidMiner, Azure Machine Learning, Apache Mahout, Shogun, KNIME, Vertex AI, H2Oai, Anaconda, Keras, Tableau, Fast.ai, Catalyst, Amazon ML, MLJAR, and Spell.

[0013] Furthermore, the algorithm models include, but are not limited to, linear regression models, logistic regression models, Lasso regression models, Ridge regression models, linear discriminant analysis models, nearest neighbor models, decision tree models, perceptron models, neural network models, support vector machine models, Naive Bayes models, AdaBoost models, GBDT models, XGBoost models, LightGBM models, CatBoost models, and random forest models.

[0014] A second aspect of the present invention provides a system for evaluating the therapeutic effect of empagliflozin on atherosclerosis, the system comprising: Data acquisition unit: used to acquire expression data of mitochondrial autophagy-related proteins in atherosclerotic patient samples after empagliflozin treatment, wherein the mitochondrial autophagy-related proteins include one or more of the following: cleaved Pink1, Parkin, LC3-II, LC3-I; Data classification unit: used to classify and predict whether empagliflozin is effective in treating patients with atherosclerosis by classifying the data obtained in the data acquisition unit through the empagliflozin evaluation model obtained by the construction method described in claim 2; Result output unit: Used to output the result to the receiving unit.

[0015] Furthermore, the receiving unit includes a display screen, a computer client, a mobile client, or a tablet.

[0016] A third aspect of the present invention provides a computer device comprising a memory and a processor, the memory being used to store program instructions; the processor being used to invoke the program instructions, which, when executed, implement the method for evaluating the therapeutic effect of empagliflozin on atherosclerosis as described in the first aspect of the present invention.

[0017] A fourth aspect of the present invention provides a computer-readable storage medium having a computer program stored thereon, characterized in that, when the computer program is executed by a processor, it implements the method for evaluating the therapeutic effect of empagliflozin on atherosclerosis as described in the first aspect of the present invention.

[0018] A fifth aspect of the present invention provides a computer program product comprising a computer program, characterized in that, when the computer program is executed by a processor, it implements the method for evaluating the therapeutic effect of empagliflozin on atherosclerosis as described in the first aspect of the present invention.

[0019] The advantages and beneficial effects of this invention are as follows: This invention is the first to discover that empagliflozin alleviates atherosclerosis by promoting mitochondrial autophagy in endothelial cells. Functional experiments also show that empagliflozin upregulates mitochondrial autophagy-related proteins Pink1, Parkin, and LC3-II / LC3-I. This invention provides a method, system, and device for evaluating the therapeutic effect of empagliflozin on atherosclerosis, thereby assisting physicians in evaluating the treatment effects on atherosclerosis patients and guiding clinicians in developing individualized treatment plans for patients. Attached Figure Description

[0020] Figure 1 A flowchart of the method for evaluating the therapeutic effect of empagliflozin on atherosclerosis provided by the present invention; Figure 2 A schematic diagram of the system structure for evaluating the therapeutic effect of empagliflozin on atherosclerosis provided by the present invention; Figure 3 A schematic diagram of the structure of the computer device provided by the present invention; Figure 4 EMPZ was used to improve the progression of atherosclerosis (AS) in mice; (A) Body weight gain in mice of different groups; (B) Representative ORO staining images of the aorta in mice of different groups; (C) Representative HE staining and ORO staining images of the aortic arch in mice of different groups; (D) Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in mice of different groups; (E) Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and TNF-α in mice of different groups. P<0.05, P<0.01, P < 0.001, n = 3; Figure 5 Experimental results related to EMPZ-enhanced aortic mitochondrial autophagy in AS mice; (AB) Representative DHE staining images of aortic arch tissues from different groups of mice; (B) Quantitative analysis of DHE staining in aortic arch tissues from different groups of mice; (C) Protein bands of Pink1, Parkin, LC3-I, and LC3-II in aortic arch tissues from each group of mice; (D) Quantitative analysis of protein expression of Pink1, Parkin, and LC3-I / LC3-II ratio in aortic arch tissues from each group of mice. P<0.05, P<0.01, P < 0.001, n = 3; Figure 6 Experimental results showing that EMPZ promotes mitophagy and improves mitochondrial function in HUVECs; (A) Changes in HUVEC activity after treatment with different concentrations of EMPZ; (B) Representative JC-1 staining images of HUVECs from different groups; (C) Representative DHE staining images of HUVECs from different groups; (D) Representative MitoSOX Red staining images of HUVECs from different groups; (E) Quantitative analysis of JC-1 staining in HUVECs from different groups; (F) Quantitative analysis of DHE staining in HUVECs from different groups; (G) Quantitative analysis of MitoSOX Red staining in HUVECs from different groups; (H) Protein expression levels of Pink1, Parkin, and LC-II / LC3-I in HUVECs from different groups; P<0.05, P<0.01, P < 0.001, n = 3; Figure 7 Experimental results showing that EMPZ inhibits AS progression by promoting mitophagy; (A) Protein expression of Pink1, Parkin, and LC-II / LC3-I in the aortic arch tissue of mice in different groups; (B) Typical ORO staining images of the aorta of mice in different groups; (C) Typical HE staining and ORO staining images of the aortic arch of mice in different groups; (D) Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in mice in different groups; (E) Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and TNF-α in mice in different groups. Detailed Implementation

[0021] To enable those skilled in the art to better understand the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings.

[0022] The present invention describes the operational flow in the specification, drawings, and claims, which includes multiple operational procedures. It should be clearly understood that these operational procedures may not be executed in the order they appear in this document or the drawings, or may be executed in parallel. The labels for the operational steps, such as 101, 102, 103, etc., are only used to distinguish different operations and do not represent any execution order. Furthermore, operations not indicated by the labels may also be added to the operational procedures of the present invention and may be executed sequentially or in parallel. Additionally, all operations mentioned herein may be omitted when necessary. It should be noted that the descriptions such as "first," "second," etc., mentioned in this invention are only used to distinguish different operations, devices, modules, messages, etc., and do not limit the order or specific type.

[0023] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0024] Figure 1 This is a flowchart illustrating the method for evaluating the therapeutic effect of empagliflozin on atherosclerosis provided by the present invention. Specifically, the method includes: 101 Data Acquisition: Acquire expression data of mitochondrial autophagy-related proteins in atherosclerotic patient samples after empagliflozin treatment, wherein the mitochondrial autophagy-related proteins include one or more of the following: Pink1, Parkin, LC3-II, LC3-I; In some embodiments of the present invention, through a series of extensive and in-depth studies and analyses, it was found that empagliflozin significantly reduced the plaque area in the aorta and aortic arch. Further analysis showed that lipid levels and inflammatory cytokines were significantly reduced after empagliflozin treatment. Functional experiments showed that empagliflozin improved the mitochondrial membrane potential of aortic arch and human umbilical vein endothelial cells, reduced intracellular and mitochondrial reactive oxygen species (ROS) levels, and significantly increased the expression levels of mitophagy-related proteins Pink1, Parkin, and LC3-II / LC3-I. In addition, inhibiting mitophagy with methyladenine (3-MA) ​​weakened the therapeutic effect of empagliflozin, suggesting that empagliflozin enhances mitochondrial function of endothelial cells by promoting mitophagy, thereby inhibiting the progression of atherosclerosis. Mitophagy-related proteins Pink1, Parkin, and LC3-II / LC3-I can serve as highly efficient biomarkers for evaluating the therapeutic effect of empagliflozin on atherosclerosis.

[0025] In some embodiments, the patient may be human or non-human and may include, for example, animal strains or species used as a "model system" for research purposes. Similarly, the patient may include adults or adolescents (e.g., children). Furthermore, the patient may refer to any living organism that can benefit from empagliflozin as described in this invention, preferably a mammal (e.g., human or non-human). Examples of mammals include, but are not limited to, any member of the mammalian class: humans, non-human primates (e.g., chimpanzees) and other apes and monkeys; animals such as cattle, horses, sheep, and pigs; livestock such as rabbits, dogs, and cats; rodents such as rats, mice, guinea pigs, etc. Examples of non-mammals include, but are not limited to, birds, fish, etc.

[0026] In the context of this invention, the term "sample" as used refers to a composition obtained from or derived from a patient / subject that contains cells and / or other molecular entities to be characterized and / or identified based on, for example, physical, biochemical, chemical, and / or physiological characteristics. For example, a sample refers to any sample derived from a patient / subject that is expected or known to contain cells and / or molecular entities to be characterized. Samples include, but are not limited to, tissue samples, primary or cultured cells or cell lines, cell cultures, cell supernatants, cell lysates, platelets, serum, plasma, vitreous fluid, lymph, synovial fluid, follicular fluid, semen, pancreatic juice, amniotic fluid, milk, whole blood, blood-derived cells, urine, cerebrospinal fluid, saliva, sputum, tears, sweat, mucus, tissue culture fluid, tissue extracts, homogenized tissue, cell extracts, and combinations thereof.

[0027] In a specific embodiment of the present invention, the samples included 8-week-old C57BL / 6J mice and ApoE- / - mice, both purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., and housed in a specific pathogen-free environment. After a one-week acclimatization period, the C57BL / 6J mice were assigned to the normal diet (ND) group. The ApoE- / - mice were fed a high-fat diet (HFD) for eight weeks and then randomly divided into five groups: the HFD group, the low-dose HFD+EMPZ group (HFD+EMPZ-L), the medium-dose HFD+EMPZ group (HFD+EMPZ-M), the high-dose HFD+EMPZ group (HFD+EMPZ-H), and the HFD+EMPZ-H+3-methyladenine (3-MA) ​​group (MCE, USA). Mice in each dosage group were intraperitoneally injected daily with 1.5, 2.5, or 3.5 mg / kg EMPZ (Cat. No.: HY-15409, CAS No.: 864070-44-0, brand: MedChemExpress) for eight weeks. After eight weeks, mice were euthanized by sodium pentobarbital anesthesia, and blood and aortic samples were collected for subsequent experiments. This animal experiment was approved by the Animal Ethics Committee of Hebei General Hospital (Approval No.: 2025-DW-090). The samples also included human venous endothelial cells (HUVECs) provided by the Cell Bank of the Chinese Academy of Sciences (Shanghai, China). These cells were cultured in endothelial cell culture medium (ECM, ScienCell, USA) at 37°C and 5% carbon dioxide, supplemented with 5% fetal bovine serum (FBS, Gibco, USA) and 1% penicillin-streptomycin (Gibco, USA). The formation of foam cells, a key pathological morphology of atherosclerosis, was induced by exposing cells to 80 μg / mL oxLDL (Sigma, USA) for 24 hours.

[0028] In some embodiments, expression data of mitophagy-related proteins can be detected using methods well known in the art, including but not limited to mass spectrometry-based quantitative proteomics, immunoassay, Western blotting, spectrophotometry, enzymatic assay, ultraviolet assay, kinetic assay, electrochemical assay, colorimetric assay, turbidimetric assay, atomic absorption spectrometry, flow cytometry, mass flow cytometry, or any combination thereof.

[0029] In a specific embodiment of this invention, the expression levels of mitophagy-related proteins were obtained as follows: Western blotting was used to detect the protein expression levels of Pink1, Parkin, LC3-II, and LC3-I. Total protein was extracted from aortic tissue or human umbilical vein endothelial cells (HUVECs) using RIPA lysis buffer. Protein concentration was determined using a BCA protein quantification kit to ensure consistency in protein content across samples. Proteins were separated by SDS-PAGE and then transferred to a PVDF membrane. After blocking with 5% skim milk for 1 hour, the membrane was incubated overnight at 4°C with primary antibody. The membrane was then washed with TBST and the corresponding secondary antibody was added. After final washing, the membrane was developed using ECL chemiluminescence reagent (Bio-Rad, USA), and the protein signal intensity was analyzed using ImageJ software. Antibody specifications are detailed in Table 1.

[0030] Table 1 Antibody Information

[0031] In one embodiment, to investigate whether EMPZ has an anti-atherosclerotic effect, this study established an animal model of atherosclerosis by feeding ApoE knockout mice (HFD) for 8 consecutive weeks, followed by intraperitoneal injection of EMPZ at different doses. After 8 weeks of treatment, EMPZ caused weight loss in AS mice, with the high-dose group showing more significant weight loss. Figure 4 A). After euthanizing the mice, the thoracic and abdominal aortas were harvested for ORO and HE staining. Results showed that EMPZ significantly reduced the plaque area of ​​the entire aorta and aortic arch in a dose-dependent manner. Figure 4 B-4C). Serum analysis showed that EMPZ dose-dependently reduced total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels, while increasing high-density lipoprotein cholesterol (HDL-C). Figure 4 D). Furthermore, ELISA analysis showed that EMPZ reduced serum interleukin-1β (IL-1β), interleukin-6 (IL-6), and TNF-α levels in a dose-dependent manner. Figure 4 E). These results collectively confirm that EMPZ can effectively delay the progression of AS in mice, and its therapeutic effect is positively correlated with the dose.

[0032] AS lesion analysis: After euthanizing mice, the aorta was carefully dissected and perivascular fat was removed. The aorta was longitudinally cut and soaked in ORO solution (Beyotime, China) for 60 minutes. It was then differentiated in 60% isopropanol until no obvious red residue remained on the vessel wall. Photographs were taken to assess aortic plaque formation. The separated aortic arch tissue was embedded in OCT and sectioned using a cryostat. Sections were immersed in ORO solution for 15 minutes, rinsed with 60% ethanol, and stained with hematoxylin for 1 minute. After mounting, the sections were observed under a microscope (Olympus, Japan).

[0033] HE staining: After formaldehyde fixation, aortic tissue was dehydrated and then embedded in paraffin. After sectioning, the tissue was dewaxed and stained with HE solution (Servicebio, China). After dehydration and clearing, the samples were mounted and observed under a microscope.

[0034] Serum lipid level assay: Mouse blood samples were centrifuged at 3000 rpm for 10 minutes to separate serum. The concentrations of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in serum were determined using a commercial assay kit (Nanjing Jiancheng, China) according to the manufacturer's instructions.

[0035] ELISA detection of cytokine levels: The concentrations of cytokines in mouse serum and HUVEC culture supernatant were detected strictly according to the supplier's instructions using a commercial ELISA kit (Abcam, UK). These cytokine concentrations included interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α).

[0036] In another embodiment, the invention further investigated how EMPZ affects mitophagy in the aorta of AS mice. Dihydroethidium (DHE) staining showed that EMPZ significantly reduced reactive oxygen species (ROS) levels in the aortic arch tissue, with the reduction being greater at higher doses. Figure 5 Consistent with this, Western blot analysis showed that EMPZ increased the levels of the mitophagy-related proteins Pink1 and Parkin in a dose-dependent manner, as well as the LC3-II / LC3-I ratio (A-5B). Figure 5 These results collectively demonstrate that EMPZ alleviates oxidative stress by enhancing mitophagy in the aorta of AS mice.

[0037] Reactive oxygen species (ROS) level assessment: For tissue-level detection, frozen aortic arch sections (10 μm) were equilibrated with 200 μL of wash buffer for 3–5 minutes. Diethylhydroacetate (DHE; Beyotime, China) was diluted 1:200 with PBS. After removing the wash buffer, 150 μL of DHE staining solution was added, and the sections were incubated at 37°C in the dark for 40 minutes. After incubation, the sections were mounted and observed under a fluorescence microscope.

[0038] In a specific embodiment of this invention, since vascular endothelial cells (VECs) are a key component of the vascular system, and studies have shown that enhancing mitophagy in VECs can delay the progression of atherosclerosis (AS), this study continued to treat human umbilical vein endothelial cells (HUVECs) with oxidized low-density lipoprotein (oxLDL) to simulate an AS-like microenvironment in vitro. To inhibit mitophagy, 2.5 mM 3-methyladenine (3-MA) ​​was added to the cells 2 hours after oxLDL treatment to evaluate the regulatory effect of EMPZ on mitophagy in HUVECs. The optimal EMPZ concentration was first determined using the CCK-8 assay. The results showed that the cell death rate exceeded 50% after 24 hours of treatment with 50 μM EMPZ; therefore, subsequent experiments used 30 μM EMPZ. Figure 6 A). JC-1 staining showed that, compared with the oxLDL group, EMPZ significantly increased the mitochondrial membrane potential of HUVECs (A). Figure 6 B, 6E). DHE and MitoSOX Red staining results were consistent, indicating that EMPZ significantly reduced the levels of total intracellular reactive oxygen species (ROS) and mitochondrial ROS in HUVECs. Figure 6 C-6D, 6F-6G). Western blot analysis further confirmed that EMPZ significantly upregulated the expression of Pink1 and Parkin in HUVECs and increased the LC3-II / LC3-I ratio (C-6D, 6F-6G). Figure 6 In summary, these findings suggest that EMPZ can promote mitophagy in VECs in vitro, thereby improving mitochondrial function.

[0039] CCK-8 assay: Cells were seeded at a density of 1 × 10^5 cells per well in 96-well plates. After treatment, 10 μL of CCK-8 reagent (Beyotime, China) was added to each well at specified time intervals, and the plates were incubated in an incubator for 1.5 hours. Cell viability was then assessed by measuring absorbance at 450 nm using a microplate reader (BioTek, USA).

[0040] Mitochondrial membrane potential was measured: HUVECs from all experimental groups were collected and analyzed at 1 × 10⁻⁶ cells per well. 5Cells were seeded at a density of [number] cells per well in 6-well plates. JC-1 staining solution (Beyotime, China) was diluted 1:200. After cell attachment, 1 mL of diluted JC-1 staining solution was added to each well and mixed thoroughly. The culture plates were then incubated at 37°C for 20 minutes. After incubation, fluorescence intensity was detected using a fluorescence microscope (Leica, Germany).

[0041] Measurement of mitochondrial reactive oxygen species (ROS) levels: Human umbilical vein endothelial cells (HUVECs) were collected from each experimental group, and 1 × 10⁻⁶ cells were extracted per well. 5 Cells were seeded at a density in 6-well plates. After cell attachment, MitoSOX™ Red working solution (Invitrogen, USA) was added to a final concentration of 5 μM, and the cells were incubated at 37°C for 10 minutes. Images were then acquired using a fluorescence microscope.

[0042] In some embodiments, to assess whether EMPZ inhibits the progression of aortic atherosclerosis (AS) in mice by promoting mitophagy, this study administered intraperitoneal injections of 3-MA to AS mice. Western blot analysis showed that, compared with the HFD+EMPZ-H group, 3-MA treatment significantly reduced the expression levels of Pink1 and Parkin in the aortic arch tissue of mice and significantly decreased the LC3-II / LC3-I ratio. Figure 7 A). ORO and HE staining results showed that 3-MA significantly increased the plaque area throughout the aorta and aortic arch ( Figure 7 B-7C). Furthermore, 3-MA treatment significantly increased serum lipid levels and pro-inflammatory cytokine concentrations (B-7C). Figure 7 (D-7E). In summary, these results indicate that EMPZ improves the progression of atherosclerosis by promoting mitophagy. The expression levels of mitophagy-related proteins Pink1 and Parkin, as well as the LC3-II / LC3-I expression ratio, were significantly increased after EMPZ improved atherosclerosis.

[0043] 102: Data processing: The expression data of mitophagy-related proteins are input into the constructed empagliflozin evaluation model, which evaluates the therapeutic effect of empagliflozin on atherosclerosis based on the expression data of mitophagy-related proteins. In some embodiments of the present invention, the method for constructing the empagliflozin evaluation model is known to those skilled in the art, and the steps of associating the expression level of mitophagy-related proteins with a certain probability or risk can be implemented and realized in different ways.

[0044] In the context of this invention, the term "machine learning" refers to the use of computers to simulate or implement human learning activities, and technicians typically use various development tools to build machine learning algorithmic models. These development tools include, but are not limited to, TensorFlow, Scikit-Learn, PyTorch, OpenNN, RapidMiner, Azure Machine Learning, Apache Mahout, Shogun, KNIME, Vertex AI, H2Oai, Anaconda, Keras, Tableau, Fast.ai, Catalyst, Amazon ML, MLJAR, and Spell. The algorithmic models include, but are not limited to, linear regression models, logistic regression models, Lasso regression models, Ridge regression models, linear discriminant analysis models, nearest neighbor models, decision tree models, perceptron models, neural network models, support vector machine models, Naive Bayes models, AdaBoost models, GBDT models, XGBoost models, LightGBM models, CatBoost models, or random forest models.

[0045] 103: Output results.

[0046] Figure 2 This is a schematic diagram of the system structure provided by the present invention for evaluating the therapeutic effect of empagliflozin on atherosclerosis.

[0047] The system is programmed or otherwise configured to include a data acquisition unit 201, a data classification unit 202, and a result output unit 203. Data acquisition unit: used to acquire expression data of mitochondrial autophagy-related proteins in atherosclerotic patient samples after empagliflozin treatment, wherein the mitochondrial autophagy-related proteins include one or more of the following: cleaved Pink1, Parkin, LC3-II, LC3-I; Data classification unit: used to classify and predict whether empagliflozin is effective in treating patients with atherosclerosis by classifying the data obtained in the data acquisition unit through the empagliflozin evaluation model obtained by the construction method described in the first aspect of the present invention; Result output unit: Used to output the result to the receiving unit.

[0048] Furthermore, the receiving unit includes a display screen, a computer client, a mobile client, or a tablet.

[0049] The system may be a user's electronic device or a computer system remotely located relative to that electronic device.

[0050] Figure 3 A schematic diagram of the structure of the computer device provided by the present invention.

[0051] The computer device 300 includes a processor 301 and a memory 302 coupled to the processor 301. The memory 302 stores program instructions. When the program instructions are executed by the processor 301, the processor 301 performs the method described above for evaluating the therapeutic effect of empagliflozin on atherosclerosis.

[0052] The processor 301 can also be referred to as a CPU (Central Processing Unit). The processor 301 may be an integrated circuit chip with signal processing capabilities. The processor 301 can also be a general-purpose processor, a digital signal processor (DSP), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA), or other programmable logic devices, discrete gate or transistor logic devices, or discrete hardware components. A general-purpose processor can be a microprocessor or any conventional processor. The computer device 300 can be a mobile electronic device.

[0053] It should be understood that the systems, apparatuses, and methods described in this invention can be implemented in other ways. For example, the apparatus embodiments described above are merely illustrative; for instance, the division of modules is only a logical functional division, and in actual implementation, there may be other division methods. For example, multiple modules or components may be combined or integrated into another system, or some features may be ignored or not executed. Furthermore, the couplings or direct couplings or communication connections shown or discussed may be indirect couplings or communication connections between devices or modules through some interfaces, and may be electrical, mechanical, or other forms.

[0054] The modules described as separate components may or may not be physically separate. The components shown as modules may or may not be physical units; that is, they may be located in one place or distributed across multiple network units. Some or all of the units can be selected to achieve the purpose of this embodiment according to actual needs.

[0055] Furthermore, the functional modules in the various embodiments of the present invention can be integrated into one processing module, or each module can exist physically separately, or two or more modules can be integrated into one module. The integrated modules described above can be implemented in hardware or as software functional modules.

[0056] The above are merely embodiments of this application and do not limit the scope of this patent application. Any equivalent structural or procedural changes made using the content of this application's specification and drawings, or direct or indirect applications in other related technical fields, are similarly included within the scope of patent protection of this application.

Claims

1. A method for evaluating the therapeutic effect of empagliflozin on atherosclerosis, characterized in that, The method is performed by a computer and includes the following steps: Data Acquisition: Acquire expression data of mitochondrial autophagy-related proteins in atherosclerotic patient samples after empagliflozin treatment, wherein the mitochondrial autophagy-related proteins include one or more of the following: Pink1, Parkin, LC3-II, LC3-I; Data processing: The expression data of mitophagy-related proteins were input into the constructed empagliflozin evaluation model, which evaluated the therapeutic effect of empagliflozin on atherosclerosis based on the expression data of mitophagy-related proteins. Output results.

2. The method according to claim 1, characterized in that, The construction steps of the described empagliflozin evaluation model are as follows: Expression data of mitophagy-related proteins were obtained, including one or more of the following: Pink1, Parkin, LC3-II, and LC3-I. The expression data of mitophagy-related proteins were obtained from untreated atherosclerotic patients and atherosclerotic patients treated with empagliflozin. The expression data of mitophagy-related proteins were input into a machine learning algorithm to construct an empagliflozin evaluation model.

3. The method according to claim 1, characterized in that, The empagliflozin evaluation model obtains results using the following criteria: when the expression levels of any one or more of the mitophagy-related proteins Pink1, Parkin, and LC3-II / LC3-I are above a threshold, a classification result indicating that empagliflozin is effective in treating patients with atherosclerosis is obtained; when the expression levels of any one or more of the mitophagy-related proteins Pink1, Parkin, and LC3-II / LC3-I are below a threshold, a classification result indicating that empagliflozin is ineffective in treating patients with atherosclerosis is obtained.

4. The method according to claim 2, characterized in that, The machine learning algorithms include algorithmic models developed using various development tools.

5. The method according to claim 4, characterized in that, The development tools include, but are not limited to, TensorFlow, Scikit-Learn, PyTorch, OpenNN, RapidMiner, Azure Machine Learning, Apache Mahout, Shogun, KNIME, Vertex AI, H2Oai, Anaconda, Keras, Tableau, Fast.ai, Catalyst, Amazon ML, MLJAR, and Spell.

6. The method according to claim 4, characterized in that, The algorithm models include, but are not limited to, linear regression models, logistic regression models, Lasso regression models, Ridge regression models, linear discriminant analysis models, nearest neighbor models, decision tree models, perceptron models, neural network models, support vector machine models, Naive Bayes models, AdaBoost models, GBDT models, XGBoost models, LightGBM models, CatBoost models, and random forest models.

7. A system for evaluating the therapeutic effect of empagliflozin on atherosclerosis, characterized in that, The system includes: Data acquisition unit: used to acquire expression data of mitochondrial autophagy-related proteins in atherosclerotic patient samples after empagliflozin treatment, wherein the mitochondrial autophagy-related proteins include one or more of the following: Pink1, Parkin, LC3-II, LC3-I; Data classification unit: used to classify and predict whether empagliflozin is effective in treating patients with atherosclerosis by classifying the data obtained in the data acquisition unit through the empagliflozin evaluation model obtained by the construction method described in claim 2; Result output unit: Used to output the result to the receiving unit. Preferably, the receiving unit includes a display screen, a computer client, a mobile client, or a tablet.

8. A computer device, characterized in that, The device includes a memory and a processor, the memory being used to store program instructions; the processor being used to invoke the program instructions, and when the program instructions are executed, to implement the method for evaluating the therapeutic effect of empagliflozin on atherosclerosis as described in any one of claims 1-4.

9. A computer-readable storage medium having a computer program stored thereon, characterized in that, When the computer program is executed by a processor, it implements the method for evaluating the therapeutic effect of empagliflozin on atherosclerosis as described in any one of claims 1-4.

10. A computer program product comprising a computer program, characterized in that, When the computer program is executed by a processor, it implements the method for evaluating the therapeutic effect of empagliflozin on atherosclerosis as described in any one of claims 1-4.

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