468 results about "Immune microenvironment" patented technology

The invention provides a tumor detection data analysis method based on a peripheral blood immune marker, and belongs to the technical field of immunodetection.The tumor detection data analysis method comprises the steps that firstly, a peripheral blood sample of a patient is collected, and plasma and cell components are separated; analyzing various immune cell phenotypes by using flow cytometry; determining the concentration of key cell factors; analyzing the molecular expression level of the immune checkpoint; establishing an immune cell subset proportion empirical function; analyzing a cell factor expression mode by using an immune lineage transcriptome analysis model; establishing a tumor immune microenvironment score by combining the immune cell subset proportion and a model output result; the accuracy of the scoring system is verified through clinical follow-up visit and iconography examination; a standardized report template is formulated to provide a tumor early detection basis. Wherein the immune lineage transcriptome analytical model adopts a multi-modal attention fusion network architecture, three different immune data streams can be processed and integrated at the same time, and accurate evaluation of tumor-related immune states is realized.

The invention discloses a lung adenocarcinoma prognosis risk prediction model and a construction method and application thereof, and belongs to the technical field of biomedical detection. The lung adenocarcinoma (LUAD) prognosis model is successfully constructed by systematically analyzing the immune infiltration related gene (CAFRG) of tumor-associated fibroblasts (CAF), and the application value of the lung adenocarcinoma (LUAD) prognosis model in prediction of patient prognosis is verified. The CAFRG risk score is negatively related to the immune microenvironment score and is remarkably related to immune checkpoint gene expression, which suggests that a high-risk patient may have the characteristic of immune escape. Furthermore, based on TIDE tool analysis, the patients in the low-risk group have more active T cell immune response. The risk score is also closely related to the sensitivity of antitumor drugs, especially Doramapimod. Therefore, a new theoretical basis is provided for personalized treatment of lung adenocarcinoma, and a new direction is provided for future clinical research.

The method and system for evaluating the curative effect of hepatocellular carcinoma based on immune microenvironment characteristics are high in accuracy and reliability of evaluating the curative effect of hepatocellular carcinoma. The method comprises the following steps: (1) preparing a sample; (2) carrying out multiple immunohistochemical staining; (3) image acquisition and analysis; (4) analyzing spatial distribution characteristics; (5) multiplying the input image voxel signal numerical value by the weight vector of the convolution kernel, transmitting the multilayer convolution kernel, and finally obtaining a calculation result output by each network; and (6) establishing a prediction model: based on the spatial distribution characteristics and clinical characteristics of immune cells, constructing the prediction model by using the positive rate of CD8 + PD-L1 + and CD103 + CD8 + cells in the total area and the number of CD103 + cells within 30 microns around tumor cells so as to predict the immunotherapy curative effect of the HCC patient.

The invention belongs to the technical field of biotechnology and animal models, and discloses a double-person-derived mouse model for simulating a tumor immune microenvironment and a construction method and application thereof. The method comprises the following steps: firstly, pretreating NSG immunodeficient mice by adopting low-dose whole-body irradiation in combination with double-antibody targeted bone marrow depletion, and transplanting CD34 + hematopoietic stem cells from the same human donor to complete human immune system reconstruction; separating tumor primary cells, tumor-related fibroblasts and tumor vascular endothelial cells of the same donor, performing three-dimensional co-culture to obtain homologous human tumor organs, and performing in-situ inoculation to immune reconstruction mice to obtain a target model. The core defects of MHC mismatching, low immune reconstruction efficiency, poor tumor immune microenvironment simulation degree, low clinical consistency and the like of an existing model are overcome, and the method can be used for tumor immune treatment drug screening, microenvironment mechanism research and personalized tumor treatment scheme verification.

The invention relates to the technical field of medicines, in particular to a construction method and application of a photothermal conversion platform for treating osteoarthritis by regulating synovial macrophage polarization. According to the present invention, the M2 membrane-structured black phosphorus selenium carbon body (M2-BPSeC) photo-thermal nano-platform is innovatively provided, the triple functions of bionic targeting delivery, precise thermal control intervention and immune microenvironment remodeling are integrated, and the excellent synergistic treatment effect is represented in the in-vitro cell model and the OA animal model. The technology breaks through the technical bottleneck that traditional treatment is insufficient in targeting and single in intervention dimension, precise functional coupling of the physical thermal effect and immunoregulation is achieved for the first time, and a brand new strategy of targeting-temperature control-immunity integration is provided for osteoarthritis treatment. The efficient and controllable preparation process and the remarkable multi-dimensional treatment effect open up a new path for cartilage regeneration and immune balance regulation and control.

The invention discloses application of docosapentaenoic acid or medicinal salt thereof in preparation of a medicine for preventing and / or treating systemic lupus erythematosus. The invention aims to provide novel application of docosapentaenoic acid in treatment of systemic lupus erythematosus. In view of various immune abnormalities existing in the systemic lupus erythematosus morbidity process, the docosapentaenoic acid has potential application value in the field of systemic lupus erythematosus treatment due to the effects of regulating immune cell functions and improving immune microenvironment.

A hybrid liver cancer prognosis model, prognosis system and medium, the model takes independent influence factors as input and outputs hybrid liver cancer postoperative risk scores, the hybrid liver cancer postoperative risk scores are used for dividing risk levels, and the risk levels are used for hybrid liver cancer prognosis evaluation. And / or is used for postoperative adjuvant chemotherapy decision-making of mixed liver cancer. The hybrid liver cancer prognosis model is jointly constructed by combining the traditional clinical pathological characteristics and immune microenvironment indexes, the key effect of the tumor immune microenvironment in CHC prognosis is indicated, and the constructed hybrid liver cancer prognosis model has good CHC prognosis prediction performance; in addition, decisions of postoperative adjuvant chemotherapy can be provided for patients with different risk levels, precise treatment of the CHC patients is achieved, and long-term survival prognosis of the CHC patients is improved.

The invention relates to the technical field of biomedical materials, in particular to engineered small extracellular vesicle hydrogel enriched with PD-L1 and Siglec-15 as well as a preparation method and application of the engineered small extracellular vesicle hydrogel. The engineering small extracellular vesicle hydrogel is enriched with PD-L1 and Siglec-15 at the same time, the engineering small extracellular vesicle hydrogel comprises a hydrogel base body and PDL1-Siglec15-sEVs loaded in the hydrogel base body, and the PDL1-Siglec15-sEVs are small extracellular vesicles with the PD-L1 and the Siglec-15 in an overexpression mode. Compared with natural small extracellular vesicles and a traditional wound surface treatment strategy, the engineered small extracellular vesicle hydrogel has the advantages that PD-L1 and Siglec-15 can be enriched in the vesicles, so that more accurate immune microenvironment regulation and control can be realized on the local part of a wound surface, excessive inflammatory response is moderately inhibited, phenotype transformation of macrophages to be beneficial to tissue regeneration is promoted, and the wound surface treatment effect is improved. The hydrogel is used as a carrier and can provide a moist healing environment and a three-dimensional scaffold structure, so that the residence time of the engineered small extracellular vesicles on the local wound surface is remarkably prolonged, and slow release is realized.

The invention belongs to the technical field of high polymer material synthesis, and particularly relates to an artificial antioxidant enzyme material with an interlayer structure and a preparation method of the artificial antioxidant enzyme material. The preparation method of the artificial antioxidant enzyme material comprises the following steps: dissolving an aldehyde monomer and an amine monomer in a reaction solvent, performing thermal polymerization under the action of an acid catalyst, and then loading interlayer coordination metal, and further defining an aldehyde monomer and an amine monomer as well as an interlayer coordination metal. According to the present invention, the treatment-level oxidation resistance can be achieved through the space-optimized catalysis center and the fully-conjugated frame structure, and the innovative strategy is provided for solving the inflammation-driven tissue damage through the precise oxidation-reduction regulation and the immune microenvironment engineering.

The invention belongs to the technical field of biomedical materials, and particularly relates to application of a HAp-MXene nano composite material in regulation and control of an osteogenesis immune microenvironment. The HAp and MXene nanocomposite is obtained by combining hydroxyapatite nanorods and MXene nanosheets, the HAp and MXene nanocomposite is interfered by adjusting an external magnetic field, so that the HAp and MXene nanocomposite shows one effect of regulating and controlling polarization of macrophage M1 or macrophage M2; then, the HAp-MXene nanocomposite is implanted into a bone defect area, and in the initial stage of the operation, the magnetoelectric effect of MXene is excited by applying a rotating magnetic field, polarization of M1 type macrophages is promoted, proinflammatory factors are generated, and bacterial infection is inhibited; then, in the middle stage, through removing a magnetic field, releasing calcium ions, promoting polarization of the M2 type macrophages, relieving inflammatory response and promoting bone regeneration, programmed regulation and control of the macrophages are achieved in different repair stages.

The present invention relates to the technical field of tumor immune microenvironment detection and analysis, and discloses an apparatus and method for detecting and analyzing the immune microenvironment of solid tumors. The apparatus for detecting and analyzing the immune microenvironment of solid tumors includes: a detection mechanism: used to contact with a tumor sample or puncture a part of the tumor sample and upload data for operators to analyze; a transportation and cleaning mechanism integrating transportation, cleaning and adjustment functions: cleaning both sides of the sample synchronously during transportation and adapting to different sample sizes; a clamping and turning mechanism: clamping the sample and turning it to position to expose the cleaning surface; a collection component: detachably recovering the shed impurities; a wiping component: used to clean the detection area of the detection mechanism after detection to prevent residual substances from affecting subsequent detection results. The transportation and cleaning mechanism of the present invention can automatically clean the impurities outside the sample while transporting the tumor sample, and can also adjust according to samples of different sizes, improving the accuracy of subsequent detection.

The invention relates to the technical field of data management, and discloses a data management platform and management method for tumor immunoassay. The method comprises the following steps: performing standardized acquisition and preprocessing on multi-source tumor immune data to obtain a standardized data set; performing wavelet decomposition and dimension reduction processing on the standardized data set to obtain a dimension reduction feature set; performing cross-center data calibration on the dimension reduction feature set to obtain a calibrated merged data set; performing annotation expansion on the calibrated merged data set to obtain a complete annotation data set; and performing immune feature weight calculation and hierarchical data management according to the complete annotation data set, and generating a hierarchical tumor immune data management structure with differentiated storage priorities. The method is different from a traditional unified storage mode, the heterogeneity of the tumor immune microenvironment is considered, differentiated storage priorities are distributed according to the immune value of the sample, and the computing resource distribution and data access efficiency is optimized.

The invention belongs to the technical field of pharmaceutical preparations. The invention discloses a multifunctional bionic nano preparation, a preparation method and application. According to the multifunctional bionic nano preparation, the ginsenoside Rg3 has the dual functions of a medicine and a membrane stabilizer, the platelet membrane has the natural targeting capability on circulating tumor cells and metastases, and meanwhile, the cationic liposome is used for adsorbing negatively-charged NETs nucleic acid protein compounds, so that potential reversal and active targeting are achieved, and the multifunctional bionic nano preparation has a good application prospect. And by co-carrying paclitaxel (PTX) and a photothermal agent (PCP) and integrating photothermal-chemotherapy-immunogenic death (ICD) induction functions, the tumor-related fibroblast activation can be effectively inhibited, circulating tumor cells can be efficiently captured, a tumor immune microenvironment can be remodeled, the tumor cells can be effectively killed, and tumor distal metastasis can be inhibited.

The invention relates to the technical field of biological medicines, in particular to a CKAP4-targeted tumor antigen peptide, a vaccine and application of the CKAP4-targeted tumor antigen peptide. The invention provides a high-immunogenicity tumor antigen peptide RLTELTKSI targeting human and mouse homologous CKAP4 protein, and the tumor antigen peptide and a vaccine thereof can realize efficient killing of CKAP4 positive tumor cells and remarkable inhibition of CT26 subcutaneous tumor by activating specific CD8 + T cell immune response. The traditional single-target limitation is broken through, the co-expression characteristic of CKAP4 in tumor cells and immunosuppressive cells (TAM / TAN) is utilized, a double-target and double-channel mechanism is initiated, and the immunosuppressive state of cold tumors is effectively reversed by inducing T cells to synchronously kill tumor cells and remodel an immune microenvironment. According to the technology, CKAP4 is expanded from an antibody target to a T cell vaccine target, lasting specific CTL response can be stimulated, the off-target risk of antibody treatment is avoided, a universal treatment scheme can be provided for solid tumors, and the clinical transformation potential and the treatment broad spectrum are remarkably improved.

The invention provides a piezoelectric dressing for promoting nerve repair of a diabetic wound and a preparation method and application of the piezoelectric dressing, and belongs to the technical field of piezoelectric dressings. The preparation method comprises the following steps: firstly, respectively preparing a polymer solution and a conductive polymer dispersion liquid, then mixing the polymer solution and the conductive polymer dispersion liquid, carrying out secondary stirring to obtain an electrostatic spinning solution, and then carrying out electrostatic spinning and post-treatment in sequence to obtain the piezoelectric dressing for promoting neural restoration of the diabetic wound. By optimizing the ratio of the raw materials and cooperating with an electrostatic spinning process, triple functions of high-strength piezoelectric response, peripheral nerve repair and macrophage polarization regulation are realized, and the separation limitation of the prior art on nerve repair and immune microenvironment dynamic regulation is broken through; and an integrated solution of electrical stimulation, nerve regeneration, immune regulation and wound healing is provided for the diabetic wound.

The invention relates to a lung cancer organoid and peripheral blood source immune cell co-culture model and a construction method thereof. Specifically, the invention provides a construction method of a macrophage and tumor organoid co-culture model for evaluating anti-tumor activity, monocytes of autologous or allogeneic peripheral blood of a patient are induced and differentiated into high-purity macrophages in vitro, and the high-purity macrophages and lung cancer tumor organoid are subjected to three-dimensional co-culture in matrigel; the model aims at highly reducing a core interaction network of tumor cells and macrophages in TME; the dynamic change of the polarization state of the macrophage is simulated and observed; the problem that an organ-like model is incomplete due to immune component deficiency or spatial positioning distortion of an existing model is effectively solved, an experimental platform closer to the physiological state is provided for tumor immune microenvironment research, and therefore development of the tumor immune treatment field is promoted.

The invention discloses a myocardial ischemia reperfusion injury animal model construction method and application thereof in the technical field of model animal preparation. The method comprises the steps of hypertension and hyperlipidemia pretreatment, standardized ischemia-reperfusion operation, immune microenvironment regulation and control and model evaluation and verification. According to the invention, model construction is carried out on an integrated model operation table, so that a standardized ischemia-reperfusion process is realized, reproducibility of a myocardial injury degree and an immune cell infiltration rule of the model is realized, and suitability of the model and nano-drug research is enhanced; and a reliable tool is provided for research and development of targeted drugs such as immune cell membrane coated nanoparticles.

The invention relates to the technical field of solid tumor immunotherapy, in particular to an IL-2mRNA multichannel delivery method for solid tumor immunotherapy, which comprises the following steps: designing a DNA template, using a plasmid containing an IL-2 gene sequence such as human IL-2cDNA, adding a T7 promoter, a 5'untranslated region UTR and a 3 'UTR at two ends to enhance translation efficiency, carrying out in-vitro transcription through T7 RNA polymerase, and carrying out in-vitro transcription through T7 RNA polymerase. And adding a 5 '-end cap analogue such as CleanCapAG to realize co-transcription cap adding, and then preparing lipid nanoparticle LNP encapsulation and carrying out surface modification. According to the IL-2mRNA multi-channel delivery method for solid tumor immunotherapy, through multi-channel delivery design, targeting optimization and combined treatment cooperation, the toxicity problem of a traditional IL-2 therapy and the drug resistance of MHC-I defective tumors are remarkably solved, meanwhile, efficient conversion is achieved through existing equipment, IL-2 expression can be accurately regulated and controlled, the immune microenvironment can be remodeled, and the immunotherapy effect is good. Meanwhile, the system is compatible with various treatment means such as chemotherapy, radiotherapy and immune checkpoint inhibitors.

The invention discloses a carbon dot, hydrogel containing the carbon dot as well as a preparation method and application of the hydrogel, and relates to the technical field of carbon materials. The carbon dot is prepared from the following raw materials: a hydroxyl-containing flavonoid compound and epsilon-polylysine; the carbon dots contain aniline bonds formed by hydroxyl groups of the hydroxyl-containing flavonoid compounds and amino groups of the epsilon-polylysine. The carbon dot shows higher tumor cell killing property and lower normal cell toxicity than the raw material hydroxyl-containing flavonoid compound at the cellular level, can obviously induce immunogenic death of cancer cells and does not induce up-regulation of extracellular matrix collagen, and also has a better effect of regulating a tumor immune microenvironment.

The invention discloses a black phosphorus hydrogel microneedle patch loaded with trained mesenchymal stem cells as well as a preparation method and application of the black phosphorus hydrogel microneedle patch, and belongs to the technical field of biological medicines. The micro-needle patch comprises a hydrogel substrate layer loaded with black phosphorus nanosheets and a hydrogel needle tip part for packaging the stem cells. The mesenchymal stem cells are subjected to combined domestication with low oxygen and high active oxygen, so that the anti-oxidative stress, anti-inflammatory and angiogenesis promoting capabilities of the mesenchymal stem cells are remarkably enhanced. After the patch is subcutaneously delivered, the black phosphorus component can efficiently remove bacteria and reduce drug resistance; after being domesticated, the stem cells can adapt to the immune microenvironment of the wound surface, and the immune regulation, inflammation inhibition and tissue regeneration promotion are synergistically realized by continuously releasing anti-inflammatory and angiogenesis promoting factors, so that the refractory wound surface caused by immune disorders such as systemic lupus erythematosus (SLE) and the like is effectively treated. The invention provides an innovative treatment strategy for chronic inflammatory wound healing.

The invention discloses a brain glioma animal model construction method based on an AAV mediated immune microenvironment. The method comprises the following steps: selecting an immunodeficient mouse at the right age; human CD34 + hematopoietic stem cells are injected for immune system reconstruction; human CD45 + immune cells in the peripheral blood PBMC are detected; the method comprises the following steps: selecting tumor tissues with high-expression brain glioma marker genes, carrying out rapid qPCR (quantitative polymerase chain reaction) or targeted RNA-seq immunohistochemical multiple verification, and screening consistent tumor tissues; the method comprises the following steps: physically dicing tumor tissues, treating the tumor tissues with pretreatment liquid, digesting the tumor tissues into single-cell suspension, and inoculating the single-cell suspension into a mouse cranium; an AAV vector carrying a specific immune regulation gene is injected into the tail vein of the mouse, and the brain glioma immune microenvironment is regulated; when it is observed that the tumor tissue grows stably and has immune cell infiltration characteristics, construction of the brain glioma animal model is completed. Compared with an existing model, the brain glioma model which is more stable, more scientific and closer to the human immune background is provided, and the brain glioma model is suitable for related immunotherapy drug screening and mechanism research.

The invention discloses a clostridium praeparatum vesicle targeting inflammatory bowel disease tissues as well as preparation and application of the clostridium praeparatum vesicle. The vesicle is secreted by clostridium praeparatum ATCC27766, and the average particle size of the vesicle is 100-250 nm. Experimental data show that the vesicles have intestinal disease site targeting, can effectively remodel the intestinal immune microenvironment of ulcerative colitis patients, and inhibit the inflammation process through chemotactic factor secretion of macrophages. The clostridium praeparatum vesicle and the preparation can effectively overcome the defect that clostridium praeparatum and butyrate secreted by the clostridium praeparatum are prone to failure, the treatment means of ulcerative colitis are enriched, and the application prospect of anaerobic probiotics is widened.

The invention relates to a Chinese herbal medicine vesicle-loaded temperature-sensitive hydrogel for regulating immunity and a preparation method thereof, and belongs to the technical field of biological medicines. The raw materials are wide in source, methacrylated gelatin (GelMA) has good biocompatibility, poly (N-isopropylacrylamide) (PNIPAM) and GelMA hydrogel are combined, meanwhile, lycium barbarum leaf source extracellular vesicle-like particles (LBL-EVLPs) are introduced, certain thermal responsiveness is achieved, the local immune microenvironment can be adjusted, and oxidative stress reaction can be effectively relieved. The temperature-sensitive hydrogel loaded with the Chinese herbal medicine vesicles provided by the invention has multiple effects of promoting tissue repair, removing reactive oxygen species (ROS), regulating immunity and the like, and has the advantages of simple preparation, low cost and the like.

The present invention relates to a complex comprising a polysaccharide conjugate, an anti-PD-L1 monoclonal antibody, and a PKM2 inhibitor. The complex of the present invention can accumulate and remain in tumor tissue, effectively stimulate dendritic cell maturation, alleviate the inhibitory immune microenvironment, and trigger a specific anti-tumor immune response. It can effectively inhibit the expression of PKM2, thereby inhibiting glycolysis in tumor tissue and providing a more favorable environment for T lymphocytes to infiltrate tumor tissue. The complex of the present invention is expected to enhance the therapeutic effect of RFA on patients with advanced HCC by reprogramming iRFA-induced tumor immunosuppression, and has great potential in improving the prognosis of patients with advanced HCC treated with RFA.

The present invention relates to a method for identifying immune-related microorganisms in colorectal cancer based on multi-omics features, and belongs to the field of biomedicine technology. The method includes analyzing the diversity and composition of intestinal flora in colorectal cancer patients and healthy controls; identifying intestinal microorganisms significantly associated with patients through the LASSO algorithm; selecting characteristic intestinal microorganisms of colorectal cancer by the SVM-RFE method; obtaining overlapping genes between the two algorithms, and incorporating the overlapping genes into ROC and DCA analysis verification; the method includes screening key microorganisms for immune regulation, predictive analysis of immune-related intestinal microbial functions, analysis of immune-related microorganisms and immune microenvironment, and prediction of the mechanism of action of immune-related intestinal microorganisms; the method of the present invention can screen out key microorganisms with immune regulatory effects in colorectal cancer, laying the foundation for studying the mechanism of action of intestinal flora and formulating personalized precision medication plans.

The invention provides a model for predicting lung adenocarcinoma prognosis and immunotherapy response based on copper death related LncRNAs, and belongs to the technical field of bioinformatics. According to the prediction model provided by the invention, the accuracy and the stability of prognosis judgment of a lung adenocarcinoma patient can be remarkably improved, and the defects of a traditional staging system in the aspects of reflecting tumor heterogeneity and individual treatment reaction difference are effectively overcome; the model not only can realize reliable individual risk grading, but also can further evaluate the tumor immune microenvironment state and predict the potential reaction of a patient to immunotherapy, so that a powerful auxiliary tool is provided for clinically formulating an accurate treatment strategy, in particular to the application decision of an immune checkpoint inhibitor; and finally, the method has important practical application value for improving treatment selection and life quality of patients.

The invention relates to antioxidant sonodynamic hydrogel as well as a preparation method and application thereof, the yield and sonodynamic performance of ROS (reactive oxygen species) can be improved, and the prepared hydrogel can realize efficient antibiosis in the early stage of infection, exert antioxidant and repair promoting effects in the later stage of infection, and can promote angiogenesis and collagen deposition, optimize inflammation and immune microenvironment, improve the immunity of the ROS and improve the ROS yield and the sonodynamic performance of the ROS. The dynamic balance of antibiosis, antioxidation and healing promotion is realized, and the treatment effect is comprehensively improved.

The invention provides an allosteric nanogel adjuvant as well as a preparation method and application thereof, and belongs to the technical field of vaccines. The allosteric nanogel adjuvant comprises a self-assembly motif, a responsive site and an immunomodulatory peptide fragment, and the self-assembly motif is composed of 2-5 amino acids; the allosteric nanogel adjuvant has a structure as shown in a formula I, and is named as NTP5 for short; the allosteric nanogel adjuvant is self-assembled into nanoparticles, the nanoparticles are allosteric into a nanofiber structure through responsive broken bonds, nanogel is further formed, and the key problems of a traditional vaccine in the aspects of antigen delivery and immune activation are effectively solved. The nanogel adjuvant can efficiently load various antigens to form a stable nano vaccine, activate an immune microenvironment and provide more means and thoughts for vaccine development.

The invention relates to the technical field of biological medicines, and particularly discloses an application of Dehydrovomigol sensitized bevacizumab in treatment of cervical cancer. The invention further relates to a preparation method of the Dehydrovomigol sensitized bevacizumab. Compared with a bevacizumab single drug, the effect of the bevacizumab on growth and proliferation inhibition, invasion blocking and angiogenesis inhibition of cervical cancer cells can be remarkably enhanced by combining the Dehydrovomifolol, and the drug resistance of the bevacizumab is reversed. In different experimental models, the Q value of the combination scheme is greater than or equal to 1.15, and the stable synergistic anti-cervical cancer effect is shown. Dehydrovomifolol realizes the effect of enhancing the anti-cervical cancer activity of the bevacizumab by virtue of triple mechanisms of reversing drug resistance, enhancing anti-angiogenesis and regulating an immune microenvironment. According to the combination scheme, the anti-cervical cancer curative effect can be improved, the clinical medication dosage of bevacizumab is reduced, the occurrence risk of toxic and side effects such as hypertension and proteinuria is reduced, and a novel, safe and efficient treatment strategy is provided for cervical cancer treatment.

The invention relates to a co-culture microsphere model with a core-shell structure and a preparation method of the co-culture microsphere model. The co-culture microsphere model comprises a core-shell microsphere, the core-shell microsphere is composed of an inner core and an outer shell, the inner core is an organoid loaded by matrigel, the outer shell is formed by crosslinking a photo-crosslinking hydrogel material, co-culture cells are doped in the photo-crosslinking hydrogel material, and the inner core is wrapped by the outer shell. According to the co-culture microsphere model, double-layer structure microspheres of co-culture cell wrapped organoids are formed, immune infiltration and in-vivo characteristics can be simulated, and a similar in-vivo three-dimensional tumor immune microenvironment is provided. And the types of cells loaded on the inner layer and the outer layer can be flexibly replaced to form a microsphere model for co-culture of single or multiple cells and organoids. The co-culture microsphere model is more stable in structure, the size of the diameter of the core-shell microsphere can be optimized by changing 3D printing parameters, the operability of subsequent research is high, and the co-culture microsphere model is suitable for different research application scenes.