Glioma, also known as glioma, is a tumor that occurs in the neuroectodermal tissue. Among the tumors of neuroepithelial tissue, the incidence of glioma (glioma for short) accounts for about 50%, and in China, it accounts for 33.3% to 58.9% of intracranial tumors, with an average of 43.5%. Gliomas are tumors originating from glial cells, including astrocytic tumors, oligodendroglial cell tumors, mixed glial cell tumors, and ventriculomembranous tumors.Kleihues and Cavenee [1], in the WHO classification of nervous system tumors published in 2000, further divided these four types of tumors into 20 different types and subtypes: their growth sites, pathomorphology, Their growth sites, pathological patterns, molecular biology, biological behaviors (grades I-IV), imaging, therapeutic countermeasures and outcomes are also different. Currently, gliomas are incurable, and only 5.5% of patients diagnosed with glioblastoma nationwide in the United States in 1980 survived for more than 5 years. After more than 20 years of exploration and development, the treatment of glioma has made great progress, but the average survival of glioma patients is still less than 1 year. Therefore, glioma is one of the most challenging tumors in neurosurgery. Wei Lin, Department of Neurosurgery, Qianfoshan Hospital, Shandong Province, China 1 Biological characteristics, treatment difficulties and development trend of gliomas The infiltrative growth pattern of gliomas determines their malignant biological behavior. Tumor invasiveness is a complex process of interaction between tumor cells and host and extracellular matrix. Multiple growth factors are involved in the hyperproliferative and invasive behavior of glioma cells. The hyperproliferative and invasive behavior of gliomas is a major challenge in the treatment of gliomas today, and has been likened to the ability of gliomas to effectively “evade” surgical, radiotherapy, chemotherapy, and immunotherapy regimens, resulting in the eventual incurable death of the patient [2]. Currently, microsurgery can only achieve visual resection, and many glioma cells with “root-like” growth infiltrate into normal brain tissue, which becomes the root cause of the inability of total resection; radiotherapy has a large side effect, and myelosuppression is common; the toxicity reaction of chemotherapy and “multidrug resistance” cannot be solved yet. The toxic reaction of chemotherapy and “multi-drug resistance” cannot be solved yet. Gene therapy for gliomas is the most interesting research field in recent years. 2 Surgery Surgery is still the most effective treatment method at present, which aims to clarify the diagnosis, improve the symptoms, reduce the tumor load and create conditions for further treatment. With the wide application and improvement of microsurgery and laser, ultrasound attraction and navigation systems, tumors that were previously considered inoperable can now be surgically resected. In particular, the application of intraoperative magnetic resonance and navigation systems has greatly improved the rate of total surgical resection while reducing the risk of surgery. Intraoperative magnetic resonance can measure the size of the resected area, and functional neuronavigation systems can show the location of the surgical field and prevent the addition of needless neurological function damage [3]. In order to further improve the therapeutic effect of glioma, omaya reservoir capsules can be placed in the capsular cavity after resection of the tumor, and chemotherapeutic drugs can be injected into the capsular cavity intraoperatively and postoperatively to improve the killing effect on tumor cells and prolong the patient’s survival [4, 5]. At present, we have applied this technology to clinical research, has achieved preliminary results, the long-term therapeutic effect remains to be further observed. 3 Radiation therapy In recent years, radiation therapy, the main progress is focused on the application and selection of radiation sensitizer, the improvement of radiation dose, radiation field and time interval. Most gliomas are not sensitive to radiation, so the application of sensitizers to improve the effect of radiation can improve the killing effect of radiation on tumor cells. Radiosensitizers are substances in ionizing radiation that enhance the biological effect. It is clinically used to enhance the killing ability of rays on tumors and has great application value in radiation therapy of tumors. At present, commonly used sensitizers include nitroimidazoles and biological reducing agents. Nitroimidazoles, such as Misonidazole, SR-2508, R0-03-8799 and other radiosensitizers, can selectively enhance the sensitivity of hypoxic cells to rays, and increase the effect of radiation therapy by 30% to 70% compared with that of radiotherapy alone [6]. The application of gamma knife therapy is effective for tumors that cannot be completely resected and for recurrent tumors. It has been reported that for grade II astrocytoma, the local tumor control rate of gamma knife reaches 70% to 93% [7]. Brachytherapy (radioactive particle implantation)[8] 125I implanted in the tumor bed can prevent recurrence of glioma.Femandez et al. reported that 58 cases of malignant gliomas with permanent implantation of 125I in the tumor bed had a median survival of more than 30 months, and the reoperation rate was only 45%.Patel et al. treated 40 recurrent glioblastomas with surgery plus permanent implantation of 125I in the tumor bed, with a dosage of 120-160 Gy. Actual survival from implantation was 47 weeks, with 7 cases still alive at 59 weeks. None of the cases developed symptoms attributable to radiation necrosis or injury. 4 Chemotherapy Chemotherapy is an important part of the treatment of gliomas. Surgery or (and) radiotherapy has resulted in better outcomes for some gliomas, however, most tumors also inevitably recur. Chemotherapy plays an important role in further killing residual tumor cells. There are many regimens of chemotherapy for glioma, but the main drugs used are still single or combined drugs with nitrosoureas as the main body. The commonly used programs in Europe and America are: PCV program (lomustine, methylbenzylhydrazine, vincristine), which is mainly used for highly malignant astrocytoma, oligodendroglioma, glioblastoma multiforme, and mesenchymal astrocytoma; BC program (cisplatin, BCNU), which is mainly used for highly malignant astrocytoma; and single-administration of cyclophosphamide or cisplatin, which is of good effect for medulloblastoma; For recurrent disease, a combination of drugs is used, such as EC regimen (VP-16+carboplatin); MeCCNU+Vm-26 is mainly used for low-grade malignant glioma, and vincristine and cisplatin have also been applied to treat low-grade malignant glioma. For different types of tumors, there should be some differences in the chemotherapeutic agents chosen; medulloblastoma, especially those with recurrence or disseminated implants, choose PCV regimen, brainstem glioma with CCNU or BCNU alone can also be combined with PCZ or VCR ventricular meningioma responds significantly to BCNU. Compared with radiotherapy, the therapeutic effect of chemotherapy on brain glioma is not ideal, and its role in increasing the survival time of patients is not as significant as that of radiotherapy. There are at least 2 reasons for the unsatisfactory effect of chemotherapy on glioma: (1) the existence of blood brain barrier (BBB) affects the entry of anti-tumor drugs into the brain; (2) a considerable portion of tumors are resistant to anticancer drugs. 5 Photodynamic therapy Photodynamic therapy (PDT) is a kind of treatment method for malignant tumors developed in the 1970s, and it has been known by various names, including photo-therapy, photochemotherapy, photo-irradiation therapy and phototherapy. ), light irradiation therapy (photoradiationtheyapy). Its basic principle is that the body ingests and stores a considerable dose of photosensitizer, and then irradiates the tumor site with a certain wavelength light source to activate the photosensitizer, produce a photochemical reaction, damage the multicellular targets, and intervene in the proliferation of tumor cells and tissues to achieve therapeutic goals [9].PDT is applicable to many different types of malignant tumors, and is particularly effective in controlling local growth. Effective, in theory, PDT has a special therapeutic effect on brain tumors, especially gliomas, which is due to the high uptake of photosensitizer by brain tumor cells. The Royal Melbourne Hospital in Australia used PDT to treat 116 cases of gliomas, including highly malignant glioblastoma multiforme. 36 cases of glioblastoma multiforme had a median survival of 24 months, and 50% of the patients survived for more than 2 years, 39 cases of recurrent glioblastoma multiforme had a median survival of 10 months, and 37% survived for more than 2 years, while 100 cases of glioblastoma multiforme, which were used as controls, had a median survival of 10 months, and 37% of them survived for more than 2 years. Glioblastoma multiforme had a median survival of only 8 months, and none survived for more than 3 years. 6 Biological therapy Tumor biological therapy is known as the 4th tumor treatment method after the 3 major conventional therapies of surgery, radiotherapy and chemotherapy, which is mainly used to achieve the effect of inhibiting tumor growth by mobilizing the body’s own natural defense mechanism or giving certain substances to the organism [10]. Biological therapy mainly includes: cytokines, hematopoietic immune cells, monoclonal antibodies, gene guides and vaccines, etc., of which immunotherapy and gene therapy and the combination of the two constitute the main part of tumor biological therapy. 6.1 Immunotherapy, including active immunization and tumor vaccination, injection of immune ribonucleic acid into lymph nodes and application of immunomodulators such as levamisole, etc., has been applied in clinic, which can reduce the reaction of radiotherapy and chemotherapy and enhance the immunity of the organism. At present, immunotherapy for glioma mainly focuses on the following aspects: 6.1.1 Tumor cell vaccine: applying irradiated or virus-infected tumor cells or their lysis products as immunogens to study their therapeutic effects on the tumor-bearing organisms, the remission rate is very low due to the weak immunogenicity of the tumor cells. troillas et al. used autologous tumor cell extracts and Fuchs’ adjuvant as the vaccine components, and 65 cases were treated. malignant astrocytomas were randomized into 4 groups and given radiotherapy, vaccine, radiotherapy plus vaccine, and supportive care, respectively. 24 of 28 patients who received the vaccine developed delayed hypersensitivity reactions, and the mean survival in the radiotherapy plus vaccine group was 10.1 months, compared with only 7.5 months in the radiotherapy group. However, most of the other trials of autologous or allogeneic tumor cell vaccines for glioma treatment during the same period were poor. 6.1.2 Dendritic cell-based tumor vaccines [11]: Siejo et al. were the first to report the results of animal experiments on dendritic cell DC vaccines for brain tumors, in which they used B16 glioma cell-sensitized autologous DC to immunize tumor-bearing rats to regress intracranial tumors. Subsequently, some studies have reported that DC vaccines sensitized with brain tumor RNA, antigenic peptides or tumor cell extracts have achieved better therapeutic results in ruffed-tumor animals. 6.1.3 Cytokine therapy: Cytokine therapy is a non-specific immunotherapy method, in which cytokines are given systemically or locally to exert their direct anti-tumor effects or anti-tumor immunomodulation. Cytokines used in glioma immunotherapy mainly include interferons, interleukins and tumor necrosis factors. 6.2 Gene therapy Gene therapy has been used in the treatment of glioma [12]. By applying a vector retrovirus with relative specificity for tumors, the gene expressing scar simplex virus type I thymidine kinase (HSVtk) is introduced into glioma cells, and then the prodrug pentacyclic guanosine (GCV) is given. In the presence of HSVtk, GCV is converted to its triphosphate, which kills the tumor cells through direct toxicity and a “bystander effect.” In 1992, Culver et al. assembled murine cells with a retrovirus (VPC) expressing the HSVtk gene, implanted them into experimental brain tumors, and then administered GCV, which caused the tumors to decrease in size. The result caused the tumor to become smaller. 1997 Ram et al. tested 15 cases of recurrent primary or metastatic brain tumors, applying the stereotactic method, implanting murine VPCs into the tumor enhancement area shown by MRI, and after 7d, injecting GCV intravenously every day for a total of 2 weeks, which showed that the tumor enhancement area was reduced by more than 50% in 5 out of 19 lesions, and the response was maintained for 1 to 3 months. There was a case of 47-year-old male recurrent glioblastoma multiforme who showed complete response after treatment, and MRI examination showed complete disappearance of the tumor after 1 year, and recurrence was still seen at the end after 5 years. 7 Combined treatment of western and eastern medicine As a traditional Chinese medicine, arsenic trioxide has been recognized worldwide for its role in the treatment of hematological diseases. Scholars in China have found that arsenic trioxide can inhibit the growth of glioma by inducing apoptosis of glioma cells, capturing glioma cells in the G2/M phase, and increasing the expression of p53 protein, among other multifaceted mechanisms [13, 14, 15]. Wang et al [16] made a controlled observation on the efficacy of traditional Chinese medicine identification + chemotherapy in the treatment of malignant brain tumors and the efficacy of conventional radiotherapy. Among them, the control group was treated with conventional radiotherapy or chemotherapy, and 38 cases in the treatment group were treated with VM-26+MeCCNU chemotherapy combined with traditional Chinese medicine identification, using Liuwei Di Huang Tang to tonify the kidneys, together with Tao Hong Si Wu Tang to activate blood and transform pang. Results The total effective rate (CR+PR) of the treatment group was 76.3%, including 91.6% for glioma, which was significantly different from 33.3% in the radiotherapy-only group. Most of the patients can achieve the purpose of “increasing the effect” and “reducing the toxicity” through traditional Chinese medicine. Zhou Yuxin et al [17] studied the inhibitory effect of Lei Gongteng monomer on glioma cells in vitro. Their method was to determine the in vitro inhibitory effects of three regnantine monomers (metanephrines, erythroxins and Wilforol A) on glioma cell lines SHG44, C6 and 251U by MTT; and to observe the changes of bax and bcl-2 protein expression in SHG44 glioma cells after the application of regnantine metanephrines and regnantine erythroxins by immunohistochemistry. RESULTS: The dicotyledonous monomers of rhamnogonin had extremely obvious inhibitory effects on glioma cells; the monomers of tricotyledonin and rhamnogonin had the second most inhibitory effects. Both increased bax expression and decreased bcl-2 expression in SHG44 cells. CONCLUSION: Radix et Rhizoma Triptolide and Radix et Rhizoma Erythrorhizoma have obvious inhibitory effects on glioma cells, and their effects are related to the promotion of bax expression, inhibition of bcl-2 expression, and leading to cell apoptosis. 8 Other therapies Warm heat therapy. Research shows that the sensitivity of tumor cells to heat is higher than that of normal cells, and the blood circulation of tumor tissues is poor, the blood flow is slow or even stagnant, so the heat dissipation is slower, and the temperature inside the tumor can be higher than that of normal tissues by 5℃～9.5℃ when subjected to heat. Under the high heat state, the fine meningeal membrane is destroyed and the nucleus coagulates, resulting in cell death. The decomposition products of necrotic cells can stimulate the immune function of human body, and the tumor after thermotherapy can increase the sensitivity to radiotherapy and chemotherapy. Therefore, it is said that thermotherapy is the “5th therapy” for malignant tumors. The effective temperature for destroying tumor cells is 41℃～43℃, and brain tumors are suitable for local heating, specific methods include radio frequency, ultrasound, microwave and so on. In conclusion, any one of these methods cannot completely cure glioma. Neurosurgeons must not be satisfied with the removal of the tumor to complete the task. Surgery is only the beginning of treatment, and it is necessary to apply multiple methods of comprehensive treatment in stages according to the relevant knowledge of tumor biology, cell dynamics, radiotherapy, pharmacology and immunology, etc., so as to obtain better therapeutic effect.