| Glioma is a tumor that originates from glial cells.It is the most common brain malignant tumor.WHO divides gliomas into grades Ⅰ-Ⅳ,grades Ⅰ and Ⅱ are low-grade gliomas,and grades Ⅲ and Ⅳ are high-grade gliomas.From the pathological classification point of view,common high-grade gliomas include anaplastic astrocytoma,anaplastic oligodendrocytoma.anaplastic oligodendroblastoma,and glioblastoma.In recent years,gliomas have been increasing year by year.Especially in the elderly,the incidence rate in men is higher than that in women.Glioma usually has a chronic onset,usually manifested as symptoms of increased intracranial pressure such as dizziness,headache,nausea and vomiting,vision changes,and mental symptoms.At the same time,the compression and invasion of intracranial tumors can cause partial neurological deficits and seizures.Wait.At present,the treatment of glioma is based on surgery,combined with radiotherapy,chemotherapy and other comprehensive treatment modes.After comprehensive western medicine treatment,patients face two main problems.One is that high-grade gliomas are prone to recurrence.There is currently no effective means to prevent recurrence.At the same time,there is a lack of effective treatment methods after recurrence,which seriously affects the survival of patients after recurrence.The second is that the patient will be left with nerve damage after treatment,which will seriously affect the quality of life of the patient.Therefore,the study of traditional Chinese medicine has great practical significance in preventing recurrence and improving symptoms.For the understanding of glioma,Chinese medicine believes that under the condition of the deficiency of righteous qi,wind,phlegm,blood stasis,and toxins are treated together with multiple pathological factors.The Huatan Sanyu Xiaoliu Decoction adopts the methods of dispelling wind and phlegm,dispersing blood stasis and detoxification to eliminate tumors to eliminate wind and phlegm,fight toxins and dispel lumps.Under the guidance of Chinese medicine theory,this study uses Huatan Sanyu Xiaoliu Decoction as the treatment drug to design clinical clinics And experiment to verify the efficacy and explore possible mechanisms.1 ObjectiveThrough clinical observation of Huatan Sanyu Xiaoliu Decoction combined with chemotherapy and chemotherapy alone for high-grade glioma patients after radiotherapy,the DFS,OS,quality of life.Karnofsky score,TCM syndromes,and TCM syndromes of the two groups of patients were objectively evaluated.The improvement of the stroke scale is used to evaluate the clinical efficacy.At the same time,the specific tumor-inhibiting effect of Huatan Sanyu Xiaoliu Recipe on human glioma cell U87 was explored through animal experiments,and the tumor tissue vascular endothelial growth factor and related autophagy were further detected.The expression of factors,analysis of possible ways of Huatan Sanyu Xiaoliu Recipe inhibiting U87 cells.2 Method2.]Clinical research method:According to certain diagnosis,inclusion,and exclusion criteria,patients with high-grade glioma who were treated at Guang’anmen Hospital,Tiantan Hospital,and Youanmen Hospital from January 2019 to December 2019 after postoperative radiotherapy were selected and followed up to In December 2021,excluding cases of dropout and loss to follow-up,32 patients finally enrolled in Guang’anmen Hospital were the experimental group,and 31 patients enrolled in Tiantan Hospital and Youanmen Hospital were the control group.The experimental group was treated with Huatan Sanyu Xiaoliu Decoction for 24 weeks on the basis of Western medicine standard treatment.The control group was treated with Western medicine standard chemotherapy for 24 weeks.Evaluate the patient’s disease-free survival and overall survival,and evaluate the patient’s quality of life,the improvement of TCM syndromes and neurological function according to the QLQ-BN20 scale,KPS score,NIHSS scale,and TCM syndrome score,and check blood routine,Liver and kidney function to assess adverse reactions.2.2 Experimental research method:A total of 40 nude mouse tumor-bearing animal models were inoculated with human glioma cells U87.The 40 nude mice were randomly divided into model group,control group,low,medium,and high-dose Chinese medicine groups and There are 8 groups in the low,medium,and high-dose Chinese medicine combined chemotherapy group,with 5 animals in each group.The model group was given deionized water,the control group was given temozolomide solution,the 3 groups of Chinese medicine were given different doses of Huatan Sanyu Xiaoliu Recipe solution,and the 3 groups of Chinese medicine combined with chemotherapy groups were given different doses of Huatan Sanyu The tumor solution combined with temozolomide solution was given by intragastric administration.After 21 days of administration,the mice were sacrificed.and the tumor masses of each group of mice were taken and weighed;HE staining to observe the morphological and structural changes of the internal organs of the heart.liver,spleen,lung,and kidney;Western blot Detect the expression of VEGF.LC3.and P62 related proteins.3 Result3.1 Clinical observation results3.1.1 Baseline conditions:two groups of age baseline,gender baseline,tumor site baseline,pathological type baseline,radiotherapy technology,radiotherapy dose baseline,surgery based on radiotherapy start time baseline and quality of life before treatment QLQ-BN20 score,Karfel score.Chinese medicine Baseline comparison of syndrome scores and National Institutes of Health Stroke Scale(NIHSS)scores.Statistics showed that the baselines of each group were consistent,and the difference was not statistically significant(P>0.05).3.1.2 Efficacy evaluation:disease-free survival(DFS),the experimental group Huatan Sanyu Xiaoliu Decoction combined with chemotherapy can prolong the median disease-free survival compared with the control group(13.56 vs 10.00 months,P=0.007<0.05),there is a statistical difference,indicating that Huatan Sanyu Xiaoliu Decoction combined with chemotherapy can effectively prolong the disease-free survival of patients with high-grade glioma after radiotherapy.The Karnofsky score was improved after treatment in both groups.The test group score was 88.44±11.11,and the control group score was 79.68±1.64,P<0.001.There was a statistical difference,which proved that Huatan Sanyu Xiaoliu Decoction can improve the life of patients quality.The scores of TCM syndromes were improved in both groups after treatment.The scores of the test group were 10.31±0.34.and the control group was 12.65±0.49.P<0.001.which was statistically different.The results showed that the prescription of Huatan Sanyu Xiaoliu can be Improve TCM syndromes and relieve patients’ symptoms.Overall survival(OS),statistics of the overall survival of the two groups of patients,the median OS test group compared with the control group(20.59VS18.23 months.P=0.130>0.05),there was no statistical difference.The quality of life measurement scale QLQ-BN20 situation.the two groups of patients were improved after treatment,the test group score 28.75±1.34,the control group score 30.94±1.53,P=0.287>0.05,there is no statistical difference.NIHSS scores,the scores of the two groups were improved after treatment,the test group score was 2.38±0.19,and the control group was 2.77±0.18,P=0.136>0.05.there was no statistical difference.No serious adverse reactions occurred during the treatment of Huatan Sanyu Xiaoliu Recipe,which is safe and effective.3.2 Experimental research results3.2.1 After successful modeling,the nude mice were sacrificed for 21 consecutive days of administration,and the tumor masses of each group were taken,weighed,and the difference of tumor weight in each group was counted.By measuring the tumor weight data,we can get the comparison model group,the control group,the high-dose Chinese medicine group,the low-,medium-,and high-dose Chinese medicine combined chemotherapy group,the tumor weight was significantly reduced(P<0.05,P<0.001),so it can be seen that Huatan San Yu Xiaoliu Recipe can control the growth of human glioma cells U87 in nude mice.HE staining was used to observe the cell morphology and structure of heart,liver,spleen,lung and kidney tissues.Compared with the model group,there was no obvious damage,indicating that traditional Chinese medicine and traditional Chinese medicine combined with temozolomide are safe.3.2.2 Take each group of tumor tissues for WB detection,compared with the model group,the control group,Chinese medicine medium and high-dose group,chemotherapy combined Chinese medicine medium and high-dose group.VEGF expression was significantly reduced(P<0.001).suggesting Chinese medicine and Chinese medicine Combination chemotherapy can inhibit the expression of VEGF.which is one of the mechanisms of action of Huatan Sanyu Xiaoliu Decoction in the treatment of high-grade gliomas.3.2.3 After 21 days of administration to nude mice in each group,the ratio of tumor tissue to autophagy-related protein LC3-Ⅱ/LC3-Ⅰ and the relative expression of P62 protein were detected by WB.Compared with the model group,the control group and the Chinese medicine dose LC3-Ⅱ/LC3-Ⅰ was significantly increased in the low.medium,and high-dose groups of chemotherapy combined with Chinese medicine(P<0.00]),and LC3-Ⅱ/LC3-Ⅰ was significantly reduced in the low and high-dose groups of Chinese medicine(P<0.001);Compared with the model group,P62 in the control group,Chinese medicine medium dose group and chemotherapy combined with Chinese medicine low,medium and high dose groups increased significantly(P<0.001),and P62 in the low and high dose groups of Chinese medicine decreased significantly(P<0.001),p62 The increase in the level is often accompanied by the activation of autophagy.The mechanism believes that p62 is a stress protein.Under certain conditions,such as chemotherapy or traditional Chinese medicine,the expression level of p62 can be stimulated to increase.The regulation of this process is Transcription factor EB.Based on the regulation effect of P62,this experiment can see that compared with the model group,P62 in the control group,the Chinese medicine medium dose group,and the low,medium and high dose combination chemotherapy group of Chinese medicine is significantly increased,and it can play an anti-tumor effect.It is to reduce the nutrient supply of the tumor while regulating the tumor microenvironment so that the tumor cells cannot adapt to the state of lack of nutrients and inhibit tumor growth.The second is that the treatment of drugs leads to the activation of autophagy,thereby inhibiting the tumor.In this experiment,compared with the model group,LC3-Ⅱ/LC3-Ⅰ in the control group,Chinese medicine medium dose group and chemotherapy combined with Chinese medicine low,medium and high dose groups were significantly increased,indicating that the mechanism may increase the level of autophagy.Inhibit the role of tumors.4 Conclusion4.1 Clinical observation:For patients with high-grade glioma after postoperative radiotherapy,observe the comparison of Huatan Sanyu Xiaoliu Decoction combined with chemotherapy and chemotherapy alone.The disease-free survival,overall survival,quality of life,TCM syndromes,and neurological function of patients are observed Observe the degree of defect.Results Huatan Sanyu Xiaoliu Decoction combined with chemotherapy can prolong the disease-free survival of patients,improve the quality of life of patients,and reduce related symptoms.It is safe and effective.4.2 Experimental study:Huatan Sanyu Xiaoliu Recipe can control the growth of human glioma cells U87 in nude mice,and its possible mechanism is to inhibit the expression of VEGF to achieve the anti-angiogenesis effect,and Huatan Sanyu Xiaoliu Recipe The activation of autophagy can be achieved through the regulation of P62,LC3-Ⅱ/LC3Ⅰ to inhibit tumor growth. |
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