| Purpose:At present,the radical surgery and western chemotherapy with partial or partial gastrectomy mostly are the standard treatments for the gastric cancer patients,under this condition,it is an important clinical research whether traditional Chinese Medicine can make the gastric cancer patients’ quality of life and survival period benefit by reconstructing the Zhongqi,dispelling the pathogenic substance such as phlegm,blood stasis and cancer toxin,protecting and/or loading western chemotherapy.Oncology Department of Affiliated Hospital of Liaoning University of traditional Chinese Medicine proposed the treatment method of "reconstruction of Zhongqi,anti-cancer and detoxification" and established"Reconstruction of Zhongqi Anti-cancer Decoction",and a large number of clinical practices have been carried out under the guidance of the hypothesis of relative unity of physique and spirit.Which was based on the theory of body and spirit in traditional Chinese Medicine.Therefore,under the guidance of the theory of physique and spirit,this study mainly observed the changes of physique and spirit in different stages of gastric cancer patients in order to master whole process changes of gastric cancer,tried to revise the negative effects of chemotherapy of physique and spirit,and evaluated the clinical effect of Reconstruction of Zhongqi Anti-cancer Decoction on gastric cancer patients through the method of clinical study;finally tried to explain part of mechanism of Zhongqi Anti-cancer Decoction on gastric cancer through the method of research methods of network pharmacology and cell experimental research.Material and method:1In the first part of study,prospective single center study was used to observe the patients who are diagnosed gastric cancer in the oncology ward and outpatient department of Affiliated Hospital of Liaoning University of traditional Chinese Medicine,the visit time was selected from January 2018 to October 2019,and the syndrome differentiation of patients must be mainly spleen and stomach deficiency.All the patients were treated with Reconstruction of Zhongqi Anti-cancer Decoction of traditional Chinese Medicine,every patient of each group was treated with corresponding western medicine according to treatment requirements,such as postoperative adjuvant chemotherapy,palliative chemotherapy,symptomatic support treatment,and so on.According to the stage of the patients disease and the treatment method,the included patients were divided into 9 groups:group of before the adjuvant chemotherapy,group of adjuvant chemotherapy,group of after radical operation,group after radical treatment(more than 6 months after the end of adjuvant chemotherapy),group of before palliative chemotherapy,group of palliative chemotherapy,group of after Palliative chemotherapy(more than 1 month after palliative chemotherapy),group of traditional Chinese medicine treatment,group of hospice care(Within 3 months before death).the physique and spirit injury scale of patients was developed according to the corresponding physique and spirit characteristics of gastric cancer patients,we mainly observed the general baseline characteristics including patients age,gender,western medicine treatment,the physique and spirit damage characteristics of different periods of disease and the application of anti-tumor Chinese herbs,summarized laws of anti-tumor Chinese herbs;according to the corresponding evaluation criteria,we also evaluated the effect of Reconstruction of Zhongqi Anticancer Decoction on improving the spirit damage of patients,which should be used as a preliminary exploration for the follow-up promotion,comprehensive treatment affected the effect of positive transfer between treatment groups.2In the second part of this study,using TCMSP database to screen and predict the active components of Reconstruction of Zhongqi Anticancer Decoction,then using genecards and other databases to screen gastric cancer possible targets,and then potential targets were obtained by fusing the screened drug components targets with disease targets,intersection of drug components targets and disease targets after screening.Through GO analysis and KEGG pathway analysis of common protein,we intended to infer the possible molecular mechanism of Reconstruction of Zhongqi Anticancer Decoction in the treatment of gastric cancer 3In the third part of this study,Wistar rats were randomly divided into control group,Reconstruction of Zhongqi Anticancer Decoction low dose group,medium dose group,high dose group and 5-FU group to prepare drug serum.CCK8 method was used to determine the inhibition rate of serum containing drugs on SGC7901 cell proliferation;and Transwell cell invasion test was used to detect the cell invasion ability of serum containing drugs on SGC7901 cells;gradient PCR and Western blot were used to detect the HH signal expression through factors SMO,PTCH1,Glil gene and protein influences separatelyResult:1The first part of this study included 173 patients in total,and age of patients ranged from30 to 88 years old,and included 115 males and 58 females,with a ratio of 1.98:1.Among 9 groups,the most cases were group after radical treatment of 43 cases,39 cases in group of traditional Chinese medicine treatment,and at least 2 cases in group of before palliative chemotherapy.In terms of chemotherapy program,group of adjuvant chemotherapy was mainly combined chemotherapy,while the group of palliative chemotherapy was mainly single chemotherapy1.1 The characteristics of physique and spirit damage in the initial treatmentPhysique and spirit score:the group of hospice care had the most severe physique and spirit injuries,with a score of 19 points,significantly higher than that in the group of palliative chemotherapy(with the points of 5.7),and there was a statistical difference between them.and the group of traditional Chinese medicine treatment(with the points of 8.8,p<0.05),The symptom score of spirit damage was 15 points,which was higher than other groups.with the lowest score of spirit damage in group after radical treatment,with statistical significance compared with the group of after radical operation.The research results showed that there was a positive correlation between physique and spirit damage and the progression of gastric cancer patients,while the treatment of traditional Chinese Medicine had a protective effect on physique and spirit damage of gastric cancer patients,and the treatment of traditional Chinese Medicine was beneficial to the rehabilitation treatment of the patients returning to society and family,and lived a normal lifeWeight:the lowest group was group of hospice care,indicating that weight loss might be one of the markers of gastric cancer progression;and the weight in the group of adjuvant chemotherapy was the highest,group of after Palliative chemotherapy was lower than that in group of palliative chemotherapy,and there was a statistical difference between them.It is suggested that Fuzheng as the main traditional Chinese herbs may counteract some side effects of western chemotherapy;the weight of group after radical treatment was slightly higher than that in the group of after radical operation,It is suggested that Reconstruction of Zhongqi Anticancer Decoction can ultimately maintain or increase the weight of gastric cancer patients after radical gastrectomyKamosky performance status score:the highest score was in the group after radical treatment,compared with that in the group of after radical operation,there was a statistical difference between them.The score in group of adjuvant chemotherapy was significantly higher than that in the group of palliative chemotherapy,there was a statistical difference between them,group of after Palliative chemotherapy was lower than that in group of palliative chemotherapy,there was a statistical difference between them.It also showed that Kamosky performance status score is related to the disease stage of gastric cancer patients traditional Chinese medicine can counteract the negative effect of western chemotherapy on Kamosky performance status score and maintain or improve the activity ability of gastric cancer survivors1.2 application of anti-tumor/exorcism traditional Chinese medicineThere was no significant difference between the group after radical treatment and group of traditional Chinese medicine treatment,both of them are more than 8 anti-tumor traditional Chinese herbs,In the application of pangolin and Sagittarius,the group of traditional Chinese medicine treatment was significantly higher than that in the group after radical treatment,but there was no statistical significance in the use of Fritillaria thunbergii and Curcuma.It showed that both of them are treated by TCM alone,but the group of traditional Chinese medicine treatment was the gastric cancer patients with tumor in their bodies,so the intensity of exorcism should be maximized the gastric cancer patients could accept as much as possibleThere were more than 6 traditional Chinese herbs in group of after radical operation,compared with that in the group after radical treatment,and there was a significant difference between them,the application of Zhebeimu and Ezhu in the group after radical treatment was significantly higher than that in group of after radical operation,but there was no significant difference in the application of oyster and Trichosanthes;It is suggested that after gastric cancer operation and adjuvant chemotherapy,the use of traditional Chinese herbs should be strengthened gradually in process of Reconstruction of Zhongqi Anticancer DecoctionThere were 7.6 traditional Chinese herbs in the group of palliative chemotherapy,the application of pangolin in group of traditional Chinese medicine treatment was significantly higher than that in the group of palliative chemotherapy,and there was a significant difference between them;but there was no significant difference in the application of Zhebeimu and Ezhu,Shancigu.It was suggested that exorcism herbs should be maximized in patients with gastric cancer,but exorcism should be reduced in palliative chemotherapy gastric cancer patients.1.3Evaluation curative effect of Reconstruction of Zhongqi Anticancer DecoctionFirstly,the disease control rate of the group of palliative chemotherapy was higher than that in the group of after Palliative chemotherapy and the group of traditional Chinese medicine treatment,but there was no statistical difference between them;in the comparison of tumor markers,the markers were in the normal range after treatment in the group after radical treatment,and there was a slight decrease after treatment.CEA and CA72-4 in the group of adjuvant chemotherapy and group of palliative chemotherapy decreased significantly after treatment,CA19-9 in group of adjuvant chemotherapy decreased significantly after treatment,and there was no significant difference between the two groups;CEA and CA72-4 in group of palliative chemotherapy and group of traditional Chinese medicine treatment decreased slightly after treatment,but there was no significant difference between the two groups;CA19-9 in group of palliative chemotherapy and group of traditional Chinese medicine treatment increased after treatment,considering the cause of disease progression.It showed that the effect of Reconstruction of Zhongqi Anti cancer Decoction combined with chemotherapy is better than that of single use of adjuvant chemotherapyIn the aspect of the evaluation of the spirit effect,the patients in group of adjuvant chemotherapy and the group of palliative chemotherapy had a slight increase in symptom scores,and there was a slight decrease in weight and Kamosky performance status compared with the before treatment,maybe it mainly due to the impairment of spleen and stomach function and the decline in functional state caused by the patients undergoing western medicine chemotherapy.After treatment,the symptom scores in the group after radical treatment and the group of traditional Chinese medicine treatment decreased significantly,and the spleen and stomach function of the patients were improved by reconstruction of Zhongqi,and the body weight was basically maintained at the original level.That is to say,traditional Chinese medicine has a stronger effect on the correction of spirit injury and the maintenance of the external performance of life activities,and it can be inversely related to the degree of physical injury when the disease progresses1.4 neutrophil to lymphocyte ratio and migration changesBefore the treatment,neutrophil to lymphocyte ratio in the group of palliative chemotherapy and the group of traditional Chinese medicine treatment was significantly higher than that in the group of adjuvant chemotherapy and the group after radical treatment And it is considered to be related to the late stage of primary mass existence,distant metastasis and disease.The neutrophil to lymphocyte ratio decreased slightly in the treatment of traditional Chinese Medicine alone,but it decreased significantly in combination with chemotherapy.From one side,the importance of Reconstruction of Zhongqi Anticancer Decoction combined with palliative chemotherapy in the treatment of gastric cancer was explained.On the other hand,it also shows the important role of reconstruction in the treatment of gastric cancerIn the aspect of migration,by the end of the follow-up time of the study,132 of 173 patients did not have treatment group migration and they all received current treatment plan And the results showed that the Reconstruction of Zhongqi Anticancer Decoction improved the patients’ physical and mental injury to a certain extent.For 41 patients with treatment group migration,except 12 patients in the group of traditional Chinese medicine treatment entered into the group of hospice care,and end with death.the other treatment group migration was positive ending:normal treatment sequence migration;Under the guidance of the theory of physique and spirit,after evaluating the patient’s mental injury,it can be restored by Reconstruction of Zhongqi Anticancer Decoction,improving the functional state and enabling the patients to carry out western medicine anti-tumor treatment;nearly half of the patients have completed the prescribed chemotherapy scheme and cycle;Chemotherapy(including adjuvant/palliative)should be carried out and the proportion of patients who are receiving chemotherapy is more than 90%2 in the second part of this study,220 effective components and 1095 targets Reconstruction of Zhongqi Anticancer Decoction were obtained through query and screening in total,and the PPI network of the first 2014 disease related targets related to gastric cancer was constructed,107 targets obtained by intersection in all.According to GO analysis of common points,the information of biological process of Reconstruction of Zhongqi Anticancer Decoction includes:steroid mediated signal pathway,MAPK activation,carbon metabolism process,serine end opeptidase activity,steroid receptor activity,cell solute,and so on;then analyzing the common protein in "pathway in cancer",it showed that there were 56 gene pathways related to the target of Reconstruction of Zhongqi Anticancer Decoction,including 12 gastric cancer related pathways.The target proteins in the pathway in cancer pathway were analyzed MAPK signaling pathways,HH signaling pathways and PI3K-Akt signaling pathways were involved in the forefront of the pathways3 in the third part of this study,SGC7901 cell was treated with different concentrations of serum containing medicine:low dose group,middle dose group and high dose group.The results showed that:with the increase of concentration,the inhibition rate of cell proliferation was more and more obvious,and there was a significant difference between the experimental groups,the inhibition rate of proliferation was the most significant in high dose group;as for the number of membrane penetrating cells,the number of membrane penetrating cells in the experimental groups was significantly reduced,compared with the control group,with statistical differences,the high concentration group was significantly lower than the middle and low concentration group,with statistical differences.Compared with the control group,the mRNA expression of SMO,PTCH1 and Glil in different concentration groups was significantly down regulated,with statistical difference;the gene expression in high concentration group was significantly lower than that in medium and low concentration group,with statistical significance;Compared with the control group,the protein expression of SMO,PTCH1 and Glil in different concentration groups was significantly down regulated,with statistical difference;the protein expression in high concentration group was significantly lower than that in medium and low concentration group,with statistical significanceConclusion:1 gastric cancer grows in the stomach,and the cost of radical treatment is to remove part or most of the stomach organs.For the treatment of this kind of patients’ Zhongqi injury,the Reconstruction of Zhongqi Anticancer Decoction firstly proves that it has the function of reconstructing Zhongqi and maintaining the function of spleen and stomach by keeping or recovering the weight,and then Reconstruction of Zhongqi Anticancer Decoction maintains the life activities of patients2Chemotherapy,including that adjuvant chemotherapy for cancer free patients and palliative chemotherapy for cancer patients,is the main treatment for gastric cancer.In particular,the extensive use of oral chemotherapy drugs increases the time for patients to contact with chemotherapy drugs.When Reconstruction of Zhongqi Anticancer Decoction to treat gastric cancer under the guidance of the theory of physique and spirit,according to the presence or absence of tumor,the presence or intensity of chemotherapy(adjuvant chemotherapy or palliative chemotherapy),the stage of disease and the damage of physique and spirit of patients,and so on.To determine the reasonable proportion of Fuzheng traditional Chinese herbs and Exorcism traditional Chinese herbs in the prescription,the number and strength of the herbs,and the adjustment of the proportion of Fuzheng and Exorcism herbs with the change of the patients’ condition and chemotherapy plan,etc.,the results showed that Reconstruction of Zhongqi Anticancer Decoction can make some patients meet the requirements of chemotherapy,and the symptom score of chemotherapy patients does not increase significantly,it makes patients who are in need of chemotherapy can complete the chemotherapy cycle on time and smoothly,and partially reduce the level of tumor markers and neutrophil to lymphocyte ratio in vivo,and as much as possibly control the patients with tumor the disease progress.reconstruction of Qi therapy should run through the treatment of gastric cancer3 According to the network pharmacological research on the treatment of gastric cancer by Reconstruction of Zhongqi Anticancer Decoction,Reconstruction of Zhongqi Anti cancer Decoction may be possible to intervene gastric cancer through multi-channel and multi-target,and its pharmacological mechanism may play an anti-tumor role with the influence of HH signaling pathways、MAPK signaling pathways、PI3K-AKT signaling pathways and other channels.And experimental studies have proved that Reconstruction of Zhongqi Anticancer Decoction with different concentrations of serum can inhibit the proliferation and invasion of gastric cancer SGC-7901 cells,with the increase of concentration,the difference is more and more significant.And it can down regulate the expression of SMO,Gli-1,PTCH1 gene and protein in HH signal pathway4.Under theory of physique and spirit of traditional Chinese Medicine,the application of Reconstruction of Zhongqi Anticancer Decoction can improve the quality of patients’life and it could make the comprehensive treatment of gastric cancer go on smoothly and orderly according to the treatment plan.the research between Reconstruction of Zhongqi anticancer Decoction and its relationship with survival are in progress. |
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