| ObjectiveChronic atrophic gastritis(CAG)is a common clinical digestive system disease,and intestinal metaplasia or(and)dysplasia associated with chronic atrophic gastritis is called gastric precancerous lesions(PLGC).Because gastric cancer has the characteristics of high incidence,low survival rate,late discovery,etc.,precancerous lesions of gastric cancer is an important intermediate link in the development of intestinal gastric cancer.Early and effective intervention at this stage is crucial for preventing the occurrence of gastric cancer development.Western medicine's treatment of this disease is mainly focused on symptomatic and causative treatment,including eradication of Helicobacter pylori,anti-biliary reflux,antioxidant,folic acid,and COX-2 inhibitors.There is no specific intervention.Under the guidance of the holistic view and the theory of dialectical theory,Chinese medicine has shown a bright future.Domestic and foreign studies have found that Chinese medicine has played a unique role in delaying,blocking and even reversing PLGC,and has gradually become a research hotspot.Based on the pathogenesis characteristics of PLGC and long-term clinical experience,the group summarized the intervention of PLGC using the regulating qi,activating blood and detoxifying method,and concluded in previous clinical studies that the method is indeed effective in the treatment of PLGC,but its specific molecular mechanism is still unclear.Therefore,this subject intends to conduct research from two parts:clinical efficacy and molecular mechanism:the clinical efficacy part,which is intended to clarify the clinical efficacy of the treatment of PLGC by the method of syndrome,gastroscopy,and histopathology;in the molecular mechanism part,it is planned to use the network pharmacology technology and multi-color immunofluorescence technology to explore the mechanism of regulating qi,activating blood and detoxifying method intervening the precancerous lesions of chronic atrophic gastritis.MethodThis study consists of a literature review,clinical efficacy studies and molecular mechanism studies.The literature review is divided into the following two parts:"Progress in Traditional Chinese Medicine Research on Precancerous Lesions of Chronic Atrophic Gastritis",which discusses the disease name,etiology,pathogenesis characteristics,typing treatment,and treatment characteristics of modern physicians;The part of "Progress in Western Medicine Research on Precancerous Lesions of Chronic Atrophic Gastritis" mainly focuses on the epidemiology,etiology,treatment methods and pathogenesis of the diseaseIn the clinical efficacy research section,30 patients with precancerous lesions of chronic atrophic gastritis of liver and stomach stagnation,qi deficiency and blood stasis type were collected in the outpatient clinic of Dongzhimen Hospital.Interventions were performed using the method of regulating qi,activating blood and detoxifying,and comparing the clinical symptoms and gastroscopy of patients pathological manifestations,trying to explore the clinical efficacy of regulating qi,activating blood and detoxifying method of chronic atrophic gastritis precancerous lesions.For the molecular mechanism,firstly use the network pharmacology technology to initially explore the mechanism of the regulating qi and activating blood and detoxifying method intervening the precancerous lesions of chronic atrophic gastritis,and then use the regulating qi,activating blood and detoxifying method to intervene 30 cases of chronic atrophic gastritis of liver and stomach stagnation,qi deficiency and blood stasis.For patients with precancerous lesions,the levels of PI3K,AKT,Bcl-2,P53,ERBB4,and PTEN on PI3K/AKT pathway key molecules before and after treatment was detected by multi-color immunofluorescence technology.Trying to explore the treatment of chronic atrophic gastritis Molecular mechanisms of precancerous lesions.Results(1)In general,30 patients were included in this study.The oldest was 68 years old and the youngest was 35 years old.The average age was 53.93±7.87,including 19 males and 11 females.There was no statistical difference in age distribution by sex(P>0.05);there were many with education levels below the undergraduate level,of which 21 were in high school,accounting for 70.00%;the consultation season is mostly winter(46.67%)and autumn(40.00%);Anxiety(63.33%),irritability(60.00%),and nervousness(43.33%)are more common in the emotional factors that induce the disease.Most Patients' eating habits are oily(70.00%),sweet(60%).and Spicy(40.00%);in daily life and rest,more regular(46.67%)than stay up late(40.00%)and fatigue(30.00%)patients;in the history of tobacco and alcohol,more patients smoking(43.33%)and drinking(36.67%)(2)The clinical efficacy is mainly evaluated from the clinical symptom score and histopathological scoreUsing Nimodipine method to calculate the clinical symptom score,2 cases were cured(6.67%),5 cases were markedly effective(16.67%),19 cases were effective(63.33%),4 cases were ineffective(13.33%),and the total effective rate was 86.67%.And the difference of total symptom score,major symptom score and minor symptom score of patients before and after treatment had significant statistical significance(P<0.01).In addition,the scores before and after the treatment of each symptom were counted,and the symptoms of gastric congestion,upset and irritability,acid reflux,heartburn,mouth pain,dry mouth,belching,weight burnout,mental fatigue,poor appetite,shortness of breath,and thin stools were obtained.The difference in scores before and after treatment was statistically significant(P<0.01).The differences in scores before and after treatment of gastric pain and lazyness were statistically significant(P<0.05).There was no significant difference in scores before and after treatment of noisy stomach and dry stool symptoms(P>0.05).Statistical analysis of the pathological histological scores of patients before and after treatment showed that the differences in total pathological scores of patients before and after treatment were significantly statistically significant(P<0.01),and the four pathological manifestations of atrophy,intestinalization,dysplasia and chronic inflammation had differences in points before and after treatment.The differences had statistical significance(P<0.05)(3)Molecular mechanism research results include network pharmacology results and multi-color immunofluorescence detection results of key molecules on the PI3K/AKT pathway.A total of 858 compounds were collected from the network pharmacology results.Using OB? 30%and DL? 0.18 as the screening conditions,a total of 83 candidate compounds with good oral availability and drug-like properties were obtained;the compound-target network had 41 hubs of which 11 compounds have greater than or equal to 35 targets,13 targets can interact with greater than or equal to 20 compounds;target-disease network has 54 nodes,including 31 targets and 23 diseases;GO enrichment analysis was performed on the targets corresponding to the six herbs in Shenbai Granules,and 324 GO entries were identified.KEGG pathway enrichment analysis was performed on some of the up-regulated differential genes,and 24 KEGG pathway information were obtained according to FDR<0.01.Multicolor immunofluorescence detection of key molecules in the gastric tissue PI3K/AKT pathway before and after treatment in 30 patients showed that the optical density difference of PI3K before and after treatment was significantly statistically significant(P<0.01).The optical density difference of AKT and Bcl-2 before and after treatment was statistically significant(P<0.05),and there was no significant difference in optical density of ERBB4,P53 and PTEN before and after treatment(P>0.05).Conclusion(1)In general,from the analysis of gender and age,the disease is more common in middle-aged and elderly people aged 45-65,and the incidence is higher in men.Moreover,the incidence of patients is related to season,diet and mood.Among them,the medical season is mostly winter and autumn.The anxiety,irritability,and nervousness had a greater impact.Most patients preferred oily,sweet,spicy and cold food,and the history of tobacco and alcohol is also one of the important influencing factors of the disease.(2)The use of self-contrast clinical trials has shown that the clinical symptoms and histopathological manifestations of patients have been significantly improved before and after treatment.Therefore,it can be found that regulating qi,activating blood and detoxifying method have a clear clinical effect on precancerous lesions of chronic atrophic gastritis.(3)The results of network pharmacology found that 17 pathways such as apoptosis,P53,ERBB4,and cancer pathways are related to the PI3K/AKT pathway.It is speculated that the intervention of Shenbai Granules in precancerous lesions of chronic atrophic gastritis may pass PI3K/AKT pathway.Further observing the intervention of regulating qi,activating blood and detoxifying method on PI3K/AKT pathway key molecules PI3K,AKT,Bcl-2,ERBB4,P53,and PTEN in precancerous lesions of chronic atrophic gastritis.It was found that the method of regulating qi,activating blood and detoxifying can down-regulate the expression levels of PI3K,AKT and Bcl-2,so the treatment of chronic atrophic gastritis precancerous lesions may play a role by inducing apoptosis and inhibiting cell proliferation,thereby affecting the development of cancer. |
PDF Full Text Request