| BackgroundChina is a region with a high incidence of gastric cancer,with a 5-year survival rate of over 90%for early gastric cancer(EGC),while patients with gastric cancer in China are often at a middle or advanced stage when diagnosed clinically,with poor outcomes.Therefore,the prevention of gastric cancer needs to move forward and actively monitor and intervene in gastric precancerous lesions(GPL)and precancerous diseases,thereby effectively reducing the incidence and mortality of gastric cancer in China.Patients with gastric precancerous lesions have atypical or even asymptomatic clinical symptoms,which is characterized by insidious onset,complex pathogenesis and long-term persistence,and some patients also suffer from anxiety,tension and fear of cancer.Modern medicine has no consensus on the effective treatment of precancerous lesions in the stomach,while the long-standing theory of spleen and stomach and the theory of "treating the disease before it happens in TCM are unique in treating precancerous lesions in the stomach.The etiology and pathogenesis of GPL have been discussed by Chinese medicine scholars for many generations,and it is believed that the disease is mainly related to external evil offending the stomach,improper diet,emotional and mental disorders,and deficiency of the spleen and stomach.In this study,based on the core pathogenesis of GPL,we set up Moluodan+sanqi powder as Jianpi-Huoxue principle to evaluate its curative effect and safety on GPL and explore the possible mechanisms of its efficacy.ObjectiveTo observe the curative effect and safety and to explore the efficacy mechanism of Moluodan+sanqi powder in the treatment of GPL.Methods1.Research designRandomized controlled,double-blind,double-dummy clinical study was carried out.2.Research objectA total of 60 patients with pathologically confirmed mild to moderate dysplasia and Spleen Deficiency and Blood Stasis Syndrome who attended the outpatient or inpatient departments of Xiyuan Hospital between June 2019 and July 2021 were randomly allocated to the Moluodan+sanqi powder group or the Folic acid group for treatment in a 2:1 ratio,numbered sequentially according to the time of enrolment.There were 40 patients in the Moluodan+sanqi powder group and 20 patients in the Folic acid group.3.Therapeutic methodMoluodan+sanqi powder group:Moluodan 16 capsules/time,3 times/day with warm water before meals;Sanqi powder 3g/time,2 times/day with warm water before mealsand placebo tablet of folic acid 5mg/time,3 times/day,half an hour after meals.The course of treatment is 6 months.Folic acid group:placebo pills for Moluodan 16 capsules/dose,3 times/day with warm water before meals;placebo powder for sanqi 3g/dose,2 times/day with warm water before meals and folic acid tablet 5mg,3 times/day,half an hour after meals.The course of treatment is 6 months.4.Observation indicatorsPrimary Outcome indicators:①Disappearance rate of LGD/IFND②Response rate of pathological lesions③Change in histological scoreSecondary Outcome indicators:①Changes of Endoscopic Findings②Change in symptom scores ③Disappearance rate of symptoms④Change in PRO Instrument Score5.Safety observation indicatorsRoutine blood,urine,liver and kidney function and electrocardiogram.6.Preliminary mechanism exploration test indexesCompare the changes of CD68 and CD45 immunohistochemistry scores before and after treatment in Moluodan+Sanqi powder group and folic acid group.CD68 marked macrophages and CD45 marked lymphocytes.Results1.Baseline informationThe actual number of subjects included in this clinic was 60,40 patients were included in the Moluodan+sanqi powder group and 20 patients were included in the Folic acid group.There were 32 males(53.33%)and 28 females(46.67%).The mean age was 57.4±11.10 years,with the oldest age being 75 years and the youngest 28 years.Two pathologically confirmed LGD/IFND lesions were found in 4 of the 60 subjects,making a total of 65 lesions.These lesions were predominantly mild Dys(78.5%),with the most common lesion sites being the gastric antrum(40%),followed by the gastric incisura,body,pylorus and cardia.Baseline data such as gender,height,weight and BMI were not statistically significantly different between the two groups(P>0.05)and were comparable.2.Primary Outcome(1)Disappearance rate of LGD/IFNDThe disappearance rate of LGD/IFND rate was 42.4%in the Moluodan+sanqi powder group and 26.3%in the folic acid group,with no statistically significant difference between the groups.(2)Response rate of pathological lesionsThe Response rate of dysplasia,atrophy,intestinal metaplasia,chronic inflammation,and active inflammation were 48.5%,63.7%,39.4%,21.2%,and 42.4%in the Moluodan+sanqi powder group and 31.6%,42.1%,36.9%,15.8%,and 26.3%in the Folic acid group,respectively,with no statistically significant difference between the two groups.(3)Change in histological scorePatients in the Moluodan+sanqi powder group(P<0.001)and the Folic acid group(P=0.014)had significantly lower LGD/IFND scores,with no statistically significant difference between the group.Atrophy score(P=0.001)was significantly lower in patients in the Moluodan+sanqi powder group after six months of medication,while atrophy score was not significantly lower in patients in the folic acid group,but the difference between the two groups was not statistically significant.There was no statistically significant difference between the two groups in the scores for intestinal metaplasia,chronic inflammation and active inflammation.3.Secondary Outcomes(1)Changes of Endoscopic FindingsPatients in the Moluodan+sanqi powder group had significantly lower total endoscopic scores compared to baseline(P<0.001),but not in the folic acid group with a significant difference between groups(P=0.012).Also,patients in the Moluodan+sanqi powder group had significantly lower scores in mucosal color(P<0.001),mucosal texture(P<0.001)and erosion(P=0.003)as endoscopic manifestations,while patients in the folic acid group had significantly lower scores in mucosal color(P=0.003)only,with no significant difference between the two groups.(2)Change in symptom scoresThere was a statistically significant improvement in the scores of epigastric pain,epigastric fullness,epigastric congestion,heartburn,acid reflux,belching,nausea,decreased food intake,no hunger,abdominal pain,bloating,dry mouth,bitter mouth,bad breath,fatigue and poor sleep in the Moluodan+sanqi powder group compared with the baseline level(P<0.05).The folic acid group also showed improvement in epigastric pain,epigastric fullness,belching,abdominal pain,bloating,bad breath and fatigue after medication compared to baseline levels,with statistically significant differences(P<0.05).A comparison of the differences between the two groups revealed that the Moluodan+sanqi powder group was better than the folic acid group in improving dry mouth scores,with a statistically significant difference(P=0.037).(3)Disappearance rate of symptomsThe disappearance rate of epigastric pain was 54.2%and 45.5%in the Moluodan+sanqi powder and folic acid groups,respectively;the disappearance rate of epigastric fullness was 63.0%and 45.5%,respectively;the disappearance rate of epigastric congestion was 52.9%and 44.4%,respectively;the disappearance rate of heartburn was 61.9%and 50.0%,respectively;and the disappearance rate of acid reflux was 54.2%and 44.4%,respectively.61.9%and 50.0%for heartburn,54.2%and 44.4%for acid reflux,63.0%and 44.4%for belching,100.0%and 33.3%for nausea,83.3%and 80.0%for loss of appetite,100.0%and 50.0%for decreased food intake;no hunger(100.0%and 50.0%respectively;abdominal pain(64.7%and 66.7%respectively;and bloating(64.7%and 66.7%respectively.47.1%and 55.6%for bloating;60.9%and 38.5%for dry mouth;73.7%and 64.3%for bitter mouth;66.7%and 42.9%or bad breath;34.8%and 14.3%for fatigue and 36.4%and 18.2%for poor sleep respectively.In this group,Moluodan+sanqi powder was superior to folic acid in improving nausea(p=0.038),with no statistical difference in the improvement of the remaining symptoms between the two groups.(4)Change in PRO Instrument ScoreThe reduction in the PRO scale scores for acid reflux,dyspepsia,defecation,psychological,social,systemic symptoms and total score in the Moluodan+sanqi powder group was statistically significant compared to baseline(P<0.01).In the Folic acid group,there was a statistically significant reduction in acid reflux,defecation,psychological,social,systemic symptoms and total score compared to baseline(P<0.05 or P<0.01),and no statistically significant reduction in dyspepsia compared to baseline.There were no statistically significant between-group differences in any of the dimensions in either group.4.Immunohistochemical testsThe CD68 and CD45 scores in the Moluodan+sanqi powder group decreased significantly after 6 months of medication compared to baseline,and the difference was statistically significant(P<0.05),while the CD68 and CD45 scores in the folic acid group tended to decrease after 6 months of medication compared to baseline,but the difference was not statistically significant(P>0.05).5.Safety observationThree adverse events were recorded in this study but not related to the drugs used in this study and no serious adverse events occurred.6.Falling off and eliminating casesIn the Moluodan+sanqi powder group,a total of 3 patients were shed due to 2 adverse events and 1 patient who left the country and could not continue taking the drug.No patients were dropped from the folic acid group.Conclusion1.Moluodan combined with Sanqi powder significantly improved the pathological LGD/IFND and atrophy scores of gastric mucosa,and the disappearance rate of heterogeneous hyperplasia could reach 42.4%,which was 16.1%higher than that of the folic acid group.At the same time,Moluodan combined with Sanqi powder significantly improved the endoscopic manifestations such as mucosal colour,mucosal texture and erosion of patients,and the improvement of the total score of gastroscopic manifestations was significantly better than that of folic acid.Moluodan combined with Sanqi powder showed significant improvement on various symptoms such as epigastric pain,epigastric fullness,epigastric congestion and PRO scale scores.2.Moluodan combined with Sanqi powder could significantly reduce CD68 and CD45 immunohistochemical staining scores,suggesting that it may inhibit or block the progression of gastric precancerous lesions by regulating the immunoregulatory direction of macrophages and lymphocytes and reducing chronic inflammatory stimulation and excessive immune response of host cells. |
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