| Background:Gastric Cancer(GC),one of the most common malignancies of the digestive system,is the third most common cause of cancer death in the world.chronic atrophic gastritis(CAG)is considered a precancerous lesion of gastric cancer,while Incomplete intestinal metaplasia(IM)and Dysplasia(Dys)are defined as gastric precancerous lesions(GPL),The WHO(2019)classification divides Dys into low-grade dysplasia(LGD)and high-grade dysplasia(HGD),early detection and intervention of GPL can effectively prevent the occurrence and development of gastric cancer and reduce its mortality.At present,the treatment of gastric precancerous lesions in western medicine at home and abroad is mainly eradication of Helicobacter pylori and symptomatic treatment,lack of internal medicine system treatment,and can not reverse IM and Dys and other pathological changes.The research on the intervention of traditional Chinese medicine(TCM)on precancerous lesions of stomach is increasing gradually.Most of the studies have confirmed that TCM exerts its advantages of overall regulation,syndrome differentiation and treatment,it is of great significance in improving the clinical symptoms and reversing the pathological changes.The accuracy,standardization and standardization of TCM syndromes are the prerequisite for the popularization of TCM and the evaluation of its curative effect.Therefore,if TCM syndromes are related to pathological changes and molecular biology,the distribution characteristics and evolution rules of TCM syndromes are sought,to provide an objective basis for clinical syndrome differentiation and treatment will help to improve the accuracy of syndrome differentiation,so that its clinical efficacy can be repeated test and widely recognized at home and abroad.Objective:1.This study summarized the TCM syndromes and their distribution characteristics by collecting the information of the four medical diagnosis of GPL patients.2.Explore the correlation between TCM syndromes and histopathology and molecular markers,assist in identifying high-risk GPL patients,and provide references for their clinical monitoring and treatment.Methods:The study was conducted from January 2018 to December 2020 IN the outpatient department,Inpatient Department and Endoscopy Center of Xiyuan Hospital,China Academy of Chinese Medical Sciences,collecting the basic information,filling in the syndrome evaluation form,filling in the gastroscope evaluation form and the pathology evaluation form by the experienced senior gastroscopy doctors and pathologists,and completing the corresponding pathology immunohistochemistry by the pathologists,the expression of MUC2,MUC5AC,MUC6,CD 10,SOX2,CDX2 and Ki-67 were observed.Build a database and input the data,carry out the corresponding statistical analysis,analyze the distribution characteristics of TCM syndromes of GPL,analyze the molecular biological characteristics of precancerous lesions of stomach,to summarize the characteristics of pathological histology and expression of molecular markers of each syndrome.Results:1.Study the distribution of cases(1)Included cases:this study included a total of 216 patients,all patients with CAG as their background lesions.(2)General demography:there were 107 males(49.54%)and 109 females(50.46%),the average age was 57.53±9.94 years,and the average age of females was higher than that of males(p>0.05).The mean BMI was 23.45±2.88,for males(24.33±2.71)>for females(22.58±2.78)(p<0.05).(3)Distribution of IM degree:mild IM 122 cases(56.48%)>moderate and severe IM 94 cases(43.06%);IM location distribution:93 cases(43.06%)of mild antrum IM>36 cases(16.67%)of moderate and severe antrum IM>58 cases(26.85%)of moderate and severe antrum IM>29 cases(13.43%)of mild antrum IM;Type distribution of intestinal metaplasia:incomplete intestinal metaplasia in 119 cases(55.09%)>complete intestinal metaplasia in 97 cases(44.91%);Dys Severity Distribution:no Dys 141 cases(65.28%)>LGD 75 cases(34.72%);Hp infection distribution:HP negative in 189 cases(87.50%)>Hp positive in 27 cases(12.50%).(4)Distribution of TCM Syndrome:54 cases(25.00%)of deficiency of spleen and stomach syndrome(deficiency cold syndrome of spleen and stomach)>47 cases(21.768%)of spleen-stomach damp-heat syndrome>37 cases(17.13%)of stomach-collateral blood stasis syndrome>34 cases(15.74%)of liver-stomach stagnation syndrome>27 cases(12.50%)of liver-stomach stagnation syndrome>17 cases(7.87%)of stomach-yin deficiency syndrome;The distribution characteristics of deficiency-excess syndrome were 145 cases(67.13%)>71 cases(32.87%).(5)Positive expression rate of molecular marker:MUC2 positive rate 96.30%,MUC5AC positive rate 88.9%,MUC6 positive rate 87.50%,CD10 positive rate 57.41%,CDX2 positive rate 96.00%,SOX2 positive rate 4%,Ki-67 positive rate 82.67%.2.Distribution of general information(1)Sex:male>female in LGD(p=0.05);male>female in damp-heat syndrome of spleen and stomach(p<0.05);female>male in deficiency of stomach-yin syndrome(p<0.05).(2)Age:there was no significant difference in age distribution among pathological changes and TCM syndromes(p>0.05).(3)BMI:Mild IM>moderate and severe IM(p<0.05);BMI>non-spleen-stomach dam-p-heat(p<0.05).(4)Hp infection:the difference of HP distribution between spleen-stomach damp-heat syndrome and non-spleen-stomach damp-heat syndrome was statistically significant(p<0.05);HP positive rate(15.86%)in positive group was higher than that in deficiency group(5.63%),the difference was significant(p<0.05).3.TCM Syndromes and Intestinal Metaplasia(1)IM degree:in mild IM patients,spleen-stomach deficiency syndrome(spleen-stomach deficiency cold syndrome)is the main type,damp-heat of the spleen and stomach,stagnation of the liver and stomach,stagnation of Qi in the liver and stomach,blood stasis in the stomach collaterals,and deficiency of stomach-yin account for the least,the syndrome of blood stasis in the stomach and collaterals accounted for the highest proportion,the syndrome of damp-heat in the spleen and stomach,the syndrome of weakness(cold)in the spleen and stomach,the syndrome of stagnation of heat in the liver and stomach,the syndrome of stagnation of Qi in the liver and stomach,and the syndrome of deficiency of yin in the stomach accounted for the least.The distribution of mild IM(68.5%)was significantly higher than that of moderate and severe IM(31.48%)(p<0.05),and the distribution of moderate and severe IM(64.86%)was significantly higher than that of mild IM(35.14%)(p<0.05)The distribution of deficiency syndrome in mild IM(67.61%)was significantly higher than that in moderate IM(32.39%)(p<0.05).(2)IM scope:in mild IM,the main symptoms of gastric antrum and antrum body were weakness of spleen and stomach,damp-heat of spleen and stomach,and deficiency of stomach-yin was the least;in moderate and severe IM,the symptoms of gastric antrum and antrum body were blood stasis of stomach collaterals,spleen-stomach deficiency syndrome(spleen-stomach deficiency cold syndrome),spleen-stomach dampness-heat syndrome,liver-stomach qi stagnation syndrome,liver-stomach stagnation-heat syndrome were followed by,and deficiency of stomach-yin syndrome was the least.There was no significant difference among TCM syndromes in the distribution of lesion area(p>0.05).4.Expression of molecular markers4.1 Mucin index(1)Mucin index and IM:with the development of IM from mild to moderate to severe,the positive rates of MUC2 and CD 10 increased gradually,while the positive rates of MUC5AC and MUC6 decreased,but there was no significant difference between groups(p>0.05),in mild IM group,the positive rate of CD 10 in antrum(46.24%)<Antrum body(68.97%),the difference was statistically significant(p<0.05).(2)Mucin index and deficiency-excess syndrome of TCM:there was no significant correlation between deficiency-excess syndrome of TCM and positive expression of MUC2,MUC5AC,MUC6 and CD10(p>0.05).4.2 Genes encode proteins(1)Gene-coding proteins and IM:with the increase of intestinal metaplasia,the expression of CDX2 was up-regulated and the expression of SOX2 was down-regulated.(2)There was no significant correlation between CDX2,SOX2 positive expression and TCM syndrome(p>0.05).4.3 Proliferation-associated antigen Ki-67(1)Ki-67 and IM:The positive rate of Ki-67 in mild IM group(80.95%)was lower than that in moderate IM group(84.85%),but there was no significant difference between the two groups(P>0.05).(2)There was no significant correlation between the positive expression of Ki-67 and TCM syndromes(P>0.05).5.Types of intestinal metaplasia and distribution of related factorsOf the 216 patients included,119(55.09%)had incomplete intestinal metaplasia and 97(44.91%)had complete intestinal metaplasia.(1)HP infection:the positive rate of HP in complete IM patients(15.46%)was higher than that in incomplete IM patients(10.08%),but there was no statistical difference between the two groups(P>0.05).(2)Degree of IM:the proportion of incomplete IM group was higher than that of complete IM group,but there was no significant difference between the two groups(P>0.05).The proportion of incomplete IM group in LGD(73.33%)was significantly higher than that of complete IM group(26.67%).The difference between the two groups was statistically significant(P<0.05).(3)Mucin expression:The positive expression rate of MUC2 and CD10 in complete IM group was higher than that in incomplete IM group,and the difference was statistically significant(P<0.05).MUC5AC and MUC6 had no significant difference in different intestinal classification groups(P>0.05).(4)Gene encoding protein expression:the positive expression rate of CDX2 in patients with complete IM group(100%)was higher than that in patients with incomplete IM group(94.55%),while the expression of SOX2 was basically opposite to that of CDX2.(5)TCM syndrome:in this study,it was found that there was no significant difference in the distribution of syndromes in different IM types.The syndromes of spleen and stomach weakness(cold)and spleen and stomach damp-heat syndrome were the main ones,and the deficiency of stomach yin accounted for the least.6.Distribution of dysplasia and related factorsOf the 216 patients included,75(34.72%)were associated with LGD and 141(65.28%)were n ot associated with Dys.(1)HP infection:In 75 Dys patients,the positive rate of HP in LGD patients(18.44%)was significantly lower than that in non-Dys patients(1.33%),the difference was statistically significant(P<0.05).(2)Degree of IM:the proportion of LGD in moderate and severe IM group(35.11%)>the proportion of LGD in mild IM group(34.43%),there was no significant difference(P>0.05),in mild IM group,the ratio of gastric antrum lesion(39.8%)>body antrum(17.2%),the difference was statistically significant(P<0.05),and LGD accounted for(46.22%)of incomplete IM significantly higher than complete IM(20.62%),the difference was statistically significant(P<0.05).(3)Molecular markers:the positive rates of MUC2,MUC5AC,MUC6 and CD10 in the LGD group were lower than those in the non-Dys group(P<0.05).(4)TCM syndromes:according to TCM syndromes,the distribution of TCM syndromes in LGD Group is:spleen-stomach deficiency syndrome(spleen-stomach deficiency cold syndrome)>liver-stomach stagnation syndrome>liver-stomach qi stagnation syndrome>blood stasis syndrome>spleen-stomach damp-heat syndrome>deficiency of stomach-yin syndrome.There was significant difference in Dys distribution between spleen-stomach deficiency syndrome(spleen-stomach deficiency cold syndrome)and non-spleen-stomach deficiency syndrome(spleen-stomach deficiency cold syndrome)(P<0.05)There was significant difference in Dys distribution between spleen-stomach damp-heat syndrome and non-spleen-stomach damp-heat syndrome(P<0.05).The percentage of deficiency syndrome in LGD group(47.89%)was significantly higher than that in substantial syndrome(28.28%),the difference was statistically significant(P<0.05).CONCLUSIONS:1.1 Distribution characteristics of TCM syndromes(1)General factors:Insufficiency of stomach yin is mostly female,while spleen and stomach damp-heat syndrome is mostly male;BMI of patients with spleen-stomach damp-heat syndrome>non-spleen-stomach damp-heat syndrome;Hp infection is dominated by spleen-stomach damp-heat syndrome/experience.(2)TCM syndromes and histopathology:The majority of patients with mild IM and LGD have deficiency syndrome,especially spleen and stomach weakness(cold)syndrome;moderate to severe IM has more evidence,especially stomach collateral blood stasis syndrome.(3)TCM syndromes and molecular markers:The positive expression rate of MUC2,MUC5AC,MUC6,CD 10,SOX2,and Ki-67 in empirical syndrome>deficiency syndrome,and the positive expression of CDX2 in deficiency syndrome>positivity,but there is no obvious correlation.1.2 TCM syndromes and histopathology:The positive expression rate of MUC2 and CD 10 was higher in the complete IM group;the positive expression rate of Ki-67 was higher in the incomplete IM group.1.3 The correlation between dysplasia and various factors:(1)Extensive sinus body IM and incomplete IM are risk factors for Dys;(2)In LGD,the positive expressions of MUC2,MUC5AC,MUC6 and CD 10 were all lower than those of the non-Dys group.Deficiencies and prospectsThis study is a single center cross-sectional study,with small sample size and uneven distribution of various histopathological types,which can not systematically and comprehensively reflect the objective changes in the process of disease progression.In the later stage,the sample size could be enlarged and the follow-up could be increased to establish the long-term follow-up database of special diseases,tracking the dynamic condition and exploring its evolution law. |
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