Study On The Basic Rules Of TCM Syndrome Of Primary Liver Cancer And The Essence Of Spleen Deficiency Syndrome

Objective This study retrospectively studied Primary carcinoma of liver(PLC)cases to explore the correlation between TCM syndromes and objective indicators.The correlation between liver stagnation and spleen deficiency and dampness and sleepiness of spleen deficiency in liver cancer and serum miRNA was explored from the molecular biological level to preliminarily reveal the biological nature of spleen deficiency in liver cancer and provide objective basis for TCM syndrome differentiation and classification of liver cancer.Methods In the first part of this paper,retrospective study method was used to include patients who were diagnosed with primary liver cancer,met the inclusion criteria and had complete information in the hepatology ward of Hubei Hospital of Traditional Chinese Medicine from January 2017 to November 2020.The basic information of patients,the information of the four diagnoses of traditional Chinese medicine,and the relevant laboratory examination indexes were collected and recorded.The TCM syndrome differentiation and classification were conducted according to the unified standard,the distribution characteristics of TCM syndrome types of primary liver cancer were summarized,and the correlation between TCM syndrome differentiation and clinical indexes of primary liver cancer was discussed.In the second part of this paper,using modern molecular biology techniques,the differential miRNAs(miR-122-5p,miR-148a-3p,miR-92a-3p,miR-10a-5p,miR-22-3p,miR-26a-5p,miR-146-5p,miR-143-3p,miR-27b-3p,and miR-10a-5p)screened for liver cancer in the previous stage d were verified by qPCR to detect the expression of differential miRNAs in the serum of liver cancer patients(6 cases of liver depression and spleen deficiency syndrome,6 cases of spleen deficiency and dampness syndrome)and6 controls.To explore the correlation between the syndrome of liver stagnation and spleen deficiency and the syndrome of dampness and sleepiness of spleen deficiency and miRNA,and to explore the biological nature of spleen deficiency in liver cancer from the miRNA level.SPSS26.0 software was used for statistical analysis,and P<0.05 was considered statistically significant.Results1.313 patients with HCC were mainly male,ranging in age from26 to 90 years old,with an average age of 59.58 years old.Among them,59-69 years old(33.2%)was the age group with high incidence.The primary disease was hepatitis B,followed by cirrhosis,and hepatitis B cirrhosis was the dominant disease.Smoking and drinking alcohol are risk factors for liver cancer.2.The clinical manifestations of this disease are varied,with fatigue,dry mouth,poor appetite,hypochondriac pain,abdominal distension,poor sleep,yellow urine,yellow eyes,abdominal pain,bitter mouth as the common clinical symptoms.3.The TCM syndromes of this disease are mostly distributed in liver stagnation and spleen deficiency syndrome,spleen deficiency dampness trapped syndrome.4.Relationship between TCM syndromes and objective indicators:(1)Correlation with blood routine: among the WBC indexes,dampness-heat toxicity syndrome>spleen deficiency and dampness trap syndrome>qi stagnation and blood stasis syndrome>liver stagnation and spleen deficiency syndrome>liver kidney Yin deficiency syndrome;Among the PLT indexes,qi stagnation and blood stasis syndrome> dampness-heat toxicity syndrome >liver stagnation and spleen deficiency syndrome>spleen deficiency and dampness trap syndrome>liver kidney Yin deficiency syndrome;There was no significant difference in WBC and PLT indexes among different syndrome types(P>0.05),indicating that there was no correlation between WBC,PLT and TCM syndrome types of liver cancer.Among the RBC indexes,qi stagnation and blood stasis syndrome > liver stagnation and spleen deficiency syndrome >liver and kidney Yin deficiency syndrome>dampness-heat toxicity syndrome>spleen deficiency and dampness trap syndrome,and qi stagnation and blood stasis syndrome was the highest,while spleen deficiency and dampness trap syndrome was the lowest.The difference between qi stagnation and blood stasis syndrome and spleen deficiency dampness trap syndrome,damp-heat toxicity syndrome was statistically significant(P<0.05).The difference of spleen deficiency and dampness trap syndrome and liver stagnation and spleen deficiency was statistically significant(P<0.05).The results showed that RBC had a certain correlation with TCM syndromes of liver cancer.Among the HGB indicators,liver stagnation and spleen deficiency syndrome>qi stagnation and blood stasis syndrome >liver and kidney Yin deficiency syndrome>dampness-heat toxicity syndrome>spleen deficiency dampness trap syndrome,liver stagnation and spleen deficiency syndrome was the highest and spleen deficiency dampness trap syndrome was the lowest.Among them,there was statistical difference between liver stagnation and spleen deficiency syndrome and spleen deficiency and dampness trap syndrome,dampness-heat toxicity syndrome(P<0.05).The difference between spleen deficiency and dampness trap syndrome and qi stagnation and blood stasis syndrome was statistically significant(P<0.05),indicating that there was a certain correlation between HGB and the TCM syndromes of liver cancer.(2)Correlation with liver function: among the ALT indexes,dampness-heat toxicity syndrome>liver stagnation and spleen deficiency syndrome>spleen deficiency and dampness trap syndrome>qi stagnation and blood stasis syndrome>liver kidney Yin deficiency syndrome,dampness-heat toxicity syndrome was the highest,liver and kidney Yin deficiency syndrome was the lowest,but there was no statistical significance between different syndrome types(P>0.05);Among the AST indexes,dampness-heat toxic syndrome>spleen deficiency and dampness trapped syndrome >qi stagnation and blood stasis syndrome>liver and kidney Yin deficiency syndrome>liver stagnation and spleen deficiency syndrome, dampness-heat toxic syndrome was the highest and liver stagnation and spleen deficiency syndrome was the lowest.The difference between the syndrome of liver stagnation and spleen deficiency and the syndrome of dampness-heat accumulation,dampness-trapped with spleen deficiency was statistically significant(P<0.01).Among the TBIL indexes,dampness-heat toxicity syndrome >spleen deficiency and dampness trap syndrome>liver and kidney Yin deficiency syndrome>liver depression and spleen deficiency syndrome > qi gnation and blood stasis syndrome,dampness-heat toxicity syndrome was the highest and qi stagnation and blood stasis syndrome was the lowest.Among them,the difference between the syndrome of damp-heat toxic accumulation and the syndrome of liver stagnation and spleen deficiency,the syndrome of liver and kidney Yin deficiency,and the syndrome of qi stagnation and blood stasis was statistically significant(P<0.01).The difference between qi stagnation and blood stasis syndrome and spleen deficiency and dampness trap syndrome was statistically significant(P<0.01).In ALT,AST and TBIL indexes,ALT values among the syndrom types had no statistical significance(P>0.05),indicating that TCM syndrom types had no correlation with ALT.The differences of AST and TBIL among syndromes were statistically significant(P<0.05),indicating that TCM syndromes were correlated with AST and TBIL to a certain extent.Among the ALP and GGT indexes,spleen deficiency and dampness trap syndrome >damp-heat toxicity syndrome>qi stagnation and blood stasis syndrome>liver and kidney Yin deficiency syndrome> liver stagnation and spleen deficiency syndrome,spleen deficiency and dampness trap syndrome was the highest and liver depression and spleen deficiency syndrome was the lowest.In the ALP index,the difference between the syndrome of dampness of spleen deficiency and the syndrome of liver stagnation and spleen deficiency,the syndrome of liver and kidney Yin deficiency was statistically significant(P<0.01).In the GGT index,there was a statistically significant difference between spleen deficiency and dampness trap syndrome and liver stagnation and spleen deficiency syndrome(P<0.01),indicating that there was a certain correlation between TCM syndromes and ALP and GGT.Among the ALB indexes,qi stagnation and blood stasis syndrome > liver and kidney Yin deficiency syndrome>liver stagnation and spleen deficiency syndrome>dampness-heat toxicity syndrome> spleen deficiency and dampness trap syndrome;The syndrome of qi stagnation and blood stasis was the highest was the highest and the syndrome of spleen deficiency and dampness trap was the lowest.The difference between qi stagnation and blood stasis syndrome and spleen deficiency and dampness trap,dampness-heat toxicity syndrome was statistically significant(P<0.01).Compared with the syndrome of spleen deficiency and dampness trap and liver kidney Yin deficiency syndrome,liver stagnation and spleen deficiency syndrome,the difference was statistically significant(P<0.01).The results showed that ALB was correlated with TCM syndromes.(3)The relationship between renal function: Among the indexes of UREA,spleen deficiency and dampness trap syndrome>dampness-heat toxicity syndrome>liver and kidney Yin deficiency syndrome>qi stagnation and blood stasis syndrome>liver stagnation and spleen deficiency syndrome,spleen deficiency and dampness trap syndrome was the highest and liver stagnation and spleen deficiency syndrome was the lowest,and the difference between spleen deficiency and dampness trap syndrome and qi stagnation and blood stasis syndrome was statistically significant(P<0.01).Compared with the syndrome of liver stagnation and spleen deficiency and the syndrome of liver and kidney Yin deficiency,spleen deficiency and dampness trap syndrome,the difference was statistically significant(P<0.05),indicating that UREA had a certain correlation with the traditional Chinese medicine syndrome type of liver cancer.Among the index of CREA,dampness-heat toxicity syndrome,spleen deficiency and dampness trap syndrome > liver kidney Yin deficiency syndrome > qi stagnation and blood stasis syndrome,liver depression and spleen deficiency syndrome,with wet dampness-heat toxicity syndrome,spleen deficiency and dampness trap syndrome was was the highest,qi stagnation and blood stasis syndrome and liver stagnation and spleen deficiency syndrome was the lowest,but there was no statistically significant difference between the each card type(P > 0.05),showed that CREA no correlation with syndrome of liver cancer.Among the e GFR indicators,qi stagnation and blood stasis syndrome>liver stagnation and spleen deficiency syndrome>liver and kidney Yin deficiency syndrome>dampness-heat toxicity syndrome > spleen deficiency and dampness trap syndrome;qi stagnation and blood stasis syndrome was the highest,spleen deficiency and dampness trap syndrome was the lowest,but there was no statistical significance between different syndrome types(P >0.05),dicating that there was no correlation between e GFR and traditional Chinese medicine syndrome types of liver cancer.(4)The relationship between spleen deficiency and blood coagulation function: The results of this study showed that among the PT indexes,spleen deficiency and dampness-trapping syndrome >dampness-heat toxicity syndrome>liver and kidney Yin deficiency syndrome>qi stagnation and blood stasis syndrome>liver stagnation and spleen deficiency syndrome;spleen deficiency and dampness-trapping syndrome was the highest,and the syndrome of liver stagnation and spleen deficiency was the lowest.The difference between the syndrome of liver stagnation and spleen deficiency and spleen deficiency and dampness trap syndrome,dampness-heat toxicity syndrome was statistically significant(P<0.05),indicating that PT had a certain correlation with the syndrome types of liver cancer.Among the PTA indexes,qi stagnation and blood stasis syndrome >liver stagnation and spleen deficiency syndrome>liver and kidney Yin deficiency syndrome>spleen deficiency dampness-trapping syndrome > dampness-heat toxicity syndrome;qi stagnation and blood stasis syndrome was the highest,and dampness-heat toxicity syndrome was the lowest.The difference between qi stagnation and blood stasis syndrome and spleen deficiency and dampness trap syndrome,dampness-heat toxicity syndrome was statistically significant(P<0.05).There was statistical significance between dampness-heat toxicity syndrome and the syndrome of stagnation of liver and deficiency of spleen(P<0.05),indicating that there was a certain correlation between PTA and the syndrome type of liver cancer.Among the D-dimer indexes,spleen deficiency and dampness trap syndrome > qi stagnation and blood stasis syndrome>liver and kidney Yin deficiency syndrome>dampness-heat toxicity syndrome >liver stagnation and spleen deficiency syndrome,spleen deficiency and dampness trap syndrome was the highest,liver stagnation and spleen deficiency syndrome was the lowest,and spleen deficiency dampness strap syndrome compared with liver stagnation and spleen deficiency syndrome,and liver and kidney Yin deficiency syndrome,the difference was statistically significant(P<0.01).The results showed that D-dimer had a certain correlation with the syndromes of liver cancer.(5)Among the AFP indexes,qi stagnation and blood stasis syndrome>liver and kidney Yin deficiency syndrome>spleen deficiency and dampness trap syndrome >liver stagnation and spleen deficiency syndrome> dampness-heat toxicity syndrome,there was no statistical significance among the syndrome types(P>0.05).5.Relationship between TCM syndromes and miRNAs:(1)Compared with control group,miR-148a-3p,miR-92a-3p,miR-146-5p,miR-27b-3p,miR-192-5p,miR-130b-3p,miR-4429,miR-4488,and miR-483-5p were down-regulated in the liver depression and spleen deficiency group.,statistically significant difference(P<0.05),indicating that the nine of micrornas with liver cancer liver spleen deficiency has certain relevance.It is suggested that it can be used as a biomarker to distinguish liver stagnation and spleen deficiency syndrome of liver cancer in control group;The expressions of miR-122-5p,miR-10a-5p,miR-22-3p,miR-26a-5p and miR-143-3p were down-regulated,and the differences were not statistically significant(P>0.05).(2)Compared with control group,The expressions of miR-122-5p,miR-148a-3p,miR-146-5p,miR-27b-3p,miR-192-5p,miR-130b-3p, miR-4429,miR-4488 and miR-483-5p were down-regulated in the group of spleen deficiency dampness,statistically significant difference(P < 0.05),suggesting these nine miRNAS could be used as biomarkers for differentiating dampness and spleen deficiency trap syndrome in liver cancer in control group;The expressions of miR-92a-3p,miR-10a-5p,miR-22-3p,miR-26a-5p and miR-143-3p were down-regulated,and the differences were not statistically significant(P>0.05).(3)Compared with the syndrome of spleen deficiency and dampness trap,the expression of miR-22-3p was up-regulated in the syndrome of liver depression and spleen deficiency,while the expression of miR-143-3p and miR-4488 were down-regulated,with statistical significance(P<0.05).The expressions of miR-122-5p,miR-148a-3p,miR-10a-5p,miR-130b-3p,miR-4429,and miR-483-5p were up-regulated,while the expressions of miR-92a-3p,miR-26a-5p,miR-146-5p,miR-27b-3p,and miR-192-5p were down-regulated,and the differences were not statistically significant(P>0.05).It is suggested that miR-22-3p,miR-143-3p and miR-4488 can be used as biomarkers for the differentiation and classification of the syndrome of liver stagnation and spleen deficiency and dampness and trapping of spleen deficiency.(4)Compared with the control group,the expression of miR-148a-3p,miR-146-5p,miR-27b-3p,miR-192-5p,miR-130b-3p,miR-4429,and miR-483-5p were all down-regulated.The difference was statistically significant(P<0.05),suggesting that this syndrome may be correlated with the common syndrome of spleen deficiency and can be used as a biomolecular marker of spleen deficiency syndrome.Conclusions1.This study found that TCM syndrome type had certain correlation with blood routine indexes(RBC,HGB),liver function indexes(AST,ALP,GGT,ALB,TBIL),renal function indexes(UREA),and coagulation function indexes(PT,PTA,D-dimer).There was no correlation with WBC,PLT,ALT,CREA,AFP.Among the five syndromes,the indexes of ALP,GGT,UREA,PT and D-dimer in syndrome of dampness of spleen deficiency were the highest.RBC,HGB and ALB were the lowest.AST,ALP,GGT,UREA,PT and D-dimer were the lowest in patients with liver stagnation and spleen deficiency.It suggested that spleen deficiency and dampness trap syndrome was more serious and that of liver depression and spleen deficiency was less serious.2.This study found that miR-92a-3p can be used as a biomarker for liver stagnation and spleen deficiency syndrome of liver cancer;Mi R-122-5p can be used as a specific biomarker for spleen deficiency dampness syndrome of liver cancer.3.In this study,it was found that miR-22-3p,miR-143-3p and miR-4488 could be used as biomarkers to distinguish the syndrome of dampness and trapping of spleen deficiency from the syndrome of liver stagnation and spleen deficiency.4.In this study,it was found that miR-148a-3p,miR-146-5p,miR-27b-3p,miR-192-5p,miR-130b-3p,miR-4429,miR-4488,miR-483-5p had a certain correlation with spleen deficiency syndrome.It is involved in the proliferation,invasion,migration,apoptosis and other biological processes of liver cancer cells and can be used as a biomarker of spleen deficiency syndrome.