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OBJECTIVES@#To evaluate the methodological quality of randomized controlled trials (RCTs) of traditional Chinese medicines for the treatment of gastric precancerous lesions in the past 20 years.@*METHODS@#The RCTs on traditional Chinese medicines for gastric precancerous lesions were searched from the CNKI, Wanfang database, VIP, PubMed, and Embase from January 2001 to December 2021. The retrieved articles were screened, extracted and evaluated based on the 2010 edition of CONSORT statement, Cochrane Risk of Bias Assessment Scale and additional evaluation indicators.@*RESULTS@#A total of 840 papers were included. According to the Cochrane Risk of Bias Assessment Scale, the high risk of bias in the application of randomized methods was 5.95%; the risk of uncertainty for the allocation scheme concealment was 98.93%; the risk of uncertainty for blinding of patients or testers was 98.69%; the risk of uncertainty for blinding of the outcome assessor was 100.00%; the risk of bias for completeness of the outcome data was 2.86%; and the risk of uncertainty for selective reporting was 98.45%. The CONSORT statement evaluating the quality of reporting showed that 100.00% of the RCT articles reported the 8 entries; 36.79% of the literature mentioned the method of randomized sequence generation, but only 27.62% of the literature mentioned who implemented the randomized program, 1.07% of the literature hid the randomized program and 1.31% of the studies were blinded; 36.67% of the literature reported adverse reactions; no literature reported sample size prediction methods. Additional evaluation indicators showed that 17.02% of the studies had ethical approval; 43.81% of the literature specified Chinese medicine evidence; 16.55% of the studies excluded severe heterotrophic hyperplasia; 7.26% of the studies conducted follow-up; and 65.12% of the literature used composite efficacy indicators; 46.67% of the literature applied pathological histological evaluation; 2.62% of the literature applied quality of life evaluation.@*CONCLUSIONS@#The overall risk of bias in RCTs of traditional Chinese medicines for gastric precancerous lesions is high, and the quality of most of the study reports needs to be improved. In the future, it is necessary to strengthen the study design of RCTs and refer to appropriate traditional Chinese medicines evidence grading standards, select study protocols according to different purposes, provide objective and strong evidence for clinical studies on traditional Chinese medicines, and carry out clinical study design and result reporting suitable for traditional Chinese medicines according to the CONSORT principle.
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Humans , Medicine, Chinese Traditional , Randomized Controlled Trials as Topic , Precancerous Conditions/drug therapyABSTRACT
Objective:To observe the effect of modified Si Junzitang on the level of lactic acid in gastric mucosa and the expression of Carboxylic acid transporter 1（MCT1）， monocarboxylic acid transporter 4（MCT4）， and extracellular matrix metalloproteinase inducer （CD147）in rats with gastric precancerous lesions（GPL）. Method:Seventy-four SD male rats were randomly divided into normal group （12 rats） and model group （62 rats）. <italic>N</italic>-methyl-<italic>N'</italic>-nitro-<italic>N</italic>-nitrosoguanidine（MNNG）-ammonia compound method was used to establish GPL rat models， and at the 9<sup>th</sup> week， the model rats were randomly divided into model group， folic acid group（2.7 mg·kg<sup>-1</sup>）， modified Si Junzitang high， medium and low dose groups（12.6， 6.3， 3.15 g·kg<sup>-1</sup>）， with 12 rats in each group. After intragastric administration for 12 weeks， the general conditions of the rats were observed. Hematoxylin-eosin（HE）staining was used to observe the histopathological changes of gastric mucosa in rats， chemical colorimetry was used to detect the content of lactic acid in gastric mucosa； immunohistochemistry and real-time polymerase chain reaction（Real-time PCR）were used to detect MCT1， MCT4， CD147 protein and mRNA expression in gastric mucosal tissues. Result:Modified Si Junzitang significantly improved the pathological manifestations in GPL rats such as gastric mucosal epithelial gland structure， disorder of arrangement and cell atypia. Compared with the normal group， the lactic acid content of the gastric mucosa tissue in the model group increased significantly（<italic>P</italic><0.01）， and the protein and mRNA expressions of MCT1， MCT4， CD147 significantly increased（<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， the lactic acid content in each dose group of modified Si Junzitang was significantly reduced（<italic>P</italic><0.05， <italic>P</italic><0.01）， and the protein expression levels of MCT4 and CD147 were also significantly reduced in each dose group of modified Si Junzitang（<italic>P</italic><0.05， <italic>P</italic><0.01）. The mRNA expression of MCT4 was significantly reduced in the middle and high dose groups（<italic>P</italic><0.05， <italic>P</italic><0.01）， and the mRNA expression of CD147 was significantly reduced in the high dose group（<italic>P</italic><0.05）. Modified Si Junzitang showed no significant regulatory effect on MCT1. Conclusion:Modified Si Junzitang can significantly improve the abnormal histopathology of gastric mucosal epithelium in GPL model rats. Its mechanism may be related to down-regulating the overexpression of MCT4 and CD147， inhibiting lactic acid outflow， and improving the acidic microenvironment of gastric mucosal epithelium.
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Objective:To explore the therapeutic effects of lamb′s tripe extract and vitamin B12 (hereinafter referred to as lamb′s tripe) capsule on precancerous lesions of gastric mucosa in rats.Methods:Thirty-two rats of the 42 Wistar rats (model group) were selected for modelling, and in model group six rats died due to gavage, 10 rats were sacrificed for observing the results of modeling, and the left 16 rats were divided into administration group (eight rats) and non-administration group (eight rats). After modeling, five of the 10 rats without modelling treatment were selected as the normal control of the model group, the other five (negative control group) rats were included in drug intervention experiment. The drug intervention program was as follows: in administration group, rats were gavaged with lamb′s tripe 0.2 g/kg once per day for three months; in non-administration group and negative control group, rats were gavaged with 0.9% sodium chloride solution 0.2 g/kg once per day for three months. One rat died in each for the administration group and non-administration group due to gavage. Body weight gain, pH value of gastric juice and pathological changes of gastric mucosa of the three groups were evaluated. The number of nodules on gastric mucosal surface and the incidence and scores of precancerous lesions (intraepithelial neoplasia) in gastric mucosal were analyzed. The therapeutic effects of lamb′s tripe capsule on gastric mucosal precancerous lesions in rats were evaluated. Independent sample t test , Mann Whitney U test and chi-square test were used for statistical analysis. Results:The body weight gain of rats at the 6th week in the administration group was higher than that of rats in the non-administration group ((508.26±33.96) g vs. (495.50±23.01) g), and the pH value of gastric juice of rats in the administration group was lower than that of rats in the non-administration group (3.07±0.55 vs. 4.45±0.72), and the differences were statistically significant (both P<0.05). The number of proliferative nodules on the gastric mucosal surface of the rats in the administration group was less than that of rats in the non-administration group (the ratio of gastric fundus: 6.00(3.00, 7.00) vs. 11.00(7.00, 13.00); the ratio of gastric antrum: 0.00(0.00, 1.00) vs. 3.00(2.00, 4.00); the ratio of whole stomach: 7.00(3.00, 10.00) vs. 15.00(13.00, 17.00)), and the differences were statistically significant ( U=43.50, 49.00, 49.00, all P<0.05). The score of gastric mucosal precancerous lesions in the administration group was lower than that in the non-administration group(1.00±0.00 vs.1.14±0.38), and the incidence of precancerous lesions in the administration group was lower than that in the non-administration group (1/7 vs. 5/7), and the differences were statistically significant ( t=2.45, χ2=4.67, both P=0.031). Conclusions:Lamb′s tripe capsule can significantly inhibit the progression of precancerous lesions of gastric mucosa in rats, so as to play a role in preventing the occurrence of gastric cancer.
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Objective: To study the potential mechanisms of Yiwei Decoction on intervening gastric precancerous lesions by using metabolomics technology combined with ingenuity pathway analysis (IPA). Methods: Gastric precancerous lesion rat model induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was established and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was utilized to detect and characterize rat serum metabolites. Metabolites with significant changes in model group and Yiwei Decoction group were screened out; The IPA software was used to analyze the potential targets and mechanisms. Results: Yiwei Decoction effectively interfered with the progress of gastric precancerous lesions. A total of 23 metabolites in the serum of gastric precancerous lesion rat model were significantly changed (P < 0.05), 13 metabolites were significantly regulated to normal level in Yiwei Decoction group (P < 0.05), the metabolic pathways mainly involved in the biosynthesis of unsaturated fatty acids, biosynthesis of valine, leucine and isoleucine, sphingolipid metabolism, arachidonic acid metabolism and steroid hormone synthesis, etc. The effect of Yiwei Decoction on intervening with the progression of gastric precancerous lesions was related to the inhibition of ET-1 and IL-8 signaling pathway. Conclusion: Yiwei Decoction can inhibit the progress of gastric precancerous lesions and improve the inflammatory environment by regulating arachidonic acid metabolism and inhibiting ET-1 and IL-8 signaling pathways.
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Chronic atrophic gastritis with gastric precancerous lesions is a kind of difficult disease of digestive disease, with long course of disease and difficulty in cure. This article believed that the main pathogenesis was spleen-stomach deficiency, qi-blood stasis and blood stasis poison accumulation by analyzing the causes, pathogenesis and pathology, which should be treated by nourishing spleen and stomach, regulating qi and blood circulation, detoxifying and dissipating stasis.
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Objective To evaluate the diagnostic value of VS classification of magnifying endoscopy with blue laser imaging ( ME-BLI) for gastric precancerous lesion and early gastric cancer. Methods A retrospective study was performed on the data of 313 patients ( 322 lesions) with gastric mucosal lesions undergoing ME-BLI in digestive endoscopy center of Renmin Hospital of Wuhan University from January 2014 to January 2017. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of VS classification by ME-BLI in diagnosis of gastric precancerous lesion and early cancer were analyzed. Results Among the 322 lesions, 57 were pathologically diagnosed as cancerous lesions and 265 were non-cancerous lesions. According to VS classification of ME-BLI, 98. 2%(56/57) VS structures of the cancerous lesions were irregular or disappearing, and 100. 0%( 57/57 ) cancerous lesions had clear demarcation. Taking the pathological diagnosis as the gold standard, the accuracy of VS classification of ME-BLI was 93. 8%(302/322), with a good consistency with pathological diagnosis(Kappa＝0. 810). The sensitivity, specificity, positive predictive value, and negative predictive value were 98. 2%( 56/57), 92. 8%( 246/265 ), 74. 7%( 56/75 ) and 99. 6%( 246/247 ), respectively. Conclusion The VS classification of ME-BLI is an effective method with high accuracy, sensitivity and specificity for diagnosis of gastric precancerous lesion and early gastric cancer.
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Objective To analyze the accuracy of staging among the combination of endoscopic biopsy sites,operative link for gastritis assessment (OLGA) and operative link for gastric intestinal metaplasia assessment (OLGIM) with five different biopsy sites.Methods From January 2014 to September 2015,patients with functional dyspepsia and undergoing gastroendoscopy examination were enrolled.According to update Sydney system,a total of five biopsy pieces were obtained from lesser curvature of gastric body,larger curvature of gastric body,gastric angle,larger curvature of antrum and lesser curvature of antrum.The degrees of atrophy and intestinal metaplasia were determined and staged according to OLGA and OLGIM.Kappa test and chi-square test were performed for the statistical analysis.Results A total of 268 patients were enrolled.The incidences of atrophy and intestinal metaplasia in different sites were as follow:30.4％ (113/372) and 31.0％ (111/358) in lesser curvature of antrum;26.1％(97/372) and 25.1％(90/358) in gastric angle;20.2％(75/372) and 15.4％(56/358) in larger curvature of antrum;14.8％(55/372) and 15.4％(55/358) in lesser curvature of gastric body;8.6％(32/372) and 8.1％(29/358) in larger curvature of gastric body.The incidences of atrophy and intestinal metaplasia of lesser curvature of antrum were significantly higher than those of larger curvature of gastric body,lesser curvature of gastric body and larger curvature of antrum (x2 =45.248,48.029,20.024,18.892,7.681 and 7.848;all P＜＜0.05).The incidences of atrophy and intestinal metaplasia of gastric angle were significantly higher than those of lesser curvature and larger curvature of gastric body(x2 =32.752,31.269,11.605 and 8.448;all P＜0.05).The incidences of atrophy and intestinal metaplasia of the lesser curvature of gastric body and larger curvature of antrum were higher than those of larger curvature of gastric body,and the differences were statistically significant (x2 =6.080,8.048,17.280,18.980,all P＜0.05).The incidences of mild atrophy and intestinal metaplasia of the lesser curvature of antrum were 20.2 ％ (75/ 372) and 21.2％ (76/358),respectively,which were higher than those of larger curvature of antrum (12.9％,48/372 and 12.8％,46/358),and the differences were statistically significant (x2 =5.927 and 7.377,both P＜0.05).The incidence of severe atrophy of lesser curvature of antrum was 2.4％ (9/372),respectively,which was higher than that of larger curvature of antrum (0.8％,3/372),and the difference was statistically significant (x2 =3.000,P =0.015).The incidences of mild atrophy and intestinal metaplasia of the lesser curvature of gastric body were 10.5％ (39/372) and 11.2％ (40/358),respectively,which were higher than those of larger curvature of gastric body (5.4 ％,20/372 and 5.9 ％,21/358),and the differences were statistically significant (x2 =6.119 and 5.918,both P＜0.05).The consistency of staging by three biopsy sites (lesser curvature of gastric body,gastric angle and lesser curvature of antrum) and five biopsy sites with OLGA and OLGIM was 94.0 ％ (95 ％ confidence interval (CI) =91.2％ to 96.9％,Kappa value=0.912,P＜0.01) and 92.9％ (95％CI:89.8％ to 96.0％,Kappa value=0.893,P＜0.01).Conclusion Three biopsy sites (lesser curvature of gastric body,gastric angle and lesser curvature of antrum) could accurately reflect gastric mucosa lesions with less biopsy tissues and it is worthy of clinical popularization and application.
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<p><b>OBJECTIVE</b>To study the effects of Weipixiao (胃痞消, WPX) on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions (GPL).</p><p><b>METHODS</b>Sprague Dawley rats were randomly divided into control, model, vitacoenzyme (0.2 g·kg(-1)·day(-1)), WPX high-dose (H-WPX, 15 g·kg(-1)·day(-1)), WPX medium-dose (M-WPX, 7.5 g·kg(-1)·day(-1)) and WPX low-dose (L-WPX, 3.75 g·kg(-1)·day(-1)) groups. After successfully establishing the GPL model, the rats were consecutively administered WPX or vitacoenzyme by gastrogavage for 10 weeks. Differential expression of Leucine-rich repeat-containing G-proteincoupled receptor 5 (Lgr5), matrix metalloproteinase-7 (MMP-7), Wnt1, Wnt3a, and β-catenin in gastric mucosal epithelial cells in all groups were immunohistochemically detected, and the images were taken and analyzed semiquantitatively by image pro plus 6.0 software.</p><p><b>RESULTS</b>Gastric epithelium in the model group showed significantly higher expression levels of Lgr5, MMP-7, Wnt1, Wnt3a and β-catenin than those of the control group(P<0.01). Interestingly, we also observed Lgr5+ cells, which generally located at the base of the gastric glandular unit, migrated to the luminal side of gastric epithelium with GPL. The expression levels of Lgr5, MMP-7, Wnt1, and β-catenin were all down-regulated in the L-WPX group as compared with those of both model and vitacoenzyme groups (P<0.05). A similar, but nonsignificant down-regulation in expression level of Wnt3a was noted in all WPX groups (P>0.05).</p><p><b>CONCLUSION</b>Our findings suggested that the therapeutic mechanisms of WPX in treating GPL might be related with its inhibitory effects on the expressions of Lgr5, MMP-7, Wnt1, β-catenin and the aberrant activation of Wnt/β-catenin pathway.</p>
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Animals , Male , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Epithelial Cells , Metabolism , Pathology , Gastric Mucosa , Pathology , Immunohistochemistry , Matrix Metalloproteinase 7 , Metabolism , Precancerous Conditions , Drug Therapy , Pathology , Rats, Sprague-Dawley , Receptors, G-Protein-Coupled , Metabolism , Staining and Labeling , Stomach Neoplasms , Drug Therapy , Pathology , Wnt Proteins , Metabolism , Wnt Signaling Pathway , beta Catenin , MetabolismABSTRACT
OBJECTIVE@#To build the rat model of gastric precancerous lesions and discuss the effect of transplantation of mesenchymal stem cells (BMMSCs) on the pathological change.@*METHODS@#The rat model of gastric precancerous lesions was built using N-methyl-N'-nitro-N'-nitrosoguanidine. After the intravenous transplantation of BMMSCs, the migration and colonization location was then observed, as well as its effect on the related factors of gastric precancerous lesions, including VEGF, IL-10 and IFN-γ.@*RESULTS@#BMMSCs were mainly colonized in the gastric body and gastric antrum, which could be differentiated into the epithelial and interstitial cells. The expression of VEGF in the transplantation group and non-transplantation group was significantly higher than that in the control group (P < 0.05); while the expression of VEGF in the transplantation group was significantly higher than that in the non-transplantation group (t = 3.88, P < 0.001). The expression of serum IL-10 and IFN-γ in the transplantation group and non-transplantation group was significantly higher than that in the control group (P < 0.05), while the expression of IL-10 and IFN-γ in the transplantation group was significantly lower than that in the non-transplantation group (t = 3.03, P = 0.004; t = 3.80, P < 0.001).@*CONCLUSIONS@#BMMSCs can be directionally differentiated into the epithelial and interstitial cells and can also regulate the related growth factors and inflammatory factors to reduce the injury of inflammation, relieve or reverse the process of gastric precancerous lesions.
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Objective: To build the rat model of gastric precancerous lesions and discuss the effect of transplantation of mesenchymal stem cells (BMMSCs) on the pathological change. Methods: The rat model of gastric precancerous lesions was built using N-methyl-N'-nitro-N'-nitrosoguanidine. After the intravenous transplantation of BMMSCs, the migration and colonization location was then observed, as well as its effect on the related factors of gastric precancerous lesions, including VEGF, IL-10 and IFN-γ Results: BMMSCs were mainly colonized in the gastric body and gastric antrum, which could be differentiated into the epithelial and interstitial cells. The expression of VEGF in the transplantation group and non-transplantation group was significantly higher than that in the control group (P < 0.05); while the expression of VEGF in the transplantation group was significantly higher than that in the non-transplantation group (t = 3.88, P < 0.001). The expression of serum IL-10 and IFN-γ in the transplantation group and non-transplantation group was significantly higher than that in the control group (P < 0.05), while the expression of IL-10 and IFN-γ in the transplantation group was significantly lower than that in the non-transplantation group (t = 3.03, P = 0.004; t = 3.80, P < 0.001). Conclusions: BMMSCs can be directionally differentiated into the epithelial and interstitial cells and can also regulate the related growth factors and inflammatory factors to reduce the injury of inflammation, relieve or reverse the process of gastric precancerous lesions.
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Objective To observe the effect of Weipixiao, a compound recipe which has the actions of strengthening spleen, resolving stasis and removing toxins, on the histopathological changes of gastric mucosal tissue in rats with gastric precancerous lesions ( GPL) . Methods SD rats were randomly divided into normal group, model group, Vitacoenzyme group (0.2 g·kg-1·d-1), and high-, middle-, and low-dose Weipixiao groups ( in the dose of 15, 7.5, 3.75 g·kg-1·d-1, respectively) . Except for the normal control group, the rats in other groups received spontaneous intake of N-methyl-N’-nitro-nitrosoguanidine ( MNNG) solution combined with irregular diet and oral use of purgative herbs for 18 weeks to induce GPL. From the 9th week, the mediation groups were simultaneously given corresponding medicine for 10 weeks. At the end of the experiment, the histopathological changes of gastric mucosal tissue in all groups were observed. Results Pathological scores of intestinal metaplasia and epithelial dysplasia in rat gastric mucosa of the model group were significantly increased ( P<0.01 compared with those of the normal group) , but were decreased in three Weipixiao groups to various degrees, particularly in low-dose Weipixiao group ( P<0.05 or P<0.01) . Conclusion Weipixiao can block and reverse gastric intestinal metaplasia and dysplasia in GPL rats to certain degrees, and low-dose Weipixiao may have better long-term effect for the prevention and treatment of GPL.
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Objective To observe the effect of Yiqi Huayu Recipe on the expression of protein kinase C (PKC) and CyclinE in rats with gastric precancerous lesions (GPL). Methods The model of GPL was established mainly through N-methyl-N-nitro N-nitrosoguanidine (MNNG) together with other factors including alcohol stimulation and undue hunger and overeating. The survived rats after modeling were randomly divided into spontaneous recovery, and high-, moderate- and low-dose Yiqi Huayu group. After the corresponding treatment, the expression of PKC and CyclinE were detected by immunohistochemical method in each group. Results The expression of PKC and CyclinE in trement group were distinctly lower than those in spontaneous recovery group (P
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0.05). Conclusion: Eliminating turbid and detoxication can improve gastric precancerous lesions in rats and reverse the pathological changes of gastric mucosa, and its role in gastric mucosa may be related to the impact of CyclinD1, PTEN mRNA expression.
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Objective To study the clinical value of serum SA,EMA and GPDA in the diagnosis of gastric cancer.Methods To detect serum SA,EMA and GPDA in 30 patients with gastric cancer patients,25 patients with gastric precancerous lesions and 35 patients with non-atrophic gastritis with electronic gastroscope and pathological examination confirmed,compared the differences betwwen the groups,and analyze the relationship between the expressions of them and clinical biology of gastric carcinoma.Results The serum concentrations of SA and GPDA in gastric carcinoma are remarkably higher than those in non-atrophic gastritis and gastric precancerous lesions(P0.05).The concentrations of GPDA in non-atrophic gastritis group are age-related(P0.05).Conclusion It has an important reference value for the diagnosis of gastric cancer to detect serum SA and GPDA.SA and GPDA together can improve the accuracy of the diagnosis of gastric cancer.EMA serum possibly has no diagnostic value for gastric cancer.The expressions of SA,GPDA in serum are related to the biology behaviors of gastric carcinoma,and the concentrations of SA,GPDA in serum is helpful in judging metastasis and recrudescence,and monitoring prognosis.