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.
Humans ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic ; Precancerous Conditions/drug therapy*

Gastric cancer(GC), one of the most common malignancies worldwide, seriously threatens human health due to its high morbidity and mortality. Precancerous lesion of gastric cancer(PLGC) is a critical stage for preventing the occurrence of gastric cancer, and PLGC therapy has frequently been investigated in clinical research. Exploring the proper animal modeling methods is necessary since animal experiment acts as the main avenue of the research on GC treatment. At present, N-methyl-N'-nitro-N-nitroso-guanidine(MNNG) serves as a common chemical inducer for the rat model of GC and PLGC. In this study, MNNG-based methods for modeling PLGC rats in related papers were summarized, and the applications and effects of these methods were demonstrated by examples. Additionally, the advantages, disadvantages, and precautions of various modeling methods were briefly reviewed, and the experience of this research group in exploring modeling methods was shared. This study is expected to provide a reference for the establishment of MNNG-induced PLGC animal model, and a model support for the following studies on PLGC.
Animals ; Gastric Mucosa ; Methylnitronitrosoguanidine/toxicity* ; Precancerous Conditions/chemically induced* ; Rats ; Stomach Neoplasms/drug therapy*

Gastric dysplasia is a neoplastic lesion and a precursor of gastric cancer. The Padova, Vienna, and World Health Organization classifications were developed to overcome the discrepancies between Western and Japanese pathologic diagnoses and to provide a universally accepted classification of gastric epithelial neoplasia. At present, the natural history of gastric dysplasia is unclear. Much evidence suggests that patients with high-grade dysplasia are at high risk of progression to carcinoma or synchronous carcinoma. Therefore, endoscopic resection is required. Although patients with low-grade dysplasia have been reported to be at low risk of progression to carcinoma, due to the marked histologic discrepancies between forceps biopsy and endoscopic specimens, endoscopic resection for this lesion is recommended, particularly in the presence of other risk factors (large size; depressed gross type; surface erythema, unevenness, ulcer, or erosion; and tubulovillous or villous histology). Helicobacter pylori eradication in patients with dysplasia after endoscopic resection appear to reduce the incidence of metachronous lesions.
Anti-Bacterial Agents/therapeutic use ; Biopsy ; Carcinoma in Situ/classification/microbiology/*pathology/*surgery ; Disease Progression ; *Gastrectomy/adverse effects/methods ; Gastric Mucosa/microbiology/*pathology/*surgery ; Gastroscopy ; Helicobacter Infections/drug therapy/microbiology ; Helicobacter pylori/drug effects ; Humans ; Neoplasm Grading ; Precancerous Conditions/classification/microbiology/*pathology/*surgery ; Predictive Value of Tests ; Risk Factors ; Stomach Neoplasms/classification/microbiology/*pathology/*surgery ; Treatment Outcome

OBJECTIVETo 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).

METHODSSprague 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.

RESULTSGastric 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).

CONCLUSIONOur 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.

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Gastric Mucosa ; pathology ; Immunohistochemistry ; Male ; 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 ; drug effects ; beta Catenin ; metabolism

OBJECTIVETo explore the effect of Jianpi Tongluo Jiedu Recipe (JTJR) on protein expression levels of COX-2, NF-kappaBp65, Bcl-2, and Bax, mRNA expression levels of COX-2 and Bcl-2, and the apoptotic index (Al) in gastric mucosa of patients with precancerous lesions of gastric cancer (PL-GC).

METHODSTotally 65 PLGC patients were recruited and treated by JTJR (modified by syndrome typing), one dose per day for six successive months. Protein expression levels of COX-2, NF-KBp65, Bcl-2, and Bax were detected in 65 patients using immunohistochemical (IHC) assay before and after treatment. mRNA expression levels of COX-2 and Bcl-2 were detected in 54 patients using reverse transcription-polymerase chain reaction (RT-PCR). Meanwhile, changes of Al was detected in 65 patients using TdT-mediated dUTP-biotin nick end labeling (TUNEL) fluorescence method.

RESULTSAfter treatment with JTJR, positive protein expression levels of COX-2, NF-KBp65, and Bcl-2 were obviously decreased in the gastric mucosa of PLGC patients (P <0.01), but Bax positive protein expression was found to be higher (P < 0.05). At the same time mRNA expression levels of COX-2 and Bcl-2 were significantly lower after treatment than before treatment (P < 0.05, P < 0.01); Al also increased after treatment (P < 0.05).

CONCLUSIONJTJR could promote apoptosis possibly via NF-kappaBp65/COX-2, COX-2/Bcl-2, and NF-kappaBp65/Bcl-2 signaling pathways, thereby affecting PLGC patients.

Apoptosis ; Cyclooxygenase 2 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Gastric Mucosa ; metabolism ; Humans ; NF-kappa B ; metabolism ; Precancerous Conditions ; drug therapy ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Signal Transduction ; Stomach Neoplasms ; drug therapy ; metabolism ; bcl-2-Associated X Protein ; metabolism

Endometrial Neoplasms ; drug therapy ; pathology ; Female ; Humans ; Precancerous Conditions ; drug therapy ; pathology ; Progestins ; therapeutic use

OBJECTIVETo explore the effect of Yanghe Huayan Decoction (YHD, a representative recipe for warming yang mass dissipating) in inhibiting precancerosis of breast cancer (PBC) and on the protein and mRNA expression of ki67.

METHODSThe PBC rat model was established by dimethylbenzanthracene (DMBA), and 9 weeks later rats were randomly divided into the blank control group, the model group, the YHD group, the Sanjie Huatan Decoction group (SHD), the Pingxiao Tablet group (PT), and the tamoxifen group. Rats in the model group were administered with water by gastrogavage. Rats in the YHD group received YHD (deglued antler powder 12 g, prepared rhizome of rehmannia 9 g, cassia bark 6 g, white mustard seed 3 g, zedoary root 12 g, appendiculate cremastra pseudobulb 15 g, chekiang fritillary bulb 9 g, licorice root 6 g) at the daily dose of 7.2 g/kg by gastrogavage. Rats in the SHD group received SHD (oldenlandia diffusa 15 g, Scutellaria Barbata 15 g, Trichosanthes Kirilowii 15 g, pinellia 9 g) at the daily dose of 5.4 g/kg by gastrogavage. Rats in the PT group received PT at the daily dose of 144 mg/kg by gastrogavage. Those in the tamoxifen group received tamoxifen at the daily dose of 4 mg/kg by gastrogavage. Pathomorphological changes of the breast tissue were observed by HE staining. The positive rate and the gray value of ki67 expression were detected by immunohistochemical assay. And the expression of ki67 mRNA was detected by q-PCR.

RESULTSCompared with the model group, the general hyperplasia and the occurrence rate of precancerous lesion were higher and the occurrence rate of invasive carcinoma was lower in each treatment group (P < 0.05). Except the SHD group, the intensity of ki67 grey value increased in each treatment group (P < 0.05, P < 0.01). Except the PT group, the positive rate of ki67 and mRNA expression of ki67 increased in the rest treatment groups (P < 0.05, P < 0.01). Compared with the YHD group, there was no statistical difference in the occurrence rate of infiltration or the occurrence rate of precancerous lesion (P > 0.05). The positive rate of ki67 expression and mRNA expression of ki67 increased in the PT group, showing statistical difference (P < 0.05).

CONCLUSIONSYHD could partially inhibit and reverse canceration of breast cancer. It also could inhibit ki67 protein and mRNA expression. Its effect was similar to tamoxifen and superior to PT. So it was suitable for prevention and treatment of precancerous lesion of breast cancer.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Ki-67 Antigen ; metabolism ; Mammary Neoplasms, Experimental ; chemically induced ; drug therapy ; metabolism ; Precancerous Conditions ; drug therapy ; metabolism ; Rats ; Rats, Sprague-Dawley

Drugs, Chinese Herbal ; therapeutic use ; Humans ; Phytotherapy ; Precancerous Conditions ; drug therapy ; pathology ; Stomach Neoplasms ; drug therapy ; pathology

OBJECTIVETo explore the possible angiogenesis mechanism of Huazhuo Jiedu Hewei Recipe (HJHR) in preventing and treating precancerous lesions of gastric cancer (PLGC).

METHODSTotally 66 Wistar rats were randomly divided into 6 groups, i.e., the normal control group, the model group, the retinoic acid (RA) group, the high dose HJHR group, the middle dose HJHR group, the low dose HJHR group, 11 in each group. PLGC model was duplicated by inserting a spring with Helicobacter. Corresponding medicines were administered to rats in each medicated group once daily by gastrogavage, 2 mL each time for 12 successive weeks. The effect of HJHR on hypoxia induced factor (HIF-1alpha) and vascular endothelial growth factor (VEGF) of PLGC in chronic atrophic gastritis (CAG) rats' gastric mucosa was observed by immunohistochemical assay and Western blot method.

RESULTSCompared with the normal control group, the expression of VEGF and HIF-1alpha increased in the model group (P < 0.05). Compared with the model group, the expression of VEGF and HIF-1alpha decreased in each medicated group (P < 0.05). Besides, they were lower in the high and middle dose HJHR groups than in the RA group and the low dose HJHR group (P < 0. 05). There was no statistical difference between the low dose HJHR group and the RA group (P > 0.05).

CONCLUSIONHJHR could prevent and treat PLGC of CAG rats possibly through decreasing the expression of HIF-1alpha and VEGF in a dose-dependent manner.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Gastric Mucosa ; metabolism ; Gastritis ; metabolism ; microbiology ; Helicobacter ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Male ; Neovascularization, Pathologic ; Precancerous Conditions ; blood supply ; drug therapy ; metabolism ; Rats ; Rats, Wistar ; Stomach Neoplasms ; blood supply ; drug therapy ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism

BACKGROUND/AIMS: Eradication of Helicobacter pylori reduces the incidence of gastric cancer, and may inhibit gastric dysplasia progression into gastric cancer. The aim of this study was to investigate the effect of eradication of Helicobacter on the incidence of subsequent gastric dysplasia development after endoscopic resection. METHODS: Medical records of patients who underwent endoscopic resection for gastric dysplasia were retrospectively reviewed. Presence of H. pylori was assessed by the Campylobacter-like organism test and histology. The rate of subsequent dysplasia development after endoscopic resection between the eradication group and non-eradication group was compared. RESULTS: Total of 129 patients positive for H. pylori infection were included for analysis. Of these, 85 patients received successful eradication therapy and 44 patients did not receive eradication therapy or failed to achieve successful eradication. Sex, mean age and pathologic grade of dysplasia did not differ between the two groups. In univariate analysis, the grade of intestinal metaplasia (p=0.013) significantly differed between metachronous dysplasia group and non-metachrounous dysplasia group. In multivariate analysis, eradication of H. pylori (p=0.014) was related to reduced incidence of subsequent gastric dysplasia development after endoscopic resection. CONCLUSIONS: Eradication of H. pylori likely has a beneficial effect in preventing the development of subsequent gastric dysplasia, a premalignant lesion of gastric cancer, after endoscopic resection.
Aged ; Anti-Bacterial Agents/*therapeutic use ; Female ; Gastric Mucosa/pathology/surgery ; Gastroscopy ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Male ; Metaplasia/pathology ; Middle Aged ; Neoplasm Recurrence, Local/pathology ; Precancerous Conditions/*pathology ; Proportional Hazards Models ; Retrospective Studies ; Stomach Neoplasms/pathology/*surgery