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AIM:To observe the effect of Pingwei capsule on the precancerous lesions of gastric cancer(PLGC)cell model induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG),and to preliminarily explore its mecha-nism.METHODS:Blank serum and Pingwei capsule-containing serum were prepared for later use.A PLGC cell model was established by MNNG-induced human gastric mucosal epithelial cell line GES-1.To evaluate the model,cell morpho-logical changes were observed under inverted microscope,and the expression of proliferating cell-related antigen Ki67 was detected by immunofluorescence staining.CCK-8 assay was used to screen the optimal intervention concentration and time of serum containing drugs.Reactive oxygen species(ROS)content in cells was detected using a fluorescent probe DCFH-DA.Malondialdehyde(MDA)content was detected by ELISA,and the activity of superoxide dismutase(SOD)and gluta-thione peroxidase(GSH-Px)was detected using biochemical reagents.A novel fluorescent probe JC-10 was used to detect mitochondrial membrane potential.The mRNA expression levels of Ki67 and melanoma differentiation-associated gene-7(MDA-7)were detected by real-time fluorescence quantitative PCR.The protein expression levels of Ki67,interleukin-6(IL-6)and MDA-7 were detected by Western blot.RESULTS:Compared with normal group,the ROS and MDA levels in model group and blank serum group were significantly increased(P<0.01),while the activity of SOD and GSH-Px was significantly decreased(P<0.01).The mitochondrial membrane potential was significantly decreased(P<0.01).The protein expression levels of Ki67 and IL-6 were significantly increased(P<0.01),while the protein expression level of MDA-7 was significantly decreased(P<0.01).There were no significant differences of the above indicators between model group and blank serum group(P>0.05).Compared with blank serum group,the Pingwei capsule-containing serum group showed significantly decreased ROS and MDA levels(P<0.01),significantly increased activity of SOD and GSH-Px(P<0.05),significantly increased mitochondrial membrane potential(P<0.01),significantly decreased protein expres-sion levels of Ki67 and IL-6(P<0.01),and significantly increased protein and mRNA expression levels of MDA-7(P<0.01).CONCLUSION:Pingwei capsule can significantly alleviate MNNG-induced oxidative damage and inflammatory response,and regulate the expression of oncogenes and tumor suppressor genes,thereby playing a role in prevention and treatment of PLGC.
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Objective To analyze the diagnostic efficacy and clinical significance of magnifying endoscopy combined with narrow-band imaging(ME-NBI),acetate-indigo rouge staining and multi-slice spiral CT for early gastric cancer and precancerous lesions.Methods 202 patients with suspected early gastric cancer and precancerous lesions from February 2019 to March 2022 were regarded as the subjects of this study,all the patients underwent ME-NBI,acetate-indigo rouge staining,and multi-slice spiral CT examination;The diagnostic value of different examination methods for early gastric cancer and precancerous lesions was analyzed using the receiver operator characteristic curve(ROC curve),using the pathological results of gastric cancer as the gold standard,the diagnostic value of ME-NBI,acetate-indigo rouge staining combined with multi-slice spiral CT and their combination in early gastric cancer and precancerous lesions was analyzed using a four grid table.Results The image quality of ME-NBI and acetate-indigo rouge staining combined examinations was significantly higher than that of their respective independent examinations(P<0.05).There was significant difference in the degree of differentiation in the clinical features of patients with early gastric cancer and precancerous lesions(P<0.05).The area under the curve(AUC)of ME-NBI for the diagnosis of early gastric cancer and precancerous lesions was 0.853,the accuracy was 85.64%,the sensitivity was 88.37%,and the specificity was 83.62%.The AUC of acetate-indigo rouge staining for the diagnosis of early gastric cancer and precancerous lesions was 0.814,the accuracy was 81.68%,the sensitivity was 83.72%,and the specificity was 80.17%.The AUC of multi-slice spiral CT for the diagnosis of early gastric cancer and precancerous lesions was 0.804,with an accuracy of 80.69%,a sensitivity of 82.56%,and a specificity of 79.31%.And the AUC of the three methods combined to diagnose early gastric cancer and precancerous lesions was 0.893,with an accuracy of 89.60%,a sensitivity of 93.02%,and a specificity of 87.07%.Conclusion ME-NBI,acetate-indigo rouge staining combined with multi-slice spiral CT has high diagnostic efficacy in early gastric cancer and precancerous lesions,and can be used in clinical practice.
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The angiogenic microenvironment is a new blood vessel with different molecular and functional characteristics that sprouts on the original blood vessels through different mechanisms,which directly affects the process of tumor cell growth,proliferation,and migration and has an important impact on the occurrence and development of precancerous lesions of gastric cancer.Correa mode has shown that precancerous lesions of gastric cancer is the key pathological stage before the occurrence of gastric cancer,and it is of great significance to advance the prevention and treatment strategy to this stage.TCM believes that qi deficiency and blood stasis is the key pathogenesis of precancerous lesions of gastric cancer,and its basic treatment is to replenish qi and remove blood stasis,and based on the syndrome differentiation,drugs with the efficacy of nourishing yin and tonifying stomach,soothing the liver and regulating qi,resolving phlegm and dispersing lumps,and clearing heat and dampness for treatment.This article discussed the correlation between precancerous lesions of gastric cancer and angiogenic microenvironment and its regulatory pathways,and summarized the methods and mechanisms of TCM in the treatment of precancerous lesions of gastric cancer from the perspective of regulating angiogenic microenvironment-related pathways,in order to provide a reference for the treatment of precancerous lesions of gastric cancer with TCM.
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ObjectiveThis study aims to investigate the mechanism in which Celastrus orbiculatus extract （COE） affects the proliferation and differentiation of gastric organoids and the expression of Lgr5 and thus reverses the precancerous lesions of gastric cancer （PLGC） by regulating the leucine-rich repeat containing G protein-coupled receptor 5 （Lgr5）/Wingless （Wnt）/β-catenin signaling pathway based on a gastric organoid injury model. MethodGastric organoids were established based on stem cells of the mouse gastric gland. Gastric organoid injury models were constructed by treating gastric organoids with N-methyl-N'-nitro-N-nitrosoguanidine （MNNG， 0.02 mg·L-1）. Gastric organoid injury models were randomly divided into normal group， model group （0.02 mg·L-1 MNNG）， low， medium， and high dose （5， 10， 20 mg·L-1） groups of COE， and Wnt inhibitor Dickkopf-related protein 1 （DKK1） （0.5 mg·L-1） group， and they were treated with respective agents for 24 h. The number and volume of gastric organoids under different drug concentrations were observed under a microscope. The viability of the gastric organoid injury models was detected by Methyl thiazolyl tetrazolium （MTT） assay. The morphology and pathology of gastric organoids were observed using Hematoxylin and Eosin （HE） staining. The expression levels of Lgr5， Mucin2 （MUC2）， Mucin5AC （MUC5AC）， Mucin6 （MUC6）， Wnt， and β-catenin in gastric organoids under different drug concentrations were detected by Western blot （WB）. ResultCompared with the normal group， the number， volume， and activity of gastric organoids in the model group were decreased （P<0.01）， while the expressions of Lgr5， MUC2， Wnt， and β-catenin were significantly increased （P<0.01）. The expressions of MUC5AC and MUC6 were significantly decreased （P<0.01）. Compared with the model group， the number and volume of gastric organoids in the low， medium， and high dose groups of COE were all improved （P<0.01）， and the vitality of gastric organoids was significantly enhanced （P<0.01）. The effect was the most significant at a COE concentration of 20 mg·L-1 （P<0.01）. The expressions of Lgr5 and MUC2 in the medium and high dose groups of COE were significantly reduced （P<0.01）， while the expression of MUC5AC and MUC6 were significantly increased in the low， medium， and high dose groups of COE （P<0.05， P<0.01）. Compared with the model group， Wnt inhibitors could promote the expression of MUC5AC and MUC6 in gastric organoids （P<0.05， P<0.01） and reduce the expression of MUC2， Wnt， and β-catenin. In addition， the combined use of COE at high concentrations and Wnt inhibitors could further promote this trend （P<0.01）. ConclusionCOE inhibits the Wnt/β-catenin pathway by inhibiting the expression of Lgr5， MUC2， Wnt， and β-catenin and promoting the expression of MUC5AC and MUC6， thus promoting the proliferation and differentiation of gastric organoids and reversing the PLGC process.
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Malignant tumors have surpassed stroke and coronary heart disease to become the main cause of death before the age of 70 in the world. The incidence of malignant tumors is increasing year by year， which seriously affects the living standards and social and economic development of Chinese people. Surgery， radiotherapy， chemotherapy， targeted therapy， and immunotherapy are the main means of Western medicine to intervene in tumors， which are of great significance for prolonging the survival time of patients. However， there are many disadvantages such as adverse reactions and drug resistance. Traditional Chinese medicine has become a research hotspot in recent years because of its definite curative effect and wide application in tumor treatment. Xiao Chaihutang is derived from the Treatise on Febrile and Miscellaneous Diseases. It is composed of Bupleuri Radix， Scutellariae Radix， Ginseng Radix， Pinelliae Rhizoma， Glycyrrhizae Preparata Radix， Ginger， and Jujube. It has the effects of reconciling Shaoyang， reconciling cold and heat Yin and Yang， soothing the liver， and relieving depression. This prescription and the prescriptions based on it are widely used in various stages of tumors. This study summarized the Chinese and foreign research of Xiao Chaihutang in the field of tumors in the past 10 years and explored the role and mechanism of Xiao Chaihutang in blocking precancerous lesions， controlling the development of malignant tumors， reducing the occurrence of adverse reactions after intervention， and alleviating common complications， with a view to expanding the clinical medication ideas.
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OBJECTIVE To investigate the correlation between the expression levels of tissue inhibitor of metalloproteinases 1(TIMP-1)and drosophila mothers against DDP homolog 4(Smad4)in vocal cord precancerous lesions and postoperative recurrence and malignant transformation.METHODS The clinical and pathological data of 162 patients with vocal cord precancerous lesions admitted to the First Affiliated Hospital of Zhengzhou University from August 2018 to August 2021 were retrospectively analyzed.The expression of TIMP-1 and Smad4 in the surgically removed precancerous tissues(precancerous lesion group)and adjacent normal mucosal tissues(control group)were detected by immunohistochemical method.The relationship between the positive rate of TIMP-1 and Smad4 and clinicopathological features was analyzed.Kaplan-Meier method and Cox regression analysis were used to analyze the effect on postoperative recurrence and malignant transformation.RESULTS Compared with the normal mucosa of the control group,the positive rate of TIMP-1 was higher and the positive rate of Smad4 was lower in the precancerous lesion group(P<0.05).The positive rates of TIMP-1 and Smad4 in patients with different lesion ranges,anterior commissure involvement and different degree of epithelial dysplasia were different(P<0.05).Postoperative follow-up lasted from 24 to 60 months,with a median follow-up time of 36 months.During the follow-up,6 patients were lost to follow-up,with a follow-up rate of 96.30%(156/162).During the follow-up,35 patients had postoperative recurrence(21.60%)and 16 patients had postoperative malignant transformation(9.88%).Kaplan-Meier survival analysis showed that the postoperative recurrence rate and malignant change rate of TIMP-1 positive patients were higher than those of TIMP-1 negative patients(P<0.05),amd the recurrence rate and malignant change rate of Smad4-negative patients were higher than those of Smad4-positive patients(P<0.05).Multivariate Cox regression analysis showed that laryngeal reflux,lesion scope>1/2,moderate/severe dysplasia,TIMP-1 positive and Smad4 negative were independent risk factors for recurrence(P<0.05),and age>60 years old,anterior union involved,TIMP-1 positive and Smad4 negative were independent risk factors for malignant transformation(P<0.05).CONCLUSION The patients with high expression of TIMP-1 and low expression of Smad4,positive expression of TIMP-1 and negative expression of Smad4 have higher risk of postoperative recurrence and malignant transformation.
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Objective To investigate the therapeutic effect and mechanism of Jianwei Xiaozhang Tablets on rats with precancerous lesions of gastric cancer(PLGC).Methods Forty male SD rats were randomly divided into the normal group,the model group,the folic acid group and the Jianwei Xiaozhang Tablets group,with 10 rats in each group.In addition to the normal group,the other three groups of rats were prepared by gavage with Ranitidine Aqueous Solution combined with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)solution drinking method for the preparation of PLGC model.After successful modeling,drugs were administered accordingly for 7 weeks.The changes in body mass of rats during modeling and drug administration were recorded,the gross view of the stomach was observed and scored pathologically,the coefficients of spleen and liver were determined,the pathological changes in gastric tissue were observed by hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA)was used to measure serum gastrin(GAS),motilin(MTL)and glucagon(GC),Alisin Blue-Periodic Acid Schiff's(AB-PAS)staining was used to observe the thickness of the mucosal layer of gastric tissues,the expressions of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),and endothelial-type nitric oxide synthase(eNOS)proteins in gastric tissues were detected by protein immunoblotting(Western Blot),and the expression of vascular endothelial growth factor A(VEGFA)protein in gastric tissues was detected by immunofluorescence staining.Results Compared with the normal group,the body mass of rats in the model group grew slowly during the experimental period,gastric macroscopic pathological scores were significantly increased(P＜0.01),splenic coefficient and hepatic coefficient were significantly decreased(P＜0.01),the gastric tissues showed cuprocyte hyperplasia and intestinal chemotaxis,gastric tissues'inflammation scores were significantly increased(P＜0.01),the serum GAS content was significantly increased(P＜0.01),and the MTL,GC contents were significantly reduced(P＜0.05),and the thickness of the mucous membrane layer of gastric tissue was significantly reduced(P＜0.05),the protein expression levels of PI3K,p-PI3K,Akt,p-Akt and eNOS were reduced(P＜0.01),and the protein expression level of VEGFA was reduced(P＜0.01);compared with the model group,the above indexes of the Jianwei Xiaozhang Tablets group and the folic acid group were all significantly improved(P＜0.05 or P＜0.01),among which,the Jianwei Xiaozhang Tablets group had a better improvement effect in the proliferation of cup cells and intestinal chemotaxis in gastric tissues,the content of serum GAS,and the thickness of the mucous layer in gastric tissues.Conclusion The mechanism of the improvement of PLGC in rats by Jianwei Xiaozhang Tablets may be related to the activation of the PI3K-Akt-eNOS pathway,which in turn promotes the angiogenesis and repair of gastric damaged tissues.
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@#Esophageal cancer is an aggressive malignancy with high morbidity and poor prognosis. Symptoms of early esophageal cancer are insidious and difficult to detect, while advanced esophageal obstruction, lesion infiltration and metastasis seriously affect patients’ quality of life. Early detection and treatment can help to increase the survival chance of patients. Recently, artificial intelligence (AI) has shown remarkable success in diagnosis of esophageal cancer, highlighting the great potential of new AI-assisted diagnostic modalities. This paper aims to review recent progress of AI in the diagnosis of esophageal cancer and to prospect its clinical application.
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The UPLC-MS/MS was established for the determination of acetyl-11-keto-beta-boswellic acid(AKBA) and β-boswellic acid(β-BA), the main active components of Olibanum and Myrrha extracts in Xihuang Formula, in rat plasma and urine. The effects of compatibility on the pharmacokinetic behaviors of AKBA and β-BA in rats were investigated, and the differences in pharmacokinetic behaviors between healthy rats and rats with precancerous lesions of breast cancer were compared. The results showed that compared with RM-NH and RM-SH groups, the AUC_(0-t) and AUC_(0-∞) of β-BA increased(P<0.05 or P<0.01), T_(max) decreased(P<0.05 or P<0.01), and C_(max) increased(P<0.01) after compatibility. The trends of AKBA and β-BA were the same. Compared with RM-SH group, the T_(max) decreased(P<0.05), C_(max) increased(P<0.01), and the absorption rate increased in the normal group of Xihuang Formula. The results of urinary excretion showed that there was a decreasing trend in the urinary excretion rate and total urinary excretion of β-BA and AKBA after compatibility, but there was no statistical difference. Compared with normal group of Xihuang Formula, the AUC_(0-t) and AUC_(0-∞) of β-BA increased(P<0.05), T_(max) increased(P<0.05), and the clearance rate decreased in the breast precancerous lesion group. AUC_(0-t) and AUC_(0-∞) of AKBA showed an increasing trend, the in vivo retention time was prolonged, and the clearance rate was reduced, but there was no significant difference compared with the normal group. The cumulative urinary excretion and urinary excretion rate of β-BA and AKBA decreased under pathological conditions, indicating that pathological conditions could affect the in vivo process of β-BA and AKBA, and reduce their excretion in the form of prototype drugs, showing different pharmacokine-tic characteristics from normal physiological conditions. In this study, UPLC-MS/MS analysis method was established, which was sui-table for in vivo pharmacokinetic analysis of β-BA and AKBA. This study laid a foundation for the development of new dosage forms of Xihuang Formula.
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Ratas , Animales , Cromatografía Liquida , Espectrometría de Masas en Tándem , Medicamentos Herbarios Chinos , Lesiones Precancerosas , Triterpenos/farmacologíaRESUMEN
Objective:To evaluate the clinical efficacy and safety of endoscopic submucosal dissection (ESD) for early colorectal cancer and its precancerous lesions by using novel lifting clip-assisted traction.Methods:From March to July 2021, 42 patients with colorectal lesions who received ESD at the Digestive Endoscopy Center of Shanghai Tenth People's Hospital were included in the retrospective study. Nineteen patients were enrolled as the observation group using the novel lifting clip, and 23 others in the control group without the help of an auxiliary method. The operation time, the hospital stay, hospital expenses and the incidence of complications of the two groups were compared.Results:All 42 patients successfully received ESD. The operation time of the observation group was significantly shorter than that of the control group [31.00 (21.00, 58.00) min VS 60.00 (30.00, 75.00) min, Z=-2.04, P=0.04]. The postoperative hospital stay of the observation group was significantly shorter than that of the control group [2.00 (1.00, 2.00) d VS 2.00 (2.00, 3.00) d, Z=-1.99, P=0.04]. The hospital cost was lower than that of the control group, but the difference was not statistically significant (19 331.42 ± 3 481.20 yuan VS 19 802.40 ± 2 548.50 yuan, t=-0.49, P=0.63). No intraoperative perforation occurred in either group. There was no significant difference in intraoperative blood loss between the observation group and the control group [0.00 (0.00, 5.00) mL VS 3.00 (0.00, 7.00) mL, Z=-1.42, P=0.16]. There was 1 case of postoperative abdominal pain in the observation group, 2 cases of postoperative abdominal pain and 1 case of fever in the control group. There was no significant difference in the overall incidence of postoperative complications between the observation group and the control group [5.3% (1/19) VS 13.0% (3/23), χ2=0.73, P=0.39]. Conclusion:The novel lifting clip-assisted colorectal ESD is safe and effective, which can significantly shorten the ESD operation time and postoperative hospital stay without increasing the economic burden of patients.
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Objective:To investigate the risk factors for positive margins after endoscopic submucosal dissection (ESD) for early gastric cancer and precancerous lesions, and to follow up the recurrence.Methods:The endoscopic, clinical and pathological data of 489 patients with early gastric cancer or precancerous lesions treated by ESD in Fujian Provincial Hospital from January 2015 to December 2020 were retrospectively collected. They were categorized into a negative group (371 cases), a low-grade intraepithelial neoplasia (LGIN)-positive group (79 cases), and a high-grade intraepithelial neoplasia (HGIN) or cancer-positive group (39 cases) according to the different margins. Logistic regression was used to analyze the risk factors for positive margins, the Kaplan-Meier method and log-rank test to compare the risk of recurrence in different margin groups, and the Cox proportional risk regression model to explore the associated factors that caused recurrence in those with positive margins.Results:In the 489 patients, the positive resection margin rate was 24.1% (118/489), of which HGIN or cancer accounted for 33.1% (39/118). LGIN-positive margin was more likely to occur for lesions larger than 10 cm 2 ( OR=1.58, 95% CI: 1.13-2.08, P=0.033), in the presence of ulcers ( OR=2.92, 95% CI: 1.37-4.54, P=0.012) and for 1-2 years of ESD experience [ OR=1.69 (1-2 years VS 5-6 years), 95% CI: 1.51-1.94, P=0.026]. Those located in the upper 1/3 of the stomach [ OR=3.64 (upper 1/3 VS lower 1/3), 95% CI: 1.27-5.50 P=0.010] and submucosal infiltration (SM1 VS M1+M2: OR=2.37, 95% CI: 1.04-5.72, P=0.028; SM2 VS M1+M2: OR=6.08, 95% CI: 1.31-12.75, P=0.002) were high risk factors for HGIN/cancer-positive margin. Postoperative follow-up was completed in 337 patients, with a median follow-up time of 26.0 (22) months. The overall cumulative recurrence was 5.3% (18/337), 2.1% (5/239) in the negative margin group, 8.3% (6/72) in the LGIN-positive margin group, and 26.9% (7/26) in the HGIN/cancer-positive group, with statistically significant differences among the 3 groups ( P<0.05). Risk factors for recurrence in the positive margin group included positive basal margins ( HR=5.17, 95% CI: 1.47-14.09, P=0.011) and SM1 invasion ( HR=4.82, 95% CI: 1.38-14.77, P=0.013). Conclusion:Positive margins after ESD for early gastric cancer and precancerous lesions are related to lesion location, size, presence of ulceration, depth of infiltration, and endoscopists' experience. The overall risk of recurrence is higher in those with positive margins than in those with negative margins. Additional treatments need to be considered comprehensively for those with submucosal invasion and positive basal margins.
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According to the latest statistical data, the incidence and mortality rate of hepatocellular carcinoma in China are still on the rise, posing a major threat to the health of the Chinese population. The occurrence is closely related to the formation of precancerous lesions in the liver. The clinical and basic research on precancerous lesions of hepatocellular carcinoma has developed rapidly, and the concepts and specific techniques for diagnosis and treatment have also undergone new changes and advancements. Therefore, based on the first version in 2020, this consensus has organized multidisciplinary experts to compile and improve a new version by integrating the latest progress in their respective professional fields at home and abroad. It aims to enhance clinicians' understanding of precancerous lesions of hepatocellular carcinoma standardize the pathology, imaging, and molecular diagnostic criteria, broaden early screening methods, formulate scientifically rational treatment plans, and help promote the advancement of diagnosis and treatment strategies and to enhance the overall 5-year survival rate of patients with hepatocellular carcinoma.
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Humanos , Carcinoma Hepatocelular/terapia , Consenso , Neoplasias Hepáticas/terapia , Lesiones Precancerosas/terapiaRESUMEN
Precancerous lesions of gastric cancer (PLGC) is a pathological change accompanied by intestinal metaplasia and dysplasia on the basis of chronic atrophic gastritis. It is also an important stage of "inflammation-cancer transformation" on gastric mucosa. Paying attention to the intervention of PLGC has important value and significance for the secondary prevention of gastric cancer. PLGC has the characteristics of occult onset, toxin damaging collaterals, and long course of disease, which is highly consistent to the pathogenesis characteristics of incubative pathogenic factors. Based on the relevance of incubative pathogenic factors and PLGC, treatment of PLGC from the perspective of incubative pathogenic factors should be mainly strengthening the spleen and stomach, and combined with the methods of regulating qi and dissipating dampness, and removing blood stasis and detoxification. It should also pay attention to the prognosis.Paying attention to the body-mind treatment can reduce the re-occurrence , so as to provide a new way of thinking for treating PLGC from incubative pathogenic factors.
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ObjectiveTo investigate the effect of Qi-invigorating and blood-activating therapy on the miR216b/Beclin1 pathway in mice with atrophic precancerous lesions of gastric cancer （PLGC） and analyze its mechanism in autophagy of PLGC. MethodSeventy-five healthy male SPF KM mice were randomly divided into a blank group and a model group. Mice in the model group were given 1-methyl-3-nitroso-1-nitrosoguanidine （MNNG） solution （150 mg·L-1） for free drinking and gavage and ranitidine solution （0.03 g·kg-1） daily for 12 weeks. According to the random control table， mice were divided into a model group， a Qi-invigorating group （3.5 g·kg-1 of Astragali Radix）， a blood-activating group （0.7 g·kg-1 of Notoginseng Radix et Rhizoma powder）， a Qi-invigorating and blood-activating group （3.5 g·kg-1 of Astragali Radix + 0.7 g·kg-1 of Notoginseng Radix et Rhizoma powder）， and a folic acid group （2 mg·kg-1）. The corresponding drugs were given to mice in each group for 8 weeks and then the tissues were collected. Hematoxylin-eosin （HE） staining was carried out to observe the changes in gastric mucosa. Western blot was used to detect the protein expression of microtuble-associated protein 1 light chain 3 （LC3）Ⅰ， LC3Ⅱ， and Beclin1. Real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of Beclin1 and miR-216b. ResultPathological observation showed that as compared with the blank group， the intrinsic glands of gastric mucosa decreased with atrophy and intestinal metaplasia in the model group， which were improved in all treatment groups， and the improvement of the Qi-invigorating and blood-activating group was the most obvious. As compared with the blank group， the content of LC3Ⅰ， LC3Ⅱ， LC3Ⅱ/LC3Ⅰ， and Beclin1 protein in gastric tissues of the model group was significantly decreased （P<0.05）. As compared with the model group， the content of LC3Ⅰ， LC3Ⅱ， LC3Ⅱ/LC3Ⅰ， and Beclin1 protein in gastric tissues of each treatment group was increased （P<0.05， P<0.01）. The increase was most obvious in the Qi-invigorating and blood-activating group. As compared with the blank group， the mRNA expression of Beclin1 in the model group was decreased （P<0.05）， and that of miR216b was increased （P<0.05）. As compared with the model group， the mRNA expression of Beclin1 was increased and that of miR216b was decreased in each treatment group （P<0.05）， and the changes were the most obvious in the Qi-invigorating and blood-activating group. ConclusionThe mechanism of the Qi-invigorating and blood-activating therapy， represented by Astragali Radix and Notoginseng Radix et Rhizoma， in treating PLGC may be through inhibiting the expression of miR216b and activating Beclin1， thus promoting autophagy and repairing gastric mucosa.
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To investigate the effect of Zhiwei Fuwei Pills (ZWFW) on the expression of mammalian target of rapamycin (mTOR)/autophagy key molecule yeast Atg6 homologue (Beclin1)/microtubuleassociated protein 1 light chain 3 (LC3) signaling axis key molecules in gastric antrum tissue of rats with precancerous gastric lesions (PLGC). METHODS: SPF SD rats were randomly divided into normal group, model group, folic acid group, ZWFW low-dose, medium-dose, high-dose group. In addition to the normal group, the model group, folic acid group, ZWFW low-dose, medium-dose and high-dose groups, were used to establish the PLGC rat model by five factors compound modeling methods: N-methyl-N ' - nitro-n-nitroguanidine (MNNG) combined with hunger and satiation, ethanol intragastric administration, free drinking of ammonia and ranitidine feed. The rats were treated with normal saline, folic acid tablet aqueous solution (0.002 g/kg), ZWFW low-dose, medium-dose, high-dose aqueous solution (0.42, 0.84, 1.67 g/kg) for 4 weeks, and the stomach was removed by laparotomy. Hematoxylineosin (HE) staining was used to observe the histopathological changes in the antrum of rats, and real-time polymerase chain reaction (real-time PCR), Western blot (WB) and immunohistochemistry (IHC) were used to detect the expression of mammalian target of rapamycin mTOR, yeast Atg6 homologue 1 (Beclin1), microtubule-associated protein 1 light chain 3β (LC3B) mRNA and protein in the antrum of rats. RESULTS: Compared with the normal group, the Gastric antrum tissue of the model group was distended, thinner gastric wall, palegastric mucosa, atrophic and flat folds, disordered course and nodules and vegetations were visible. HE staining showed that compared with the normal group, the gastric mucosal glands in the model group were crowded and disordered, and the cell morphology was different, including a large number of goblet cells, basophilic cytoplasm, large, hyper-chromatic and irregular nuclei, and mucosal muscle infiltration and destruction. Compared with the model group, treated by ZWFW can significantly improve the pathological manifestations of gastric mucosal gland structure disorder and cell atypia. Compared with the normal group, mTOR mRNA and protein expression were significantly increased (P< 0.05) and Beclin1 and LC3B mRNA and protein expression were significantly decreased (P<0.05) in the antral tissue of rats in the model group; compared with the model group, mTOR mRNA and protein expression were decreased (P<0.05) in the medium and high dose groups of ZWFW, Beclin1 and LC3B protein expression in the antral tissue of rats in the low dose group of ZWFW and Beclin1 and LC3B mRNA and protein expression were increased (P<0.05) in the medium and high dose groups. CONCLUSION: Zhiwei Fuwei Pills can significantly improve the abnormal histopathological findings of gastric mucosa in PLGC model rats, and the mechanism may be related to the down-regulation of mTOR expression, up-regulation of Beclin1 and LC3B expression and then promoting autophagy.
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Gastric cancer is one of the most common malignant tumors of the digestive system， with a high incidence， a low overall survival rate， and poor prognosis after treatment. It has become a major public health problem that threatens the lives and health of people. Since the pathogenesis of gastric cancer is still not fully unraveled， it is difficult to implement primary prevention. Therefore， the research on secondary prevention of gastric cancer， i.e.， precancerous lesions of gastric cancer， is extremely important and has become the focus of many researchers. Precancerous lesions of gastric cancer are the key pathological links in the transformation of inflammatory lesions of gastric mucosa into gastric cancer， including chronic atrophic gastritis， intestinal metaplasia， and dysplasia. Relevant studies have confirmed that with the aggravation of gastric mucosal lesions， the incidence and risk of gastric cancer also increase. Therefore， early diagnosis and effective intervention in the pathological link of gastric precancerous lesions is a key measure to prevent and reduce the incidence of gastric cancer， with great significance. More studies have shown that traditional Chinese medicine （TCM） can truncate and reverse the pathological grading of gastric mucosa， and can also effectively improve the clinical symptoms and quality of life of patients， with few adverse reactions and low recurrence rate， which has unique advantages and characteristics. The theory of ''pathogen invading nutrient and blood aspects'' was first proposed by WU Youxing， a febrile disease doctor， in Treatise on Pestilence （《温疫论》）. It was originally used for the treatment of syndrome changes in the late stage of febrile epidemics， but after being enriched and developed by different doctors， it is now mostly used to guide the treatment of various chronic diseases. Precancerous lesions of gastric cancer are a common and difficult disease in clinical practice. Its evolution process is characterized by asthenia in origin and sthenia in superficiality and deficiency-excess in complexity， which is consistent with the core pathogenesis of ''pathogen invading nutrient and blood aspects''， namely， positive deficiency and intruding pathogen， and intruding pathogen cementation in the blood vessels. They are also interlinked in terms of treatment principles. Therefore， with the theory of ''pathogen invading nutrient and blood aspects'' as the breakthrough point， this article expounded the intervention effect of TCM on precancerous lesions of gastric cancer from the perspective of this theory， reflecting its important guidance and application value and providing new ideas for clinical treatment of diseases.
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The purpose of this study was to explore the effect and mechanism of Xihuang Pills on rats with precancerous lesions of the breast. Of 48 healthy female rats, 8 were randomly selected as blank group, and the other 40 were treated with 7,12-dimethylbenzanthracene(DMBA) combined with estrogen and progestin to establish a model of precancerous lesions of the breast. The successfully modeled rats were randomly divided into a model group, a tamoxifen group(1.8 mg·kg~(-1)·d~(-1)), a Xihuang Pills low-dose group(0.3 g·kg~(-1)·d~(-1)), a medium-dose group(0.6 g·kg~(-1)·d~(-1)) and a high-dose group(1.2 g·kg~(-1)·d~(-1)). After 30 days of admi-nistration, the histopathological changes of viscera and breast were observed by haematoxylin and eosin(HE) staining, and the visceral index was calculated. Enzyme linked immunosorbent assay(ELISA) was used to detect the contents of estradiol(E_2) and progesterone(P) in serum. The protein expressions of vascular endothelial growth factor(VEGF) and fibroblast growth factor 2(FGF2) were detected by immunohistochemistry. The protein expressions of VEGF, vascular endothelial growth factor receptor 2(VEGFR2), phosphorylated-vascular endothelial growth factor receptor 2(p-VEGFR2), B-cell lymphoma-2(Bcl-2), and Bcl-2 associated X protein(Bax) were detected by Western blot and the mRNA expressions of VEGF, FGF2, CXC-chemokine receptor 4(CXCR4), cysteine aspartic acid-specific protease(caspase-3), and stromal cell-derived factor 1(SDF-1) were detected by real-time polymerase chain reaction(RT-PCR). HE staining revealed that the model group had some liver and kidney damages and severe hyperplastic mammary tissue, while the Xihuang Pills high-dose group had mild hyperplasia. Compared with the model group, the Xihuang Pills groups had lo-wer ovarian coefficient(P<0.05 or P<0.01) and Xihuang Pills high-dose group had lower uterine coefficient(P<0.01). ELISA results showed that compared with the model group, expressions of E_2 and P in Xihuang Pills high-dose group were significantly decreased(P<0.05 or P<0.01). Immunohistochemistry, Western blot and RT-PCR indicated that compared with the conditions in the model group, the protein and mRNA expressions of VEGF and FGF2 in the Xihuang Pills groups were down-regulated(P<0.05 or P<0.01), and the protein expression of Bcl-2 was lowered(P<0.01); there was a decrease in the protein expressions of VEGFR2 and p-VEGFR2(P<0.01), a down-regulation in the mRNA expressions of CXCR4 and SDF-1(P<0.01), while an increase in the mRNA expression of caspase-3(P<0.01) in both Xihuang Pills medium-dose and high-dose groups; the protein expression of Bax in Xihuang Pills high-dose group was increased(P<0.01). The above results indicated that Xihuang Pills can effectively intervene in precance-rous lesions of the breast, and the mechanism may be related to the regulation of E_2 and P secretion as well as the inhibition of angiogenesis and chemokine receptor expression, thus controlling the occurrence of precancerous lesions of the breast in rats.
Asunto(s)
Ratas , Femenino , Animales , Ratas Sprague-Dawley , Proteína X Asociada a bcl-2 , Factor A de Crecimiento Endotelial Vascular/metabolismo , Caspasa 3 , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Factor 2 de Crecimiento de Fibroblastos , Proteínas Proto-Oncogénicas c-bcl-2 , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Lesiones Precancerosas , Hiperplasia , Receptores de Quimiocina , ARN MensajeroRESUMEN
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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Humanos , Medicina Tradicional China , Ensayos Clínicos Controlados Aleatorios como Asunto , Lesiones Precancerosas/tratamiento farmacológicoRESUMEN
Objective:To analyze the risk factors of recurrence and canceration for premalignant vocal fold lesions after surgery, and to provide a reasonable basis for preoperative evaluation and postoperative follow-up. Methods:This study retrospective analyzed the relationship between clinicopathological factors and clinical outcome（recurrence, canceration, recurrence-free survival, and canceration-free survival） in 148 patients undergoing surgical treatment in Chongqing General Hospital from 2014 to 2017. Results:The five-year overall recurrence rate was 14.86% and the overall recurrence rate was 8.78%. Univariate analysis showed that smoking index, laryngopharyngeal reflux and lesion range were significantly associated with recurrence（P<0.05）, and smoking index and lesion range were significantly associated with canceration（P<0.05）. Multivariate logistic regression analysis showed that smoking index ≥600 and laryngopharyngeal reflux were independent risk factors for recurrence（P<0.05）, and smoking index ≥600 and lesion range ≥1/2 vocal cord were independent risk factors for canceration（P<0.05）. The mean carcinogenesis interval for the postoperative smoking cessation group was significantly longer（P<0.05）. Conclusion:Excessive smoking, laryngopharyngeal reflux and a wide range of lesions may be related to postoperative recurrence or malignant progression of precancerous lesions in the vocal cord, and further large-scale multi-center prospective randomized controlled studies are needed to clarify the effects of the above factors on recurrence and malignant changes in the future.
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Humanos , Pliegues Vocales/patología , Estudios Retrospectivos , Reflujo Laringofaríngeo/complicaciones , Estudios Prospectivos , Lesiones Precancerosas/patología , Factores de RiesgoRESUMEN
Objective:To evaluate the value of serum pepsinogen Ⅰ and Ⅱ combined with gastrin-17 in screening precancerous lesions of gastric cancer in physical examination population.Methods:Serum pepsinogen, gastrin-17 and Helicobacter pylori (Hp) antibody were detected in 18 354 physical examination people from July to December 2017 in Wenrong Hospital, Hengdian, Dongyang. The patients were divided into youth group (18 to 39 years old), middle-aged group (40 to 59 years old) and elderly group (≥60 years old) according to their ages. The correlation between the serological level of the above indexes and age was analyzed; according to the new ABC method, the test results were divided into groups A, B, C and D. The patients in group C and D were examined by gastroscopy. The differences of gastric mucosal atrophy or intestinal metaplasia and other precancerous lesions detected by gastroscopy in different age groups were compared.Results:Finally, 18 354 cases were enrolled, including 9 614 males and 8 740 females. With the increase of age, the proportion of group C and D increased gradually. In group C, 181 cases underwent gastroscopy, including 39 cases of atrophic gastritis, 29 cases of intestinal metaplasia and 3 cases of dysplasia/intraepithelial neoplasia, the detection rate of precancerous lesions was 39.23%; in group D, 94 cases underwent gastroscopy, including 22 cases of atrophic gastritis and 13 cases of intestinal metaplasia, the detection rate of precancerous lesions was 37.23%. The proportion of gastric precancerous lesions in group C and D was 29.63% in the young group, 69.70% in the middle-aged group and 71.58% in the old group, respectively. There was significant difference compared with the young group ( P<0.01); atypical hyperplasia occurred in 2.02% and 9.47% of the middle-aged group and the elderly group. Conclusions:The combined detection of serum pepsinogen Ⅰ and Ⅱ and gastrin-17 levels is of great value in the screening of precancerous lesions of gastric cancer; when this method used for early gastric cancer screening in healthy population, it is necessary to consider the influence of age for the risk stratification of gastric cancer.