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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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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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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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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.
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Traditional Chinese Medicine (TCM) has certain advantages in the treatment of precancerous lesions of gastric cancer (PLGC) based on the holistic concept and the thought of syndrome differentiation. Currently, it is generally divided into 6 kinds of syndromes: liver and stomach qi stagnation syndrome, liver and stomach heat stagnation syndrome, spleen and stomach weakness syndrome (including spleen and stomach qi deficiency syndrome with coldness), spleen and stomach damp heat syndrome, stomach yin deficiency syndrome and blood stasis in stomach collateral syndrome. Clinically, the doctor should treat PLGC patients according to different syndrome types by using Chinese medicine prescription, which could improve the gastric mucosal pathological state, gastroscopy and clinical symptoms, to rehibit the development of precancerous lesions, reduce the incidence rate of gastric cancer. In the future, the doctors shouldreach the consensus of treating PLGC with TCM diagnosis, and focus on the research of TCM compounds or monomers with obvious curative effect, increase the times of follow-up, and evaluate the long-term curative effect.
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At present， the incidence and mortality of gastric cancer in China are 10.26% and 12.45%， ranking the second and third places， respectively， in the incidence and mortality of malignant tumors in China. Cancer often goes through three stages： precancerous lesions， carcinoma in situ， and invasive carcinoma. It is of great significance to advance cancer prevention and control to the stage of precancerous lesions. The popularization of digestive endoscopy-assisted diagnosis and treatment has enabled the timely diagnosis and treatment of early gastric cancer and severe dysplasia. However， the endoscopic mucosal resection is not suitable for most precancerous lesions of gastric cancer （PLGC）， and the effective drugs are not available. The long-term clinical dynamic monitoring has imposed considerable physical and mental burdens on patients. Gastrointestinal microenvironment is a dynamic balance system composed of gastrointestinal flora， chemical barrier， mechanical barrier， immune barrier， and gastrointestinal nerves. The imbalance of gastric microenvironment has been proved to be the key mechanism of PLGC. According to traditional Chinese medicine （TCM）， PLGC is a result of long-term interaction between deficient healthy Qi and excessive pathogens. In syndrome differentiation and treatment， PLGC is often believed to be developed from chronic gastritis. Besides， the inflammation-cancer transformation model put forward by Correa and the evolution of its TCM pathogenesis are also considered. Guided by the basic treatment principle of reinforcing healthy Qi to eliminate pathogenic factors， we determined the basic therapeutic methods as follows： invigorating spleen， clearing heat， and resolving dampness. At the same time， such methods as soothing liver and regulating Qi， resolving phlegm and dissipating mass， activating blood and resolving stasis， clearing heat and removing toxin， and tonifying deficiency can be combined based on the results of syndrome differentiation. After discussing the correlation between the imbalance of gastric microenvironment and PLGC and summarizing TCM intervention methods and mechanisms against PLGC from the perspective of gastric microenvironment regulation， this paper believed that TCM improved the gastric microenvironment by regulating the disorder of gastric flora， eliminating the gastric mucosal inflammation， and relieving the abnormal immune response， thereby preventing and controlling the PLGC.
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Objective To establish a rat chronic atrophic gastritis with dysplasia model and observe the effect of Shidan granules on the positive expression of NF-κB p65 in gastric tissues and the extent of IKKβprotein content in gastric tissues of chronic atrophic gastritis with dysplasia model rats. Methods Seventy SPF male Wistar rats were randomly divided into the blank group and 60 into the model group. In addition to the blank group, the modeling group was made using the MNNG-based comprehensive modeling method (150 μg/ml MNNG 5 ml/kg each stomach, containing 0.03％ ranitidine feed, free drinking 0.1％ ammonia), and then model successed at the 28th week. The remaining rats in the modeling group were randomly divided into 5 groups: the model group with intragastric administration of gavage, the western medicine group with intragastric administration of viralin, the Shidan granules group with intragastric administration of low/medium/high concentration Chinese medicine decoction. After 12 weeks of treatment, they were sacrificed and the expression of NF-κB p65 and IKKβ was measured and compared. Results Compared with the model group, the average optical density of NF-κBp65 (0.387 ± 0.011, 0.252 ± 0.022, 0.193 ± 0.003 vs. 0.442 ± 0.035) and the expression level of IKKβ (0.309 ± 0.056, 0.216 ± 0.025, 0.125 ± 0.016 vs. 0.405 ± 0.042) in the low-, middle- and high-dose Shidan granules groups significantly decreased (all Ps<0.01). Conclusions The mechanism of improving the precancerous lesions of gastric cancer by Shidan granules may be achieved by inhibiting the expression of IKK, reducing the abnormal activation of NF-κB.
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Gastric cancer is a disease with high morbidity and mortality in the world, and also obtains attention in the global medicine. The occurrence of gastric cancer is a multi-stage and multi-factor process. A large number of epidemiological, pathological and clinical evidences have confirmed that the risk of gastric cancer in patients with chronic atrophic gastritis (CAG) is significantly correlated with the mortality of gastric cancer. Gastric mucosal atrophy, intestinal metaplasia (especially incomplete colonic metaplasia) and dysplasia are the main stages of precancerous lesions of precancerous lesions of gastric cancer (PLGC). Monitoring the condition of CAG patients, especially those with intestinal metaplasia and dysplasia, is of great significance for the discovery of early gastric cancer. CAG and PLGC are great significance in the pathological stage of gastric carcinogenesis. In recent years, more and more in-depth clinical and experimental studies have been carried out in this direction. So far, animal experiment is the main research way for CAG and PLGC disease, so it is very important to explore the modeling method. Choosing a stable and reliable model is the primary factor to study animal experiment. In view of the relationship between two diseases, this paper will summarize the methods of establishing animal models for CAG and PLGC in recent years, generally including chemical drug mutagenesis, physical stimulation, immune modeling, Helicobacter pylori infection replication and surgical modeling. Examples would be given for the application of various methods in the previous experiments, and the author would make a brief comment on the merits and demerits of these methods, which have been explored and successfully made by the author. This study would provide certain reference for the establishment and application of animal models in further CAG and PLGC experiments.
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Objective To discuss the clinical efficacy of compound gastritis mixture (CGM) in treating precancerous lesions of gastric carcinoma (PLGC).Methods Totally 85 PLGC patients were randomly divided into treatment group and control group. The treatment group took CGM and the control group took Vitacoenzyme tablets. One therapeutic course was three months, and the treatment lasted for two courses. The clinical symptoms, electronic gastroscopy presentation, and pathological tissues before and after treatment were observed, the clinical efficacy was evaluated.Results There was statistical significance in TCM syndrome between the two groups (P<0.05), and the effective rate in the treatment group was more obvious than that in the control group (P<0.01). The symptoms of the two groups were significantly improved (P<0.05,P<0.01), but the improvements of the main symptoms in the treatment group were superior to those in the control group (P<0.05,P<0.01). The total effective rate of electronic gastroscopy presentation was 80.0% (36/45) in the treatment group, which was better than that of the control group (P<0.05). Pathological curative effects of chronic atrophic gastritis, intestinal metaplasia, and dysplasia in the treatment group were also better than those in the control group (P<0.05).Conclusion CGM has definite clinical efficacy in treating PLGC.
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Objective To observe the effects of Weipixiao on the ultrastructure of gastric mucosa capillaries in rats with precancerous lesions of gastric cancer ( PLGC). Methods The rats were randomized into six groups, including normal group, model group, Vatacoenayme Tablets group ( 0.2 g·kg-1·d-1) , and high-, middle-, and low- dose Weipixiao groups ( 15, 7.5, and 3.75 g·kg-1·d-1 respectively) . The rats received spontaneous intake of N-methyl-N’-nitro-nitrosoguanidine ( MNNG, 200 μg/mL) solution combined with irregular diet and intragastric administration of purgative herbs Xiao Chengqi Decoction ( 2 mL, containing 1 g/mL crude drug) for 18 weeks to induce spleen-deficiency PLGC. The pathological changes in gastric mucosa and the ultrastructure of gastric mucosa capillaries were observed under the transmission electron microscope. Results The model has been established successfully. Transmission electron microscopy results in the model group showed as severely swollen endothelial cells of gastric mucosa capillaries, severely-narrowing or even blocked vascular lumens, rough and discontinuous basement membrane, and swollen, degenerated or even absent pericytes. And the ultrastructure of gastric mucosa capillaries in high-, middle-, and low- dose Weipixiao groups were improved to some degrees, the effect of low-dose Weipixiao group being the best. Conclusion The improvement of the mucosal microcirculation of spleen-deficiency PLGC rats may be one of the pathohistological mechanisms of Weipixiao for spleen-deficiency PLGC.
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This study was aimed to observe the therapeutic effect and mechanism ofQi-Zhu Er-Zhu Er-Cao Tang(QZEZECT) in the treatment of chronic atrophic gastritis (CAG) precancerous lesion. A total of 56 clean grade healthy Wistar rats were randomly divided into 6 groups. In the negative control group (NC), model group,Wei-Fu-Chun(WFC) group,Ren-Zhu Jian-Wei Ke-Li(RZJWKL, RZ) group, there were 10 rats in each group. In the high-dose QZEZECT (QZ-H) group and low-dose QZEZECT (QZ-L) group, there were 8 rats in each group. CAG/PLGC model was established by MNNG in the model group, WFC group, RZ group, QZ-H group and QZ-L group. Intragastric administration of corresponding decoctions at the dose of 0.39 g·kg-1, 3.2 g·kg-1, 54.4 g·kg-1, 13.6 g·kg-1 were given to rats in the WFC, RZ, QZ-H and QZ-L groups once a day for 28 consecutive days, respectively. The same volume of normal saline was given to the NC group and the model group. Histomorphological changes of gastric mucous membrane in rats of each group were observed. Expressions of NF-κB/p65 and CyclinE protein were detected. The results showed that compared with the NC group, the degrees of infiltration and dysplasia and expressions of NF-κB/p65 and CyclinE significantly increased in the model group with statistical significance (P < 0.01). Compared with the model group, the expression of NF-κB/p65 and CyclinE in the WFC group reduced with statistical significance (P < 0.05). The expression of NF-κB/p65 and CyclinE in the RZ and QZ-L group obviously reduced with statistical significance (P < 0.01). The overall effective rates of WFC group, RZ group, QZ-H group and QZ-L group were 50%, 63.3%, 43.3% and 73.3%, respectively. It was concluded that QZEZECT can treat CAG precancerous lesion, which may take effect by improving and inhibiting pathologic changes of the transcription factor of inflammation.
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Objective: To observe the curative effect of Yiwei Huayu Powder (YHP) and the expression of Th1/Th2 cytokines in patients with precancerous lesions of gastric cancer (PLGC). Methods: There were 100 diagnosed chronic atrophic gastritis (CAG) with gastric mucous membrane dysplasia (Dys) and/or intestinal metaplasia (IM) patients who were randomly divided into treatment group (50 cases) and control group (50 cases). The patients in the treatment group were administrated with YHP for three months, while the other one with Teprenone Capsules and folic acid. Results: Compared with the control group, the symptom scores of the patients in the treatment group decreased more obviously (P < 0.05). Compared with the control group, the pathological scores of the patients in the treatment group decreased more obviously (P < 0.05). After the treatment, the expression of the Th1 (IL-2, INF-γ) level escalated and the Th2 (IL-4, IL-6) level decreased in the treatment group, which existed an obvious difference compared to the control group (P < 0.05). Conclusion: YHP has played a therapeutic effect in patients with PLGC through intervening immune drift and inducing tumor cell apoptosis, thereby blocking or reversing the development of PLGC.
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0.05). The PCNA and Ki-67 expression of blood stasis syndrome is more evident than of Qi stagnation (P
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Objective To explore the effect of Renzhu Jianwei Granules(Granule of Semen Coicis and Rhizoma Atractylodis Macro- cephalae for strengthening the stomach)on the patients with precancerous lesions of gastric cancer(PLGC)and its mechanism. Methods The 58 patients of chronic atrophic gastritis(CAG)complicated with intestinal metaplasia(IM)and/or dysplasia(Dys) were randomized into treatment group and control group with 29 in each.The treatment group was administered Renzhu Jianwei Gran- ules while the control group was given Weifuchun Tablets.The numbers of positive cells of carcinoembryonic antigen(CEA)and cy- clooxygenase 2(COX-2)of gastric mueosa before and after treatment were observed.Results The scores of positive cells of CEA and COX-2 of gastric mucosa of both groups were greatly reduced after treatment(P0.05).Conclusion Renzhu Jianwei Granules can reduce CEA and COX-2 of PLGC patients,possibly being one of the mechanisms in treating PLGC.