1. Hp infection and chronic gastritis In patients with chronic gastritis, the rate of Hp infection exceeds 95%, and the rate of infection increases with age. hp infection can cause three different types of gastritis: ① superficial gastritis; ② diffuse gastric sinusitis; ③ multifocal atrophic gastritis. the pathological features of Hp-associated gastritis are: ① mucosal epithelial degeneration; ② neutrophil and chronic inflammatory cell infiltration; ③ intestinal epithelial hyperplasia; ④ atypical hyperplasia; ⑤ glandular atrophy. ; ④ atypical hyperplasia; and ⑤ glandular atrophy. Degenerative epithelial changes such as mucus depletion, epithelial cell degeneration, exudation and detachment are the distinctive features of chronic gastritis. The glandular atrophy may be a result of bacterial action or a response to long-term chronic inflammation. intestinal epithelial hyperplasia caused by Hp infection is an adaptation of the gastrointestinal mucosa to slow-onset infection. According to the mucus content and cell morphology, intestinal epithelial chemosis can be divided into 3 main types: ① type I (complete): the chemosis epithelium is similar to the normal small intestine type epithelium; ② type IIa (incomplete) ③ type IIb or III (incomplete): its columnar epithelium is similar to the colonic epithelium that secretes sulfuric acid mucus. type III enterosis is a high risk factor for the development of gastric adenocarcinoma, and with the aggravation of intestinal chemosis, it is not suitable for the settlement of Hp and thus the bacteria gradually disappears, and the disappearance of Hp is accompanied by the reduction or disappearance of Hp detection rate in the later stages of chronic gastritis, accompanied by the reduction or disappearance of chronic inflammatory cells. 2. Hp infection and gastric cancer Epidemiological studies have concluded that there are many similarities between the occurrence of gastric cancer and the prevalence of Hp: ① the rate of Hp infection and the incidence of gastric cancer are significantly positively correlated, and the risk value of gastric cancer increases in Hp-infected patients; ② the occurrence of both Hp infection and gastric cancer increases with age; ③ the occurrence of both Hp infection and gastric cancer is related to the economic status, social status and health conditions of the population; ④ (3) the occurrence of both Hp infection and gastric cancer is related to the economic status, social status and health conditions of the population; (4) race: both have a high incidence rate among blacks; (5) in terms of the site of gastric cancer, Hp mainly settles in the gastric sinus, which is consistent with the preferred site of gastric cancer. Epidemiological survey studies show that: the area with high incidence of gastric cancer is also the area with high incidence of Hp infection, and the age of infection is very early. The risk of gastric cancer in Hp-infected patients is higher than that of non-infected patients. In a large prospective study in China, 18,244 natural people were investigated and the incidence of gastric cancer was higher in Hp-positive than in Hp-negative patients with an OR of 1.84. However, some epidemiological surveys show different results, that is, the incidence of gastric cancer is not significantly related to Hp infection. Hp itself does not secrete carcinogens; it causes gastric cancer in an indirect form, such as vacuolar toxin, urease and other virulence factors contained in Hp can damage gastric mucosal cells, causing mucus evacuation and epithelial detachment, which can be seen by electron microscopy as swelling of gastric mucosal cells and expansion of the endoplasmic reticulum system. Hp causes an inflammatory response and releases inflammatory mediators, resulting in accelerated cell proliferation and DNA synthesis in proliferating cells, which are susceptible to mutations and deletions caused by genotoxic carcinogens, leading to cell carcinogenesis.Hp infection first causes inflammatory changes in the gastric mucosa, and long-term chronic inflammation will lead to the evolution of gastric mucosa towards gastric cancer.Correa described the natural history of gastric carcinogenesis Hp infection is associated with both intestinal gastric cancer and diffuse gastric cancer, but is generally considered to be more closely related to intestinal gastric cancer. However, this is a long process and Hp acts as one of many oncogenic factors at one stage of the process. Hp infection is mainly concentrated in the gastric sinus, which is also the site with the highest incidence of intestinal metaplasia and heterotypic hyperplasia as well as gastric cancer. It can be concluded that Hp infection is an important factor for enterosis and heteroplasia, and early infection with Hp can cause and accelerate the occurrence of enterosis and heteroplasia, and contribute to the evolution of normal gastric mucosa toward gastric cancer. Both domestic and foreign studies have reported that after Hp eradication, some of the intestinal chemosis and heterotypic hyperplasia can be reversed. If Hp infection persists, the damage to gastric mucosa caused by Hp infection can change the living environment of Hp itself. Although Hp can be detected in a considerable part of the early stage of gastric mucosal enterosis, with the aggravation of the lesion, Hp cannot adapt to the change of environment and eventually die out, which is the reason why it is believed that Hp cannot settle in the site of intestinal metaplasia. Nowadays, many studies at home and abroad have shown that Hp infection can cause mutation of gastric cancer-related genes, including activation of proto-oncogenes such as ras, c-met, c-myc, c-erbB-2, etc.; and mutation and inactivation of oncogene p53. Our study found that the c-met gene expression rate was significantly higher in Hp-infected patients (61.4%) than in uninfected patients (35.4%) in precancerous lesions. In superficial gastritis, atrophic gastritis, intestinal chemosis, and atypical hyperplastic lesions, the c-met expression and overexpression rates were 22.2% (5.5%); 44.1% (26.4%); 67.6% ( 37.8%); 61.9% (38.1%); and 69.2% in the gastric cancer group. c-met expression and overexpression rates gradually increased with the aggravation of lesions from superficial → atrophic → enteric → atypical hyperplasia → gastric cancer [5]. In vitro, the use of Hp culture filtrate cultured with GES-1 cells can cause overexpression of mRNA of c-met and c-myc proto-oncogene in GES-1 cells, indicating that the toxin has an effect on the growth and differentiation of GES1 cells. Three hypotheses have been proposed for Hp causing gastric cancer: (i) the metabolites of the cells directly transform the gastric mucosa; (ii) a virus-like pathogenesis in which the DNA of Hp is integrated into the host gastric mucosal cells and causes transformation; and (iii) Hp causes an inflammatory response, and inflammation has a genotoxic effect. Most of the above studies support the third theory. Their findings suggest an association with Hp-induced inflammation. Recently, it was reported [8] that Hp-infected Mongolian gerbils were successfully induced to develop gastric cancer after 1-1.5 years, and it was through the evolution of inflammatory cell infiltration → atrophic gastritis → intestinal epithelial hyperplasia → atypical hyperplasia → gastric cancer. Attempts have also been made to integrate Hp-DNA into the chromosomes of gastric mucosal cells as a way to elucidate the mechanism of Hp-causing gastric cancer, but no successful report has been seen so far. About how Hp causes transformation of gastric mucosa, including direct or indirect effects on cell membrane, cytoplasmic conduction, and DNA synthesis and transcription, more and more in-depth studies are needed in the future. (1) The discovery of Hp is a revolution in the pathogenesis and etiology of peptic ulcer. The pathogenesis of peptic ulcer is very complex, and it is usually believed that ulcers occur because of the imbalance between damaging factors and defensive factors, including gastric acid, pepsin, H. pylori, non-steroidal anti-inflammatory drugs, alcohol, smoking, bile reflux and inflammatory mediators; defensive factors include gastric mucosa-mucus barrier, bicarbonate, phospholipids, mucosal blood flow, cell renewal, prostaglandins and epidermal growth factor. Among the attack factors gastric acid plays a dominant role. As early as 1910, Schwartz famously stated that “there is no ulcer without gastric acid”, so gastric acid has been dominant in the pathogenesis of peptic ulcer disease. Since the isolation of Hp from the gastric mucosa of patients with chronic active gastritis by Warren and Marshall in 1982, the role of Hp in the pathogenesis of ulcer disease has challenged gastric acid, and some scholars have suggested that “there is no ulcer without Hp”; “there is no ulcer recurrence without Hp”. Some scholars have also suggested that “no ulcer without Hp” and “no ulcer recurrence without Hp”. The discovery of Hp has led to a revolution in the pathogenesis and treatment of peptic ulcer, and Schwartz’s famous saying “no ulcer without gastric acid” is still in use today. However, today’s new view must add “no ulcer and no ulcer recurrence without Hp”. It is widely accepted that Hp-related ulcers will recur if Hp is not eradicated and that Hp must be eradicated to reduce or prevent ulcer recurrence. The pathogenesis of peptic ulcers is complex, and overall, about 5-10% of peptic ulcers do not have a co-infection with Hp. These ulcers may be associated with the destruction of the gastric mucosal barrier due to long-term use of drugs such as aspirin/NSAIDs. Therefore, the principle of treatment for ulcer disease today is the need to eradicate Hp and protect the gastric mucosa along with traditional acid suppression therapy. There is now sufficient theoretical evidence that the discovery of Hp has led to a new change in the pathogenesis and treatment strategy of ulcer disease. (2) The pathogenic role of Hp in the formation of peptic ulcer and its pathogenic mechanism (1) Relationship between Hp and peptic ulcer recurrence: “healing” and “cure” are two medical terms with different concepts, and before the discovery of Hp, peptic ulcer was considered to be a recurrent disease of unknown origin. Before Hp was discovered, peptic ulcer was considered to be a recurrent disease of unknown cause, and it was usually believed that peptic ulcer could only be “healed” but not “cured”, and the application of acid suppressants or maintenance therapy only caused the ulcer to heal temporarily, but once the therapy was stopped, the ulcer would soon recur. Therefore, the previous view was that peptic ulcer is an incurable disease. Since the discovery of Hp in 1982, there has been a new understanding of the natural course of peptic ulcer, and a large number of clinical studies at home and abroad have confirmed that the recurrence of gastric and duodenal ulcers can be reduced or prevented after the eradication of Hp. The recurrence rate was only 4% in patients with Hp eradication, and the same was true for gastric ulcers. Our past group of studies also confirmed complete healing of ulcers in Hp-eradicated patients and a 61.9% healing rate in non-eradicated patients. At six-month follow-up, there was no recurrence within six months and 4% recurrence within one year in those with Hp eradication, and 58% recurrence within six months and 100% recurrence within one year in those with Hp non-eradication. The results of a multicenter clinical study in Beijing on 248 patients with duodenal ulcer treated with Hp eradication for one year showed that the recurrence rate of ulcer in the Hp eradication group was only 2.3%, while in the Hp non-eradicated group, the recurrence rate was 58.9% in one year. 20 years of research on the treatment of Hp-related ulcer confirmed that peptic ulcer is a curable disease. (2) The pathogenic mechanism of Hp in ulcer formation: The mechanism of H. pylori causing damage to the gastroduodenal mucosa is very complex, and there are four main theories as follows: ① “Leaky roof theory”: Goodwin compares the inflamed gastric mucosa to a leaky roof, without rain it is temporarily dry, meaning that without gastric acid there is no ulcer. After the administration of antisecretory drugs, the gastric acid is suppressed and the ulcer is healed, but only a short-term effect is obtained because the leaky roof is not repaired after all and the natural course of ulcer disease is not changed. The rate of ulcer recurrence in the natural course of peptic ulcer is >70%. If Hp treatment (eradication of Hp) related to inflammation and ulcers is targeted, ulcers are less likely to recur. Therefore, only through mucosal repair, i.e., repairing the roof, can we prevent rain in the long term, i.e., achieve a cure for ulcer disease. ②”Gastrin-related theory”: Levi proposed that the ammonia cloud around Hp can increase the pH of the gastric sinus and increase the feedback release of gastrin in the sinus, thus increasing gastric acid secretion, which plays an important role in the formation of duodenal ulcer. For Hp-associated duodenal ulcer, if Hp can be truly eradicated, the ulcer should not recur, and the incidence of re-sensitization is very low, about 1% per year in western countries. (3) Gastric epithelial chemotaxis theory: Hp causes mucosal damage and leads to duodenal ulcer formation by colonizing the gastric chemotaxis epithelium in the duodenum. the toxins released by Hp and the immune response it stimulates lead to the development of duodenal inflammation. Ulcers develop as a result of decreased tolerance of the inflamed mucosa to attack by other ulcerogenic factors, or severe inflammation itself leads to ulcer development. In the duodenum, Hp only attaches and colonizes the site of gastric epithelial chemosis, which is a strong evidence for this theory. ④Media flushing theory: It has been shown that Hp infection leads to the release of various inflammatory mediators that are flushed to the duodenum during gastric emptying and cause damage to the duodenal mucosa. Together with the fact that Hp can colonize the duodenal mucosa with gastric epithelial metaplasia, this explains the presence of Hp mainly in the gastric sinus but can lead to the development of duodenal ulcers. (3) Relationship between Hp and refractory ulcers: H2RAs are applied to treat duodenal ulcers for 8 weeks; gastric ulcers for 12 weeks, if the ulcer still does not heal, it is generally considered to be a refractory ulcer. Hp infection and the application of NSAIDs may be important underlying factors for refractory ulcers, and factors such as heavy smoking, alcohol abuse, and excessive gastric acid secretion (e.g., gastrinoma) can delay ulcers from healing. Infection is an important factor in recalcitrant ulcers, and many research data show that eradication of Hp can accelerate the healing of recalcitrant ulcers and reduce the high recurrence rate. We have found 6 cases of duodenal ulcer patients who were treated with H2RAS for 6 months without healing of ulcers, all of which were examined for combined Hp infection, but after anti-Hp infection treatment, the ulcers healed in 5 cases and shrank significantly in the other case. Therefore, Hp should be carefully examined for recalcitrant ulcers and Hp eradication therapy should be performed for recalcitrant ulcers with combined Hp infection. For Hp-negative recalcitrant ulcers, other factors affecting ulcer healing should be addressed. (4) New strategies for the treatment of Hp-positive peptic ulcers: There are now sufficient theoretical grounds to prove that the discovery of Hp has led to significant changes in the pathogenesis of peptic ulcers, so with the changes in the pathogenesis of peptic ulcers, the treatment strategies have also undergone significant changes. Nowadays, the treatment strategy of peptic ulcer should include three aspects: (1) suppression of gastric acid; (2) eradication of Hp; and (3) protection of gastric mucosa. Only by following these three principles can we achieve a cure for ulcers.