The pathogenesis of peptic ulcers is very complex, and it is generally believed that ulcers occur due to an imbalance between damaging factors and defensive factors. As early as 1910, Schwartz suggested that “there is no ulcer without gastric acid”, and therefore the role of gastric acid has been dominant in the pathogenesis of peptic ulcers. Since 1982, when Warren and Marshall first isolated Helicobacter pylori (Hp) from the gastric mucosa of patients with chronic active gastritis, numerous studies have demonstrated the close relationship between Hp and peptic ulcers, and the role of Hp in the pathogenesis of ulcer disease has challenged gastric acid. Schwartz’s famous saying “no ulcer without gastric acid” is still in use today, but to the pathogenesis of ulcers it is necessary to add “no ulcer and no ulcer recurrence without Hp”. The discovery of Hp was a revolution in the etiology and treatment of peptic ulcers, allowing doctors to cure peptic ulcers through the application of antibiotic therapy, and it was for this great discovery that two Australian academics, Warren and Marshall, were awarded the 2005 Nobel Prize in Physiology or Medicine. 1, the close relationship between Helicobacter pylori and peptic ulcer (1) peptic ulcer patients have a high rate of Hp detection Hp infection rate in the world more than 50%, in some underdeveloped areas Hp infection rate can exceed 80%, China’s epidemiological survey shows that the rate of Hp infection in various regions of China is 40%-90%, the average is 59%. hp-infected people have a higher risk of duodenal ulcer than non-hp-infected people. The risk of duodenal ulcer in Hp-infected people is more than 9 times that of non-Hp-infected people. Most studies show that more than 80% or even 100% of patients with duodenal ulcers have Hp infection, and more than 60% of patients with gastric ulcers have Hp infection, especially in developing countries where the prevalence of Hp infection is high, and the detection rate of Hp in patients with peptic ulcers is higher. (2) Hp eradication can accelerate ulcer healing and reduce ulcer recurrence In peptic ulcer patients with Hp infection, ulcer healing is delayed, and the annual recurrence rate of ulcer patients healed only by conventional acid suppression therapy can reach 40% to 80%, while the annual recurrence rate of peptic ulcer after Hp eradication is less than 5% Hp infection is an important factor in persistent ulcer, and many research data show that Hp eradication can accelerate the healing of persistent ulcer. Many studies have shown that Hp eradication can accelerate the healing of persistent ulcers and reduce their high recurrence rate. This is the strongest evidence of the role of Hp in the pathogenesis of ulcers. 2, the pathogenesis of H. pylori in the development of ulcer disease The mechanism of H. pylori damage to the gastroduodenal mucosa is very complex, the following five main theories: (1) “leaky roof theory”: Goodwin compared the presence of inflammation of the gastric mucosa as a leaky roof, due to damage to the mucosa, resulting in H + (acid rain) reverse As a result of the damage to the mucosa, the mucosa is further damaged and ulcers are formed. After treatment with acid-suppressing drugs, the stomach acid is suppressed and the ulcer heals, 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 recurrence rate of ulcers 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 to prevent rain in the long term, i.e., to achieve the purpose of ulcer cure. (2) “gastrin-related theory”: Levi proposed that the urease secreted by Hp can hydrolyze urea to produce ammonia, and the ammonia cloud formed around Hp can increase the pH of the gastric sinus, which feedback causes an increase in gastrin secretion and thus an increase in gastric acid secretion, which plays an important role in the formation of duodenal ulcer. (3) Gastric epithelial chemotaxis theory: Hp causes mucosal injury and leads to the formation of duodenal ulcer by colonizing the gastric chemotaxis epithelium in the duodenum. Gastric epithelial metaplasia in the duodenum is a prerequisite for Hp colonization and ulcer formation, and the toxins and destructive enzymes released by Hp and its stimulated immune response lead to the development of duodenal inflammation. Ulcers develop due to decreased tolerance of the inflamed mucosa to attack by other ulcerogenic factors, or severe inflammation itself leads to ulcer production. In the duodenum, Hp only attaches and colonizes the site of gastric epithelial metaplasia, which is a strong evidence for this theory. (4) Mediator flushing theory: It has been shown that Hp infection leads to the release of various inflammatory mediators, including vacuolar toxin, acetaldehyde, platelet-activating factor, interleukins, etc. These inflammatory mediators 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. (5) Immune damage theory: Hp causes ulcers through immune mechanisms. Hp can lead to a series of immune reactions from acute inflammatory response to humoral and cellular immunity, and lead to the occurrence of mucosal damage. The discovery of Hp has now been well documented and has led to significant changes in the pathogenesis of peptic ulcers, so with the change in the pathogenesis of peptic ulcers, the treatment strategy has also undergone significant changes. Nowadays, the treatment strategy of peptic ulcer should include three aspects: suppression of gastric acid, eradication of Hp, and protection of gastric mucosa. These three principles should be followed to achieve the purpose of curing ulcers. 4, H. pylori eradication treatment indications (1) China 2003 Tongcheng meeting consensus opinion: this meeting listed Hp-positive peptic ulcer (active or inactive, with or without complications), early gastric cancer postoperative, gastric mucosa-associated lymphoid tissue lymphoma, and chronic gastritis with significant abnormalities as mandatory treatment. (2) Consensus opinion of European 2005 Florence meeting: This meeting expanded the indications for Hp eradication, and in addition to the above-mentioned indications listed in the consensus opinion of Chinese Tongcheng meeting, the following conditions were listed as indications with recommendation level A, namely, Hp-positive non-ulcer dyspepsia, patients on long-term aspirin should be detected and eradicated if they bleed, Hp eradication can stop the atrophic gastritis Hp eradication can stop the progress of atrophic gastritis and possibly reduce atrophy, Hp eradication can prevent precancerous lesions of the gastric mucosa. 5, H. pylori eradication treatment options Although there are numerous treatment options for Hp infection, there are few treatment options that are truly effective, have few side effects, and are appropriately priced. There are three main first-line treatment regimens recommended, namely a triple therapy based on bismuth, PPI (proton pump inhibitor) or RBC (ranitidine bismuth citrate) plus two antibiotics. The triple regimen consisting of PPI preparation and two antibiotics in combination is the most effective drug combination with wide clinical application in recent years. The strong acid-suppressive effect of PPI raises the pH value in the stomach and increases the effect of antibiotics, and the activity of PPI is enhanced in the acidic environment and can penetrate the mucus and combine with the surface urease to inhibit the urease activity and achieve the effect of inhibition and eradication of Hp; the commonly used PPIs at present are omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole, etc. In addition, many studies have shown that RBC triple therapy is superior to PPI triple therapy in the treatment regimen of drug-resistant Hp strains. The main antibiotics commonly used today include amoxicillin, clarithromycin, metronidazole, furazolidone, tetracycline, etc. Due to the increasing problem of antibiotic resistance of Hp, especially the resistance of Hp to metronidazole is close to 80% in China, most studies suggest that the triple therapy of PPI combined with amoxicillin and clarithromycin (standard dose of PPI, amoxicillin 1000mg, clarithromycin 250-500mg, twice a day for 7-14 days) should be the preferred treatment regimen. Alternatively, treatment with RBC (350 mg twice a day)/PPI combined with furazolidone (100 mg 2-3 times a day) and amoxicillin/clarithromycin can be considered, thus reducing the cost of treatment. In patients who fail first-line therapy and enter second-line therapy, both PPI and bismuth can overcome the primary resistance of Hp and avoid the development of secondary resistance to some extent, therefore, the quadruple therapy of PPI combined with bismuth is used as second-line or remedial therapy in national and regional consensus of Hp. Hp infection plays an important role in the pathogenesis of peptic ulcers, but some peptic ulcers are not combined with Hp infection, and these ulcers may be associated with disruption of the gastric mucosal barrier due to long-term use of drugs such as aspirin/NSAIDs, which are both important independent causative factors of peptic ulcers, and Hp infection. In addition, there are some ulcers that are not related to either of these etiologies. Although Hp infection still plays an important role in the development of peptic ulcer, the detection rate of Hp in peptic ulcer patients is decreasing, while the incidence of NSAIDs-related ulcers and non-Hp non-NSAIDs ulcers is increasing. The incidence is on the rise. For example, in a study of 2260 patients, the results showed that Hp-associated ulcers accounted for 53% of 271 duodenal ulcers, NSAIDs-associated ulcers accounted for 10%, non-Hp non-NSAIDs ulcers accounted for 29%, and co-infection with Hp and NSAIDs accounted for 8%. Therefore, before deciding to treat a patient for Hp eradication, it is important to confirm the presence of Hp infection and determine the treatment strategy according to the cause of the patient’s peptic ulcer, rather than blindly giving the patient antibiotic therapy.