The development and application of protonpumpinhibitors (PPls) have ushered in a new era of drug therapy for various acid-related diseases. However, with the wide application in clinical practice, the application of PPIs is no longer limited to gastroenterology, but is also frequently found on prescriptions in departments such as neurosurgery and oncology, which warrants increasing attention and discussion. I. PPIs for upper peptic ulcers Gastric ulcer, duodenal ulcer, reflux esophagitis, Zollinger-Ellison syndrome (Zollinger-Ellison syndrome), anastomotic ulcers, etc. These are the more familiar applications. Proton pump inhibitors are “precursor drugs” that need to be activated in an acidic environment, and after activation, they specifically act on the proton pump (K+-H+-ATPase) of gastric lining cells, blocking gastric acid secretion for one week. The main mechanism is that PPIs inhibit acid secretion and increase gastric pH, which provides a better pH base for antibiotics to work, thus enabling acid intolerant antibiotics to exert their maximum bactericidal ability. A triple 1-week regimen based on PPIs and combined with two of clarithromycin, amoxicillin, tetracycline and metronidazole is the first-line regimen for Hp eradication treatment, and adding bismuth to the triple regimen containing PPIs to become a quadruple regimen can achieve higher eradication rates. II. PPIs for stress ulcers Stress ulcer (SU) refers to acute gastrointestinal erosions and ulcers that occur in the body under severe stress conditions such as various types of severe trauma and critical illness, which can eventually lead to gastrointestinal bleeding, perforation and deterioration of the original lesions. Among the most common sources of stress are: heavy cranial trauma (also known as Cushing’s ulcer), severe burns (also known as Curling’s ulcer), severe trauma and various difficult and complex postoperative major surgeries, etc. Regarding stress ulcers, firstly, not all major and minor surgeries should be prevented, and secondly, do stress ulcers have to be treated with PPIs? Only the following conditions are classified as high risk for stress ulcers. (i) advanced age (age ≥65 years); (ii) severe trauma (craniocerebral trauma, burns, complex chest and abdomen, difficult major surgery, etc.); (iii) combined shock or persistent hypotension; (iv) severe systemic infection; (v) complicated MODS, mechanical ventilation >3d; (vi) severe jaundice; (vii) combined coagulation mechanism disorder; (viii) post-organ transplantation; (ix) long-term application of immunosuppression with extra-gastrointestinal nutrition; (x) history of ulcer within 1 year. When diseases or factors that may cause stress ulcers exist, before they occur, oral acid suppressants or antacids may be applied within one week before perioperative surgery to raise the pH in the stomach in patients who are proposed for major surgery and are estimated to have possible postoperative complications of SU. Commonly used therapies such as: proton pump blocker (PPI) omeprazole 20mg, 1 time/d. For prevention of severe trauma and high-risk groups: PPI should be given intravenously after the onset of the disease so that the intragastric pH rises rapidly above 4, such as omeprazole (40mg. 2 times/d). Once symptoms of gastrointestinal bleeding such as vomiting blood or black stool are found, suggesting that SU has occurred, PPIs injections such as omeprazole, 80mg for the first dose and 40mg later, q8h for maintenance. In addition, H2 receptor antagonists and gastric mucosal protectors can also have the effect of preventing stress ulcers, and the medication can be chosen considering the patient’s own situation and cost. Do I need to use H2 receptor blockers after using PPIs? Some people believe that H2 receptor antagonists are effective in controlling gastric acid at night, and adding H2 receptor antagonists at bedtime while using PPIs can strengthen the control of gastric juice PH at night. Another view is that the inhibitory effect of PPIs on proton pump is irreversible, so the acid-suppressive effect is long, and the acid-suppressive effect can be restored only after the formation of new proton pump, and the antacid effect can be maintained for as long as 24 hours. The simultaneous use of H2 receptor antagonists is of little significance and will increase adverse reactions. Fourth, aspirin + clopidogrel and proton pump inhibitors in combination There are reports that clopidogrel and proton pump inhibitors are metabolized through the cytochrome P450 isoenzyme system, and proton pump inhibitors reduce the antiplatelet activity of clopidogrel by competitively inhibiting the cytochrome P450 isoenzyme CYP2C19, increasing the probability of recurrent cardiovascular events. Aspirin + clopidogrel is a commonly used drug in cardiology, and the need to combine PPI is also a lingering issue. Whether to apply PPI should be evaluated first to eliminate the risk of bleeding. For example, it should be used for patients of advanced age or taking NSAIDs, or for patients with combined renal insufficiency or anemia, as they are in the high-risk group for gastrointestinal bleeding. If they are not in the high-risk group for bleeding, they may not be used, or gastric mucosal protectors and H2 receptor antagonists may be considered first. After all, small doses of aspirin are less damaging to the gastric mucosa, and clopidogrel has even less impact. If it is a prophylactic medication, H2 receptor blockers can actually be used. V. Do I still need PPIs after total gastrectomy? The NCCN guidelines require that HP be tested after gastric cancer surgery, and if there is infection, it needs to be treated. So do we still need PPIs after total gastrectomy? The main reference here should be after major gastrectomy rather than after total gastrectomy, HP mainly settles in the mucosa of the gastric sinus, and Hp should not be a problem after total gastrectomy. In addition, PPIs mainly inhibit mural cell gastric acid secretion, so it is not necessary to use PPIs after total gastrectomy. Sixth, the acid rebound phenomenon of PPIs PPIs should not be used in large doses for a long time, generally after 6-8 weeks, according to the patient’s condition, consider reducing the dose or stopping the drug, patients with cerebral hemorrhage or cerebral infarction, after the acute bleeding period, a week of negative stool occult blood can be stopped. Acid rebound refers to the increase in gastric acid secretion beyond the pre-treatment level after discontinuation of acid-suppressing drugs. acid rebound of PPIs can trigger the appearance of acid-related symptoms again, which not only increases medical costs, but also poses problems for the termination of PPIs treatment. To prevent acid rebound, the indications for PPIs should be strictly controlled and overuse should be avoided. In addition, a step-down treatment can be considered, such as reducing the dose to 10 mg/d after 8 weeks of use, and then gradually reducing it to every other day, or on-demand treatment.