The bark and leaves of the willow tree have been recorded as early as ancient Egypt for their pain-relieving effects, and in 1763 the use of willow bark extracts for the treatment of arthritis was reported. 1860 saw the synthesis of “acetylsalicylic acid”, which marked the transition from a botanical to a chemical anti-inflammatory and analgesic. In 1899, acetylsalicylic acid was marketed under the trade name of “aspirin” by Bayer in Germany, and began to be used in clinical treatment of pain, arthritis and fever. In 1948, phenylbutazone (POTAXONE) was introduced as the first non-salicylic acid NSAIDs. Since then, many NSAIDs with stronger anti-inflammatory effects or lower side effects have been marketed, such as ibuprofen and indomethacin in the 1860s, diclofenac and naproxen in the 1970s, nabumetone and piroxicam in the 1980s, and meloxicam and nimesulide in the 1990s. Since aspirin has been used in clinical practice, there has been concern about the gastrointestinal safety of these drugs. In particular, salicylic acid and early non-salicylic acid NSAIDs, such as high-dose aspirin, anti-inflammatory pain, and inflammatory painkiller, have a high rate of gastrointestinal complaints during administration, and a higher incidence of asymptomatic peptic ulcers and bleeding on gastroscopy. Although there is a wide range of NSAIDs, they inhibit cyclooxygenase (COX), which exerts anti-inflammatory and analgesic effects, but also inhibit cyclooxygenase, which has a physiological protective effect on the gastrointestinal tract, resulting in a difficult contradiction between strong anti-inflammatory and analgesic effects and low gastrointestinal safety. In the 20th century, the solution to the problem of gastrointestinal safety of NSAIDs was almost always focused on the change of dosage form, such as premedication, enteric tablets, extended release, and synthetic combination with misoprostol. These are difficult to prevent the active ingredients from reaching the gastrointestinal tract through the body circulation and producing side effects. Clinical risk factors for gastrointestinal side effects include: 1) pre-existing peptic ulcers; 2) alcohol, tobacco, strong coffee and acidic beverages; 3) combination with steroid hormones or anticoagulants; 4) children, pregnant women and elderly people over 60 years of age; 5) high doses or long-term use; 6) intolerance to these drugs; 7) recent epigastric pain; 8) combined cardiovascular disease, hypertension, renal disease, hepatic disorders, and hepatic disorders. Hypertension, kidney disease, liver disease and other chronic diseases. For those who have more than 2 risk factors, if NSA IDs have to be used, they should choose drugs with less inhibitory effect on COX-1 or add proton pump inhibitors as much as possible. In 1999, celecoxib, a COX-2 inhibitor developed to address the COX isomer theory, was launched in the United States. Nabumetone and meloxicam are more potent against COX-2 and less potent against COX-1, and have a better gastrointestinal safety profile. These have been confirmed by several important clinical studies (including multicenter randomized controlled trials and systematic review Meta-analyses). Diclofenac and ibuprofen have also been favored by clinicians for their strong anti-inflammatory and analgesic effects and better overall safety profile. Of course, this year’s study also found that even COX-2 inhibitors do not completely eliminate the effect on COX C 1, so celecoxib still has gastrointestinal side effects, and some scholars claim that the risk of cardiovascular events (such as a potential increased risk of myocardial infarction) associated with celecoxib is not necessarily less than the gastrointestinal side effects it mitigates. However, as a basic drug for rheumatic diseases, the powerful anti-inflammatory and analgesic effects of NSAIDs cannot be ignored, so we still need to widely apply NSAIDs in clinical practice, and this process requires close attention to cardiovascular events and gastrointestinal side effects.