(1) There are still the following factors: 1. Bile in acidic medium, especially under ischemic conditions, aggravated the damage to gastric mucosa. 2. Bile plus pancreatic juice and duodenal juice containing lysolecithin have the greatest destructive effect on gastric mucosa. 3. In patients with gastric ulcer, the growth of gram-negative aerobic bacteria in gastrointestinal aspirate of patients with high bile concentration in stomach increased. 4. In patients with clinical symptoms, the concentration of deoxycholic acid in gastric juice increased. 5. Slow gastric emptying prolongs the contact time between bile and gastric mucosa. (2) Pathogenesis 1. The mechanism of DGR The physiological study of gastric motility proves that pylorus is open most of the time, and a small amount of duodenal reflux is not enough to cause symptoms and damage gastric mucosa, which is called physiological DGR. The occurrence of a large number of DGR is common in the following situations: (1) DGR after gastric surgery: the incidence of postoperative gastric DGR is 5% ~ 60%. After operation, the normal anatomical structure and physiological function of pylorus in the stomach were damaged, which led to the loss of pylorus' anti-DGR barrier effect, which caused excessive alkaline intestinal juice containing bile components to reflux into the stomach, leading to residual gastritis and bile vomiting. Griffiths reported 71 cases of postoperative stomach, 4 1.9% had bile reflux and 6 1.5% had diffuse gastritis. Bile flows back to the stomach from the duodenum or small intestine after gastric surgery. Because some operations are gastrojejunostomy, they should be called intragastric gastroreflux. The severity of gastro-intestinal reflux is obviously related to the surgical methods, which are arranged as follows: ① Pyloriplasty. ② Vagal trunk transection plus pyloroplasty. ③ Gastrojejunostomy. ④ Billroth Ⅰ gastrectomy. ⑤ Billroth Ⅱ gastrectomy. (2) Primary pyloric dysfunction: Modern gastrointestinal motility studies have proved that some pathological DGR did not occur after gastric surgery, but originated from the defect of pylorus itself. Dysfunction of pyloric sphincter, such as prolonged pyloric opening time and dysfunction of pyloric hypertension area, leads to a large number of duodenal contents reflux into the stomach. 1973, Fisher measured the pressure of pyloric high pressure band by perfusion method as (5.3? 0.5)mmHg, China and Romania also confirmed the existence of pyloric hypertension zone by intracavity metal sensor method. People think that the gastroduodenal barrier pressure (GDBP= pyloric pressure-duodenal pressure) has anti-reflux effect. DGR occurs when GDBP decreases. According to domestic reports, the gastroduodenal barrier pressure of DGR patients is lower than that of normal control group. It was observed in animal experiments that atypical segmental contraction was accompanied by DGR in the second stage of moving complex (MMC) during digestion. In humans, DCR also occurs in MMC ⅱ stage, and its mechanism may be as follows: ① In MMC ⅱ stage, bile and pancreas secrete and gather in the duodenum. ② Due to the slight regular movement and pressure change of MMCⅱⅱ phase, a certain pressure gradient is generated, which increases the internal pressure of duodenum and leads to gastrointestinal reflux. (3) Delayed gastric emptying: Whether it is idiopathic or secondary delayed gastric emptying (such as idiopathic gastroparesis and diabetic gastroparesis), gastric peristalsis and pyloric dysfunction reduce GDBP, leading to a large number of duodenal reflux. Once DGR occurs, it can further slow down gastric emptying, so some people think that slow gastric emptying and DGR can be mutually causal (DGR). (4) Hepatobiliary diseases: The incidence of DGR in patients with cirrhosis and portal hypertension is high, and its mechanism is thought to be due to circulatory disorder caused by portal hypertension, coupled with secondary hypergastrinemia, which inhibits the regulation of cholecystokinin and glucagon on pyloric sphincter and Oddi sphincter, reduces the tension of the latter two, and causes bile and pancreatic juice to return to the stomach. Many biliary diseases (cholecystitis, gallstones, after cholecystectomy, etc. ) are accompanied by obvious DGR phenomenon. Due to biliary diseases, the function of gallbladder to store and concentrate bile is reduced and disappeared, which leads to bile flowing from bile duct into duodenum and retrograde into stomach through pylorus. Disorder of autonomic nervous system, excessive smoking, drinking, mood fluctuation and lifestyle change can cause disorder of gastrointestinal hormone secretion, reverse peristalsis of gastric antrum and duodenum, and decrease of pyloric tension, resulting in gastric and duodenal dyskinesia, which provides necessary pressure gradient for reflux to pass through pylorus and promotes DGR. 2. Pathogenesis of Bile Reflux Gastritis (BRG) Gastric surgery, such as subtotal gastrectomy, usually produces residual gastritis or bile reflux gastritis (BRG) after several months or years due to bile reflux, and produces symptoms such as upper abdominal pain or bile vomiting. A large number of animal experiments and clinical observations have proved that the reflux of bile and duodenal contents to the stomach can cause gastritis, and it is found that the scope and severity of gastritis are linearly related to the degree of bile reflux and related to reflux components. Cholic acid and lysolecithin are the main components that damage gastric mucosa. Bile salt can dissolve phospholipids and cholesterol in gastric mucosa, interfere with the energy metabolism of gastric mucosal epithelial cells, rupture lysosomal membrane, remove mucus on the surface of gastric mucosa, destroy the barrier of gastric mucosa, and increase the reverse diffusion of H, thus making mast cells release histamine, leading to gastritis. A large number of DGR not only directly damages gastric mucosa to produce gastritis, but also is related to the occurrence of gastric ulcer. Rhodes J et al. (1972) found that the DGR of patients with gastric ulcer was higher than that of normal people. The mechanism may be that the gastric mucosa was first damaged by excessive cytotoxic bile salts and trypsin, and then proliferative changes, intestinal metaplasia and ulcer formation occurred. In addition, DGR can reflux to esophagus at the same time, which plays an important role in the pathogenesis of reflux esophagitis and Barrett's esophagus, and is called duodenogastroesophageal reflux (DGER).