ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

Chronic atrophic gastritis （CAG）， a common digestive system disease， has an unclear pathogenesis. Currently， it is mostly believed to be related to Helicobacter pylori （Hp） infection， immune factors， dietary factors， bile reflux， long-term use of antibiotics and anti-inflammatory drugs， and other factors. Ferroptosis is a regulated cell death mechanism that is iron-dependent and characterized by disruption of iron metabolism and accumulation of lipid peroxides. More and more studies have found that ferroptosis is closely related to the onset of CAG. Professor LI Diangui， a master of traditional Chinese medicine， first proposed the turbid toxin theory， which holds that spleen deficiency and turbid toxin is the main pathogenic mechanism of CAG. Abnormal iron metabolism regulation is a prerequisite for the accumulation of turbid toxin in CAG， and ferroptosis is in accordance with the pathogenic mechanism （spleen deficiency and turbid toxin） of CAG. This article explores the pathological mechanism of spleen deficiency and turbid toxin in CAG from the perspectives of iron metabolism， oxidative stress， and lipid peroxidation， providing theoretical support of traditional Chinese medicine for the modern research on CAG. It enriches the modern scientific connotation of the turbid toxicity theory and provides new ideas and breakthrough points for the clinical treatment of CAG.

Chronic atrophic gastritis （CAG）， a common digestive system disease， has an unclear pathogenesis. Currently， it is mostly believed to be related to Helicobacter pylori （Hp） infection， immune factors， dietary factors， bile reflux， long-term use of antibiotics and anti-inflammatory drugs， and other factors. Ferroptosis is a regulated cell death mechanism that is iron-dependent and characterized by disruption of iron metabolism and accumulation of lipid peroxides. More and more studies have found that ferroptosis is closely related to the onset of CAG. Professor LI Diangui， a master of traditional Chinese medicine， first proposed the turbid toxin theory， which holds that spleen deficiency and turbid toxin is the main pathogenic mechanism of CAG. Abnormal iron metabolism regulation is a prerequisite for the accumulation of turbid toxin in CAG， and ferroptosis is in accordance with the pathogenic mechanism （spleen deficiency and turbid toxin） of CAG. This article explores the pathological mechanism of spleen deficiency and turbid toxin in CAG from the perspectives of iron metabolism， oxidative stress， and lipid peroxidation， providing theoretical support of traditional Chinese medicine for the modern research on CAG. It enriches the modern scientific connotation of the turbid toxicity theory and provides new ideas and breakthrough points for the clinical treatment of CAG.

ObjectiveTo investigate the therapeutic effect and mechanism of coptisine on chronic atrophic gastritis （CAG） in rats based on the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodA CAG rat model was induced by multiple factors， including sodium salicylate， N-methyl-N′-nitro-N-nitrosoguanidine （MNNG）， and irregular feeding. The successfully modeled rats were randomly divided into the model group， folic acid group， and high- and low-dose coptisine groups. The high- and low-dose coptisine groups were given coptisine （50， 10 mg·kg^-1， respectively）， and the folic acid group was given folic acid at 2 mg·kg^-1 for 60 days. The pathological changes were detected by hematoxylin-eosin （HE） staining. The ultrastructure of gastric mucosal cells was observed by electron microscopy. Serum pepsinogen Ⅰ （PGⅠ）， pepsinogen Ⅱ （PGⅡ）， and PGⅠ/PGⅡ ratio （PGR） were detected by immunoturbidimetry. Serum gastrin-17 （G-17） level was detected by radioimmunoassay. The content of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in serum of rats was detected by enzyme-linked immunosorbent assay （ELSIA）. Western blot analysis was used to detect the expression levels of TGF-β₁， PI3K， phosphorylated-Akt （p-Akt）， mTOR， and phosphatase and tensin homolog deleted on chromosome 10 （PTEN） in gastric mucosa. The mRNA levels of TGF-β₁， PI3K， Akt， mTOR， PTEN， microtubule-associated protein light chain 3Ⅱ （LC3Ⅱ）， and Beclin-1 were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， the model group showed atrophy and reduced number of intrinsic glands in the gastric mucosal tissues， as well as inflammatory cell infiltration. The ultrastructure of gastric mucosal cells in the model group displayed nuclear condensation， reduced and swollen mitochondria， and abnormal structure. The serum levels of G-17， PGⅠ， PGR， and the protein and mRNA levels of PTEN in gastric tissues were significantly lower in the model group （P<0.01）， while serum levels of IL-6， IL-1β， TNF-α， and the protein and mRNA levels of TGF-β₁， PI3K， Akt， and mTOR in gastric tissues were significantly higher （P<0.01）. Compared with the model group， various drug intervention groups showed different degrees of improvement in pathological damage and gastric mucosal cell ultrastructure， significantly increased serum levels of G-17， PGⅠ， and PGR （P<0.05，P<0.01）， and significantly decreased levels of IL-6， IL-1β， and TNF-α （P<0.05，P<0.01）. The high-dose coptisine group significantly downregulated the protein and mRNA levels of TGF-β₁， PI3K， Akt， and mTOR （P<0.05，P<0.01）. ConclusionBerberine has a therapeutic effect on CAG in rats， possibly exerting a protective effect on gastric mucosa by inhibiting inflammation and blocking the PI3K/Akt/mTOR signaling pathway.

ObjectiveTo explore the mechanism of Xianglian Huazhuo prescription in the treatment of chronic atrophic gastritis （CAG） based on network pharmacology and animal experiments，so as to provide scientific basis for clinical application. MethodThe possible targets and pathways of Xianglian Huazhuo prescription in the treatment of CAG were obtained based on the prediction of network pharmacology. The CAG rat model was induced by sodium salicylate，N-methyl-N'-nitro-N-nitrosoguanidine （MNNG） and hunger and satiety disorder. Then the CAG rats were treated with Xianglian Huazhuo prescription and morodan for 60 days. After administration，the rats were sacrificed，and the content of interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β） and vascular endothelial growth factor （VEGF） in serum was determined by enzyme linked immunosorbent assay（ELISA）. In addition， the protein expression of Bad and Bcl-2 in gastric mucosa was detected by immunohistochemistry （IHC）. ResultA total of 241 active components of Xianglian Huazhuo prescription and 53 core targets were obtained. Xianglian Huazhuo prescription affected multiple biological processes，such as cell proliferation and apoptosis，inflammatory reaction，regulation of DNA metabolism，and cell response to redox，as well as phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt），TNF，mitogen-activated protein kinase （MAPK），cancer and cancer-related signaling pathways. The animal model verification showed that Xianglian Huazhuo prescription lowered the levels of IL-6，TNF-α，IL-1β and VEGF in serum of CAG rats，and reduced the protein expression of Bad and Bcl-2 in gastric tissue. ConclusionXianglian Huazhuo prescription could regulate PI3K/Akt signal pathway and improve gastric mucosal injury in CAG by participating in biological processes such as cell proliferation，apoptosis and inflammation.