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.

ObjectiveTo construct a scale for the diagnosis of chronic atrophic gastritis （CAG） with turbid toxin accumulating in the stomach. MethodsFirst， a research group was established to construct the scale framework. Relevant literature of CAG with syndrome of turbid toxin accumulating in the stomach was searched in CNKI， Wanfang Database （WF）， and VIP Database （CQVIP） from April 1， 2003 to April 1， 2023， and items were preliminarily selected after standardization of terms. Through clinical investigation， the discrete trend method， correlation coefficient method， Cronbach's coefficient method， and factor analysis method were used to screen symptom items， and the frequency method was used to screen signs， tongue coating， and pulse conditions. Three rounds of Delphi expert consultation were conducted to determine the items of the scale. The weight of each item was obtained by the analytic hierarchy process. ResultsA total of 49 articles were included， and 45 items were obtained after primary screening， including 28 symptoms， 2 signs， 10 tongue coatings， and 5 pulse conditions. After clinical investigation， 15 symptoms were retained， and 8 signs and pulse conditions of tongue coating were retained. The positive coefficients of experts in three rounds of Delphi expert consultation were 100%， 96.67%， and 100%， respectively. The expert authority coefficients were 0.86， 0.87， and 0.87， respectively， and the coordination coefficients were 0.18， 0.25， and 0.30. After core group discussion， Delphi method investigation， and AHP weight assignment， the diagnostic scale items of CAG with turbid toxin accumulating in stomach syndrome were finally established， namely， dark red or purplish tongue proper with yellow greasy （or dry） coating （30 points）， epigastric stuffiness and fullness or pain （15 points）， sticky and unsmooth defecation （10 points）， taste disturbance （sticky mouth， fetid breath， bitter taste， 7 points）， heartburn or acid regurgitation （6 points）， dizziness and clouding （5 points）， general heaviness and fatigue （5 points）， slippery， string‑slippery， or slippery‑rapid pulse （5 points）， dysuria （or yellow or deep yellow urine， 4 points）， poor appetite （4 points）， dull complexion （3 points）， sticky， greasy， and fetid secretions （3 points）， and poor sleep （3 points）. ConclusionBased on the establishment， screening， confirmation， and weighting of an item pool， combined with subjective and objective approaches as well as qualitative and quantitative methods， a diagnostic scale for CAG with the syndrome of turbid toxin accumulating in the stomach was successfully constructed.

Objective To investigate occupational exposure levels of lead, arsenic and cadmium in the lead smelting plant of Hunan Shui Kou Shan Nonferrous Metals Group Co. Ltd., analyze their effects on health of employees, and compare the applicability of different occupational health risk assessment methods, and to provide a basis for prevention and control of occupational exposure risks in enterprises. Methods According to systematic sampling method, 380 employees with lead, arsenic and cadmium exposure (exposure group) and 100 non-exposure employees (non-exposure group) were selected from 2022 to 2024 for on-site investigation of occupational health [concentration time-weighted average (C_TWA)] and physical examination. The risk was evaluated by qualitative assessment method, the U.S. Environmental Protection Agency (EPA) inhalation risk assessment method, and the Singapore Ministry of Manpower (MOM) semi-quantitative method. The consistency was analyzed by the Kappa test. Results C_TWA values of lead, arsenic, and cadmium in all positions were lower than the occupational exposure limit (OEL). The levels of blood lead, urine arsenic, and urine cadmium, as well as the prevalence of multiple systems in the exposure group were significantly higher than those in the non-exposure group (P<0.05). The proportions of chronic lead, arsenic, and cadmium poisoning were increasing year by year in the exposure group (P<0.05). The qualitative assessment method mainly indicated low and medium risk, while the EPA and MOM methods mainly indicated medium and high risk, with good agreement between the two methods (Kappa=0.676, P<0.05). Conclusion Although the enterprise meets the C_TWA standards, there are still occupational health risks of lead, arsenic, and cadmium. The EPA inhalation risk assessment method is more applicable.

Patients with inflammatory bowel disease (IBD) require long-term pharmacotherapy. Due to the wide variety of clinically available drugs, medication safety has become increasingly concerning. As an indispensable component of pharmaceutical formulations, drug excipients may induce various adverse reactions, including rash, allergic responses, and gastrointestinal discomfort, and may even lead to severe organic injury. However, they are often overlooked in clinical practice. Therefore, identifying and managing excipient-related adverse reactions is crucial for ensuring medication safety. To address this issue, this article systematically reviews common excipients in IBD therapeutics, the underlying mechanisms of excipient-induced adverse reactions, and corresponding management strategies, aiming to enhance clinicians' awareness of excipient-related issues, improve their ability to recognize and manage such reactions, and ultimately ensure patient safety.

ObjectiveTo investigate the mechanism by which Xianglian Huazhuo prescription alleviates chronic atrophic gastritis （CAG） through modulating the nuclear factor erythroid 2-related factor 2 （Nrf2）/quinone oxidoreductase 1 （NQO1）/heme oxygenase-1 （HO-1） pathway of oxidative stress （OS） based on animal experiments. MethodsFifty rats were modeled for CAG by gavage of 2% sodium salicylate （10 mL·kg^-1）， free access to 180 mg·L^-1 N-methyl-N′-nitro-N-nitrosoguanidine （MNNG）， and periodic diet intervention （72 h cycle： 24 h fasting + 48 h free access to food）. The modeled rats were grouped by a random number method as follows： low-， medium-， and high-dose （9， 18，36 g·kg^-1， respectively） Xianglian Huazhuo prescription， Moradan， and model， with 10 rats in each group. The general state of all rats was observed. Hematoxylin-eosin （HE） staining was employed to observe the pathological changes of the gastric mucosal tissue. The ultrastructure of cells was observed under transmission electron microscopy. Biochemical methods were adopted to determine the levels of malondialdehyde （MDA） and total superoxide dismutase （T-SOD） in the rat serum. The mRNA and protein levels of Kelch-like ECH-associated protein 1 （Keap1）， Nrf2， NQO1， and HO-1 in the gastric mucosal tissue of rats from each group were measured by Real-time polymerase chain reaction （Real-time PCR） and Western blot， respectively. Reactive oxygen species （ROS） staining was employed to detect the fluorescence intensity of ROS in the gastric mucosal tissue of rats in each group. ResultsCompared with the normal group， the modeled rats were sluggish， had yellowing and sparse hair， short and dark tail， loose stool， and reduced food intake， and showed the gastric mucosa characterized by atrophy， thinning， congestive edema， declined gland density and disarrangement， and apparent inflammatory cell infiltration， irregular nucleus morphology， nuclear condensation， mitochondria with decreased number， declined density， and abnormal morphology， vacuolization， declined serum T-SOD level （P<0.05）， elevated serum MDA level （P<0.05）， downregulated mRNA and protein levels of Nrf2， NQO1， and HO-1 （P<0.05）， upregulated mRNA and protein levels of Keap1 （P<0.05）， and enhanced mean fluorescence intensity of ROS （P<0.05）. Compared with the model group， each treatment group exhibited improved general state， alleviated histopathological changes in gastric mucosa， improved ultrastructural characteristics of cells， elevated T-SOD level and declined MDA level in the serum （P<0.05）， upregulated mRNA and protein levels of Nrf2， NQO1， and HO-1， downregulated mRNA and protein levels of Keap1 （P<0.05）， and attenuated mean fluorescence intensity of ROS （P<0.05）. ConclusionXianglian Huazhuo prescription can improve the general status， ameliorate pathological changes of gastric mucosa， and repair the cell ultrastructure to varying degrees， demonstrating a definite therapeutic effect on CAG. It may restrain OS and safeguard the natural physiological function of gastric mucosa in CAG rats by regulating the Nrf2/NQO1/HO-1 signaling pathway.

ObjectiveTo investigate the mechanism by which Xianglian Huazhuo prescription alleviates chronic atrophic gastritis （CAG） through modulating the nuclear factor erythroid 2-related factor 2 （Nrf2）/quinone oxidoreductase 1 （NQO1）/heme oxygenase-1 （HO-1） pathway of oxidative stress （OS） based on animal experiments. MethodsFifty rats were modeled for CAG by gavage of 2% sodium salicylate （10 mL·kg^-1）， free access to 180 mg·L^-1 N-methyl-N′-nitro-N-nitrosoguanidine （MNNG）， and periodic diet intervention （72 h cycle： 24 h fasting + 48 h free access to food）. The modeled rats were grouped by a random number method as follows： low-， medium-， and high-dose （9， 18，36 g·kg^-1， respectively） Xianglian Huazhuo prescription， Moradan， and model， with 10 rats in each group. The general state of all rats was observed. Hematoxylin-eosin （HE） staining was employed to observe the pathological changes of the gastric mucosal tissue. The ultrastructure of cells was observed under transmission electron microscopy. Biochemical methods were adopted to determine the levels of malondialdehyde （MDA） and total superoxide dismutase （T-SOD） in the rat serum. The mRNA and protein levels of Kelch-like ECH-associated protein 1 （Keap1）， Nrf2， NQO1， and HO-1 in the gastric mucosal tissue of rats from each group were measured by Real-time polymerase chain reaction （Real-time PCR） and Western blot， respectively. Reactive oxygen species （ROS） staining was employed to detect the fluorescence intensity of ROS in the gastric mucosal tissue of rats in each group. ResultsCompared with the normal group， the modeled rats were sluggish， had yellowing and sparse hair， short and dark tail， loose stool， and reduced food intake， and showed the gastric mucosa characterized by atrophy， thinning， congestive edema， declined gland density and disarrangement， and apparent inflammatory cell infiltration， irregular nucleus morphology， nuclear condensation， mitochondria with decreased number， declined density， and abnormal morphology， vacuolization， declined serum T-SOD level （P<0.05）， elevated serum MDA level （P<0.05）， downregulated mRNA and protein levels of Nrf2， NQO1， and HO-1 （P<0.05）， upregulated mRNA and protein levels of Keap1 （P<0.05）， and enhanced mean fluorescence intensity of ROS （P<0.05）. Compared with the model group， each treatment group exhibited improved general state， alleviated histopathological changes in gastric mucosa， improved ultrastructural characteristics of cells， elevated T-SOD level and declined MDA level in the serum （P<0.05）， upregulated mRNA and protein levels of Nrf2， NQO1， and HO-1， downregulated mRNA and protein levels of Keap1 （P<0.05）， and attenuated mean fluorescence intensity of ROS （P<0.05）. ConclusionXianglian Huazhuo prescription can improve the general status， ameliorate pathological changes of gastric mucosa， and repair the cell ultrastructure to varying degrees， demonstrating a definite therapeutic effect on CAG. It may restrain OS and safeguard the natural physiological function of gastric mucosa in CAG rats by regulating the Nrf2/NQO1/HO-1 signaling pathway.

Premature ovarian insufficiency(POI)is a complex endocrine disorder that significantly affects the physiological and repro-ductive functions of women,and it has become one of the main causes of infertility in women of childbearing age.The clinical features of POI include amenorrhea or oligomenorrhea,low estrogen or estrogen deficiency,and an increase in the level of gonadotropin.The in-cidence rate of POI tends to increase,yet its etiology and pathogenesis remain unclear.At present,the conventional treatment methods for POI have limited efficacy in fundamentally improving ovarian function or addressing the fertility issue.With the development of re-generative medicine,mesenchymal stem cells(MSCs)have become one of the research hotspots in POI therapy,and their exosomes have attracted wide attention as a promising"cell-free therapy".A number of animal experimental studies have shown that MSCs and their exosomes can exert a therapeutic effect on POI by affecting granulosa cell proliferation and apoptosis,promoting ovarian angiogen-esis,reducing oxidative stress and fibrosis,enhancing follicular development,and regulating immunity.In addition,related clinical studies have also made some progress.This article reviews the mechanisms and clinical effect of MSCs and their exosomes in the treatment of POI,in order to provide a reference for further research and bench-to-bedside translation of POI therapies.