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.

Background Work-related musculoskeletal disorders (WMSDs) are one of the major occupational health problems faced by bus drivers and should receive special attention. Objective To explore the associations of weekly working hours and sleep quality with neck and lower back WMSDs among bus drivers, as well as assess the potential mediating role of sleep quality. Methods From June to December 2022, we recruited bus drivers from 5 subsidiaries of the Shenzhen Bus Group by convenient sampling method. Demographic characteristics, lifestyles, and work-related features of the bus drivers were collected through a questionnaire survey. The Pittsburgh Sleep Quality Index (PSQI) scale and the Musculoskeletal Disorders Survey Questionnaire were used to assess sleep quality and WMSDs respectively. Logistic regression models were applied to analyze the associations of weekly working hours and sleep quality with WMSDs in neck and lower back. Furthermore, mediation analysis was performed to investigate the role of sleep quality in the associations between weekly work hours and neck and lower back WMSDs. Results A total of 1792 valid questionnaires were collected, with a response rate of 95.07%. Among these, 89.3% of the bus drivers worked more than 40 h per week, and the positive rate of poor sleep quality was 28.2%. The overall positive rate of WMSDs within one year before the survey was 69.12%. Among different body regions, the leading positive rates were identified in neck and lower back regions, at 55.92% and 53.68%, respectively. The logistic regression model showed that compared to the bus drivers with weekly work hours ≤40 h, those weekly worked (40~48] h (OR=1.43, 95%CI: 1.02, 2.01; OR=1.65, 95%CI: 1.17, 2.34), (48~56] h (OR=2.69, 95%CI: 1.89, 3.83; OR=2.30, 95%CI: 1.62, 3.29) and ＞56 h (OR=2.63, 95%CI: 1.86, 3.74; OR=3.23, 95%CI: 2.27, 4.62) had significantly increased risk of WMSDs in neck and lower back. Additionally, when compared to those with good sleep quality, bus drivers with poor sleep quality had higher risks of both neck and lower back WMSDs (OR=4.08, 95%CI: 3.20, 5.23; OR=4.15, 95%CI: 3.26, 5.30, respectively). Further mediation analysis indicated that sleep quality partially mediated the associations between weekly working hours and both neck and lower back WMSDs, with 36.15% and 33.68% as the respective proportion of mediation. Conclusion The positive rate of WMSDs is high among bus drivers, and the most common WMSDs occur in neck and lower back. Long working hours and poor sleep quality are significantly associated with increased risks of neck and lower back WMSDs. Sleep quality may mediate the associations of weekly working hours with neck and lower back WMSDs.

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 explore the therapeutic effect and mechanism of Xianglian Huazhuo prescription on chronic atrophic gastritis （CAG） in rats based on the Hedgehog signaling pathway. MethodsThe CAG rat model was established by sodium salicylate， N-methyl-N′-nitro-N-nitroguanidine （MNNG）， and irregular feeding. The successfully modeled rats were randomly divided into a model group （180 mg·L^-1）， a moradan group （1.4 g·kg^-1）， and Xianglian Huazhuo Prescription groups with high， medium， and low doses （36， 9， 18 g·kg^-1）， followed by drug intervention. Hematoxylin-eosin （HE） staining was used to observe morphological changes in the gastric mucosa. Transmission electron microscopy was used to observe the ultrastructure of gastric mucosa cells. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of Sonic Hedgehog （Shh）， Patched 1 （Ptch1）， and Glioma-associated oncogene homolog 1 （Gli1）. Western blot was used to detect the protein expression levels of Shh， Ptch1， and Gli1 in the gastric mucosa. Immunohistochemistry was used to observe the protein expression of the epithelial marker E-cadherin. ResultsCompared with the normal group， the CAG model group showed a reduction in gastric mucosal intrinsic glands and infiltration of inflammatory cells. The ultrastructure of gastric mucosal cells showed nuclear pyknosis， fewer mitochondria， and abnormal mitochondrial structure. The mRNA and protein expression of Shh， Ptch1， and Gli1 in the gastric mucosa were significantly decreased （P<0.05）， and E-cadherin protein expression was decreased. Compared with the model group， the intervention groups showed varying degrees of improvement in histopathological morphology and cellular ultrastructure. The mRNA and protein expression of Shh， Ptch1， Gli1， and E-cadherin increased to varying degrees. Xianglian Huazhuo Prescription upregulated the expression of key Hedgehog pathway factors and E-cadherin at both the mRNA and protein levels （P<0.05）. ConclusionXianglian Huazhuo prescription has a therapeutic effect on CAG in rats， and its mechanism may be related to activation of the Hedgehog signaling pathway and inhibition of epithelial-mesenchymal transition （EMT）.

Objective To investigate the therapeutic effects and mechanism of Qidan Granules(QDG)on glucose and lipid metabolism disorders in type 2 diabetes mellitus(T2DM).Methods Rats were randomly divided into normal group,model group,QDG low-dose group,QDG high-dose group,and QDG high-dose+PI3K inhibitor group.The normal group received standard chow,while other groups were fed a high-fat/high-sugar diet and injected with streptozotocin(STZ)to establish T2DM.After modeling,rats received corresponding treatments.General conditions were monitored,with body mass,fasting blood glucose(FBG),lipid profiles[total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)],and fasting insulin levels recorded.Homeostatic model assessment of insulin resistance(HOMA-IR)was calculated.Hepatic mRNA expression of PI3K,AKT,and GSK3β was quantified via qRT-PCR,while protein levels of PI3K,AKT,GSK3β were measured by Western Blot.Results Compared with the model group,the QDG high-dose group showed reduced body mass(P＜0.05),reduced FBG(P＜0.05),decreased TC,TG,and LDL-C,elevated HDL-C,and lower HOMA-IR;mRNA levels of hepatic PI3K,AKT,and GSK3β and protein expression of p-PI3K,p-AKT,p-GSK3β were significantly upregulated,the differences being statistically significant(P＜0.05).The QDG low-dose and QDG high-dose+PI3K inhibitor groups exhibited attenuated improvements in these parameters versus the QDG high-dose group.Conclusion QDG ameliorates body mass loss,glucose/lipid metabolism,and insulin resistance in T2DM rats,likely by activating the PI3K/AKT/GSK3β pathway.

'Zhizhang Guhong Chongcui' is a new cultivar of Prunus mume with cross-cultivar group characteristics. It has typical characteristics of cinnabar purple cultivar group and green calyx cultivar group. It has green calyx, white flower, and light purple xylem, but the mechanism remains unclear. In order to clarify the causes of its cross-cultivar group traits, the color phenotype, anthocyanin content and the expression levels of genes related to anthocyanin synthesis pathway of 'Zhizhang Guhong Chongcui', 'Yuxi Zhusha' and 'Yuxi Bian Lü'e' were determined. It was found that the red degree of petals, sepals and fresh xylem in branches was positively correlated with the total anthocyanin content. MYBɑ1, MYB1, and bHLH3 were the key transcription factor genes that affected the redness of the three cultivars of flowers and xylem. The transcription factors further promoted the high expression of structural genes F3'H, DFR, ANS and UFGT, thereby promoting the production of red traits. Combined with phenotype, anthocyanin content and qRT-PCR results, it was speculated that the white color of petals of 'Zhizhang Guhong Chongcui' were derived from the high expression of FLS, F3'5'H, LAR and ANR genes in other branches of cyanidin synthesis pathway, and the low expression of GST gene. The green color of sepals might be originated from the relatively low expression of F3'H, DFR and ANS genes. The red color of xylem might be derived from the high expression of ANS and UFGT genes. This study made a preliminary explanation for the characteristics of the cross-cultivar group of 'Zhizhang Guhong Chongcui', and provided a reference for molecular breeding of flower color and xylem color of Prunus mume.
Animals ; Anthocyanins ; DNA Shuffling ; Flowers/genetics* ; Porifera ; Prunus/genetics* ; Glutamine/analogs & derivatives* ; Plant Extracts