ObjectiveTo reveal the compatibility rules of the core compound formula and traditional Chinese medicine （TCM） components for prevention and treatment of chronic atrophic gastritis （CAG） by Huazhuo Jiedu （turbidity-resolving and detoxifying） therapy through uniform design in view of the potential regulatory pathway of endogenous turbid-toxin retention in CAG， elucidate the potential pathway by which the compound formulas regulate the Wnt/β-catenin-connexin 43 （CX43） signaling axis， demonstrated the efficacy enhancement and toxicity attenuation among the components， thus providing experimental evidence for the scientific application of multi-component， multi-target compatibility in TCM compound formulas. MethodsA mouse model of CAG was established with N-methyl-N-nitrosourea （MNU）. Sixty mice were randomly allocated into 5 groups （n=12 per group）： blank control， model， low-dose Huazhuo Jiedu core compound formula （HXFF-L， 4.004 g·kg^-1）， high-dose Huazhuo Jiedu core compound formula （HXFF-H， 8.008 g·kg^-1）， and positive control （folic acid at 11 mg·kg^-1 + vitamin B₁₂ at 14 mg·kg^-1）. The therapeutic efficacy and molecular mechanism of the core compound formula were evaluated by hematoxylin-eosin （HE） staining， Alcian blue-periodic acid-Schiff （AB-PAS） staining， enzyme-linked immunosorbent assay （ELISA）， transmission electron microscopy （TEM）， immunofluorescence assay， and Western blot. The chemical components of the core compound formula were detected and effective components were screened by ultra-high performance liquid chromatography coupled with quadrupole-orbitrap high-resolution mass spectrometry （UHPLC-Q-Orbitrap HRMS）. Another 120 mice were randomized into blank control， model， and 8 HXFF component-combination groups with different dosages （uniform design groups 1-8， n=12 per group）. A uniform design was adopted， with pathological scores of mouse gastric tissue as well as serum levels of pepsinogen Ⅰ （PGⅠ）， pepsinogen Ⅱ （PGⅡ）， and gastrin 17 （GAS17） set as dependent variables. Multivariate linear regression analysis was performed to predict the optimal proportion of core components in the compound formula and explore its compatibility rules. ResultsPharmacodynamic validation showed that compared with the blank control group， the model group had decreased gastric weight index （P<0.01） and increased pathological damage score and inflammatory factor levels （P<0.01）. Compared with the model group， these indicators were reversed in the HXFF-L， HXFF-H， and positive control groups （P<0.05， P<0.01）. Immunofluorescence results showed that CX43 expression was downregulated in the model group compared with the blank control group （P<0.01） and upregulated in the HXFF-H and positive control groups compared with the model group （P<0.05， P<0.01）. Western blot results showed that compared with the blank control group， the model group demonstrated upregulated protein levels of Wnt and β-catenin in the gastric tissue （P<0.01）. Compared with those in the model group， the protein level of Wnt was downregulated in the HXFF-L， HXFF-H， and positive control groups （P<0.05， P<0.01）， while that of β-catenin was downregulated only in the HXFF-H group （P<0.05）. A total of 25 compounds were identified in the core compound formula， including 9 from Coptidis Rhizoma， 10 from Pogostemonis Herba， 2 from Scorpio， and 4 from Lilii Bulbus. According to the category and origin of compounds， Coptidis Rhizoma alkaloids， Pogostemonis Herba volatile oils， Scorpio peptides， and Lilii Bulbus alkaloids were finally selected for component research. The predicted optimal combination of TCM components was as follows： Coptidis Rhizoma alkaloids at 75 mg·kg^-1， Pogostemonis Herba volatile oils at 2.25 mg·kg^-1， Scorpio protein extract at 90 mg·kg^-1， and Lilii Bulbus alkaloids at 9 mg·kg^-1. Coptidis Rhizoma alkaloids， Scorpio protein extract， Pogostemonis Herba volatile oils， and Lilii Bulbus alkaloids can ameliorate pathological lesions of the gastric tissue. Scorpio protein extract exerted positive regulatory effects on the gastric function， while Pogostemonis Herba volatile oils and Lilii Bulbus alkaloids showed negative correlations with partial gastric function indicators. Further investigations are required to clarify their dose-effect relationships and safety profiles. ConclusionThis study， for the first time， predicts the optimal proportion and synergistic regulatory mechanism of the core compound formula of Huazhuo Jiedu therapy， revealing the synergistic compatibility logic of its components. It provides a novel strategy for the precise TCM treatment of CAG and the modern development of compound formulas.

ObjectiveTo reveal the compatibility rules of the core compound formula and traditional Chinese medicine （TCM） components for prevention and treatment of chronic atrophic gastritis （CAG） by Huazhuo Jiedu （turbidity-resolving and detoxifying） therapy through uniform design in view of the potential regulatory pathway of endogenous turbid-toxin retention in CAG， elucidate the potential pathway by which the compound formulas regulate the Wnt/β-catenin-connexin 43 （CX43） signaling axis， demonstrated the efficacy enhancement and toxicity attenuation among the components， thus providing experimental evidence for the scientific application of multi-component， multi-target compatibility in TCM compound formulas. MethodsA mouse model of CAG was established with N-methyl-N-nitrosourea （MNU）. Sixty mice were randomly allocated into 5 groups （n=12 per group）： blank control， model， low-dose Huazhuo Jiedu core compound formula （HXFF-L， 4.004 g·kg^-1）， high-dose Huazhuo Jiedu core compound formula （HXFF-H， 8.008 g·kg^-1）， and positive control （folic acid at 11 mg·kg^-1 + vitamin B₁₂ at 14 mg·kg^-1）. The therapeutic efficacy and molecular mechanism of the core compound formula were evaluated by hematoxylin-eosin （HE） staining， Alcian blue-periodic acid-Schiff （AB-PAS） staining， enzyme-linked immunosorbent assay （ELISA）， transmission electron microscopy （TEM）， immunofluorescence assay， and Western blot. The chemical components of the core compound formula were detected and effective components were screened by ultra-high performance liquid chromatography coupled with quadrupole-orbitrap high-resolution mass spectrometry （UHPLC-Q-Orbitrap HRMS）. Another 120 mice were randomized into blank control， model， and 8 HXFF component-combination groups with different dosages （uniform design groups 1-8， n=12 per group）. A uniform design was adopted， with pathological scores of mouse gastric tissue as well as serum levels of pepsinogen Ⅰ （PGⅠ）， pepsinogen Ⅱ （PGⅡ）， and gastrin 17 （GAS17） set as dependent variables. Multivariate linear regression analysis was performed to predict the optimal proportion of core components in the compound formula and explore its compatibility rules. ResultsPharmacodynamic validation showed that compared with the blank control group， the model group had decreased gastric weight index （P<0.01） and increased pathological damage score and inflammatory factor levels （P<0.01）. Compared with the model group， these indicators were reversed in the HXFF-L， HXFF-H， and positive control groups （P<0.05， P<0.01）. Immunofluorescence results showed that CX43 expression was downregulated in the model group compared with the blank control group （P<0.01） and upregulated in the HXFF-H and positive control groups compared with the model group （P<0.05， P<0.01）. Western blot results showed that compared with the blank control group， the model group demonstrated upregulated protein levels of Wnt and β-catenin in the gastric tissue （P<0.01）. Compared with those in the model group， the protein level of Wnt was downregulated in the HXFF-L， HXFF-H， and positive control groups （P<0.05， P<0.01）， while that of β-catenin was downregulated only in the HXFF-H group （P<0.05）. A total of 25 compounds were identified in the core compound formula， including 9 from Coptidis Rhizoma， 10 from Pogostemonis Herba， 2 from Scorpio， and 4 from Lilii Bulbus. According to the category and origin of compounds， Coptidis Rhizoma alkaloids， Pogostemonis Herba volatile oils， Scorpio peptides， and Lilii Bulbus alkaloids were finally selected for component research. The predicted optimal combination of TCM components was as follows： Coptidis Rhizoma alkaloids at 75 mg·kg^-1， Pogostemonis Herba volatile oils at 2.25 mg·kg^-1， Scorpio protein extract at 90 mg·kg^-1， and Lilii Bulbus alkaloids at 9 mg·kg^-1. Coptidis Rhizoma alkaloids， Scorpio protein extract， Pogostemonis Herba volatile oils， and Lilii Bulbus alkaloids can ameliorate pathological lesions of the gastric tissue. Scorpio protein extract exerted positive regulatory effects on the gastric function， while Pogostemonis Herba volatile oils and Lilii Bulbus alkaloids showed negative correlations with partial gastric function indicators. Further investigations are required to clarify their dose-effect relationships and safety profiles. ConclusionThis study， for the first time， predicts the optimal proportion and synergistic regulatory mechanism of the core compound formula of Huazhuo Jiedu therapy， revealing the synergistic compatibility logic of its components. It provides a novel strategy for the precise TCM treatment of CAG and the modern development of compound formulas.

Objective:To explore the value of nomogram based on dual-energy CT (DECT) enhanced imaging in predicting postoperative recurrence-free survival (RFS) of early-stage glottic carcinoma (EGC).Methods:The clinicopathological and DECT data of patients with EGC confirmed by pathology in the Tianjin First Central Hospital from January 2015 to July 2018 were analyzed retrospectively. A total of 178 patients were enrolled, including 162 males and 16 females, with the age from 44 to 86 (62±9) years old. According to the follow-up data, the patients were divided into recurrent group ( n=32) and non-recurrent group ( n=146). The differences of clinicopathological data and DECT iodine maps parameters between the two groups were analyzed using χ 2 test, independent-sample t test and Mann-Whitney U test. The survival related cut-off values of the quantitative data between the two groups were selected by X-tile software. The survival curve was drawn using Kaplan-Meier method, and the difference of survival rate was tested with log-rank analysis. The variables with statistical differences were included in the Cox proportional hazard model for multivariate analysis to select the independent predictors of postoperative RFS. Based on the multivariate Cox analysis, the nomogram was drawn to predict the RFS at 1, 2 and 5 years. The prediction efficiency and clinical benefit of the nomogram were evaluated by C-index, calibration curve and decision curve analysis. Results:The median follow-up time was 24.3 months, ranging from 2 to 63 months. There was a significant difference in T-stage between recurrent and non-recurrent groups (χ2=9.21, P=0.002). The prognostic cutoff values obtained by X-tile software were arterial phase standardized iodine concentration (SIC AP)=0.28 and venous phase standardized iodine concentration (SIC VP)=0.87. The results of log-rank test showed that there were significant differences in RFS among patients with different T-stage, SIC AP and SIC VP (χ2=10.74, 15.50, 17.97, P=0.001,<0.001,<0.001). T-stage, SIC AP and SIC VP were identified as independent predictors of postoperative RFS (hazard ratio=2.271, 3.552, 3.266, P=0.026,<0.001, 0.003). The C-index of the nomogram combined with DECT parameter and T-stage was 0.785, which was higher than that of T-stage alone (0.622). The calibration curve showed that there was good consistency between the actual and predicted probability of the sample. The decision curve analysis showed that the clinical benefit of the nomogram was higher than that of the T-stage alone. Conclusion:The nomogram based on preoperative clinical factors (T-stage) and DECT iodine map factors (SIC AP and SIC vp) can predict the postoperative RFS of patients with EGC.