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.

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Objective:To comparative analyze the role and effectiveness of different healthcare consortium support models in enhancing the capacity of community health centers.Methods:Using community health service centers under the loose medical association support mode and the close medical association support mode as research subjects,the data on medical service capacity were quantitatively analyzed using DID(Difference-in-Difference).Results:Both close medical association and the loose medical association support models have increased the number of outpatient and emergency room visits,Chinese medicine consultations,and referrals to community health centers.The close medical association support model also increased the number of discharges from the community health centers.Conclusion:Close medical consortium can enhance the capacity of community health centers,and the effect is better than loose medical consortium.

Objective:To comparative analyze the role and effectiveness of different healthcare consortium support models in enhancing the capacity of community health centers.Methods:Using community health service centers under the loose medical association support mode and the close medical association support mode as research subjects,the data on medical service capacity were quantitatively analyzed using DID(Difference-in-Difference).Results:Both close medical association and the loose medical association support models have increased the number of outpatient and emergency room visits,Chinese medicine consultations,and referrals to community health centers.The close medical association support model also increased the number of discharges from the community health centers.Conclusion:Close medical consortium can enhance the capacity of community health centers,and the effect is better than loose medical consortium.

Objective:To comparative analyze the role and effectiveness of different healthcare consortium support models in enhancing the capacity of community health centers.Methods:Using community health service centers under the loose medical association support mode and the close medical association support mode as research subjects,the data on medical service capacity were quantitatively analyzed using DID(Difference-in-Difference).Results:Both close medical association and the loose medical association support models have increased the number of outpatient and emergency room visits,Chinese medicine consultations,and referrals to community health centers.The close medical association support model also increased the number of discharges from the community health centers.Conclusion:Close medical consortium can enhance the capacity of community health centers,and the effect is better than loose medical consortium.

Objective:To comparative analyze the role and effectiveness of different healthcare consortium support models in enhancing the capacity of community health centers.Methods:Using community health service centers under the loose medical association support mode and the close medical association support mode as research subjects,the data on medical service capacity were quantitatively analyzed using DID(Difference-in-Difference).Results:Both close medical association and the loose medical association support models have increased the number of outpatient and emergency room visits,Chinese medicine consultations,and referrals to community health centers.The close medical association support model also increased the number of discharges from the community health centers.Conclusion:Close medical consortium can enhance the capacity of community health centers,and the effect is better than loose medical consortium.

Objective:To comparative analyze the role and effectiveness of different healthcare consortium support models in enhancing the capacity of community health centers.Methods:Using community health service centers under the loose medical association support mode and the close medical association support mode as research subjects,the data on medical service capacity were quantitatively analyzed using DID(Difference-in-Difference).Results:Both close medical association and the loose medical association support models have increased the number of outpatient and emergency room visits,Chinese medicine consultations,and referrals to community health centers.The close medical association support model also increased the number of discharges from the community health centers.Conclusion:Close medical consortium can enhance the capacity of community health centers,and the effect is better than loose medical consortium.

Objective:To comparative analyze the role and effectiveness of different healthcare consortium support models in enhancing the capacity of community health centers.Methods:Using community health service centers under the loose medical association support mode and the close medical association support mode as research subjects,the data on medical service capacity were quantitatively analyzed using DID(Difference-in-Difference).Results:Both close medical association and the loose medical association support models have increased the number of outpatient and emergency room visits,Chinese medicine consultations,and referrals to community health centers.The close medical association support model also increased the number of discharges from the community health centers.Conclusion:Close medical consortium can enhance the capacity of community health centers,and the effect is better than loose medical consortium.

Objective:To comparative analyze the role and effectiveness of different healthcare consortium support models in enhancing the capacity of community health centers.Methods:Using community health service centers under the loose medical association support mode and the close medical association support mode as research subjects,the data on medical service capacity were quantitatively analyzed using DID(Difference-in-Difference).Results:Both close medical association and the loose medical association support models have increased the number of outpatient and emergency room visits,Chinese medicine consultations,and referrals to community health centers.The close medical association support model also increased the number of discharges from the community health centers.Conclusion:Close medical consortium can enhance the capacity of community health centers,and the effect is better than loose medical consortium.