1.Banxia Xiexin Decoction inhibits colitis-associated colorectal cancer development by modulating STAT3 signaling and gut microbiota.
Yinzi YUE ; Lianlin SU ; Yahui WANG ; Xiaoman LI ; Xiaoyan XIAO ; Jin XIE ; Shuai YAN
Chinese Herbal Medicines 2025;17(2):380-391
OBJECTIVE:
To investigate the therapeutic effects of Banxia Xiexin Decoction (BXD), a herbal medicine formula, on inflammation and the imbalance of the gut microbiota in a rat model of colorectal cancer (CRC) induced by azoxymethane (AOM) /dextran sulfate sodium (DSS).
METHODS:
A total of 75 male C57BL/6 mice were randomly divided into five groups: normal control group (NC), model group (MODEL), low-dose BXD treatment group (L-BXD), high-dose BXD treatment (H-BXD) group and MS treatment group (MS). BXD and MS were used in CRC mice at the doses of 3.915 g/kg, 15.66 g/kg, 0.6 g/kg for 3 weeks consecutively. Histopathological changes in the colon were observed using hematoxylin-eosin (HE) staining. The content of inflammatory factors in serum was detected by an enzyme-linked immunosorbent assay (ELISA), and the expression of mRNA and protein of genes related to immunity, apoptosis, inflammation, and inflammatory factors was evaluated. Changes in the intestinal flora of mouse fecal were determined based on high-throughput sequencing of the 16S rRNA microbial gene.
RESULTS:
Compared to the model group, the low-dose BXD and high-dose BXD groups decreased the number of colon tumors, reversed weight loss, and shortened colon length of mice. The pathological examination showed that BXD alleviated the malignancy of intestinal tumors. It also suppressed signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase-9 (MMP-9), and transforming growth factor beta 1 (TGF-β1) expression, while increasing the expression of the tight junction protein ZO-1 in colon tissues. Additionally, the levels of key pathway proteins involved in inflammation (phosphorylated-STAT3, Bcl-2, COX-2) and cell cycle regulatory molecules (c-Myc and PCNA) were reduced. According to 16S rRNA sequence analysis, BXD enhanced the relative abundance of potentially beneficial bacteria, while that of cancer-related bacteria decreased.
CONCLUSION
BXD plays a preventive role in developing colorectal cancer; its mechanisms are related to the inhibition of inflammation and tumor proliferation, as well as maintenance of intestinal homeostasis.
2.Protective Effect of Banxia Xiexin Decoction on AOM/DSS-induced Colitis Associated Cancer Mice
Yinzi YUE ; Yunhui GU ; Yuanyuan QIN ; Lianlin SU ; Xiaodong HUA ; Yahui WANG ; Xiaoman LI ; Xiaopeng WANG ; Shuai YAN
Chinese Journal of Modern Applied Pharmacy 2024;41(7):917-926
OBJECTIVE
To investigate the effect of Banxia Xiexin decoction(BXD) on colitis associated cancer(CAC) mice and its related mechanism.
METHODS
Seventy-five C57BL/6 mice were randomly divided into normal group, model group, Banxia Xiexin decoction low-dose group, high-dose group and mesalazine group. Except for the normal group, the mice in the other groups were intraperitoneally injected with azoxymethane combined with oral dextran sodium sulfate to establish the CAC model. BXD and mesalazine were given respectively for intervention. The general conditions of all mice were observed and recorded, and the changes of body weight, disease activity index, colon length and tumor number were monitored. HE staining was utilized to observe the pathological changes of colon tissue. The expression levels of PCNA, NF-κB P65 and IκB-α were detected by immunohistochemistry. The mRNA levels of IL-17A, N-cadherin, E-cadherin and Bcl-2 were detected by qRT-PCR. Macrophage infiltration was measured using immunostaining analysis. Western blotting was applied to analyze the expression of NF-κB, E-cadherin and N-cadherin proteins in colon tissues of each group.
RESULTS
There was no significant tumor occurrence in the normal group, while the body weight of the model group mice was significantly reduced and the number of colon tumors increased. The colon length, number of tumors, and degree of inflammatory cell infiltration in the BXD group were significantly improved compared to the model group. Immunohistochemical results showed that the expression of PCNA, NF-κB P65 and IκB-α protein in colon tissue of model group was remarkably increased (P<0.01). Immunofluorescence results showed that the number of F4/80, CD80 and CD206 positive macrophages in the colon tissue of the model group increased (P<0.05 or P<0.01). The results of RT-PCR demonstrated that the levels of IL-17A, N-cadherin and Bcl-2 mRNA in the colon tissue of the model group were significantly increased (P<0.01), while the level of E-cadherin mRNA was fundamentally decreased (P<0.01). Western blotting results displayed that the expression levels of NF-κB and N-cadherin protein in colon tissue of model group were up-regulated (P<0.01), while E-cadherin was significantly down-regulated (P<0.01). Compared with the model group, the changes of the above indexes in the BXD and mesalazine groups were ameliorated, with statistical differences (P<0.05 or P<0.01), and the changes in the BXD high-dose group were more significant.
CONCLUSION
BXD exhibits strong anti-inflammatory and anti-tumor benefits in CAC mice, inhibiting macrophage activation in colon tissue and promoting M2 polarization, while reducing the expression of tumor associated proteins PCNA and Bcl-2, and block the progression of EMT related proteins (E-cadherin and N-cadherin). The mechanism may connect to suppressing NF-κB P65 and IκB-α activation to regulate the NF-κB signaling pathway.
3.Protective Effect of Banxia Xiexin Decoction on AOM/DSS-induced Colitis Associated Cancer Mice
Yinzi YUE ; Yunhui GU ; Yuanyuan QIN ; Lianlin SU ; Xiaodong HUA ; Yahui WANG ; Xiaoman LI ; Xiaopeng WANG ; Shuai YAN
Chinese Journal of Modern Applied Pharmacy 2024;41(7):917-926
OBJECTIVE
To investigate the effect of Banxia Xiexin decoction(BXD) on colitis associated cancer(CAC) mice and its related mechanism.
METHODS
Seventy-five C57BL/6 mice were randomly divided into normal group, model group, Banxia Xiexin decoction low-dose group, high-dose group and mesalazine group. Except for the normal group, the mice in the other groups were intraperitoneally injected with azoxymethane combined with oral dextran sodium sulfate to establish the CAC model. BXD and mesalazine were given respectively for intervention. The general conditions of all mice were observed and recorded, and the changes of body weight, disease activity index, colon length and tumor number were monitored. HE staining was utilized to observe the pathological changes of colon tissue. The expression levels of PCNA, NF-κB P65 and IκB-α were detected by immunohistochemistry. The mRNA levels of IL-17A, N-cadherin, E-cadherin and Bcl-2 were detected by qRT-PCR. Macrophage infiltration was measured using immunostaining analysis. Western blotting was applied to analyze the expression of NF-κB, E-cadherin and N-cadherin proteins in colon tissues of each group.
RESULTS
There was no significant tumor occurrence in the normal group, while the body weight of the model group mice was significantly reduced and the number of colon tumors increased. The colon length, number of tumors, and degree of inflammatory cell infiltration in the BXD group were significantly improved compared to the model group. Immunohistochemical results showed that the expression of PCNA, NF-κB P65 and IκB-α protein in colon tissue of model group was remarkably increased (P<0.01). Immunofluorescence results showed that the number of F4/80, CD80 and CD206 positive macrophages in the colon tissue of the model group increased (P<0.05 or P<0.01). The results of RT-PCR demonstrated that the levels of IL-17A, N-cadherin and Bcl-2 mRNA in the colon tissue of the model group were significantly increased (P<0.01), while the level of E-cadherin mRNA was fundamentally decreased (P<0.01). Western blotting results displayed that the expression levels of NF-κB and N-cadherin protein in colon tissue of model group were up-regulated (P<0.01), while E-cadherin was significantly down-regulated (P<0.01). Compared with the model group, the changes of the above indexes in the BXD and mesalazine groups were ameliorated, with statistical differences (P<0.05 or P<0.01), and the changes in the BXD high-dose group were more significant.
CONCLUSION
BXD exhibits strong anti-inflammatory and anti-tumor benefits in CAC mice, inhibiting macrophage activation in colon tissue and promoting M2 polarization, while reducing the expression of tumor associated proteins PCNA and Bcl-2, and block the progression of EMT related proteins (E-cadherin and N-cadherin). The mechanism may connect to suppressing NF-κB P65 and IκB-α activation to regulate the NF-κB signaling pathway.
4.Aurantii Fructus Immaturus, Atractylodis Macrocephalae Rhizoma, and Their Combination Treat Colonic Motility Disorders in Rats with Slow Transit Constipation via PINK1/Parkin Signaling Pathway-mediated Mitophagy
Xiaopeng WANG ; Huiju YANG ; Mingming SUN ; Jing LIU ; Bensheng WU ; Yinzi YUE ; Yuanyuan QIN ; Yinghui CHEN ; Lie TIAN ; Yan LI ; Yahui WANG ; Shuai YAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):45-53
ObjectiveTo observe the effects of Aurantii Fructus Immaturus, Atractylodis Macrocephalae Rhizoma, and their combination on slow transit constipation via PTEN-induced putative kinase 1 (PINK1)/Parkin pathway-mediated mitophagy. MethodFifty-six male SD rats were randomly assigned into normal group, model group, natural recovery group, Aurantii Fructus Immaturus group, Atractylodis Macrocephalae Rhizoma group, Aurantii Fructus Immaturus combined with Atractylodis Macrocephalae Rhizoma group, and mosapride group, with 8 rats in each group. Slow transit constipation model was established by gavage with loperamide (3 mg·kg-1·d-1) for 14 days in other groups except the normal group. After successful modeling, except that the model group was continuously induced by loperamide, the normal group and the natural recovery group were administrated with 0.9% normal saline by gavage, and the rats in the Aurantii Fructus Immaturus (1.35 g·kg-1·d-1) group, the Atractylodis Macrocephalae Rhizoma (2.7 g·kg-1·d-1) group, the Aurantii Fructus Immaturus combined with Atractylodis Macrocephalae Rhizoma (4.05 g·kg-1·d-1) group, and the mosapride (1.56 mg·kg-1·d-1) group were administrated with corresponding drugs by gavage for 7 days. The amount of feces, fecal water content, and intestinal propulsion rate of rats were determined. The pathological changes of the colon were evaluated by hematoxylin-eosin (HE) staining and Alcian blue-periodic acid-Schiff (AB-PAS) staining. The activity of respiratory chain complex and the ultrastructure of the colon tissue were determined by ultraviolet spectrophotometry and observed by transmission electron microscopy, respectively. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was employed to determine the mRNA levels of PINK1, Parkin, and p62, and Western blot to determine the protein levels of microtubule-associated protein 1 light chain 3 (LC3), PINK1, and Parkin. ResultCompared with the normal group, the model group and the natural recovery group showed decreases in the amount of feces, fecal water content, intestinal propulsion rate (P<0.05,P<0.01), and activities of mitochondrial respiratory chain complexes Ⅱ, Ⅲ, and Ⅳ in the colon tissue (P<0.05,P<0.01). Further, the mRNA levels of PINK1 and Parkin and the protein levels of PINK1, Parkin, and LC3 were up-regulated (P<0.01) and the mRNA level of p62 was down-regulated in the model group (P<0.05) and the natural recovery group. Compared with the model group and the natural recovery group, the Aurantii Fructus Immaturus combined with Atractylodis Macrocephalae Rhizoma group showed increased amount of feces, fecal water content, intestinal propulsion rate, and activities of mitochondrial respiratory chain complexes Ⅱ, Ⅲ, and Ⅳ (P<0.05,P<0.01). Moreover, the combination meliorated the degree of mitochondrial swelling in the colon tissue, down-regulated the mRNA levels of PINK1 and Parkin and the protein levels of PINK1, Parkin, and LC3 (P<0.05,P<0.01), and up-regulated the mRNA level of p62 (P<0.05). ConclusionAurantii Fructus Immaturus and Atractylodis Macrocephalae Rhizoma, and their combination may remedy the colonic motility disorders in rats with slow transit constipation by blocking PINK1/Parkin signaling pathway to inhibit the excessive mitophagy in interstitial cells of Cajal in the colon tissue.
5.Effect of Rhei Radix et Rhizoma and Persicae Semen on inflammatory cytokines and intestinal mucosal barrier in rats with adhesive intestinal obstruction
Shuai YAN ; Xiaohui WANG ; Xiaopeng WANG ; Yinzi YUE
International Journal of Traditional Chinese Medicine 2021;43(2):150-155
Objective:To observe the effect of Rhei Radix et Rhizoma and Persicae Semen on inflammatory cytokines and intestinal mucosal barrier in rats with postoperative adhesive intestinal obstruction, and to explore its mechanism. Methods:Sixty SD rats were randomly divided into normal group, sham operation group, model group, low, medium and high dose of Rhei Radix et Rhizoma and Persicae Semen group. Except for the normal group and the sham operation group, and the other animals groups were established the model of postoperative adhesive intestinal obstruction. Rhei Radix et Rhizoma and Persicae Semen low, medium and high dose groups were perfused with Rhei Radix et Rhizoma and Persicae Semen decoction with the concentration of 0.2, 0.6 and 1.8 g/ml, the normal group, sham operation group and model group were gavaged with equal volume of sterile saline from the first day after the operation, once a day. After corresponding treatment, the adhesion score was observed on the 7th day after the operation, the contents of interleukin-1 β (IL-1β), D-lactic acid (D-LA), diamine oxidase (DAO) and vascular endotoxin (ET) in serum were detected by ELISA method, and the expression of SIgA, CD4 +T and CD8 +T cells in intestinal mucosa were assessed by immunohistochemical method. Results:Compared to the model group, the adhesion score in the low, medium and high dose of Rhei Radix et Rhizoma and Persicae Semen group significantly decreased ( P<0.05), the level of serum IL-1β [(8.66 ± 1.07) ng/L, (8.15 ± 1.23) ng/L, (7.99 ± 1.11) ng/L vs. (14.08 ± 2.54) ng/L] significantly decreased ( P<0.01), the expression of SIgA (1.38 ± 0.15, 2.87 ± 1.17, 2.79 ± 0.80 vs. 0.65 ± 0.12) in intestinal mucosa in the low, medium and high dose of Rhei Radix et Rhizoma and Persicae Semen group significantly increased ( P<0.01). The levels of serum D-LA [ (8.57 ± 1.73) mg/L, (7.13 ± 1.75) mg/L vs. (14.58 ± 2.81) mg/L], ET [ (77.39 ± 6.83) mg/ml, (50.49 ± 7.80) mg/ml vs. (138.22 ± 7.79) mg/ml] significantly decreased ( P<0.01), the expression of CD4 +T (2.61 ± 0.83, 2.91 ± 1.62 vs. 1.15 ± 0.98) and CD8 +T (2.88 ± 0.69, 3.01 ± 1.86 vs. 1.26 ± 0.74) cells in intestinal mucosa in the medium and high dose of Rhei Radix et Rhizoma and Persicae Semen group significantly increased ( P<0.01). Conclusion:Rhei Radix et Rhizoma and Persicae Semen decoction can improve intestinal mucosal permeability, protect intestinal mucosal immune barrier and reduce inflammatory reaction in the treatment of adhesive intestinal obstruction.
6. Study on differentiation and features of the medical records about constipation in ancient books with doctors Wumen medical school
Xiaopeng WANG ; Yinzi YUE ; Mingming SUN ; Shuguang ZHEN ; Shuai YAN
International Journal of Traditional Chinese Medicine 2019;41(9):992-997
Objective:
The characteristics of prescription medication for constipation in
7.Practice and significance of cost Accounting in scientific research projects of oversea countries
Chinese Journal of Medical Science Research Management 2015;28(1):116-120
As a method of financial management and control,the implementation of cost accounting has a significant influence on management of sicentific research projects.The model patterns of cost accounting in the United Kingdom,the United States and European Union,respectively can be served as practical frameworks to guide Chinese scientific research project funds in terms of accounting forms,methods and contents.Based on the understanding of current domestic development and problrms of cost accounting experiences learned from internation practices are signifcant for improving cost accounting system in scientific research projects of China.
8.Capacity building for primary health care reform and its effectiveness in Feixi county, Anhui province
Yinzi JIN ; Li HE ; Dahai YUE ; Weiming ZHU ; Luyu ZHANG ; Huifen MA ; Qingyue MENG
Chinese Journal of Health Policy 2015;(10):13-18
Objective:To analyze the implementation and effectiveness of primary health care reform in Feixi county, Anhui province. Methods: This paper uses data analysis of interviews with key insiders, policy documents and archives, as well as institutional questionnaire survey and other methods to collect information, and then it com-bines qualitative and quantitative research to arrive at research findings through cross-analysis and interpretation. Re-sults:From 2010 to 2014, the reform enhanced the capacity of primary health care in four main aspects, including capacity building of primary health care personnel, network construction of primary health care system, improvement of working conditions, and system construction of institutional management. Accordingly, the human capacity of pri-mary health care personnel was improved, their enthusiasm for work increased, their income was raised, the working conditions were improved, the cooperation mechanism for vertical and horizontal health care services was established, and the consultation rate and primary health care utilization in Feixi county increased. Conclusion:Both the“bottom-up” exploration approach and “from point to area” implementation strategy adopted by Feixi county have not only been the core content of primary health care system’s comprehensive reform, but also effectively leveraged the other aspects of the reform. They have played an important role in deepening medical reform and establishing institutional mechanism of health care system.
9.Reverse effects of the“primary health care strengthening” policies and their coping strategies:Case study of Feixi county, Anhui province
Dahai YUE ; Yinzi JIN ; Li HE ; Weiming ZHU ; Luyu ZHANG ; Huifen MA ; Qingyue MENG
Chinese Journal of Health Policy 2015;(10):19-23
Objective:To analyze reverse effects induced in the implementation process of“primary health care strengthening” policies, and the innovative initiatives and countermeasures raised in primary health care system’s comprehensive reform of Feixi county. Method:Based on the principles of Critical Discourse Analysis ( CDA) , this paper designs its analytical framework for policy analysis. Results:Many reverse effects appeared in the implementa-tion process of “primary health care strengthening” policies. However, through improvements in terms of manpower upgrading, network building, working conditions and management mechanisms, Feixi county has successfully strengthened the capacity building for primary health care institutions. Conclusions:The expected and unexpected re-sults should be evaluated systematically when the policies are being implemented, and local governments need to pro-ceed according to local conditions in order to prevent unintended reverse effects from happening.
10.The practice of health care alliance in Huangzhong county, Qinghai province
Luyu ZHANG ; Weiming ZHU ; Huifen MA ; Yinzi JIN ; Li HE ; Dahai YUE ; Qingyue MENG
Chinese Journal of Health Policy 2015;(10):24-28
The fragmentation of health care system within a county and serious capacity constraints of health-care services in township health centers are generally the most significant problems facing underdeveloped counties in western China. Under constraints of limited public financial resources, how to increase service capability of township health centers and improve service quality, continuity and convenience of health care system has become one of the most severe challenges in implementing China’s county health care system reform. This paper takes Huangzhong coun-ty, Qinghai province as a case study. It investigates how the locals use health care alliance to vertically integrate county health care resources during reform implementation, analyzes various aspects of reform measures and the corre-sponding structural characteristics such as the integration of administrative management, integration of human re-sources, dual diagnosis referral, interoperability of information systems, sharing of resources and test results, etc. , and provides similar China’s counties with a case study to be used for reference.


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