1.Diabetic Kidney Disease and Gut-kidney Axis: A Review
Yingchao WANG ; Yexin CHEN ; Hua ZHANG ; Jiangteng LIU ; Zhichao RUAN ; Xingru PAN ; Weijun HUANG ; Jinxi ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):310-320
With the rising incidence of diabetes, diabetic kidney disease (DKD) has become a significant global health burden. Although current prevention and treatment strategies can partially delay the progression of DKD, the risk of patients advancing to end-stage renal disease remains high. Since the concept of the "gut-kidney axis" was first introduced at the International Congress on Dialysis in 2011, research on the role of gut microbiota in the pathogenesis of DKD has received increasing attention. This review summarizes the current research on gut microbiota, explores the mechanisms through which it contributes to DKD development, and outlines clinical approaches for DKD prevention and treatment based on the "gut-kidney axis" theory. Evidence indicates that dietary interventions, intake of probiotics or prebiotics, use of metformin and novel antidiabetic drugs, and application of traditional Chinese medicine (TCM) compound formulas can effectively improve gut microbiota composition, influence metabolite production, and restore the intestinal mucosal barrier. These interventions can further regulate intestinal innate immunity and inflammatory responses, thereby modulating the progression of DKD. Despite challenges posed by the traditional oral administration of water-decocted TCM compound formulas and the complexity of their ingredients, increasing evidence suggests that TCM may indirectly affect the occurrence and development of DKD by modulating gut microbiota. This finding provides a new perspective on the potential mechanisms of TCM in DKD treatment and may offer novel strategies for DKD prevention and therapy.
2.Mechanism of Huangqi Xiayuxue Decoction Against Hepatocellular Carcinoma via PI3K/Akt/FoxO Signaling Pathway
Xingru XING ; Yuanzhou SHI ; Jiawei WANG ; Di WU ; Yuyao ZHANG ; Yalin WU ; Du CHEN ; Zhen ZHANG ; Sha TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):131-141
ObjectiveTo explore the therapeutic effect and mechanism of Huangqi Xiayuxue decoction against hepatocellular carcinoma based on network pharmacology, animal experiments, and cell experiments. MethodsThe active ingredients and corresponding targets of Huangqi Xiayuxue decoction were screened via databases including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Hepatocellular carcinoma-related targets were retrieved from the GeneCards database. The common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were subjected to Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Huangqi Xiayuxue decoction-containing plasma was prepared. The cell counting kit-8 (CCK-8) assay was adopted to observe the effects of different volume fractions (5%, 10%, 15%, and 20%) of Huangqi Xiayuxue decoction-containing plasma on the proliferation of HepG2, MHCC-97H, Hepa1-6, and Huh-7 cells, and the concentration for subsequent experiments was determined. Flow cytometry was adopted to detect the effects of Huangqi Xiayuxue decoction-containing plasma (5%, 10%, 15%, and 20%) on the apoptosis of MHCC-97H cells. A mouse model of subcutaneous xenograft hepatocellular carcinoma was established. The model mice were assigned into low-, medium-, and high-dose (4.63, 9.25, 18.5 g·kg-1) Huangqi Xiayuxue decoction and sorafenib (20 mg·kg-1) groups. Body mass and tumor volume of mice were dynamically monitored during the intervention period. After 3 weeks of intervention, hematoxylin-eosin (HE) staining was performed to observe tumor morphology. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was employed to detect cell apoptosis. Immunohistochemistry (IHC) was adopted to examine the expression of cysteinyl aspartate-specific proteinase-3 (Caspase-3), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the tumor tissue. Real-time PCR and Western blot were employed to verify the changes in apoptosis-related factors and the phosphatidylinositol 3-kinase/protein kinase B/forkhead box O1 (PI3K/Akt/FoxO1) signaling pathway. ResultsA total of 220 common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were screened out by network pharmacology, among which tumor protein p53 (TP53), Akt1, and signal transducer and activator of transcription 3 (STAT3) were the core targets. Pathway enrichment analysis indicated that the common targets were involved in cell apoptosis and proliferation, as well as the PI3K/Akt and FoxO signaling pathways. Cell experiments showed that compared with the blank plasma group, all volume fractions of Huangqi Xiayuxue decoction-containing plasma inhibited the proliferation of HepG2, MHCC-97H, Hepa1-6, and Huh-7 cells (P<0.01). The proportion of early apoptotic cells in MHCC-97H cells was increased after treatment with different volume fractions of Huangqi Xiayuxue decoction-containing plasma (P<0.01). Animal experiments revealed that Huangqi Xiayuxue decoction inhibited the growth of tumor volume, promoted tumor cell apoptosis in the high-dose group, up-regulated the protein and mRNA levels of Bax and Caspase-3, down-regulated the protein and mRNA levels of Bcl-2, and reduced the phosphorylation level of the PI3K/Akt/FoxO1 signaling pathway (P<0.05, P<0.01). ConclusionHuangqi Xiayuxue decoction exerts anti-hepatocellular carcinoma effects by inhibiting the activation of the PI3K/Akt/FoxO1 signaling pathway and promoting hepatocellular carcinoma cell apoptosis.
3.Mechanism of Huangqi Xiayuxue Decoction Against Hepatocellular Carcinoma via PI3K/Akt/FoxO Signaling Pathway
Xingru XING ; Yuanzhou SHI ; Jiawei WANG ; Di WU ; Yuyao ZHANG ; Yalin WU ; Du CHEN ; Zhen ZHANG ; Sha TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):131-141
ObjectiveTo explore the therapeutic effect and mechanism of Huangqi Xiayuxue decoction against hepatocellular carcinoma based on network pharmacology, animal experiments, and cell experiments. MethodsThe active ingredients and corresponding targets of Huangqi Xiayuxue decoction were screened via databases including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Hepatocellular carcinoma-related targets were retrieved from the GeneCards database. The common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were subjected to Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Huangqi Xiayuxue decoction-containing plasma was prepared. The cell counting kit-8 (CCK-8) assay was adopted to observe the effects of different volume fractions (5%, 10%, 15%, and 20%) of Huangqi Xiayuxue decoction-containing plasma on the proliferation of HepG2, MHCC-97H, Hepa1-6, and Huh-7 cells, and the concentration for subsequent experiments was determined. Flow cytometry was adopted to detect the effects of Huangqi Xiayuxue decoction-containing plasma (5%, 10%, 15%, and 20%) on the apoptosis of MHCC-97H cells. A mouse model of subcutaneous xenograft hepatocellular carcinoma was established. The model mice were assigned into low-, medium-, and high-dose (4.63, 9.25, 18.5 g·kg-1) Huangqi Xiayuxue decoction and sorafenib (20 mg·kg-1) groups. Body mass and tumor volume of mice were dynamically monitored during the intervention period. After 3 weeks of intervention, hematoxylin-eosin (HE) staining was performed to observe tumor morphology. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was employed to detect cell apoptosis. Immunohistochemistry (IHC) was adopted to examine the expression of cysteinyl aspartate-specific proteinase-3 (Caspase-3), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the tumor tissue. Real-time PCR and Western blot were employed to verify the changes in apoptosis-related factors and the phosphatidylinositol 3-kinase/protein kinase B/forkhead box O1 (PI3K/Akt/FoxO1) signaling pathway. ResultsA total of 220 common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were screened out by network pharmacology, among which tumor protein p53 (TP53), Akt1, and signal transducer and activator of transcription 3 (STAT3) were the core targets. Pathway enrichment analysis indicated that the common targets were involved in cell apoptosis and proliferation, as well as the PI3K/Akt and FoxO signaling pathways. Cell experiments showed that compared with the blank plasma group, all volume fractions of Huangqi Xiayuxue decoction-containing plasma inhibited the proliferation of HepG2, MHCC-97H, Hepa1-6, and Huh-7 cells (P<0.01). The proportion of early apoptotic cells in MHCC-97H cells was increased after treatment with different volume fractions of Huangqi Xiayuxue decoction-containing plasma (P<0.01). Animal experiments revealed that Huangqi Xiayuxue decoction inhibited the growth of tumor volume, promoted tumor cell apoptosis in the high-dose group, up-regulated the protein and mRNA levels of Bax and Caspase-3, down-regulated the protein and mRNA levels of Bcl-2, and reduced the phosphorylation level of the PI3K/Akt/FoxO1 signaling pathway (P<0.05, P<0.01). ConclusionHuangqi Xiayuxue decoction exerts anti-hepatocellular carcinoma effects by inhibiting the activation of the PI3K/Akt/FoxO1 signaling pathway and promoting hepatocellular carcinoma cell apoptosis.
4.The prospect of interleukin -23p19 inhibitors in precision treatment of Crohn's disease: mechanisms and clinical evidence
Yujing SUN ; Xueliang SUN ; Zhaozheng ZHANG ; Hongyan ZHENG ; Xiao YANG ; Xingru CHEN ; Ke WEN
Chinese Journal of Inflammatory Bowel Diseases 2025;09(5):390-396
Interleukin- (IL) 23 drives pathogenic differentiation of Th17 cells via the JAK2-STAT3 signaling pathway, upregulates IL-17A/IL-22 expression, and disrupts intestinal barrier integrity, thereby playing a pivotal role in the pathogenesis of Crohn's disease (CD). IL-23p19 inhibitors—exemplified by risankizumab, mirikizumab, and guselkumab—precisely block this pathway. Key phase 3 trials have demonstrated their efficacy in CD, showing significant clinical benefits in patients refractory to conventional therapies or biologics, with no new safety signals identified. The ultimate treatment goal for CD is deep healing (mucosal-transmural-biochemical composite remission) as defined by STRIDE II. However, current evidence exhibits critical limitations: absence of head-to-head drug comparisons, insufficient data on biologic-experienced subpopulations, and heterogeneous follow-up durations leading to uncertainties in long-term safety. Future studies require standardized head-to-head trials with enhanced subgroup analyses to optimize precision therapeutics.
5.Evaluation on the Operation Management of Public Traditional Chinese Medicine Hospitals in Shandong Province Based on Ecological Niche Width and Situation Model
Yingzhe ZHAO ; Xingru LIN ; Ya LIU ; Xiaolei WANG ; Shuying CHEN ; Zhiwei DONG ; Jingjie SUN ; Jianhua ZHANG ; Qi JING
Chinese Health Economics 2025;44(5):58-63
Objective:Using ecological niche width and situation model,the operation and management of public Traditional Chinese Medicine(TCM)hospitals in 16 cities in Shandong Province were evaluated to put forward countermeasures.Methods:The relevant index data of public TCM hospitals in 16 cities in Shandong Province from 2019 to 2022 were collected to analyze the development status.The ecological niche width model and niche situation model were applied to evaluate the operation and management of public TCM hospitals in 16 cities in Shandong.Results:The top three public TCM hospitals in terms of average ecological niche width were City G,City P and City F.The ecological niche situation value of public TCM hospitals in City K,City A and City J ranked the top three.Conclusion:The dimensions of operation management structure of public TCM hospitals in Shandong need to be enhanced and the development of operation management space needs to be balanced.It is feasible to evaluate operation management by using ecological niche width and situation model.It is suggested to improve the allocation efficiency of health personnel,facilities,funds and other resources;promote the spatial balanced development of operation management;promote the application of ecological niche width and situation model in the field of medicine and health management.
6.Exploration of the role of PIVAS pharmacists in optimization of parenteral nutrition prescription systems and medication safety monitoring
Xingru DOU ; Di YU ; Ying CHEN ; Xiujuan PAN ; Yi SUN ; Jianguo ZHU
China Pharmacy 2025;36(11):1394-1398
OBJECTIVE To provide references for ensuring the safety of prescription preparation, dispensing, and use of parenteral nutrition solution, as well as for expanding the scope of pharmaceutical services provided by pharmacists in the Pharmacy Intravenous Admixture Services (PIVAS). METHODS Under the guidance of PIVAS pharmacists, the rules for reviewing medical orders of parenteral nutrition in the PIVAS system and the information displayed on the infusion labels of finished parenteral nutrition solutions were refined. The process management of dispensing parenteral nutrition solution was strengthened, and detailed quality control and inspection rules were formulated. Additionally, Clinical Safety Monitoring Form for Finished Parenteral Nutrition Infusions was designed to conduct clinical monitoring and inspections for abnormalities in the finished infusions, infusion operations, and complications that may arise during the use of finished parenteral nutrition infusions. The implementation effects of the aforementioned optimization/inspection measures were evaluated by comparing data on the efficiency of medical order review for parenteral nutrition, the rate of irrational medical orders, the compliance rate of vascular access selection and infusion rate standardization, the rate of dispensing error, as well as the abnormalities occurring during clinical use, before and after the optimization/inspection initiatives were put into place. RESULTS The optimized prescription review system achieved automatic review of medical orders for parenteral nutrition, enhancing the efficiency of order review. The average time taken to review one parenteral nutrition medical order was reduced from approximately 1 minute to 10 seconds. The irrational rate of parenteral nutrition orders decreased by 31.87%. The dispensing error rate of parenteral nutrition decreased by 56.55%. The standard rate of vascular access selection and standard rate of infusion speed were increased by 13.29% and 3.54%, respectively. The PIVAS pharmacists identified and intervened in 5 abnormal cases out of 298 cases examined for use of parenteral nutrition solutions. CONCLUSIONS By optimizing the prescription review system, improving labeling information, and strengthening quality control inspections during both preparation and administration processes, PIVAS pharmacists have enhanced the safety of compounded parenteral nutrition solutions. This initiative has expanded the scope and depth of pharmaceutical care provided by dispensing pharmacists.
7.Dilation effect of luteolin in rat thoracic aortic rings based on Kv7 ion channels
Xingru WANG ; Zerong YANG ; Li WU ; Wenjuan DENG ; Haorui SONG ; Chaoyang CHEN ; Weiping LI
Chinese Journal of Comparative Medicine 2025;35(6):84-92
Objective To investigate the vasodilatory effect of luteolin on isolated denuded-endothelium rat thoracic aorta(DRTA)vascular rings,and the mechanistic role of the Kv7 ion channel.Methods The tension of DRTA vascular rings was measured using an ex vivo tissue perfusion muscle-tone detection system.DRTA vascular rings were pre-contracted with 60 mmol/L KCl or 0.3 μmol/L U46619,and the effect of luteolin on vascular-ring relaxation was observed at 1,3,10,30,100 and 300 μmol/L.The effects of 4-AP,XE-991,and ML213 on luteolin-induced vasodilation were also observed.The effect of luteolin on KCNQ1-KCNQ5 expression in the thoracic aorta was detected by real-time fluorescence quantitative polymerase chain reaction.Expression levels of Kv7.1 and Kv7.4 proteins in the DRTA were detected by Western blot.Results(1)The luteolin-induced maximum vasodilation rates in DRTA pre-contracted with 60 mmol/L KCl and 0.3 μmol/L U46619 were(97.67±8.51)%and(98.42±9.76)%,respectively.The vasodilation effect was concentration-dependent(P<0.05).(2)4-AP(3 mmol/L)significantly reduced the vasodilatory effect of luteolin on DRTA vascular rings at 10,30,and 100 μmol/L(P<0.05),and XE-991(3 μmol/L)significantly reduced the effect of luteolin at 30 and 100 μmol/L(P<0.05),while ML213(1 μmol/L)significantly enhanced the vasodilatory effect of luteolin at 3,10,and 30 μmol/L(P<0.05).(3)The relative gene expression levels of each subtype of Kv7 channel in normal DRTA were KCNQ1>KCNQ5>KCNQ4>KCNQ3>KCNQ2,with KCNQ1 being the most highly expressed.(4)Luteolin significantly enhanced the expression levels of KCNQ1 at 3,10,30,and 100 μmol/L,KCNQ2 at 1,3,10,30,and 100 μmol/L(P<0.05),KCNQ3 at 3,10,30,and 100 μmol/L,and KCNQ4 at 10,30,and 100 μmol/L(P<0.05),but did not significantly enhance the expression of KCNQ5 at 1,3,10,30,or 100 μmol/L(P>0.05).(5)Luteolin significantly increased the expression of Kv7.1 protein in DRTA at 3,10,30,and 100 μmol/L(P<0.05)and the expression of Kv7.4 at 10,30,and 100 μmol/L(P<0.05).Conclusions Luteolin-induced dilation of DRTA vascular rings may be related to the enhanced gene expression of KCNQ1-4 and increased expression of Kv7.1 and Kv7.4 channel proteins.
8.Dilation effect of luteolin in rat thoracic aortic rings based on Kv7 ion channels
Xingru WANG ; Zerong YANG ; Li WU ; Wenjuan DENG ; Haorui SONG ; Chaoyang CHEN ; Weiping LI
Chinese Journal of Comparative Medicine 2025;35(6):84-92
Objective To investigate the vasodilatory effect of luteolin on isolated denuded-endothelium rat thoracic aorta(DRTA)vascular rings,and the mechanistic role of the Kv7 ion channel.Methods The tension of DRTA vascular rings was measured using an ex vivo tissue perfusion muscle-tone detection system.DRTA vascular rings were pre-contracted with 60 mmol/L KCl or 0.3 μmol/L U46619,and the effect of luteolin on vascular-ring relaxation was observed at 1,3,10,30,100 and 300 μmol/L.The effects of 4-AP,XE-991,and ML213 on luteolin-induced vasodilation were also observed.The effect of luteolin on KCNQ1-KCNQ5 expression in the thoracic aorta was detected by real-time fluorescence quantitative polymerase chain reaction.Expression levels of Kv7.1 and Kv7.4 proteins in the DRTA were detected by Western blot.Results(1)The luteolin-induced maximum vasodilation rates in DRTA pre-contracted with 60 mmol/L KCl and 0.3 μmol/L U46619 were(97.67±8.51)%and(98.42±9.76)%,respectively.The vasodilation effect was concentration-dependent(P<0.05).(2)4-AP(3 mmol/L)significantly reduced the vasodilatory effect of luteolin on DRTA vascular rings at 10,30,and 100 μmol/L(P<0.05),and XE-991(3 μmol/L)significantly reduced the effect of luteolin at 30 and 100 μmol/L(P<0.05),while ML213(1 μmol/L)significantly enhanced the vasodilatory effect of luteolin at 3,10,and 30 μmol/L(P<0.05).(3)The relative gene expression levels of each subtype of Kv7 channel in normal DRTA were KCNQ1>KCNQ5>KCNQ4>KCNQ3>KCNQ2,with KCNQ1 being the most highly expressed.(4)Luteolin significantly enhanced the expression levels of KCNQ1 at 3,10,30,and 100 μmol/L,KCNQ2 at 1,3,10,30,and 100 μmol/L(P<0.05),KCNQ3 at 3,10,30,and 100 μmol/L,and KCNQ4 at 10,30,and 100 μmol/L(P<0.05),but did not significantly enhance the expression of KCNQ5 at 1,3,10,30,or 100 μmol/L(P>0.05).(5)Luteolin significantly increased the expression of Kv7.1 protein in DRTA at 3,10,30,and 100 μmol/L(P<0.05)and the expression of Kv7.4 at 10,30,and 100 μmol/L(P<0.05).Conclusions Luteolin-induced dilation of DRTA vascular rings may be related to the enhanced gene expression of KCNQ1-4 and increased expression of Kv7.1 and Kv7.4 channel proteins.
9.The prospect of interleukin -23p19 inhibitors in precision treatment of Crohn's disease: mechanisms and clinical evidence
Yujing SUN ; Xueliang SUN ; Zhaozheng ZHANG ; Hongyan ZHENG ; Xiao YANG ; Xingru CHEN ; Ke WEN
Chinese Journal of Inflammatory Bowel Diseases 2025;09(5):390-396
Interleukin- (IL) 23 drives pathogenic differentiation of Th17 cells via the JAK2-STAT3 signaling pathway, upregulates IL-17A/IL-22 expression, and disrupts intestinal barrier integrity, thereby playing a pivotal role in the pathogenesis of Crohn's disease (CD). IL-23p19 inhibitors—exemplified by risankizumab, mirikizumab, and guselkumab—precisely block this pathway. Key phase 3 trials have demonstrated their efficacy in CD, showing significant clinical benefits in patients refractory to conventional therapies or biologics, with no new safety signals identified. The ultimate treatment goal for CD is deep healing (mucosal-transmural-biochemical composite remission) as defined by STRIDE II. However, current evidence exhibits critical limitations: absence of head-to-head drug comparisons, insufficient data on biologic-experienced subpopulations, and heterogeneous follow-up durations leading to uncertainties in long-term safety. Future studies require standardized head-to-head trials with enhanced subgroup analyses to optimize precision therapeutics.
10.Evaluation on the Operation Management of Public Traditional Chinese Medicine Hospitals in Shandong Province Based on Ecological Niche Width and Situation Model
Yingzhe ZHAO ; Xingru LIN ; Ya LIU ; Xiaolei WANG ; Shuying CHEN ; Zhiwei DONG ; Jingjie SUN ; Jianhua ZHANG ; Qi JING
Chinese Health Economics 2025;44(5):58-63
Objective:Using ecological niche width and situation model,the operation and management of public Traditional Chinese Medicine(TCM)hospitals in 16 cities in Shandong Province were evaluated to put forward countermeasures.Methods:The relevant index data of public TCM hospitals in 16 cities in Shandong Province from 2019 to 2022 were collected to analyze the development status.The ecological niche width model and niche situation model were applied to evaluate the operation and management of public TCM hospitals in 16 cities in Shandong.Results:The top three public TCM hospitals in terms of average ecological niche width were City G,City P and City F.The ecological niche situation value of public TCM hospitals in City K,City A and City J ranked the top three.Conclusion:The dimensions of operation management structure of public TCM hospitals in Shandong need to be enhanced and the development of operation management space needs to be balanced.It is feasible to evaluate operation management by using ecological niche width and situation model.It is suggested to improve the allocation efficiency of health personnel,facilities,funds and other resources;promote the spatial balanced development of operation management;promote the application of ecological niche width and situation model in the field of medicine and health management.

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