1.Ershen Zhenwu Decoction Treats Chronic Heart Failure by Regulating miR-423-5p/Smad7/TGF-β1/Smads Axis and Myocardial Fibrosis Indicators
Lan GE ; Zhenpeng ZHU ; Xinyue WANG ; Dan CHENG ; Yulong LIU ; Maomao ZHANG ; Xiaoyu CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):157-165
ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure (CHF) due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β1 (TGF-β1)/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets, sacubitril-valsartan sodium tablets, metoprolol succinate, and spironolactone, and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance, New York Heart Association (NYHA) heart function grade, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP), angiotensin Ⅱ (Ang Ⅱ), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), interventricular septum thickness at diastole (IVSd), left ventricular end-diastolic posterior wall thickness (LVPWd), left ventricular shortening fraction (FS), miR-423-5p, Smad7, Smad2, Smad3, Smad4, TGF-β1, Ang Ⅱ, type Ⅰ collagen (Col Ⅰ), type Ⅲ collagen (Col Ⅲ), mRNA levels of fibronectin (Fn) and α-smooth muscle actin (α-SMA) in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment, both groups showed declined levels of NT-proBNP, Ang Ⅱ, miR-423-5p, Smad2, Smad3, Smad4, TGF-β1, Col Ⅰ, Col Ⅲ, and mRNA levels of Fn and α-SMA (P0.05), and the levels of the indicators above were lower in the observation group than in the control group (P0.05). After treatment, the Smad7 level increased obviously in both groups (P0.05) and was higher in the observation group than in the control group (P0.05). After treatment, both groups showed decreased MLHFQ scores and increased 6-min walking distance (P0.05), and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group (P0.05). After treatment, the control group showed increased LVEF and FS (P0.05) and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS (P0.05). Moreover, the observation group had lower LVIDd and LVIDs (P0.05) and higher LVEF and FS (P0.05) than the control group. The total response rate of cardiac function in the observation group was 90.38% (47/52), which was higher than that (70.59%, 36/51) in the control group (P0.05). No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function, exercise tolerance, and quality of life, regulate neuroendocrine factors, and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF (syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β1/Smads axis, inhibiting α-SMA and Fn expression, and alleviating myocardial fibrosis. It is worthy of further study.
2.Ershen Zhenwu Decoction Treats Chronic Heart Failure by Regulating miR-423-5p/Smad7/TGF-β1/Smads Axis and Myocardial Fibrosis Indicators
Lan GE ; Zhenpeng ZHU ; Xinyue WANG ; Dan CHENG ; Yulong LIU ; Maomao ZHANG ; Xiaoyu CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):157-165
ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure (CHF) due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β1 (TGF-β1)/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets, sacubitril-valsartan sodium tablets, metoprolol succinate, and spironolactone, and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance, New York Heart Association (NYHA) heart function grade, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP), angiotensin Ⅱ (Ang Ⅱ), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), interventricular septum thickness at diastole (IVSd), left ventricular end-diastolic posterior wall thickness (LVPWd), left ventricular shortening fraction (FS), miR-423-5p, Smad7, Smad2, Smad3, Smad4, TGF-β1, Ang Ⅱ, type Ⅰ collagen (Col Ⅰ), type Ⅲ collagen (Col Ⅲ), mRNA levels of fibronectin (Fn) and α-smooth muscle actin (α-SMA) in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment, both groups showed declined levels of NT-proBNP, Ang Ⅱ, miR-423-5p, Smad2, Smad3, Smad4, TGF-β1, Col Ⅰ, Col Ⅲ, and mRNA levels of Fn and α-SMA (P0.05), and the levels of the indicators above were lower in the observation group than in the control group (P0.05). After treatment, the Smad7 level increased obviously in both groups (P0.05) and was higher in the observation group than in the control group (P0.05). After treatment, both groups showed decreased MLHFQ scores and increased 6-min walking distance (P0.05), and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group (P0.05). After treatment, the control group showed increased LVEF and FS (P0.05) and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS (P0.05). Moreover, the observation group had lower LVIDd and LVIDs (P0.05) and higher LVEF and FS (P0.05) than the control group. The total response rate of cardiac function in the observation group was 90.38% (47/52), which was higher than that (70.59%, 36/51) in the control group (P0.05). No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function, exercise tolerance, and quality of life, regulate neuroendocrine factors, and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF (syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β1/Smads axis, inhibiting α-SMA and Fn expression, and alleviating myocardial fibrosis. It is worthy of further study.
3.Mechanism of Shenmai Injection to Improve Cisplatin Resistance in NSCLC Based on Endoplasmic Reticulum Stress Through PERK/ATF4/CHOP Signaling Pathway
Shengnan GUO ; Hao CAO ; Dan WANG ; Wenjun LIU ; Jianguang WANG ; Jialu LYU ; Chun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):70-78
ObjectiveTo explore the mechanism of Shenmai injection in improving cisplatin resistance in non-small cell lung cancer (NSCLC) based on the endoplasmic reticulum stress through protein kinase R-like endoplasmic reticulum kinase (PERK)/activated transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) signaling pathway. MethodsBALB/c nude mice bearing cisplatin-resistant human lung cancer cell line (A549/cisplatin) were randomly divided into four groups: Blank control group (0.9% sodium chloride), cisplatin group (5 µg·g-1cisplatin), Shenmai injection group (5.2 mg·g-1 Shenmai injection), and combination therapy group (5.2 mg·g-1 Shenmai injection +5 µg·g-1cisplatin). The drug intervention lasted for 4 weeks, and the changes in body weight and tumor volume were monitored. Hematoxylin-eosin (HE) staining was performed to observe tumor tissue pathology. Transmission electron microscopy (TEM) was used to assess the morphology of the endoplasmic reticulum. Immunohistochemical assay was conducted to measure the positive expressions of PERK, ATF4, and CHOP in tumor tissues. Western blot quantified the protein expression of immunoglobulin heavy chain binding protein (BIP), PERK, phosphorylated PERK (p-PERK), eukaryotic translation initiation factor 2α (eIF2α), phosphorylated eIF2α (p-eIF2α), ATF4, CHOP, B-cell lymphoma -2 (Bcl-2), and Bcl-2 Associated X protein (Bax). A549/cis cells were divided into blank group: Blank control group (normal culture medium), cisplatin group (23.3 µmol·L-1 cisplatin), Shenmai Injection group (20 g·L-1 Shenmai injection), and combination therapy group (20 g·L-1 Shenmai injection+23.3 µmol·L-1 cisplatin). Cell counting kit-8 (CCK-8) method was used to detect cell viability, TEM was used to observe the morphology of endoplasmic reticulum, and Western blot was used to detect endoplasmic reticulum stress and apoptosis-related proteins. ResultsCompared with the cisplatin group, the combination therapy group showed increased body weight (P<0.05), decreased tumor volume (P<0.05), and expanded endoplasmic reticulum in tumor cells. The positive expressions of PERK, ATF4, and CHOP increased (P<0.05). Western blot revealed elevated protein expression levels of BIP, p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, and Bax (P<0.05), while Bcl-2 expression decreased (P<0.05). As shown in the in vitro experiment, compared with the cisplatin group, the combination therapy group exhibited a reduced cell survival rate (P<0.05). TEM revealed increased endoplasmic reticulum dilation and vesicular degeneration. Western blotting showed increased protein levels of BIP, p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP and Bax (P<0.05), with decreased Bcl-2 expression (P<0.05). ConclusionShenmai injection combined with cisplatin has a synergistic antitumor effect in NSCLC, which may be attributed to the activation of endoplasmic reticulum stress response mediated by the PERK/eIF2α/ATF4/CHOP signaling pathway and the induction of tumor cell apoptosis.
4.Perioperative immune dynamics and clinical outcomes in patients undergoing on-pump cardiac surgery
Zhiyuan CHENG ; Xinyi LIAO ; Juan WU ; Ping YANG ; Tingting WANG ; Qinjuan WU ; Wentong MENG ; Zongcheng TANG ; Jiayi SUN ; Jia TAN ; Jing LIN ; Dan LUO ; Hao WANG ; Chaonan LIU ; Jiyue XIONG ; Liqin LING ; Jing ZHOU ; Lei DU
Chinese Journal of Blood Transfusion 2026;39(1):31-43
Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10
/L vs preoperative 3.07×10
/L, P<0.001), with significant upregulation of CD11b (7.30×10
/L vs preoperative 3.05×10
/L, P<0.001) and CD54 (7.15×10
/L vs preoperative 2.99×10
/L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10
/L vs preoperative 1.12×10
/L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10
/L vs preoperative 1.12×10
/L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.
5.Impact of adverse childhood experiences and psychological symptoms on health risk behaviors among college students
Chinese Journal of School Health 2026;47(3):398-402
Objective:
To explore the impact of adverse childhood experiences (ACEs) on health risk behaviors (HRBs) among college students and the mediating role of psychological symptoms, so as to provide a basis for developing intervention strategies.
Methods:
From March to April 2023, a convenience cluster sample of 1 801 students from 12 universities in Nanning, Liuzhou, Guilin, Wuzhou of Guangxi completed an online survey. A self designed questionnaire, Adverse Childhood Experiences-International Questionnaire (ACE-IQ) and Symptom Checklist-90 (SCL-90) were used for evaluation tools. Binary Logistic regression, structural equation modeling (SEM) and Bootstrap methods were used to analyze the associations and mediating effects.
Results:
Overall, 71.2% of college students experienced at least one type of ACE, with emotional neglect (40.3%) and emotional abuse ( 25.2 %) having the highest detection rates. The top three HRBs were unhealthy diet (77.8%), physical inactivity (54.1%), and smoking/alcohol use (18.5%). Logistic regression showed that poor family functioning, abuse, and extra familial violence were each associated with an increased risk of smoking/alcohol use ( OR =1.14, 1.11, 1.18) and deliberate self harm ( OR =1.26, 1.19,1.30) (all P <0.05). Experience of abuse increased the risk of high risk sexual behavior and family dysfunction increaded the risk of physical inactivity, respectively ( OR = 1.07 , 1.04, both P <0.05). Mediation analysis revealed that anxiety ( β =0.20) and depression ( β = 0.09 ) partially mediated the pathway from poor family functioning to deliberate self harm; paranoia ( β =0.02) partially mediated the pathway from abuse to high risk sexual behavior; and obsessive-compulsive symptoms ( β =0.26) and depression ( β =0.10) partially mediated the pathway from extra familial violence to deliberate self harm (all P <0.05).
Conclusion
Psychological symptoms play a mediating role in the association between ACEs and HRBs, and mental health interventions may reduce the risk of HRBs among college students.
6.Evaluation of the application effectiveness and optimization strategies of confidential unit exclusion in Zhengzhou
Dan LIU ; Hongwei MA ; Tao WEN ; Yonglei LYU ; Mengru JI ; Ge SONG ; Huanyu LIU ; Mengdi FAN
Chinese Journal of Blood Transfusion 2026;39(3):379-383
Objective: To evaluate the practical effectiveness of confidential unit exclusion (CUE) in ensuring blood safety in Zhengzhou, analyze its application characteristics and existing problems, and provide a basis for optimizing blood safety management strategies. Methods: A retrospective analysis was conducted on CUE data handled by Henan Red Cross Blood Center from January 2019 to December 2024. Parameters such as the number of cases, demographic characteristics, reasons for exclusion, and time of report were statistically analyzed and compared with those of non-CUE. Results: From 2019 to 2024, the CUE reporting rate in Zhengzhou was 0.002 6% (40/1 547 666). CUE donors were predominantly male (65.00%, 26/40), aged 18-34 years (47.50%, 19/40), had college degree orabove (50.00%, 20/40), and were employees of enterprises or public institutions (32.50%, 13/40). Among the 40 CUE blood units, only one was reactive for anti-TP, while all others were qualified. The main reasons for CUE were recent vaccination (32.50%, 13/40), medical conditions unsuitable for donation (27.50%, 11/40), and high-risk sexual behavior (17.50%, 7/40). A total of 70.00% of reports occurred within 24 hours after donation, during which none of the corresponding blood units had been released; all units reported after more than 7 days had already been issued for clinical use, with no adverse transfusion reactions reported upon follow-up. Conclusion: The confidential unit exclusion program has played an active role in establishing a supplementary information feedback channel for blood donors. The procedure can be optimized by strengthening interactive communication and confirmation before donation, improving the accuracy of donors' self-assessment, and expanding convenient and rapid information-based reporting channels.
7.Eculizumab for Refractory Immune Complex-Mediated Glomerulonephritis Following Acute Hepatitis B Infection: A Case Report
Jinyuan LIU ; Dan WANG ; Shuqin LIU ; Wenfang CHEN ; Wei CHEN ; Xin WANG
Medical Journal of Peking Union Medical College Hospital 2026;17(2):389-395
Infection-related glomerulonephritis (IRGN) is an immune-mediated glomerular injury triggered by infectious agents. This article reports a case of immune complex-mediated glomerulonephritis following acute hepatitis B virus infection, which continued to progress despite standard antiviral and immunosuppressive therapy. Given the significant elevation of soluble complement membrane attack complex (sC5b-9), an indicator of terminal complement pathway activation, the patient was treated with eculizumab. Following treatment, the patient's urine protein-to-creatinine ratio significantly decreased, hypoalbuminemia and hematuria markedly improved, and sC5b-9 levels declined. This case suggests that abnormal complement system activation may be a key mechanism driving disease persistence in some patients with IRGN. For those unresponsive to conventional therapy, complement function screening and targeted terminal complement pathway inhibition may represent an effective salvage strategy.
8.Protective effect and mechanism of chikusetsu saponin Ⅳa on the kidney in diabetic nephropathy rats
Yongli WANG ; Hai CHEN ; Xiaofang TIAN ; Xuechun WANG ; Liying YUAN ; Dan LIU ; Zhongfa LI ; Yanfang MENG ; Xiuyong YANG
China Pharmacy 2026;37(7):908-913
OBJECTIVE To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ a (chsⅣ) on renal function in diabetic nephropathy (DN) model rats. METHODS DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group (i.g. administration of normal saline, high-fat diet), chsⅣ low-dose and high-dose groups (i.g. administration of 90, 180 mg/kg chsⅣ, high-fat diet), with 12 rats in each group. Additionally, 10 normal rats were set as the control group (i.g. administration of normal saline, regular diet). From the 5th to the 12th week after streptozotocin injection, they were given intragastric administration of relevant drug or normal saline, once a day. After the last medication, the levels of fasting blood glucose, fasting insulin, blood urea nitrogen, serum creatinine and urine protein as well as the levels of reduced glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissues were measured. Additionally, the insulin resistance index was calculated. Hematoxylin-eosin, periodic acid-Schiff, and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods. RESULTS Compared with model group, the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved, with significant decreases in renal histological scores, mesangial expansion index, and glomerulosclerosis scores ( P <0.05); the levels of fasting blood glucose, fasting insulin, blood urea nitrogen, serum creatinine, urine protein and homeostasis model assessment for insulin resistance, as well as MDA content, the expression levels of Notch1, Notch intracellular domain, hairy and enhancer of Split 1 and Delta-like protein 1 in renal tissue were all significantly decreased ( P <0.05). The levels of GSH and SOD in renal tissue were significantly elevated ( P <0.05). Moreover, the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group ( P <0.05). CONCLUSIONS ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity, attenuation of renal oxidative stress, and suppression of aberrant Notch signaling pathway activation.
9.Exploring Intervention Effect of Atractylodis Macrocephalae Rhizoma Processed with Aurantii Fructus Immaturus Juice on Slow-transit Constipation and Its "Microbiota-Metabolism" Synergistic Regulation Mechanism Based on Theory of "Spleen Governing Transportation and Transformation"
Dan LI ; Xiaoxia LIU ; Xiaofen WANG ; Zuxin HE ; Junnan WEI ; Yanqing LIU ; Yuxuan GAO ; Ping LUO ; Fang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):201-209
ObjectiveBased on the theory of "spleen governing transportation and transformation", this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice(AMR-AFI) in improving slow-transit constipation(STC), as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis, thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group, model group, positive drug(mosapride) group(3 mg·kg-1), and low-, medium-, and high-dose groups of AMR-AFI(3.9, 7.8, 15.6 g·kg-1). Except for the control group, the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling, interventions were administered. All groups received continuous administration for 15 d, during which fecal samples, colon tissue, and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate, histological morphology of colonic tissue was observed via hematoxylin-eosin(HE) staining, and the levels of interleukin(IL)-6, tumor necrosis factor(TNF)-α, and IL-2 in serum were detected using enzyme-linked immunosorbent assay(ELISA). Furthermore, the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing, while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue, followed by gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Finally, Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group, the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased(P<0.01), while serum levels of IL-6, TNF-α, and IL-2 were significantly elevated(P<0.01). HE staining showed damage and shedding of colonic mucosal epithelial cells, along with a reduction in goblet cells in the model group. In comparison with the model group, all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6, TNF-α, and IL-2(P<0.01). Among these, the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats(P<0.05, P<0.01). Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group, as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis, such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice, increased species richness, downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella, and enriched beneficial and butyrate-producing bacteria, including Lachnospiraceae_NK4A136_group, Ruminococcaceae, and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast, pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota, arachidonic acid-mediated inflammatory metabolism, and aldosterone-regulated water-salt balance pathways.
10.Exploring Intervention Effect of Atractylodis Macrocephalae Rhizoma Processed with Aurantii Fructus Immaturus Juice on Slow-transit Constipation and Its "Microbiota-Metabolism" Synergistic Regulation Mechanism Based on Theory of "Spleen Governing Transportation and Transformation"
Dan LI ; Xiaoxia LIU ; Xiaofen WANG ; Zuxin HE ; Junnan WEI ; Yanqing LIU ; Yuxuan GAO ; Ping LUO ; Fang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):201-209
ObjectiveBased on the theory of "spleen governing transportation and transformation", this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice(AMR-AFI) in improving slow-transit constipation(STC), as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis, thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group, model group, positive drug(mosapride) group(3 mg·kg-1), and low-, medium-, and high-dose groups of AMR-AFI(3.9, 7.8, 15.6 g·kg-1). Except for the control group, the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling, interventions were administered. All groups received continuous administration for 15 d, during which fecal samples, colon tissue, and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate, histological morphology of colonic tissue was observed via hematoxylin-eosin(HE) staining, and the levels of interleukin(IL)-6, tumor necrosis factor(TNF)-α, and IL-2 in serum were detected using enzyme-linked immunosorbent assay(ELISA). Furthermore, the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing, while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue, followed by gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Finally, Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group, the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased(P<0.01), while serum levels of IL-6, TNF-α, and IL-2 were significantly elevated(P<0.01). HE staining showed damage and shedding of colonic mucosal epithelial cells, along with a reduction in goblet cells in the model group. In comparison with the model group, all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6, TNF-α, and IL-2(P<0.01). Among these, the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats(P<0.05, P<0.01). Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group, as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis, such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice, increased species richness, downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella, and enriched beneficial and butyrate-producing bacteria, including Lachnospiraceae_NK4A136_group, Ruminococcaceae, and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast, pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota, arachidonic acid-mediated inflammatory metabolism, and aldosterone-regulated water-salt balance pathways.


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