1.Mechanisms of Improving Hippocampal Synaptic Plasticity Through GLP-1/GLP-1r Pathway to Alleviate Anxiety and Depression-like Behaviors in Chronic Restraint Stress Rats by Xiaoyaosan
Hao WANG ; Yanan YAN ; Jiepeng WANG ; Chaoyi FANG ; Fang FANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):34-42
ObjectiveTo observe the effects of Xiaoyaosan on glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1r) and protein kinase A (PKA)/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathways in the hippocampal CA1 region of rats under chronic restraint stress (CRS),and to explore the mechanism of this formula to alleviate anxiety and depression-like behaviors. Methods40 specific pathogen-free male Sprague-Dawley (SD) rats were randomly divided into normal,model,Xiaoyaosan,and fluoxetine groups,with 10 rats in each group. CRS was used to induce anxiety and depression-like behaviors. The rats in the Xiaoyaosan group were gavaged with aqueous solution of traditional Chinese medicine formula granules (7.36 g·kg-1·d-1),while those in the fluoxetine group were gavaged with aqueous solution of fluoxetine (2 mg·kg-1·d-1). Body weight was measured on days 0,7,14,and 21 of the experiment. On days 0 and 22 of the experiment,the sucrose preference test (SPT),forced swimming test (FST),and open field test (OFT) were performed. The pathological morphology of the hippocampal CA1 region was observed by Nissl staining. The relative mRNA expression of post-synaptic density protein-95 (PSD95) and synapsin (SYP) was detected by reverse transcription quantitative real-time polymerase chain reaction. Immunohistochemistry and Western blot were used to detect expression of proteins in the GLP-1/GLP-1r and PKA/CREB/BDNF pathways in the hippocampal CA1 region. ResultsAfter CRS modeling,compared with the normal group,the rats of the model group had anxiety and depression-like behavioral manifestations,neuronal damage in the hippocampal CA1 region,significantly downregulated expression of synaptic plasticity markers PSD95 and SYP genes (P<0.01),and inhibition of GLP-1/GLP-1r and PKA/CREB/BDNF signaling pathways (P<0.05,P<0.01). Compared with the model group,the Xiaoyaosan group exhibited alleviated anxiety and depression-like behaviors,reduced neuronal damage in the hippocampal CA1 region, significantly increased expression of PSD95 and SYP genes (P<0.01),and the activation of the GLP-1/GLP-1r and PKA/CREB/BDNF signaling pathways (P<0.05,P<0.01). ConclusionXiaoyaosan can alleviate anxiety and depression-like behaviors in CRS rats by improving synaptic plasticity in the hippocampal CA1 region. The mechanisms may be related to the activation of the GLP-1/GLP-1r pathway and its mediated PKA/CREB/BDNF signaling pathway by the formula.
2.Mechanism of Yishen Huoxue Tongqiao Formula in Improving Unilateral Vestibular Labyrinth Destruction by Regulating Metabolism-neuroplasticity
Yu TIAN ; Hui LENG ; Rupeng QU ; Xianglong HAO ; Aiping WANG ; Lei SHI ; Zhongyuan QU ; Ye DONG ; Xiande MA ; Yangling HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):54-64
ObjectiveThis study aims to explore the mechanism by which Yishen Huoxue Tongqiao Formula improves metabolism-neuroplasticity and treats unilateral vestibular labyrinth destruction by regulating the metabolic balance of glutamate (Glu)/γ-aminobutyric acid (GABA). Methods48 Sprague-Dawley (SD) adult rats were randomly divided into the sham operation group, model group, Yishen Huoxue Tongqiao Formula groups with low, medium, and high doses (9.20, 18.39, 36.78 g·kg-1), and betahistine group (1.62 mg·kg-1). A unilateral vestibular labyrinth destruction (vestibular dysfunction) model was established by intratympanic injection of chloroform into the right ear, while the control group received intratympanic injection of normal saline. Drugs were administered once daily for seven consecutive days. During the period, behavioral tests were performed to evaluate the behaviors of rats after unilateral vestibular labyrinth destruction. Hematoxylin-eosin (HE) staining and Nissl staining were used to observe the neuronal morphology in the medial vestibular nucleus. Golgi staining was employed to assess the number of dendritic spines of neurons in the medial vestibular nucleus. Ultra-performance liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) was utilized to detect Glu/GABA. Immunofluorescence and immunohistochemistry were used to detect the expressions of neuronal nuclei (NeuN), growth-associated protein 43 (GAP-43), and glial fibrillary acidic protein (GFAP). Western blot and real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) were applied to determine the expressions of glutamate-immunoreactive (Glu-IR), GABA, GFAP, postsynaptic density protein 95 (PSD-95), and GAP-43. ResultsCompared with the sham operation group, the model group presented with head deviation, balance disorder, increased tail suspension score, nuclear consolidation of medial vestibular nerve neurons, and decreased Nissl bodies (P<0.01). The number of dendritic spines in neurons and NeuN-positive cells decreased. The content of Glu decreased. The content of GABA increased (Glu/GABA decreased). The expression of GAP-43 was down-regulated, and GFAP was up-regulated (P<0.05, P<0.01). The expressions of Glu-IR, PSD-95, and GAP-43 proteins, as well as Glu-IR mRNA decreased, while the expressions of GABA and GFAP proteins and mRNA increased (P<0.05, P<0.01). Compared with those in the model group, the head deviation, imbalanced behavior, and tail suspension scores in each treatment group decreased, with alleviated neuronal injury and recovered Nissl bodies (P<0.01). The number of dendritic spines of neurons increased, and the number of NeuN-positive cells rebounded. The content of Glu increased, and the content of GABA decreased (Glu/GABA increased). GFAP was down-regulated, and GAP-43 was up-regulated (P<0.05, P<0.01). The expressions of Glu-IR, PMD-95, and GAP-43 proteins, as well as Glu-IR mRNA increased, while the expressions of GABA and GFAP proteins and mRNA decreased. The effect was more significant in the high-dose group (P<0.01). ConclusionThe Yishen Huoxue Tongqiao Formula can alleviate vestibular dysfunction, and its mechanism may be associated with regulating the metabolic balance of Glu/GABA, mitigating neural damage, improving synaptic plasticity (promoting GAP-43 expression and inhibiting GFAP expression), and facilitating vestibular compensation.
3.Exploration of a new model for the construction of medical institution formulation platforms from the perspective of industry-university-research collaborative innovation theory
Kana LIN ; Anle SHEN ; Yejian WANG ; Yanqiong WANG ; Hao LI ; Yanfang GUO ; Youjun WANG ; Xinyan SUN
China Pharmacy 2026;37(2):137-141
OBJECTIVE To explore a model for constructing a platform for medical institution formulation and provide insights for promoting their development. METHODS By systematically reviewing the development status and challenges of medical institution preparations in China, and based on the theory of industry-university-research collaborative innovation, the organizational structure, collaborative processes, and safeguard mechanisms of the platform were designed. RESULTS & CONCLUSIONS Medical institution formulations in China mainly faced challenges such as weak research and development (R&D) capacity, uneven quality standards, and blocked transformation pathways. This study established a full-chain, whole- industry collaborative innovation network covering the government, medical institutions, universities/research institutes, pharmaceutical enterprises, and the market, forming a new “government-industry-university-research-application” five-in-one platform model for medical institution formulations. By establishing mechanisms such as multi-entity collaborative cooperation, full- chain intellectual property management, contribution-based benefit distribution, staged risk-sharing, and third-party evaluation, the model clarified the responsibilities and collaborative pathways of all parties. The new model highlights the whole-process transformation of clinical experience-based prescriptions, enabling precise alignment between clinical needs and technological R&D, as well as between preparation achievements and industrial transformation. While breaking down the barriers of traditional platform construction, it effectively achieves optimal resource allocation and complementary advantages, addresses problems emerging in the development of medical institution preparations, and provides reference value for the formulation of relevant systems.
4.Meta-analysis of the efficacy and safety total glucosides of paeonia in the treatment of systemic lupus erythematosus
Xiangyan HAO ; Jiahui LENG ; Zhengqi LIU ; Xinchang WANG ; Cong HUANG ; Xiaopeng LI ; Yi LING
China Pharmacy 2026;37(2):232-237
OBJECTIVE To evaluate the efficacy and safety of total glucosides of paeonia (TGP) in the treatment of systemic lupus erythematosus (SLE). METHODS Randomized controlled trial (RCT) about TGP combined with western medicine versus western medicine alone for SLE treatment were retrieved from PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIP, Wanfang Data, and CBM. The search period spanned from the inception of each database to June 1, 2025. After literature screening, data extraction, and quality assessment of the included studies, Meta-analysis was performed using RevMan 5.4 software. RESULTS Fifteen RCTs, involving 1 318 patients, were included. Meta-analysis results showed that compared with western medicine alone, TGP combined with western medicine significantly improved clinical efficacy [OR=4.96, 95%CI(3.41, 7.23), P<0.000 01], complement 3 [MD=0.18, 95%CI (0.13, 0.23), P<0.000 01] and complement 4[MD=0.08, 般021) 95%CI (0.04, 0.11), P<0.000 01], and reduced the levels of immunoglobulin G (IgG) [MD=-3.10, 95%CI (-3.59,-2.62), P<0.000 01], IgA [MD=-0.68, 95%CI (-0.78, -0.58), P<0.000 01], IgM [MD=-0.43, 95%CI (-0.53,-0.34), P<0.000 01], systemic lupus erythematosus disease activity index (SLEDAI) [MD=-1.59, 95%CI (-2.20, -0.99), P<0.000 01], recurrence rate [OR=0.23, 95%CI (0.13, 0.42), P<0.000 01] and the incidence of adverse drug reactions [OR= 0.54, 95%CI (0.36, 0.82), P=0.004]. CONCLUSIONS TGP therapy can improve clinical efficacy of SLE patients, promote the restoration of immunoglobulins and complements, reduce SLEDAI and recurrence rate and has good safety.
5.Correlation of childhood trauma and leisure activities with psychological distress among upper grade elemetary school students
Chinese Journal of School Health 2026;47(1):70-74
Objective:
To understand the impact of childhood trauma on psychological distress among upper grade elemetary school students, and to explore the mediating role of leisure activities in the relationship, so as to provide a basis for developing mental health intervention strategies.
Methods:
From August to November 2024, a combination of convenience sampling and stratified cluster random sampling was employed to recruit 1 373 fourth to sixth grade students from four primary schools in Harbin. The Childhood Trauma Questionnaire(CTQ), a self designed leisure activity scale (including active and passive leisure activities), and the Kessler Psychological Distress Scale (K10) were used to assess childhood trauma experiences, leisure activities, and levels of psychological distress. Spearman correlation analysis and linear regression analysis were conducted to explore the relationships among childhood trauma, leisure types, leisure time, and psychological distress. Based on the mediation analysis framework proposed by Hayes (Model 4), the mediating role of leisure types in the relationship between childhood trauma and psychological distress was examined.
Results:
Totally 19.1% of the upper elemetary school students exhibited psychological distress, while 30.2% had experienced childhood trauma. During school days, 64.6% of the students were reported of having leisure time concentrated between 1 and 5 hours per day, whereas 67.4% reported leisure time exceeding 5 hours per day on weekends. After controlling for potential demographic confounders such as gender, grade, ethnicity, household registration, being an only child, parents educational level, co residence, and whether parents are first time married,linear regression analysis showed that childhood trauma experience had positive predictive effect on psychological distress in upper primary school students( β =0.20, P <0.01). Leisure time showed no statistically significant association with psychological distress, both on school days ( β =-0.58 to -0.56) and weekends ( β =0.26- 0.98 )(all P >0.05). Active leisure activities were negatively associated with psychological distress ( β =-0.20), while passive leisure activities were positively associated with psychological distress ( β =0.29)(both P <0.01). Leisure type partially mediated the relationship between childhood trauma and psychological distress, accounting for 11.7% of the indirect effect.
Conclusion
Childhood trauma experiences positively predict psychological distress in upper elementary school students, and affect psychological distress through active leisure and passive leisure.
6.Suspected adverse events following immunization of domestic bivalent human papillomavirus vaccine in primary and secondary school girls in Hebei Province
WANG Yihan, WANG Yafei, WANG Jinghui, HAO Ling, LI Jing, SUN Li, WANG Lina
Chinese Journal of School Health 2026;47(1):117-120
Objective:
To analyze adverse event following immunization(AEFI) with the domestic bivalent human papilloma virus (HPV) vaccine among female students in primary, junior, and senior high schools in Hebei Province from 2022 to 2024, aiming to provide evidence for the vaccination program.
Methods:
On May 14, 2025, AEFI case data and vaccination data for the domestic bivalent HPV vaccine among female students in primary, junior, and senior high schools in Hebei Province from 2022 to 2024 were collected from the China Disease Control and Prevention Information System and the Hebei Provincial Immunization Program Information Management System, respectively. Statistical analysis was performed by using descriptive and analytical epidemiological methods, with intergroup comparisons conducted by using the Chi square test or Fisher s exact probability test.
Results:
From 2022 to 2024, a total of 817 900 doses of the domestic bivalent HPV vaccine were administered to female students in primary, junior, and senior high schools in Hebei Province. A total of 68 AEFI cases were reported, comprising 57 common vaccine reactions, 7 rare vaccine reactions, 3 coincidental events, and 1 psychogenic reaction. The overall AEFI reporting rate was 8.31 per 100 000 doses, 4 cases (2.30/100 000 doses), 31 cases (8.73/100 000 doses), and 33 cases (11.41/100 000 doses) were reported in 2022, 2023, and 2024, respectively, with a statistically significant difference across years ( χ 2=10.97, P <0.01). The reporting rates for common and rare vaccine reactions were 6.97 per 100 000 doses and 0.86 per 100 000 doses, respectively. The AEFI reporting rates were 15.14 per 100 000 doses among primary school girls and 8.20 per 100 000 doses among secondary school girls, though the difference was not statistically significant (Fisher s exact test, P =0.30). The reporting rate was higher after the first dose (10.91/100 000 doses) than after the second dose (5.96/100 000 doses; χ 2=5.85, P =0.02).The second quarter recorded the highest AEFI reporting rate at 11.21 per 100 000 doses. The majority of AEFI cases (56 cases, 82.35%) occurred within 24 hours post vaccination.
Conclusion
The domestic bivalent HPV vaccine demonstrates a favorable safety profile among female students in Hebei Province, with a low overall AEFI reporting rate that consisted predominantly of general reactions and occasional cardiac related reactions.
7.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.
8.Luotong Xianrong Yin Inhibits Pulmonary Injury in Idiopathic Pulmonary Fibrosis Rats by Regulating STAT3/HIF-1α-mediated Glycolysis
Dongna LI ; Hao WANG ; Chaoyi FANG ; Jiepeng WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):118-125
ObjectiveTo investigate the characteristics and potential mechanisms of Luotong Xianrong Yin (LTXRY) in improving lung injury in rats with idiopathic pulmonary fibrosis (IPF) by regulating glycolysis. MethodsForty specific pathogen-free (SPF) Sprague-Dawley (SD) rats were randomly divided into a sham-operated group (10 mL·kg-1), model group (10 mL·kg-1), LTXRY group (15.18 g·kg-1), and nintedanib group (0.1 g·kg-1), with 10 rats in each group. The IPF rat model was established by intratracheal instillation of bleomycin. After 28 days of gavage intervention, pulmonary function was assessed. Lung pathological changes were observed by hematoxylin-eosin (HE) and Masson staining. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, in lung tissue. Chemiluminescence assays were employed to detect lactate content and lactate dehydrogenase activity in lung tissue. Western blot was used to measure the protein expression of transforming growth factor-β1 (TGF-β1), CollagenⅠ and CollagenⅢ to evaluate collagen deposition, as well as hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) to assess glycolysis levels. Network pharmacology was applied to analyze the potential targets and signaling pathways of LTXRY in IPF, and molecular docking was conducted to evaluate the binding energy between active components and potential targets. Western blot was further used to detect the expression of target- and pathway-related proteins. ResultsCompared with the sham-operated group, rats in the model group showed significantly increased main airway resistance (Rn) and respiratory system resistance (Rrs), and significantly decreased respiratory system compliance (Crs). Inflammatory infiltration and collagen deposition were observed in lung tissue, with significantly increased levels of TNF-α, IL-1β, and IL-6, as well as elevated protein expression of TGF-β1, CollagenⅠ and CollagenⅢ. Lactate content, lactate dehydrogenase activity, and the protein expression of HK2, PKM2, and PFKFB3 in lung tissue were significantly increased. Network pharmacology analysis indicated that signal transducer and activator of transcription 3 (STAT3) was a key target of LTXRY in IPF, and hypoxia-inducible factor-1 (HIF-1) was a critical signaling pathway. The expression levels of phosphorylated STAT3 (p-STAT3) and HIF-1α in lung tissue were significantly higher than those in the sham-operated group. Compared with the model group, rats in the LTXRY group showed significantly decreased Rn and Rrs and significantly increased Crs. Lung inflammatory infiltration and collagen deposition were markedly alleviated, with significantly reduced levels of TNF-α, IL-1β, and IL-6, and decreased protein expression of TGF-β1, CollagenⅠ and CollagenⅢ. Lactate content, lactate dehydrogenase activity, and the protein expression of HK2, PKM2, and PFKFB3 were significantly decreased, accompanied by markedly reduced expression of p-STAT3 and HIF-1α. ConclusionLTXRY alleviates lung tissue injury in IPF rats by regulating glycolysis mediated by the STAT3/HIF-1α signaling pathway.
9.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.
10.Effect of Simiaowan on Promoting Ileal Uric Acid Excretion by Modulating Gut Microbiota to Improve Intestinal Barrier Function and Upregulate ABCG2 Expression in Rats
Yuan ZHANG ; Zhongyou ZHANG ; Huilin FENG ; Lian DUAN ; Lingchun WANG ; Hao DAI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):101-112
ObjectiveTo investigate the effects of Simiaowan on intestinal barrier function and adenosine triphosphate (ATP) binding cassette transporter G2 (ABCG2) expression in hyperuricemic (HUA) rats, and elucidate its therapeutic mechanisms. MethodsForty male Sprague Dawley (SD) rats were randomized into a normal group, a model group, low-dose (282.6 mg·kg-1) and high-dose (565.2 mg·kg-1) Simiaowan groups, and a Benzbromarone (4.7 mg·kg-1) group. The HUA model was established via intraperitoneal injection of potassium oxonate (ip) combined with oral gavage of hypoxanthine (ig) for 14 days. Following modeling, treatments were administered for 14 days. Samples were collected and weighed 4 h after final dosing. Blood uric acid and hepatic function were analyzed. Histopathological changes were evaluated by hematoxylin-eosin (HE) staining, and Chiu's scoring was conducted. Enzyme-linked immunosorbent assay (ELISA) quantified tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), lipopolysaccharide (LPS), diamine oxidase (DAO), and D-lactic acid (D-LA) levels. Real-time polymerase chain reaction (Real-time PCR), Western blot, and immunohistochemistry assessed the expression of Claudin-1, Occludin, occludens-1 (ZO-1), and ABCG2 mRNAs and proteins. 16S rDNA amplicon sequencing characterized ileal microbiota. ResultsCompared with the normal group, the model group exhibited epithelial shedding in the ileal villus, structural disruption, infiltration of extensive inflammatory cells, and significantly elevated Chiu's scores (P<0.01). The DAO, TNF-α, IL-6, IL-1β, LPS, and D-LA levels in the ileum were markedly increased (P<0.01), while mRNA and protein expressions of Claudin 1, Occludin, ZO-1, and ABCG2, as well as positive staining area and proportion, were significantly reduced (P<0.01). Compared with the model group, the Simiaowan groups at all doses showed improved epithelial damage in the ileal villus, significantly lowered Chiu's scores (P<0.01), significantly reduced DAO, TNF-α, IL-6, IL-1β, LPS, and D-LA levels in the ileum (P<0.01), and upregulated mRNA and protein expressions of Claudin 1, Occludin, ZO-1, and ABCG2, as well as positive staining area and proportion (P<0.01). The 16S rDNA results showed that in the model group, the α-diversity index of the ileal microbiota was increased, and species diversity and richness were enhanced, with microbiota dysfunction observed. The community structure of the gut microbiota was significantly different from that of the normal microbiota. The abundance of probiotics was decreased, and the abundance of pathogenic bacteria was increased, with butyrate-producing bacteria showing a low abundance. In contrast, Simiaowan at all doses reduced species diversity and richness, regulated microbiota dysfunction, and promoted the shift of the structure of the gut microbiota community towards a normal one. This increased the abundance of beneficial bacteria, decreased the abundance of harmful bacteria, and restored the abundance of butyrate-producing bacteria. ConclusionSimiaowan enhances ileal uric acid excretion and further alleviates HUA by modulating the gut microbiota composition to improve the intestinal barrier and upregulate the expression of the urate transporter ABCG2 in HUA rats.


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