1.Exploring Chemical Constituent Distribution in Blood/Brain(Hippocampus) and Emotional Regulatory Effect of Raw and Vinegar-processed Products of Citri Reticulatae Pericarpium Viride
Yi BAO ; Yonggui SONG ; Qianmin LI ; Zhifu AI ; Genhua ZHU ; Ming YANG ; Huanhua XU ; Qin ZHENG ; Yiting HUANG ; Zihan GAO ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):189-197
ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride(CRPV), and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts, as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards, databases, and relevant literature were utilized for compound annotation, with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups, including the blank group, model group, diazepam group(2.5 mg·kg-1), raw CRPV low/high dose groups(0.6, 1.2 g·kg-1), and vinegar-processed CRPV low/high dose groups(0.6, 1.2 g·kg-1), with 10 mice per group. Except for the blank group, all other groups underwent chronic restraint stress(2 h·d-1) for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling, with a total treatment duration of 10 d. Following model-based drug administration, mice underwent open-field, forced swimming, and elevated plus maze tests. After anesthesia with isoflurane, whole brains were collected from each group of mice, and hippocampi were dissected. Reactive oxygen species(ROS) level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei(NeuN) and peroxisome proliferator-activated receptor alpha(PPARα) expressions in hippocampal tissue. Then, pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders, exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV, with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds, including 20 flavonoids, 20 flavonoid glycosides, 3 triterpenes, 3 phenolic acids, 1 alkaloid, and 6 other compounds. Twenty-one components were detected in blood(15 methoxyflavones, 4 flavonoid glycosides, and 2 phenolic acids), with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues(all common to both forms). In regulating emotional disorders, Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology, particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS(P<0.05). ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing, but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway, thereby negatively regulating ROS generation in the hippocampus, reducing oxidative stress, and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards, pharmacodynamic material research, and active drug development of raw and vinegar-processed CRPV.
2.Drug comprehensive value assessment frameworks for medical insurance:overseas experiences and implications for China
Yijun LIU ; Dan LI ; Yu ZHANG ; Bin JIANG
China Pharmacy 2026;37(4):413-419
OBJECTIVE To systematically compare mature experiences of comprehensive drug value assessment in typical countries/regions and to provide decision-making references for China to establish a scientific and standardized comprehensive drug value assessment system for medical-insured drugs. METHODS The literature analysis was used to systematically review drug value assessment frameworks in 11 representative countries/regions, namely the UK, Canada, Italy, Australia, Germany, France, South Korea, Japan, the United States, as well as Taiwan (China) and Hong Kong (China). Comparisons were made across three dimensions: assessment entities, value dimension, and application of results. RESULTS &CONCLUSIONS In most countries/regions, independent technical assessment institutions have been established as part of the drug value evaluation system, with the involvement of multiple stakeholders (e.g., the UK, Canada). The mainstream drug value assessment frameworks have generally transcended the traditional core dimensions of safety, efficacy, and cost-effectiveness, exhibiting two major trends: the continuous expansion of assessment dimensions and stricter evidence requirements. Assessment outcomes are closely integrated with payment policies, ranging from providing technical advice for decision-making (e.g., Italy, France) to directly determining reimbursement eligibility (e.g., the UK, Germany). The following recommendations are proposed for China: first, establish an evaluation mechanism featuring multi-stakeholder participation and separation of evaluation from decision-making. Second, develop a comprehensive evaluation framework integrating clinical, economic, patient, and societal value, emphasizing quantitative indicator exploration and real-world evidence application. Third, promote direct linkage between value-based tiering outcomes and medical insurance reimbursement decisions or access negotiations to balance patient benefits, fund sustainability, and industrial innovation.
3.Effects of Huanglian Jiedutang on Neutrophil Infiltration in Brain of MCAO Mice via Regulation of Chemokine Expression in Exosomes
Haojia ZHANG ; Kai WANG ; Zijin SUN ; Chunyu WANG ; Wei SHAO ; Kunjing LIU ; Liyang DONG ; Dan CHEN ; Wenxiu XU ; Chuanzun WANG ; Wen WANG ; Changxiang LI ; Xueqian WANG ; Fafeng CHENG ; Qingguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):42-53
ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion (MCAO) mice by regulating the expression of neutrophil-related chemokines in exosomes, thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free (SPF) C57BL/6J mice were randomly divided into four groups: Sham-operated group, MCAO model group, Huanglian Jiedutang group (6 g·kg-1), and Ginaton group (21.6 mg·kg-1), with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·(10 g)-1 for 7 consecutive days, while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days, MCAO surgery was performed. The distal and proximal ends of the right common carotid artery (CCA) were ligated, a small incision was made between the two ligatures, and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling, mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin (HE) staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy, particle size analysis, and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase (MPO) in the brains of mice in each group. ResultsCompared with the sham-operated group, the model group showed decreased neurological function scores (P<0.01), obvious cerebral infarction (P<0.01), reduced cerebral blood flow (P<0.01), neuronal necrosis in the brain, and decreased numbers of Nissl bodies (P<0.01). The mRNA expression levels of IL-1β, MPO, CXCL1, CXCL2, CXCL3, CXCL10, CCL2, and CCL3 in exosomes from plasma and brain tissues were significantly increased (P<0.05, P<0.01). The protein expression levels of IL-1β, MPO, CXCL2, and CXCL10 in exosomes from brain tissues were increased (P<0.05, P<0.01), and MPO-positive rates and mean optical density values in brain tissues were elevated (P<0.01). Compared with the model group, the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores (P<0.05), reduced cerebral infarct volume (P<0.01), restored cerebral blood flow (P<0.01), reduced necrotic cells in the brain, and increased numbers of Nissl bodies (P<0.01). In the Huanglian Jiedutang group, the mRNA expression levels of IL-1β, MPO, CXCL1, CXCL2, CXCL3, CXCL10, CCL2, and CCL3 in exosomes from plasma and brain tissues were decreased (P<0.05, P<0.01). The protein expression levels of IL-1β, MPO, CXCL2, and CXCL10 in exosomes from brain tissues were reduced (P<0.05, P<0.01), and MPO-positive rates and mean optical density values in brain tissues were decreased (P<0.01). ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice, thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.
4.Effects of Huanglian Jiedutang on Neutrophil Infiltration in Brain of MCAO Mice via Regulation of Chemokine Expression in Exosomes
Haojia ZHANG ; Kai WANG ; Zijin SUN ; Chunyu WANG ; Wei SHAO ; Kunjing LIU ; Liyang DONG ; Dan CHEN ; Wenxiu XU ; Chuanzun WANG ; Wen WANG ; Changxiang LI ; Xueqian WANG ; Fafeng CHENG ; Qingguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):42-53
ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion (MCAO) mice by regulating the expression of neutrophil-related chemokines in exosomes, thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free (SPF) C57BL/6J mice were randomly divided into four groups: Sham-operated group, MCAO model group, Huanglian Jiedutang group (6 g·kg-1), and Ginaton group (21.6 mg·kg-1), with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·(10 g)-1 for 7 consecutive days, while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days, MCAO surgery was performed. The distal and proximal ends of the right common carotid artery (CCA) were ligated, a small incision was made between the two ligatures, and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling, mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin (HE) staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy, particle size analysis, and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase (MPO) in the brains of mice in each group. ResultsCompared with the sham-operated group, the model group showed decreased neurological function scores (P<0.01), obvious cerebral infarction (P<0.01), reduced cerebral blood flow (P<0.01), neuronal necrosis in the brain, and decreased numbers of Nissl bodies (P<0.01). The mRNA expression levels of IL-1β, MPO, CXCL1, CXCL2, CXCL3, CXCL10, CCL2, and CCL3 in exosomes from plasma and brain tissues were significantly increased (P<0.05, P<0.01). The protein expression levels of IL-1β, MPO, CXCL2, and CXCL10 in exosomes from brain tissues were increased (P<0.05, P<0.01), and MPO-positive rates and mean optical density values in brain tissues were elevated (P<0.01). Compared with the model group, the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores (P<0.05), reduced cerebral infarct volume (P<0.01), restored cerebral blood flow (P<0.01), reduced necrotic cells in the brain, and increased numbers of Nissl bodies (P<0.01). In the Huanglian Jiedutang group, the mRNA expression levels of IL-1β, MPO, CXCL1, CXCL2, CXCL3, CXCL10, CCL2, and CCL3 in exosomes from plasma and brain tissues were decreased (P<0.05, P<0.01). The protein expression levels of IL-1β, MPO, CXCL2, and CXCL10 in exosomes from brain tissues were reduced (P<0.05, P<0.01), and MPO-positive rates and mean optical density values in brain tissues were decreased (P<0.01). ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice, thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.
5.Multi-label fundus disease classification using dual-branch deep learning: an intelligent diagnosis framework inspired by traditional Chinese medicine Five Wheels theory
Xin HE ; Xiaohui LI ; Jun PENG ; Lei LEI ; Dan SHU ; Li XIAO ; Qinghua PENG ; Xiaoxia XIAO
Digital Chinese Medicine 2026;9(1):80-90
Objective:
To develop a dual-branch deep learning framework for accurate multi-label classification of fundus diseases, addressing the key limitations of insufficient complementary feature extraction and inadequate cross-modal feature fusion in existing automated diagnostic methods.
Methods:
The fundus multi-label classification dataset with 12 disease categories (FMLC-12) dataset was constructed by integrating complementary samples from Ocular Disease Intelligent Recognition (ODIR) and Retinal Fundus Multi-Disease Image Dataset (RFMiD), yielding 6 936 fundus images across 12 retinal pathology categories, and the framework was validated on both FMLC-12 and ODIR. Inspired by the holistic multi-regional assessment principle of the Five Wheels theory in traditional Chinese medicine (TCM) ophthalmology, the dual-branch multi-label network (DBMNet) was developed as a novel framework integrating complementary visual feature extraction with pathological correlation modeling. The architecture employed a TransNeXt backbone within a dual-branch design: one branch processed red-green-blue (RGB) images to capture color-dependent features, such as vascular patterns and lesion morphology, while the other processed grayscale-converted images to enhance subtle textural details and contrast variations. A feature interaction module (FIM) effectively integrated the multi-scale features from both branches. Comprehensive ablation studies were conducted to evaluate the contributions of the dual-branch architecture and the FIM. The performance of DBMNet was compared against four state-of-the-art methods, including EfficientNet Ensemble, transfer learning-based convolutional neural network (CNN), BFENet, and EyeDeep-Net, using mean average precision (mAP), F1-score, and Cohen's kappa coefficient.
Results:
The dual-branch architecture improved mAP by 15.44 percentage points over the single-branch TransNeXt baseline, increasing from 34.41% to 44.24%, and the addition of FIM further boosted mAP to 49.85%. On FMLC-12, DBMNet achieved an mAP of 49.85%, a Cohen’s kappa coefficient of 62.14%, and an F1-score of 70.21%. Compared with BFENet (mAP: 45.42%, kappa: 46.64%, F1-score: 71.34%), DBMNet outperformed it by 4.43 percentage points in mAP and 15.50 percentage points in kappa, while BFENet achieved a marginally higher F1-score. On ODIR, DBMNet achieved an F1-score of 85.50%, comparable to state-of-the-art methods.
Conclusion
DBMNet effectively integrates RGB and grayscale visual modalities through a dual-branch architecture, significantly improving multi-label fundus disease classification. The framework not only addresses the issue of insufficient feature fusion in existing methods but also demonstrates outstanding performance in balancing detection across both common and rare diseases, providing a promising and clinically applicable pathway for standardized, intelligent fundus disease classification.
6.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.
7.A qualitative study on the driving forces for oncology nurses’ participation in palliative care work
Xinyao YUAN ; Pengyun LI ; Sujuan HAO ; Fen WANG ; Dan XU ; Jiahe LI ; Xuancheng CHEN ; Huiling LI
Chinese Medical Ethics 2026;39(3):358-364
ObjectiveTo explore the driving forces for oncology nurses’ participation in palliative care work, thereby providing a theoretical basis for the improvement of education and training, incentive mechanisms, and other aspects of the palliative care nursing staff. MethodsEmploying a qualitative research method, semi-structured interviews lasting 40-60 minutes were conducted with 14 nurses who had participated in palliative care work. The interview data were analyzed using the Colaizzi seven-step analysis method. ResultsInternal positive driving forces were job interest, empathy, and a sense of professional responsibility, while the negative was low psychological resilience. External positive driving forces included high work support, professional identity, mutual benefits for nurses and patients, and positive patient attitudes, whereas negative driving forces comprised busy routine clinical work, lack of a reward and incentive system, and bland or negative patient attitudes. ConclusionIt is essential to provide a flexible platform for the enhancement of nurses’ professional capabilities in palliative care, intensify the publicity of palliative care and death education; intervene and guide nurses’ negative emotions, improve and implement relevant incentive systems, and standardize the job recognition and scope of responsibilities of palliative care nurses.
8.Comparative analysis of the clinical characteristics of pneumococcal meningitis in different populations in Baoji, Shaanxi Province
Ruize WANG ; Weixuan LI ; Yuanyuan DONG ; Xiaoyu ZHANG ; Tiantian ZHOU ; Dan ZHANG ; Weijun HU
Journal of Public Health and Preventive Medicine 2026;37(2):59-63
Objective To compare the clinical characteristics of pneumococcal meningitis in different age groups, and to provide a basis for early diagnosis of pneumococcal meningitis. Methods Cerebrospinal fluid and/or serum samples were collected from 1742 suspected cases of meningitis in Baoji, Shaanxi Province from August 2013 to July 2019. Streptococcus pneumoniae was detected by isolation culture and real-time fluorescence quantitative polymerase chain reaction. Retrospective analysis of clinical manifestations, biochemical indicators and other information of laboratory confirmed cases was conducted by χ2 test or Fisher's exact test. Results A total of 1742 samples of encephalitis or meningitis cases were detected, and 41 cases were confirmed as laboratory-confirmed Streptococcus pneumoniae infection. Among them, there were 12 cases (29.27%) in the infant group, 14 cases (34.15%) in the child group, and 15 cases (36.59%) in the adult group. The proportion of the adults with headache was significantly higher than that of the infants (χ2=11.408,P<0.017). The proportion of the adults with consciousness disorder, elevated white blood cells and elevated neutrophils were significantly higher than those in the infant and the child groups(Fisher's exact test, P<0.017;χ2 =6.428,P<0.017;χ2 =10.898,P<0.017;χ2 =6.421,P<0.017;χ2 =9.758,P<0.017;χ2 =7.744,P<0.017). The proportion of the infants with cerebrospinal fluid turbidity was significantly higher than that of the children (Fisher's exact test,P<0.017). The proportion of the infants with decreased white blood cells and reduced glucose in cerebrospinal fluid was significantly higher than that of the children group and the adult group(Fisher's exact test, P<0.001;Fisher's exact test, P<0.001;Fisher's exact test, P<0.017; Fisher's exact test, P<0.017). Conclusion Most adult patients with pneumococcal meningitis have headache and consciousness disorders, with significantly increased proportion of white blood cells and neutrophils. Infant patients tend to have cloudy appearance of cerebrospinal fluid, leukopenia in blood, and decreased glucose in cerebrospinal fluid.
9.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.
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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