1.Joint Relation Extraction of Famous Medical Cases with CasRel Model Combining Entity Mapping and Data Augmentation
Yuxin LI ; Xinghua XIANG ; Hang YANG ; Dasheng LIU ; Jiaheng WANG ; Zhiwei ZHAO ; Jiaxu HAN ; Mengjie WU ; Qianzi CHE ; Wei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):218-225
ObjectiveTo address the challenges of unstructured classical Chinese expressions, nested entity relationships, and limited annotated data in famous traditional Chinese medicine(TCM) case records, this study proposes a joint relation extraction framework that integrates data augmentation and entity mapping, aiming to support the construction of TCM diagnostic knowledge graphs and clinical pattern mining. MethodsWe developed an annotation structure for entities and their relationships in TCM case texts and applied a data augmentation strategy by incorporating multiple ancient texts to expand the relation extraction dataset. A cascade binary tagging framework for relation triple extraction(CasRel) model for TCM semantics was designed, integrating a pre-trained bidirectional encoder representations from transformers(BERT) layer for classical TCM texts to enhance semantic representation, and using a head entity-relation-tail entity mapping mechanism to address entity nesting and relation overlapping issues. ResultsExperimental results showed that the CasRel model, combining data augmentation and entity mapping, outperformed the pipeline-based Bert-Radical-Lexicon(BRL)-bidirectional long short-term memory(BiLSTM)-Attention model. The overall precision, recall, and F1-score across 12 relation types reached 65.73%, 64.03%, and 64.87%, which represent improvements of 14.26%, 7.98%, and 11.21% compared to the BRL-BiLSTM-Attention model, respectively. Notably, the F1-score for tongue syndrome relations increased by 22.68%(69.32%), and the prescription-syndrome relations performed the best with the F1-score of 70.10%. ConclusionThe proposed framework significantly improves the semantic representation and complex dependencies in TCM texts, offering a reusable technical framework for structured mining of TCM case records. The constructed knowledge graph can support clinical syndrome differentiation, prescription optimization, and drug compatibility, providing a methodological reference for TCM artificial intelligence research.
2.Clinical Application and Pharmacological Effects of Guizhi Fulingwan in Treatment of Uterine Fibroids: A Review
Xiang ZHANG ; Xiaoli WEN ; Biting CHENG ; Hongning LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):299-307
Uterine fibroids are a common benign tumor of the female reproductive system, characterized by increased menstrual flow, lower abdominal pain, and prolonged menstrual periods. Modern medicine believes that the onset of this disease is related to genetic factors, environmental factors, hormone levels, et al, while the specific mechanism remains unclear, and the prevention and treatment of uterine fibroids has become a hot topic of concern for many experts and scholars in the medical field. At present, the treatment of uterine fibroids in clinical practice is mainly based on hormone drugs and uterine artery embolization, and severe cases require hysterectomy. However, the use of hormone drugs for treatment has serious side effects and is prone to recurrence after surgery. Since hysterectomy can cause severe harm to women, it is necessary to explore safer and more effective treatment methods. Traditional Chinese medicine (TCM) has rich clinical experience in the treatment of uterine fibroids, advocating for syndrome differentiation and treatment. The TCM methods that regulate Qi and blood and balance Yin and Yang have been commonly adopted, with significant efficacy and minimal side effects, being more conducive to the recovery. Guizhi Fulingwan are first recorded in the Synopsis of the Golden Chamber written by the famous medical expert ZHANG Zhongjing during the Eastern Han dynasty. This prescription has the effects of activating blood, resolving stasis, and eliminating mass, and it is thus mainly used for treating abdominal mass in women. In recent years, Guizhi Fulingwan has also been applied in the clinical treatment of tumors and has demonstrated definite efficacy in the treatment of uterine fibroids. Studies have shown that the therapeutic mechanisms of Guizhi Fulingwan for uterine fibroids involve regulating cell proliferation and apoptosis, improving immune function, reducing inflammation, improving hemorheological indicators, inhibiting tumor angiogenesis, and regulating sex hormone levels. This article mainly reviews the treatment of uterine fibroids with Guizhi Fulingwan from three aspects: theoretical basis, clinical application, and pharmacological mechanism. It is expected to provide scientific research ideas and guidance for exploring the clinical treatment of uterine fibroids.
3.Visual function training combined with surgical intervention for the treatment of intermittent exotropia
International Eye Science 2026;26(1):29-34
AIM: To observe clinical outcomes of visual function training combined with surgical intervention in children with intermittent exotropia.METHODS: Retrospective study. A total of 100 pediatric patients with intermittent exotropia admitted to the Children's Hospital of Soochow University from January 2022 to December 2024 were selected and divided into two groups based on treatment modality. Both groups underwent intermittent exotropia correction surgery. The control group did not follow a visual rehabilitation program postoperatively, while the visual rehabilitation group did. The differences were compared between the two groups in preoperative and postoperative 12 wk results of perceptual eye position examinations, visual perception stereopsis function tests, multifocal visual evoked potential outcomes, Chinese version of the Child-International Quality of Life for Children with Strabismus(Child-IXTQ)scores, and strabismus angle.RESULTS: The baseline data of the two groups were comparable. Both groups showed reduced horizontal and vertical perceptual eye position deviation at 12 wk postoperatively compared to preoperative levels, with the visual group exhibiting lower values than the control group(all P<0.01). At 12 wk postoperatively, the number of children in the visual group who recovered fine and dynamic stereopsis increased compared to preoperative levels, and this number was higher than that in the control group(all P<0.05). There was no significant difference between the two groups in the number of children who recovered coarse stereopsis preoperatively and 12 wk postoperatively(all P>0.05). Both groups showed reduced latency for the first and second rings at 12 wk postoperatively compared to pre-surgery, with the visual group exhibiting lower latency than the control group(all P<0.01). There was no significant difference in latency for the third and fourth rings between pre-surgery and 12 wk postoperatively in either group(all P>0.05). Both groups showed increased Child-IXTQ scores at 12 wk postoperatively compared to preoperatively, with the visual group scoring higher than the control group(all P<0.05). Both groups exhibited reduced strabismus angles at 33 cm and 6 m at 12 wk postoperatively compared to preoperatively(all P<0.01), but the visual group showed no difference compared to the baseline group(all P>0.05).CONCLUSION: Combining visual function training with surgical intervention for intermittent exotropia can improve multifocal visual evoked potentials, promote visual function recovery, and enhance quality of life.
4.Mechanism study of SIRT3 alleviating oxidative-stress injury in renal tubular cells by promoting mitochondrial biogenesis via regulating mitochondrial redox balance
Yaojun LIU ; Jun ZHOU ; Jing LIU ; Yunfei SHAN ; Huhai ZHANG ; Pan XIE ; Liying ZOU ; Lingyu RAN ; Huanping LONG ; Lunli XIANG ; Hong HUANG ; Hongwen ZHAO
Organ Transplantation 2026;17(1):86-94
Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H2O2 and divided into four groups: control (NC), 50 μmol/L H2O2, 110 μmol/L H2O2 and 150 μmol/L H2O2. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H2O2, and siSIRT3+H2O2. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O2•−) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H2O2 decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O2•− did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O2•− level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H2O2 group exhibited decreased cellular ATP levels, elevated mitochondrial O2•− levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H2O2 group showed a decrease in cellular ATP levels, an increase in mitochondrial O2•− levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H2O2 group, the siSIRT3+H2O2 group showed a decrease in cellular ATP levels, an increase in mitochondrial O2•− levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.
5.Comparison of Wild and Cultivated Alpiniae Oxyphyllae Fructus Based on Traditional Quality Evaluation
Fengfan WANG ; Yajie XIANG ; Jian FENG ; Wencheng HOU ; Wenlan LI ; Yangyang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):235-244
ObjectiveTo compare the differences between wild Alpiniae Oxyphyllae Fructus(WAOF) and cultivated Alpiniae Oxyphyllae Fructus(CAOF) through a traditional quality evaluation system for medicinal materials. MethodsA total of 10 batches of WAOF and 12 batches of CAOF samples were collected from various regions of Hainan province. Relevant analytical methods from the 2020 edition of the Pharmacopoeia of the People's Republic of China were employed to observe the characteristics of WAOF and CAOF, followed by microscopic identification, thin-layer chromatography(TLC) identification, moisture content(toluene method), total ash, acid-insoluble ash, water-soluble and alcohol-soluble extracts(hot dipping method), water-soluble protein, total polysaccharides and total flavonoids(ultraviolet spectrophotometry), and volatile oil content(method A under general rule 2204). The contents of five active components(protocatechuic acid, chrysin, kaempferol, tectochrysin and nootkatone) were quantified using ultra-performance liquid chromatography(UPLC), and the antioxidant activity was evaluated. Building upon traditional quality evaluation of AOF, quantitative measurements were conducted on its appearance traits including diameter, length, plumpness(diameter/length ratio), and color. Canonical correlation analysis was performed using SPSS 26.0 to explore relationships between appearance traits and intrinsic quality. ResultsNo significant differences were observed between WAOF and CAOF in microscopic observation, TLC identification, moisture content, protocatechuic acid content, kaempferol content, odor, or antioxidant activity measured by 2,2ʹ-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) method. WAOF exhibited significantly higher levels in water-soluble extracts, alcohol-soluble extracts, total polysaccharide content, water-soluble protein content, 100-grain weight, length, and total color difference(ΔE*ab) compared to CAOF(P<0.01). In contrast, CAOF showed significantly higher levels of total ash, acid-insoluble ash, content of total flavonoids, volatile oil content, chrysin content, tectochrysin content, nootkatone content, diameter, plumpness, lightness(L*), red-green chromaticity(a*), yellow-blue chromaticity(b*), and antioxidant activity measured by 1,1-diphenyl-2-picrylhydrazyl(DPPH) method compared to WAOF(P<0.01). Correlation analysis between 7 phenotypic traits and 8 quality traits revealed that among the phenotypic traits, plumpness, L*, a*, and b* exerted significant influence on intrinsic quality. Among the quality traits, total flavonoids, volatile oils, nootkatone, chrysin, and tectochrysin contributed substantially to intrinsic quality. ConclusionPlumpness, L*, a*, and b* of AOF significantly influence its intrinsic quality, and higher values of these parameters indicate relatively superior intrinsic quality. The comprehensive quality evaluation reveals that CAOF samples collected in this study are superior to their wild counterparts.
6.Exploring the mechanism of myofascial trigger points deactivation by Tuina via the TGF-β1/Smad3 signaling pathway
Liya TANG ; Xiaowei LIU ; Jiadong ZANG ; Yuqiao ZHANG ; Xiang FENG ; Wu LI ; Jiangshan LI
Digital Chinese Medicine 2026;9(1):103-113
Objective:
To investigate whether Tuina alleviates fibrotic symptoms in myofascial trigger points (MTrPs) by regulating transforming growth factor (TGF)-β1/Smad3 signaling pathway, thereby deactivating these points.
Methods:
This study comprised two experimental phases. In phase 1, 27 specific pathogen-free (SPF) grade female Sprague-Dawley (SD) rats were randomized into three groups: control 1, model 1, and Tuina 1 groups. Model 1 and Tuina 1 groups underwent an 8-week MTrPs modeling protocol involving blunt impact and eccentric exercise. After successful modeling, rats in Tuina 1 group received manual pressing on nodules or cord-like taut bands on the medial aspect of the left hindlimb. Pain sensitivity and tissue stiffness were evaluated via pressure pain threshold (PPT) and soft tissue tension (STT). Muscle histopathology and fibrosis were observed using hematoxylin and eosin (HE) and Masson staining. Inflammatory factors in muscle were measured by enzyme-linked immunosorbent assay (ELISA), while immunofluorescence (IF) and Western blot (WB) were used to detect the expression levels of α-smooth muscle actin (α-SMA), collagen Ⅲ, and TGF-β1. In phase 2, 45 SPF female SD rats were randomized into five groups: control 2, model 2, Tuina 2, TGF-β1 inhibitor (TI), and Tuina + TGF-β1 agonist (Tuina + TA) groups. All groups except control 2 underwent standardized MTrPs modeling. Rats in Tuina 2 group received consistent pressing manipulation. TI group received intraperitoneal injections of oxymatrine, while Tuina + TA group received intraperitoneal injections of SRI-011381 hydrochloride followed by the same pressing protocol as Tuina 2 group. WB was used to detect the expression of collagen I, collagen III, TGF-β1, and phosphorylated-Smad3 (p-Smad3)/Smad3.
Results:
In phase 1, Tuina significantly improved PPT and STT in MTrPs of rats (P < 0.01), reversed pathological damages including disorganized muscle fiber arrangement, abnormal myocyte morphology, and exacerbated fibrosis. In addition, in MTrPs of rats in model 1 group, expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and fibrosis markers (α-SMA, collagen I, and collagen III) were upregulated, and all exhibited a significant downward trend after Tuina intervention (P < 0.05 or P < 0.01). This indicates that the therapeutic effects of Tuina are directly associated with reduced local inflammation and fibrosis in MTrPs. In phase 2, compared with model 2 group, rats in TI and Tuina 2 groups had decreased expression levels of TGF-β1 and p-Smad3/Smad3 in MTrPs, alongside reduced levels of inflammatory factors (IL-1β, IL-6, NF-κB, and TNF-α) and fibrosis markers (α-SMA, collagen I, and collagen III) (P < 0.05 or P < 0.01). When co-administered with TGF-β1 agonist, the therapeutic effects of Tuina were significantly attenuated, with rebounded TGF-β1 expression and p-Smad3/Smad3 in local MTrPs, and fibrosis and inflammatory responses were re-exacerbated (P < 0.05 or P < 0.01).
Conclusion
Tuina can effectively reduce inflammatory responses and fibrosis in MTrPs tissue, and its mechanism is closely related to the inhibition of the TGF-β1/Smad3 signaling pathway, which plays a critical role in Tuina-mediated regulation of MTrPs fibrosis.
7.Correlation between liver fibrosis degree and carotid plaque in patients with lean metabolic dysfunction-associated fatty liver disease
Shuai ZHANG ; Shoulu JIN ; Wanqing LI ; Xijing SHI ; Hao LIANG ; Hao DONG ; Dailong LU ; Ying ZHU ; Xiaoxing XIANG ; Jun LIU
Journal of Clinical Hepatology 2026;42(2):319-325
ObjectiveTo investigate the association between noninvasive liver fibrosis markers and carotid plaque (CP) in patients with lean metabolic dysfunction-associated fatty liver disease (MAFLD), and to provide a basis for screening high-risk populations. MethodsA total of 957 patients with lean MAFLD who underwent physical examination in Subei People’s Hospital from January 2021 to June 2023 was enrolled as the observation cohort, with the presence or absence of CP as the outcome, and fibrosis-4 (FIB-4) index and nonalcoholic fatty liver disease fibrosis score (NFS) were used to assess liver fibrosis degree. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression analysis, the restricted cubic spline analysis, the receiver operating characteristic curve, and the mediation effect analysis were used to investigate the association between liver fibrosis degree and CP. ResultsThe prevalence rate of CP was 36.6% in the lean MAFLD population. Compared with the non-CP group(n=607), the CP group (n=350) had a significantly higher proportion of male patients, a significantly higher proportion of patients with smoking/diabetes/hypertension, and significantly higher levels of age, creatinine, blood urea nitrogen, triglycerides, fasting blood glucose, aspartate aminotransferase, aspartate aminotransferase/alanine aminotransferase ratio, NFS, and FIB-4 index, as well as significantly lower levels of platelet count and albumin (all P<0.05). The multivariate logistic regression analysis showed that after adjustment for confounding factors, FIB-4 index (odds ratio[OR]=2.979, 95% confidence interval[CI]:2.141 — 4.219, P<0.001) and NFS (OR=1.747, 95%CI: 1.499 — 2.046, P<0.001) were positively correlated with CP. Both FIB-4 index and NFS had a good value in predicting CP. Hypertension had a significant indirect effect on the prevalence rate of CP through its impact on liver fibrosis markers, and its mediating effect accounted for 39.5% — 40.8% of the total effect (P<0.001). ConclusionIn patients with lean MAFLD, NFS and FIB-4 index are significantly positively correlated with the prevalence rate of CP, and they can be used as potential epidemiological predictive indicators. Liver fibrosis markers may play a mediating role in the association between hypertension and CP. Interventions targeting hypertension and liver fibrosis markers may help to prevent and delay the progression of CP.
8.Effect of mesaconate combined with LR on prolonging the golden treatment time window and its resuscitation efficacy for hemorrhagic shock rats under high-altitude conditions
Yuanqun ZHOU ; Xinming XIANG ; Xingnan OUYANG ; Jie ZHANG ; Qinghui LI ; Liangming LIU ; Tao LI
China Pharmacy 2026;37(6):720-726
OBJECTIVE To observe the effects of endogenous metabolite mesaconate combined with Sodium lactate Ringer’s injection (LR) on prolonging the golden treatment time window and its resuscitation efficacy in rats with hemorrhagic shock under high-altitude conditions. METHODS Rats were divided into the shock group, LR group, and 5, 20, 50 mg/kg mesaconate+LR groups, with 20 rats in each group, to investigate the effect of additional use of mesaconate on the golden treatment time window. After establishing a model of uncontrolled hemorrhagic shock under high-altitude conditions in all groups by housing in a hypobaric hypoxia chamber combined with splenic artery transection, rats in the shock group received no resuscitation, while rats in the LR group and mesaconate+LR groups underwent low-pressure resuscitation with LR or mesaconate combined with LR. Blood pressure control, fluid infusion volume, blood loss rate and survival status were observed in each group. Rats were further divided into the normal group, shock group and mesaconate (50 mg/kg)+LR group, with 10 or 20 rats in each group, to evaluate the resuscitation effects after extending the golden treatment time window by additionally using mesaconate. Except for the normal group, the other groups underwent the same procedure to establish an uncontrolled hemorrhagic shock model under high-altitude conditions. Rats in the shock group received no resuscitation. In the mesaconate+LR group, after 3 h of low-pressure resuscitation, bleeding control was performed by ligation of the spleen artery, and the infusion volume and blood loss rate were recorded; subsequently, the rats received LR resuscitation with twice the volume of blood loss. Then, blood gas indicators of the mesaconate+LR group were measured at different time points. Survival rates, indicators related to sublingual microcirculatory perfusion, liver and kidney blood flow, indicators related to the function of vital organs, and lung and brain water content were observed in all groups. RESULTS LR infusion alone could effectively maintain mean arterial pressure (MAP) within 50-60 mmHg for approximately 1 h. The administration of mesaconate combined with LR during hypotensive resuscitation could maintain MAP within 50-60 mmHg for over 3 h, with significantly reduced fluid infusion volume and blood loss rate in 50 mg/kg mesaconate+LR group, compared to the LR group ( P <0.05). In the LR group, rats maintained low pressure for up to 1 hour with a survival rate of 52.94%, and no rats survived beyond 2 h. In the 5, 20 and 50 mg/kg mesaconate+LR groups, rats maintained low pressure for up to 1 h with a survival rate exceeding 80%; in the 20 and 50 mg/kg mesaconate+LR groups, rats maintained low pressure for up to 3 h with a survival rate exceeding 70%. After complete resuscitation with mesaconate combined with LR, the 72 h survival rate of rats was 43.75%, and significant improvements in blood gas parameters were observed compared to the end of the shock phase ( P <0.05). Compared to the shock group, the mesaconate+LR group showed significant recovery in sublingual microcirculatory indicators, and liver/kidney blood flow after complete resuscitation ( P <0.05), with significant reductions in heart, liver and kidney function-related indicators and lung water content ( P <0.05). CONCLUSIONS Mesaconate combined with LR significantly extends the golden treatment time window for hemorrhagic shock in rats under high-altitude conditions, improves blood gas parameters, sublingual microcirculatory perfusion, and liver/kidney blood flow, mitigates vital organ impairment and pulmonary edema, and increases the survival rate of shocked rats.
9.Zuogui Jiangtang Shuxin Prescription Ameliorates Lipid Deposition in Diabetic Cardiomyopathy of MKR Mice by Regulating AMPK/FoxO1/CD36 Signaling Pathway
Xiu LIU ; Juping WANG ; Jiawang HUANG ; Junju ZOU ; Qin XIANG ; Yunfeng YU ; Rong YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):134-142
ObjectiveTo investigate the ameliorative effects and related mechanisms of the Zuogui Jiangtang Shuxin prescription (ZJSP) on glucose and lipid metabolism disorders in MKR mice with diabetic cardiomyopathy (DCM), with a focus on elucidating its regulatory role on the adenosine monophosphate-activated protein kinase (AMPK)/forkhead box protein O1 (FoxO1)/cluster of differentiation 36 (CD36) signaling pathway and lipid deposition. MethodsFifty 8-week-old male MKR mice were fed a high-fat diet for four weeks and then intraperitoneally injected with streptozotocin (STZ) while maintaining a high-fat diet to establish a DCM model. The mice were randomly divided into the model group, the low-dose(14.43 g·kg-1)and high-dose(28.86 g·kg-1) ZJSP groups, and the metformin group (0.25 g·kg-1), with age-matched FVB mice as a normal control group. Each group received intragastric administration of normal saline or corresponding concentrations of ZJSP at equal volumes. After four weeks, fasting blood glucose (FBG) and cardiac function were measured. Blood was collected from the eyeballs under anesthesia to detect fasting insulin (FINS) and blood lipid levels. Myocardial tissue morphology was observed by hematoxylin-eosin (HE) staining, and lipid deposition in the heart was assessed using oil red O staining. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to measure the mRNA expression levels of AMPK, FoxO1, and CD36 in myocardial tissues. Western blot was employed to detect the protein expression levels of AMPK, p-AMPK, FoxO1, p-FoxO1, and CD36. ResultsCompared with the control group, the model group showed significantly increased levels of FBG and FINS (P<0.01), elevated levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) (P<0.01), and significantly decreased left ventricular ejection fraction (EF) and fractional shortening (FS) values (P<0.01). HE staining revealed marked cardiomyocyte hypertrophy, disarray, and widened intercellular spaces in myocardial tissues. Oil Red O staining showed extensive red deposition areas and fine lipid droplet accumulation in the myocardial tissue. AMPK mRNA expression was decreased, while FoxO1 and CD36 mRNA expressions were significantly increased (P<0.01). The p-AMPK/AMPK protein expression ratio in myocardial tissues was significantly reduced, while the p-FoxO1/FoxO1 protein expression ratio and CD36 protein expression levels were significantly increased (P<0.01). Compared with the model group, all treatment groups exhibited significantly reduced FBG (P<0.01), decreased FINS and blood lipid levels (TG, TC, LDL-C) (P<0.05, P<0.01), improved cardiac function (P<0.05), noticeable amelioration of myocardial histopathological morphology and lipid deposition, increased AMPK mRNA expression (P<0.01), with significantly downregulated FoxO1 and CD36 mRNA expressions (P<0.01), elevated p-AMPK/AMPK protein expression levels in myocardial tissue (P<0.05), significantly decreased p-FoxO1/FoxO1 ratios (P<0.01), and downregulated CD36 protein expression levels (P<0.05, P<0.01). ConclusionZJSP exerts a protective effect on the heart in type 2 DCM of MKR mice, and its mechanism may be associated with the regulation of the AMPK/FoxO1/CD36 signaling pathway.
10.Zuogui Jiangtang Shuxin Prescription Ameliorates Lipid Deposition in Diabetic Cardiomyopathy of MKR Mice by Regulating AMPK/FoxO1/CD36 Signaling Pathway
Xiu LIU ; Juping WANG ; Jiawang HUANG ; Junju ZOU ; Qin XIANG ; Yunfeng YU ; Rong YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):134-142
ObjectiveTo investigate the ameliorative effects and related mechanisms of the Zuogui Jiangtang Shuxin prescription (ZJSP) on glucose and lipid metabolism disorders in MKR mice with diabetic cardiomyopathy (DCM), with a focus on elucidating its regulatory role on the adenosine monophosphate-activated protein kinase (AMPK)/forkhead box protein O1 (FoxO1)/cluster of differentiation 36 (CD36) signaling pathway and lipid deposition. MethodsFifty 8-week-old male MKR mice were fed a high-fat diet for four weeks and then intraperitoneally injected with streptozotocin (STZ) while maintaining a high-fat diet to establish a DCM model. The mice were randomly divided into the model group, the low-dose(14.43 g·kg-1)and high-dose(28.86 g·kg-1) ZJSP groups, and the metformin group (0.25 g·kg-1), with age-matched FVB mice as a normal control group. Each group received intragastric administration of normal saline or corresponding concentrations of ZJSP at equal volumes. After four weeks, fasting blood glucose (FBG) and cardiac function were measured. Blood was collected from the eyeballs under anesthesia to detect fasting insulin (FINS) and blood lipid levels. Myocardial tissue morphology was observed by hematoxylin-eosin (HE) staining, and lipid deposition in the heart was assessed using oil red O staining. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to measure the mRNA expression levels of AMPK, FoxO1, and CD36 in myocardial tissues. Western blot was employed to detect the protein expression levels of AMPK, p-AMPK, FoxO1, p-FoxO1, and CD36. ResultsCompared with the control group, the model group showed significantly increased levels of FBG and FINS (P<0.01), elevated levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) (P<0.01), and significantly decreased left ventricular ejection fraction (EF) and fractional shortening (FS) values (P<0.01). HE staining revealed marked cardiomyocyte hypertrophy, disarray, and widened intercellular spaces in myocardial tissues. Oil Red O staining showed extensive red deposition areas and fine lipid droplet accumulation in the myocardial tissue. AMPK mRNA expression was decreased, while FoxO1 and CD36 mRNA expressions were significantly increased (P<0.01). The p-AMPK/AMPK protein expression ratio in myocardial tissues was significantly reduced, while the p-FoxO1/FoxO1 protein expression ratio and CD36 protein expression levels were significantly increased (P<0.01). Compared with the model group, all treatment groups exhibited significantly reduced FBG (P<0.01), decreased FINS and blood lipid levels (TG, TC, LDL-C) (P<0.05, P<0.01), improved cardiac function (P<0.05), noticeable amelioration of myocardial histopathological morphology and lipid deposition, increased AMPK mRNA expression (P<0.01), with significantly downregulated FoxO1 and CD36 mRNA expressions (P<0.01), elevated p-AMPK/AMPK protein expression levels in myocardial tissue (P<0.05), significantly decreased p-FoxO1/FoxO1 ratios (P<0.01), and downregulated CD36 protein expression levels (P<0.05, P<0.01). ConclusionZJSP exerts a protective effect on the heart in type 2 DCM of MKR mice, and its mechanism may be associated with the regulation of the AMPK/FoxO1/CD36 signaling pathway.

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