1.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.
2.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.
3.Visualization Analysis on Research Literature about Astragalus Polysaccharides from 2013 to 2023
Hong LI ; Liu LI ; Qiuqing HUANG ; Shiyao YANG ; Junju ZOU ; Fan XIAO ; Qin XIANG ; Xiu LIU ; Yanling FU ; Yongjun WU ; Rong YU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(6):73-79
Objective To analyze the research status and hotspots in the field of astragalus polysaccharides;To provide references for further research.Methods Research literature about astragalus polysaccharides was retrieved from CNKI,Wanfang Data,VIP,PubMed,and Web of Science databases from 1st,Jan.2013 to 1st,July 2023.NoteExpress 3.7 software was used to manage the literature and ultimately establish a database.Excel 2019,CiteSpace 6.2.2R and VOSviewer 1.6.18 were used to visually analyze the publication volume,authors,institutions,and keywords of the included literature.Results A total of 2 462 articles were included,with 1 284 Chinese articles and 1 178 English articles.The main research institutions were Gansu University of Chinese Medicine,Shandong University of Traditional Chinese Medicine,and Beijing University of Chinese Medicine.The core authors of Chinese literature were Liu Yongqi,Wang Hongxin,Lu Meili,etc.The core authors of English literature included Zhang Wei,Li Ke,Yang Xiaojun,etc.High-frequency keywords of Chinese literature included Astragali Radix,rats,polysaccharides,cell apoptosis,and oxidative stress,etc.High frequency keywords in English literature included expression,in vitro,oxidative stress,apoptosis,etc.Conclusion The research on astragalus polysaccharides focuses on their pharmacological effects and mechanisms.Intestinal flora,immune regulation,autophagy and apoptosis are the hot action mechanisms in this field.The focus of disease research involves tumor and diabetes,and antiviral,anti infection and other pharmacological effects are the research trend.
4.Mechanism of Chaijin Jieyu Anshen Formula in regulating synaptic damage in nucleus accumbens neurons of rats with insomnia complicated with depression through TREM2/C1q axis.
Ying-Juan TANG ; Jia-Cheng DAI ; Song YANG ; Xiao-Shi YU ; Yao ZHANG ; Hai-Long SU ; Zhi-Yuan LIU ; Zi-Xuan XIANG ; Jun-Cheng LIU ; Hai-Xia HE ; Jian LIU ; Yuan-Shan HAN ; Yu-Hong WANG ; Man-Shu ZOU
China Journal of Chinese Materia Medica 2025;50(16):4538-4545
This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals
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Male
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Rats
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Nucleus Accumbens/metabolism*
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Drugs, Chinese Herbal/administration & dosage*
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Depression/complications*
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Membrane Glycoproteins/genetics*
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Rats, Sprague-Dawley
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Sleep Initiation and Maintenance Disorders/complications*
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Neurons/metabolism*
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Receptors, Immunologic/genetics*
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Signal Transduction/drug effects*
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Synapses/metabolism*
5.Analysis on the disease burden trend and attributable risk factors of common gynecological cancers in China from 1990 to 2021
Xiao-hui ZHOU ; Yi-xin ZOU ; Zhuo-ying LI ; Yu-xuan XIAO ; Dan-dan TANG ; Yu-xin ZHOU ; Pei-wen LU ; Qun XU ; Yong-bing XIANG
Fudan University Journal of Medical Sciences 2025;52(6):783-793
Objective To describe and analyze the current status,changing trend and influencing factors of the disease burden of cervical,endometrial and ovarian cancer in China from 1990 to 2021.Methods Data on incidence,mortality,disability-adjusted life year(DALY),and other indicators for cervical,endometrial and ovarian cancer were collected from the 2021 Global Burden of Disease database.Joinpoint regression models were used to analyze time trends,and age-period-cohort(APC)models assessed their impact on incidence and mortality.Spearman correlation analysis was performed to evaluate the relationship between the sociodemographic index(SDI)and the cancer indicators.Finally,the attributable risk factors for the disease burden were analyzed.Results From 1990 to 2021,age-standardized incidence rates of cervical and endometrial cancers in China significantly increased,while ovarian cancer showed no significant change.Age-standardized mortality,DALY,and years of life lost due to premature death(YLL)decreased significantly.The disease burden was heavier in middle-aged and older groups.APC model indicated an increase in cervical cancer incidence and a decrease in mortality over time.Furthermore,the incidence risks of cervical and endometrial cancers were elevated in successive birth cohorts,whereas a lower risk was observed for ovarian cancer.Correlation analysis showed significant associations between cancer incidence and mortality with SDI.Obesity has significantly contributed to the disease burden of common gynecologic cancers in China.Conclusion Mortality rates of cervical,endometrial and ovarian cancer have declined,while the incidence of cervical and endometrial cancers has significantly increased.The trends in incidence and mortality are influenced by age,period and cohort effects.Future efforts should focus on controlling risk factors like obesity to reduce the disease burden.
6.Analysis on the disease burden trend and attributable risk factors of common gynecological cancers in China from 1990 to 2021
Xiao-hui ZHOU ; Yi-xin ZOU ; Zhuo-ying LI ; Yu-xuan XIAO ; Dan-dan TANG ; Yu-xin ZHOU ; Pei-wen LU ; Qun XU ; Yong-bing XIANG
Fudan University Journal of Medical Sciences 2025;52(6):783-793
Objective To describe and analyze the current status,changing trend and influencing factors of the disease burden of cervical,endometrial and ovarian cancer in China from 1990 to 2021.Methods Data on incidence,mortality,disability-adjusted life year(DALY),and other indicators for cervical,endometrial and ovarian cancer were collected from the 2021 Global Burden of Disease database.Joinpoint regression models were used to analyze time trends,and age-period-cohort(APC)models assessed their impact on incidence and mortality.Spearman correlation analysis was performed to evaluate the relationship between the sociodemographic index(SDI)and the cancer indicators.Finally,the attributable risk factors for the disease burden were analyzed.Results From 1990 to 2021,age-standardized incidence rates of cervical and endometrial cancers in China significantly increased,while ovarian cancer showed no significant change.Age-standardized mortality,DALY,and years of life lost due to premature death(YLL)decreased significantly.The disease burden was heavier in middle-aged and older groups.APC model indicated an increase in cervical cancer incidence and a decrease in mortality over time.Furthermore,the incidence risks of cervical and endometrial cancers were elevated in successive birth cohorts,whereas a lower risk was observed for ovarian cancer.Correlation analysis showed significant associations between cancer incidence and mortality with SDI.Obesity has significantly contributed to the disease burden of common gynecologic cancers in China.Conclusion Mortality rates of cervical,endometrial and ovarian cancer have declined,while the incidence of cervical and endometrial cancers has significantly increased.The trends in incidence and mortality are influenced by age,period and cohort effects.Future efforts should focus on controlling risk factors like obesity to reduce the disease burden.
7.Visualization Analysis on Research Literature about Astragalus Polysaccharides from 2013 to 2023
Hong LI ; Liu LI ; Qiuqing HUANG ; Shiyao YANG ; Junju ZOU ; Fan XIAO ; Qin XIANG ; Xiu LIU ; Yanling FU ; Yongjun WU ; Rong YU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(6):73-79
Objective To analyze the research status and hotspots in the field of astragalus polysaccharides;To provide references for further research.Methods Research literature about astragalus polysaccharides was retrieved from CNKI,Wanfang Data,VIP,PubMed,and Web of Science databases from 1st,Jan.2013 to 1st,July 2023.NoteExpress 3.7 software was used to manage the literature and ultimately establish a database.Excel 2019,CiteSpace 6.2.2R and VOSviewer 1.6.18 were used to visually analyze the publication volume,authors,institutions,and keywords of the included literature.Results A total of 2 462 articles were included,with 1 284 Chinese articles and 1 178 English articles.The main research institutions were Gansu University of Chinese Medicine,Shandong University of Traditional Chinese Medicine,and Beijing University of Chinese Medicine.The core authors of Chinese literature were Liu Yongqi,Wang Hongxin,Lu Meili,etc.The core authors of English literature included Zhang Wei,Li Ke,Yang Xiaojun,etc.High-frequency keywords of Chinese literature included Astragali Radix,rats,polysaccharides,cell apoptosis,and oxidative stress,etc.High frequency keywords in English literature included expression,in vitro,oxidative stress,apoptosis,etc.Conclusion The research on astragalus polysaccharides focuses on their pharmacological effects and mechanisms.Intestinal flora,immune regulation,autophagy and apoptosis are the hot action mechanisms in this field.The focus of disease research involves tumor and diabetes,and antiviral,anti infection and other pharmacological effects are the research trend.
8.Associations between the diet-related inflammation indices and digestive system cancer:a narrative review of epidemiological studies
Jing-Yu TAN ; Yan ZHANG ; Jun CHEN ; Dan-Ni YANG ; Yi-Xin ZOU ; Wan-Shui YANG ; Yong-Bing XIANG
Fudan University Journal of Medical Sciences 2024;51(3):404-414
The inflammatory effect of dietary is strongly related to the development of cancer,therefore,the diet-related inflammatory index was developed as a methodological tool to investigate the relationship between dietary,inflammation and tumors.In this paper,we summarized the results on diet-related inflammatory indices and common cancers of the digestive system based on relevant cancer epidemiological studies.The available epidemiological evidence suggests that pro-inflammatory diet is associated with an increased risk of gastrointestinal malignancies,with the strongest association with colorectal cancer,followed by esophageal and gastric cancers,and then pancreatic cancer,and the least evidence of studies with liver cancer.Among these studies,the level of evidence for esophageal cancer is lower than colorectal cancer,the study of gastric cancer has gender differences and problems in adjusting for confounders,and the study of pancreatic cancer has heterogeneous results.In view of the current research progress and deficiencies,prospective studies or population-based cohort studies,as well as strengthening nutritional epidemiological studies related to common tumors such as liver cancer could be considered in the future.This review is expecting to provide basic information and scientific basis for strengthening the related healthy eating behavior promotion in the prevention and control of digestive system tumors.
9.Fully-automatic brain tumor segmentation based on effective receptive field and attention fusion mechanism
Xiang ZOU ; Yu WANG ; Hongbing XIAO ; Di YANG
Chinese Journal of Medical Physics 2024;41(5):563-570
Despite significant achievements of deep learning in medical image segmentation,there are challenges for brain tumor segmentation using deep learning,such as insufficient receptive field,excessive redundant information,and information loss.To address these issues,a novel brain tumor segmentation network model(EAU-Net)is proposed based on encoder-decoder structure.EAU-Net incorporates an effective receptive field expansion block and an attention fusion module to minimize the adverse effects caused by insufficient receptive field and excessive redundant information which often occurred in the current brain tumor segmentation network.Additionally,a bottleneck resampling module based on inverted residual structure is introduced to effectively avoid information loss during upsampling and downsampling,while deep convolutions are used to reduce computational complexity.Experimental results on the BraTS2020 dataset reveal that EAU-Net achieves the highest segmentation accuracy,demonstrating its feasibility and effectiveness for brain tumor segmentation.
10.Efficacy and safety of whole-brain low-dose radiotherapy combined with ICI and intrathecal chemotherapy for leptomeningeal metastases from lung cancer
Xiang LISHA ; Zhang XUANWEI ; Yu MIN ; Xiu WEIGANG ; Zou BINGWEN ; Xu YONG ; Liu YONGMEI ; Zhou LIN ; Xue JIANXIN ; Lu YOU
Chinese Journal of Clinical Oncology 2024;51(18):943-949
Objective:To explore the efficacy and safety of whole-brain low-dose radiotherapy(LDRT)combined with PD-1 inhibitor sin-tilimab and intrathecal pemetrexed(IP)for the treatment of refractory non-small cell lung cancer(NSCLC)with leptomeningeal metastases(LM).Methods:Retrospective analysies were was performed on eight NSCLC patients with LM at the West China Hospital of Sichuan Uni-versity from December 2022 to May 2024.Among the eight patients,there were four were males and four were females,with a median age of 49 years(rangeing,between 34 to 58 years).All patients were treated with whole-brain LDRT combined with immune checkpoint inhibit-or(ICI)and intrathecal chemotherapy regimens,and the therapeutic efficacy was evaluated according to the Response Assessment in Neuro-Oncology(RANO)criteria and the Karnofsky physical status(KPS)score.Adverse reactions were assessed according to the Common Criteria for the Evaluation of Adverse Events(CTCAE version 5.0).Survival analysis was performed using the Kaplan-Meier method.The classification proportion of cerebrospinal fluid subsets before and after treatment was analyzed using by single-cell sequencing,and the differential ana-lysis of gene expression in parallel cells was performed.Results:The best clinical treatment effects in eight patients were were evaluated us-ing the RANO criteria:five patients(62.5%)were evaluated as improved and three(37.5%)as stable.The median KPS score of the eight pa-tients was 30(20-50)before treatment,which was significantly improved to 60(40-90)after treatment(P=0.000 9).The remission rate of neurological symptoms was 100%(8/8)in eight patients.The median neurological progression-free survival(NPFS)was 12 months.The res-ults of single-cell sequencing in CSF of patientss(P1)showed that the proportion of T cells in the patient samples after whole-brain LDRT treatment was significantly higher than that before treatment(6.08%vs.68.87%),and the proportion of tumor cells was significantly lower(12.92%vs.0.6%).The differential analysis of gene expression showed that CCL5 and CXCL13 were significantly upregulated in T cells of CSF after WB-LDRT treatment.Conclusions:The combination of whole-brain LDRT with ICI and IP in the treatment of NSCLC with LM can signific-antly alleviate neurological symptoms,improve quality of life and prolong the NPFS of patients,which is a safe and effective treatment.

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