1.Correlation Between Traditional Chinese Medicine Syndrome Type of Unstable Angina Pectoris and Iron Metabolism Indices
Jiye CHEN ; Min WU ; Changxin SUN ; Xiaonan ZHANG ; Zeping WANG ; Longtao LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):126-136
ObjectiveTo investigate the correlation between iron metabolism parameters and various syndrome types of unstable angina pectoris (UAP). MethodsA cross-sectional study was conducted from October 2021 to October 2023, encompassing 213 patients diagnosed with UAP at Xiyuan Hospital of Chinese Academy of Chinese Medical Sciences. Additionally, 30 healthy individuals were selected as control cases. Single-factor analysis was used to investigate the differences in clinical data among different Traditional Chinese Medicine (TCM) syndrome types of UAP and their correlation with iron metabolism indices. The study conducted a comparative analysis of the aforementioned clinical data among patients with and without heat-toxic and blood-stasis syndrome. Logistic regression was used to analyze the correlation between TCM syndrome types and related factors. The receiver operator characteristic (ROC) curve was employed to assess the predictive value of iron metabolism indices, along with their sensitivity and specificity. ResultsCompared to those in the control group, serum iron (SI) and serum ferritin (SF) levels were significantly increased in the UAP group (P<0.01), while transferrin (TRF) and total iron binding capacity (TIBC) levels were decreased (P<0.01). However, there was no significant difference in unsaturated iron binding capacity (UIBC). Multivariate binary Logistic regression analysis identified apolipoprotein A1 (ApoA1), homocysteine (HCY), high-sensitivity C-reactive protein (hs-CRP), and SF as independent influencing factors for the UAP patients (P<0.05, P<0.01). Additionally, statistically significant differences were observed in SI, SF, TRF, and TIBC among 213 patients with different TCM types (P<0.01). Patients with heat-toxic and blood-stasis syndrome had higher SI and SF values than those without the syndrome (P<0.01), while their TIBC and TRF values were lower (P<0.01). Multivariate binary logistic regression analysis showed that SI and LDL-C levels were closely associated with the differentiation of heat-toxic and blood-stasis syndrome. ConclusionUAP patients often experience iron metabolism disorders, and the heat-toxic and blood-stasis syndrome are significantly correlated with iron metabolism parameters. The SI and LDL-C levels have high specificity and sensitivity in diagnosing heat-toxic and blood-stasis syndrome.
2.Taxifolin attenuates liver fibrosis by regulating the phosphorylation of NDRG1 at Thr328 via hepatocyte-stellate cell cross talk.
Chuan DING ; Zeping WANG ; Kao SHI ; Sunan LI ; Xinyue DOU ; Yan NING ; Gang CHENG ; Qiao YANG ; Xianan SANG ; Mengyun PENG ; Qiang LYU ; Lu WANG ; Xin HAN ; Gang CAO
Acta Pharmaceutica Sinica B 2025;15(4):2059-2076
Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) in vivo and in vitro, demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) in vivo and in vitro confirmed that pNDRG1T328 exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1T328 in hepatocytes.
3.A high-throughput plant canopy leaf area index inversion model based on UAV-LiDAR.
Yuming LIANG ; Xueyan FAN ; Muqing ZHANG ; Wei YAO ; Xiuhua LI ; Zeping WANG ; Sifan DONG ; Xuechen LI
Chinese Journal of Biotechnology 2025;41(10):3817-3827
To explore the feasibility of using UAV-LiDAR for measuring the leaf area index (LAI) of crop canopies, we employed UAV-LiDAR to scan sugarcane canopies during the tillering and elongation stages, acquiring canopy point cloud data. Subsequently, features such as average row height, projected row area, point cloud density at different canopy layers, and the ratios between these parameters were extracted. Three feature selection methods-partial least squares regression (PLSR), XGBoost feature importance (XGBoost-FI), and random forest-recursive feature elimination (RF-RFE)-were adopted to evaluate and identify the optimal input variables for modeling. With these selected variables, LAI inversion models were developed based on random forest (RF) and adaptive boosting (AdaBoost) algorithms, and their performance was assessed. Among the extracted features, the projected row area Sp and the total row point count Ctotal exhibited strong correlations with LAI, with correlation coefficients of 0.73 and 0.72, respectively. The AdaBoost-based LAI inversion model, using the projected row area Sp, average height Havg, mid-layer point cloud density Cm, and total row point count Ctotal as input variables, achieved the best performance, with a coefficient of determination (Rv²) of 0.713 and a root mean square error (RMSEv) of 0.25 on the validation set. This study provides an effective method for high-throughput acquisition of LAI in field crops, offering valuable scientific support for sugarcane field management and breeding efforts.
Plant Leaves/growth & development*
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Saccharum/growth & development*
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Algorithms
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Unmanned Aerial Devices
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Remote Sensing Technology/methods*
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Crops, Agricultural/growth & development*
4.An intelligent recognition method for crop density based on Faster R-CNN.
Xiuhua LI ; Qian LI ; Hanwen ZHANG ; Lu DING ; Zeping WANG
Chinese Journal of Biotechnology 2025;41(10):3828-3839
Accurately obtaining the crop quantity and density is not only crucial for the demand-based input of water and fertilizer in the field but also vital for ensuring the yield and quality of crops. Aerial photography by unmanned aerial vehicles (UAVs) can quickly acquire the distribution image information of crops over a large area. However, the accurate recognition of a single type of dense targets is a huge challenge for most recognition algorithms. Taking banana seedlings as an example in this study, we captured the images of banana plantations by UAVs from high altitudes to explore an efficient recognition method for dense targets. We proposed a strategy of "cut-recognition-stitch" and constructed a counting method based on the improved Faster R-CNN algorithm. First, the images containing highly dense targets were cropped into a large number of image tiles according to different sizes (simulating different flight altitudes), and the Contrast Limited Adaptive Histogram Equalization (CLAHE) algorithm was adopted to improve the image quality. A banana seedling dataset containing 36 000 image tiles was constructed. Then, the Faster R-CNN network with optimized parameters was used to train the banana seedling recognition model. Finally, the recognition results were reversely stitched together, and a boundary deduplication algorithm was designed to correct the final counting results to reduce the repeated recognition caused by image cropping. The results show that the recognition accuracy of the Faster R-CNN with optimized parameters for banana image datasets of different sizes can reach up to 0.99 at most. The deduplication algorithm can reduce the average counting error for the original aerial images from 1.60% to 0.60%, and the average counting accuracy of banana seedlings reaches 99.4%. The proposed method effectively addresses the challenge of recognizing dense small objects in high-resolution aerial images, providing an efficient and reliable technical solution for intelligent crop density monitoring in precision agriculture.
Musa/growth & development*
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Crops, Agricultural/growth & development*
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Algorithms
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Neural Networks, Computer
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Unmanned Aerial Devices
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Seedlings/growth & development*
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Image Processing, Computer-Assisted/methods*
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Photography
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Agriculture/methods*
5.Effect of Danhe Granules on Hypercholesterolemia Rats Based on Cholesterol Metabolism Pathway-related Proteins
Shiqiu TIAN ; Zeping ZUO ; Yingying TIAN ; Yilin LI ; Hailuan PEI ; Zhaozhou LIN ; Yingnan LYU ; Jianfang WANG ; Zhibin WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):85-94
ObjectiveTo explore the therapeutic effect and mechanism of the Danhe granules on hypercholesterolemia rats by observing the changes in the efficacy indicators and the levels of proteins related to the cholesterol metabolism pathway in the rats under the intervention of Danhe granules. MethodSD rats were randomly assigned to either the blank group or the model group based on their body weight. The blank group had normal chow diets, while the model group was fed high-fat diets for seven weeks. One week after the establishment of the model, the content of the serum total cholesterol (TC) in the model rats was detected. According to the TC value, the model group was further randomly divided into a control group, pravastatin sodium tablet group(4.02 mg·kg-1), Xuezhikang capsule group(0.12 g·kg-1), high-dose, middle-dose, and low-dose groups of Danhe granules(4.536, 2.268, 1.134 g·kg-1). After grouping the model groups, each treatment group received continuous oral gavage for six weeks, with weekly measurements of body weight and food intake (the difference between feed intake and feed surplus). Six weeks later, the levels of serum TC, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured. The liver pathology and lipid droplet distribution were evaluated by hematoxylin-eosin (HE) staining and oil red O staining, with scoring and calculation conducted. Rat liver tissue was collected, and western blot and immunohistochemistry (IHC) were used to detect the expression levels of cholesterol metabolism-related proteins namely phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK), AMPK, 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR), low-density lipoprotein receptor (LDLR), cholesterol 7α-hydroxylase (CYP7A1), Acyl-coenzyme A: cholesterol acyltransferase 2 (ACAT2), and apolipoprotein B (ApoB) in hypercholesterolemia rats. ResultCompared with the blank group, the model group showed a significantly higher level of serum TC (P<0.01). The TG level had no significant change, and the HDL-C level was significantly decreased (P<0.05). The liver index, steatosis score, total score of pathological state, and the positive area ratio of oil red O staining were significantly increased (P<0.01), and the protein expression levels of p-AMPK, p-AMPK/AMPK, LDLR, and CYP7A1 were significantly decreased (P<0.05, P<0.01), while the protein expression levels of AMPK, HMGCR, and ACAT2 were significantly increased (P<0.05, P<0.01). Compared with the model group, the TC level in each dose group of Danhe granules was significantly decreased (P<0.05), and the positive area ratio of oil red O staining in the pravastatin sodium tablet group and medium-dose group of Danhe granules was significantly decreased (P<0.05). In each administration group, the protein expression levels of p-AMPK and p-AMPK/AMPK were significantly increased (P<0.05, P<0.01), and the levels of HMGCR and ACAT2 were significantly decreased (P<0.01). The ApoB level showed a downward trend. The CYP7A1 level in the pravastatin sodium tablet group and each dose group of Danhe granules was significantly increased (P<0.05, P<0.01), and the LDLR level in the pravastatin sodium tablet group, Xuezhikang capsule group, and high-dose and medium-dose groups of Danhe granules was significantly increased (P<0.05, P<0.01). ConclusionDanhe granules can reduce serum TC levels and improve hepatic steatosis. It may activate AMPK, down-regulate the expression of HMGCR, and inhibit cholesterol synthesis. It can also up-regulate the expression of LDLR and CYP7A1, promote cholesterol uptake and excretion, down-regulate the expression of ACAT2 and ApoB, reduce cholesterol absorption and assembly of LDL and other lipoproteins, and thus play a role in the treatment of hypercholesterolemia.
6.Exploration of the Mechanism of Autophagy Induced by Morin in Non-small Cell Lung Cancer A549 Cells Based on mTOR/STAT3 Signaling Axis
Xinyue ZHAO ; Yingying TIAN ; Chuang LIU ; Yilin LI ; Yingnan LYU ; Shangyue YU ; Shiqiu TIAN ; Hailuan PEI ; Zeping ZUO ; Zhibin WANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(3):317-324
Objective To investigate the mechanism of morin-induced autophagy in non-small cell lung cancer A549 cells based on mTOR/STAT3 signaling axis.Methods A549 cells were divided into blank group and 30,60,90,120 and 150 μg·mL-1 of morin groups.After 24,48 and 72 hours of culture,the cell proliferation activity was detected by CCK-8 method,and the cell inhibition rate was calculated.A549 cells were divided into blank group and 30,90,150 μg·mL-1 morin groups.After 14 days of culture,the cell proliferation was detected by colony formation assay.After 24 hours of culture,the cell proliferation ability was detected by BeyoClickTM EdU-488.Apoptosis was detected by flow cytometry;acridine orange staining was used to detect cell autophagy;the formation of autophagosomes was observed by transmission electron microscopy.Western Blot was used to detect the expression levels of apoptosis,autophagy and mTOR/STAT3 signaling axis-related proteins in cells.A549 cells were divided into blank group,blank group + chloroquine(10 μg·mL-1)group,morin(30,150 μg·mL-1)group,morin(30,150 μg·mL-1)+ chloroquine(10 μg·mL-1)group.After 48 hours of intervention,the cell activity was detected by CCK-8 method,and the cell survival rate was calculated.Results Compared with the blank group,the inhibition rate of A549 cells in 60,90,120,150 μ g·mL-1 of morin group was significantly increased after 24 hours of intervention(P<0.05,P<0.001).The inhibition rates of A549 cells in 30,60,90,120 and 150 μg·mL-1 of morin groups were significantly increased after 48 and 72 hours of intervention(P<0.001).The number of A549 cell colonies and the number of green fluorescent proliferation positive cells in the 30,90,150 μg·mL-1 of morin groups were significantly decreased(P<0.01,P<0.001),the apoptosis rate was significantly increased(P<0.01,P<0.001),and the protein expression level of cleaved-PARP was significantly increased(P<0.001).The protein expression levels of p-P38/P38 MAPK in A549 cells of 90 and 150 μg·mL-1 of morin groups were significantly increased(P<0.01,P<0.001).Different degrees of orange fluorescence appeared in A549 cells of 30,90 and 150 μg·mL-1 of morin groups,and the orange fluorescence of 90 and 150 μg·mL-1 of morin groups was significant.Autophagosomes and autolysosomes appeared in the cytoplasm of A549 cells in 150 μg·mL-1 of morin group,respectively.The protein expression of LC3-Ⅱ in A549 cells of 150 μg·mL-1 of morin group was significantly up-regulated(P<0.05).The protein expression of Atg16L1-Ⅱ in A549 cells of 90,150 μg·mL-1 of morin group was significantly up-regulated(P<0.001),and the protein expressions of p-mTOR/mTOR and p-STAT3/STAT3 were significantly down-regulated(P<0.001).Compared with the morin(150 μg·mL-1)group,the survival rate of A549 cells in the morin(150 μg·mL-1)+chloroquine(10 μg·mL-1)group was significantly increased(P<0.05).Conclusion Morin can promote the apoptosis of A549 cells and induce autophagy in A549 cells,and the mechanism may be related to mTOR/STAT3 axis.
7.Cognitive frailty in older patients with chronic heart failure and its influencing factors
Jian LIU ; Fen WANG ; Zeping YAN ; Jiurui WANG ; Zhiwei WANG ; Qian LIANG ; Xiaorong LUAN
Chinese Journal of Geriatrics 2024;43(2):228-233
Objective:To investigate the characteristics of cognitive frailty and its influencing factors in older patients with chronic heart failure.Methods:In this cross-sectional study, 300 older patients hospitalized for chronic heart failure in a tertiary hospital in Shandong Province between September 2021 and September 2022 were selected.A general information questionnaire, the mini-nutritional assessment scale-short form(MNA-SF), the athens insomnia scale(AIS), the ulca loneliness scale, the geriatric depression scale-5 item version(GDS-5), and the social support rating scale(SSRS)were used for assessment and influencing factors were identified by univariate and Logistic regression analysis.Results:Among 300 older patients with chronic heart failure, the prevalence of cognitive frailty was 75.3%(226 cases). Logistic regression analysis showed that age between 70-79 years( OR=0.543, 95% CI: 0.299-0.987), education level( OR=3.644, 95% CI: 1.780-7.461), weekly intellectual activity( OR=2.168, 95% CI: 1.082-4.334)and loneliness( OR=1.101, 95% CI: 1.032-1.175)were factors influencing cognitive frailty in older patients with chronic heart failure. Conclusions:The prevalence of cognitive frailty in older patients with chronic heart failure is high, and age, education level, weekly intellectual activity and loneliness are influencing factors, with education level having the greatest impact on older patients with chronic heart failure.
8.Qingshen Granules alleviates renal fibrosis in mice by regulating exosomes,miR-330-3p,and CREBBP expression
Rong DAI ; Zeping CAO ; Chuanjiao LIU ; Yong GE ; Meng CHENG ; Weili WANG ; Yizhen CHEN ; Lei ZHANG ; Yiping WANG
Journal of Southern Medical University 2024;44(8):1431-1440
Objective To explore the effects of Qingshen Granules(QSG)on adenine-induced renal fibrosis in mice and in uric acid(UA)-stimulated NRK-49F cells and its mechanism for regulating exosomes,miR-330-3p and CREBBP.Methods A mouse model of adenine-induced renal fibrosis were treated daily with QSG at 8.0 g·kg-1·d-1 via gavage for 12 weeks.An adeno-associated virus vector was injected into the tail vein,and renal tissues of the mice were collected for analyzing exosomal marker proteins CD9,Hsp70,and TSG101 and expressions of Col-Ⅲ,α-SMA,FN,and E-cad using Western blotting and immunofluorescence and for observing pathological changes using HE and Masson staining.In the cell experiment,NRK-49F cells were stimulated with uric acid(400 μmol/L)followed by treatment with QSG-medicated serum from SD rats,and the changes in expressions of the exosomal markers and Col-Ⅲ,α-SMA,FN,and E-cad were analyzed.Dual luciferase reporter assay was employed to examine the targeting relationship between miR-330-3p and CREBBP,whose expressions were detected by RT-qPCR and Western blotting in treated NRK-49F cells.Results The mouse models of adenine-induced renal fibrosis showed significantly increased levels of CD9,Hsp70,and TSG101,which were decreased by treatment with QSG.The expressions of Col-Ⅲ,α-SMA,and FN increased and E-cad decreased in the mouse models but these changes were reversed by QSG treatment.QSG treatment obviously alleviated renal fibrosis in the mouse models.Intravenous injection of adeno-associated viral vector obviously inhibited miR-330-3p,increased CREBBP levels,and reduced fibrosis in the mouse models.Dual luciferase assay confirmed CREBBP as a target of miR-330-3p,which was consistent with the results of the cell experiments.Conclusion QSG inhibits renal fibrosis in mice by regulating the exosomes,reducing miR-330-3p levels,and increasing CREBBP expression.
9.Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study
Xiaoshuai ZHANG ; Bingcheng LIU ; Xin DU ; Yanli ZHANG ; Na XU ; Xiaoli LIU ; Weiming LI ; Hai LIN ; Rong LIANG ; Chunyan CHEN ; Jian HUANG ; Yunfan YANG ; Huanling ZHU ; Ling PAN ; Xiaodong WANG ; Guohui LI ; Zhuogang LIU ; Yanqing ZHANG ; Zhenfang LIU ; Jianda HU ; Chunshui LIU ; Fei LI ; Wei YANG ; Li MENG ; Yanqiu HAN ; Li'e LIN ; Zhenyu ZHAO ; Chuanqing TU ; Caifeng ZHENG ; Yanliang BAI ; Zeping ZHOU ; Suning CHEN ; Huiying QIU ; Lijie YANG ; Xiuli SUN ; Hui SUN ; Li ZHOU ; Zelin LIU ; Danyu WANG ; Jianxin GUO ; Liping PANG ; Qingshu ZENG ; Xiaohui SUO ; Weihua ZHANG ; Yuanjun ZHENG ; Qian JIANG
Chinese Journal of Hematology 2024;45(3):215-224
Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.
10.Qingshen Granules alleviates renal fibrosis in mice by regulating exosomes,miR-330-3p,and CREBBP expression
Rong DAI ; Zeping CAO ; Chuanjiao LIU ; Yong GE ; Meng CHENG ; Weili WANG ; Yizhen CHEN ; Lei ZHANG ; Yiping WANG
Journal of Southern Medical University 2024;44(8):1431-1440
Objective To explore the effects of Qingshen Granules(QSG)on adenine-induced renal fibrosis in mice and in uric acid(UA)-stimulated NRK-49F cells and its mechanism for regulating exosomes,miR-330-3p and CREBBP.Methods A mouse model of adenine-induced renal fibrosis were treated daily with QSG at 8.0 g·kg-1·d-1 via gavage for 12 weeks.An adeno-associated virus vector was injected into the tail vein,and renal tissues of the mice were collected for analyzing exosomal marker proteins CD9,Hsp70,and TSG101 and expressions of Col-Ⅲ,α-SMA,FN,and E-cad using Western blotting and immunofluorescence and for observing pathological changes using HE and Masson staining.In the cell experiment,NRK-49F cells were stimulated with uric acid(400 μmol/L)followed by treatment with QSG-medicated serum from SD rats,and the changes in expressions of the exosomal markers and Col-Ⅲ,α-SMA,FN,and E-cad were analyzed.Dual luciferase reporter assay was employed to examine the targeting relationship between miR-330-3p and CREBBP,whose expressions were detected by RT-qPCR and Western blotting in treated NRK-49F cells.Results The mouse models of adenine-induced renal fibrosis showed significantly increased levels of CD9,Hsp70,and TSG101,which were decreased by treatment with QSG.The expressions of Col-Ⅲ,α-SMA,and FN increased and E-cad decreased in the mouse models but these changes were reversed by QSG treatment.QSG treatment obviously alleviated renal fibrosis in the mouse models.Intravenous injection of adeno-associated viral vector obviously inhibited miR-330-3p,increased CREBBP levels,and reduced fibrosis in the mouse models.Dual luciferase assay confirmed CREBBP as a target of miR-330-3p,which was consistent with the results of the cell experiments.Conclusion QSG inhibits renal fibrosis in mice by regulating the exosomes,reducing miR-330-3p levels,and increasing CREBBP expression.

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