1.Impact of Maxing Kugan Decoction on Inflammatory Response and Apoptosis in Oleic Acid-induced Acute Lung Injury in Rats via p38 MAPK/NF-κB Signaling Pathway
Taiqiang JIAO ; Yi NAN ; Ling YUAN ; Jiaqing LI ; Yang NIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):108-116
ObjectiveTo investigate the effects of Maxing Kugan decoction (MKD) on inflammatory response and apoptosis in rats with oleic acid (OA)-induced acute lung injury (ALI) and explore its mechanism of action. MethodsSixty Sprague-Dawley (SD) rats were randomly assigned into six groups: a control group, a model group, a dexamethasone-treated group (2 mg·kg-1), and three MKD-treated groups at low, medium, and high doses (3.1, 6.2,12.4 g·kg-1). Each group was administered either an equivalent volume of normal saline or the corresponding concentration of MKD by gavage for seven consecutive days. The model group and each administration group were used to establish the ALI model by tail vein injection of OA (0.2 mL·kg-1). Twelve hours after modeling, blood gas analyses were conducted, and the wet-to-dry (W/D) weight ratio of lung tissue was measured for each group. Additionally, enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF) of the rats. Cell damage and apoptosis in lung tissue were examined via hematoxylin-eosin (HE) staining and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assays, and the results were subsequently scored. The expression levels of the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway and apoptosis-related proteins and mRNAs were assessed using Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the control group, the model group exhibited a significant decrease in partial pressure of oxygen (PaO2), blood oxygen saturation (SaO2), and oxygenation index (PaO2/FiO2), along with a marked increase in partial pressure of carbon dioxide (PaCO2) and lung W/D ratio (P<0.01). Additionally, levels of TNF-α, IL-6, and IL-1β in BALF were significantly elevated (P<0.01). Histopathological analysis of lung tissue showed significant inflammatory infiltration, tissue edema, alveolar septal thickening, and apoptosis of lung tissue. Pronounced increases were observed in the mRNA expression levels of p38 MAPK, NF-κB p65, inhibitor of NF-κB (IκBα), B-cell lymphoma-2 associated x protein (Bax), and Caspases-3, as well as the protein expression levels of p-p38 MAPK, p-NF-κB p65, p-IκBα, Bax, Caspases-3, and cleaved Caspases-3, while the mRNA and protein expression of Bcl-2 was downregulated (P<0.01). Compared with the model group, MKD significantly elevated PaO2, SaO2, and PaO2/FiO2 while reducing PaCO2 and W/D ratio in rats (P<0.01). It also greatly reduced TNF-α, IL-6, and IL-1β levels in BALF (P<0.01) and alleviated inflammatory infiltration, tissue edema, alveolar septal thickening, and apoptosis of lung tissue. Additionally, it downregulated the mRNA expression of p38 MAPK, NF-κB p65, IκBα, Bax, Caspases-3, as well as protein expression of p-p38 MAPK, p-NF-κB p65, p-IκBα, Bax, Caspases-3, and cleaved Caspases-3 in lung tissue (P<0.05, P<0.01), while significantly upregulating mRNA and protein expression of Bcl-2 (P<0.01). ConclusionMKD exerts a protective effect on OA-induced ALI rats, potentially through the regulation of the p38 MAPK/NF-κB signaling pathway to inhibit inflammation and apoptosis.
2.Impact of Maxing Kugan Decoction on Inflammatory Response and Apoptosis in Oleic Acid-induced Acute Lung Injury in Rats via p38 MAPK/NF-κB Signaling Pathway
Taiqiang JIAO ; Yi NAN ; Ling YUAN ; Jiaqing LI ; Yang NIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):108-116
ObjectiveTo investigate the effects of Maxing Kugan decoction (MKD) on inflammatory response and apoptosis in rats with oleic acid (OA)-induced acute lung injury (ALI) and explore its mechanism of action. MethodsSixty Sprague-Dawley (SD) rats were randomly assigned into six groups: a control group, a model group, a dexamethasone-treated group (2 mg·kg-1), and three MKD-treated groups at low, medium, and high doses (3.1, 6.2,12.4 g·kg-1). Each group was administered either an equivalent volume of normal saline or the corresponding concentration of MKD by gavage for seven consecutive days. The model group and each administration group were used to establish the ALI model by tail vein injection of OA (0.2 mL·kg-1). Twelve hours after modeling, blood gas analyses were conducted, and the wet-to-dry (W/D) weight ratio of lung tissue was measured for each group. Additionally, enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF) of the rats. Cell damage and apoptosis in lung tissue were examined via hematoxylin-eosin (HE) staining and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assays, and the results were subsequently scored. The expression levels of the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway and apoptosis-related proteins and mRNAs were assessed using Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the control group, the model group exhibited a significant decrease in partial pressure of oxygen (PaO2), blood oxygen saturation (SaO2), and oxygenation index (PaO2/FiO2), along with a marked increase in partial pressure of carbon dioxide (PaCO2) and lung W/D ratio (P<0.01). Additionally, levels of TNF-α, IL-6, and IL-1β in BALF were significantly elevated (P<0.01). Histopathological analysis of lung tissue showed significant inflammatory infiltration, tissue edema, alveolar septal thickening, and apoptosis of lung tissue. Pronounced increases were observed in the mRNA expression levels of p38 MAPK, NF-κB p65, inhibitor of NF-κB (IκBα), B-cell lymphoma-2 associated x protein (Bax), and Caspases-3, as well as the protein expression levels of p-p38 MAPK, p-NF-κB p65, p-IκBα, Bax, Caspases-3, and cleaved Caspases-3, while the mRNA and protein expression of Bcl-2 was downregulated (P<0.01). Compared with the model group, MKD significantly elevated PaO2, SaO2, and PaO2/FiO2 while reducing PaCO2 and W/D ratio in rats (P<0.01). It also greatly reduced TNF-α, IL-6, and IL-1β levels in BALF (P<0.01) and alleviated inflammatory infiltration, tissue edema, alveolar septal thickening, and apoptosis of lung tissue. Additionally, it downregulated the mRNA expression of p38 MAPK, NF-κB p65, IκBα, Bax, Caspases-3, as well as protein expression of p-p38 MAPK, p-NF-κB p65, p-IκBα, Bax, Caspases-3, and cleaved Caspases-3 in lung tissue (P<0.05, P<0.01), while significantly upregulating mRNA and protein expression of Bcl-2 (P<0.01). ConclusionMKD exerts a protective effect on OA-induced ALI rats, potentially through the regulation of the p38 MAPK/NF-κB signaling pathway to inhibit inflammation and apoptosis.
3.Assessment of muscle fatigue in school age children under different sitting postures
LUO Ling, HU Huimin, NIU Wenlei, HAO Anna
Chinese Journal of School Health 2025;46(4):558-562
Objective:
To investigate the effects of poor sitting postures on muscle fatigue in schoolage children, so as to provide evidence for developing healthy sitting guidelines.
Methods:
In May 2024,30 children aged 6-12 were recruited from Changping District in Beijing. A combination of surface electromyography (sEMG) and psychophysical scales were used to assess muscle fatigue at varying deviation angles under four sitting postures (forward head tilt, lateral head tilt, uneven shoulder height, and forward trunk inclination). Oneway ANOVA and LSD post hoc multiple comparisons were employed to analyze the differences in electromyographic (EMG) data among various deviation angles under different sitting postures.
Results:
The mean integrated electromyography (IEMG) of representative muscles showed statistically significant differences (P<0.05) across deviation angles in all postures, with muscle fatigue worsening as deviation angles increased. Forward head tilt:significant IEMG differences were observed in the left/right sternocleidomastoid and left/right splenius capitis (F=13.74, 13.21, 5.43, 6.11,P<0.05). Lateral head tilt:significant differences were found in the right sternocleidomastoid muscle (SCM), right splenius capitis, and left trapezius (F=5.13, 4.73, 12.13, P<0.05). Uneven shoulder height:significant differences occurred in the right SCM, bilateral splenius capitis, and left trapezius (F=12.46, 12.56, 32.49, 5.98, P<0.05).Forward trunk inclination, significant differences were identified in the left/right SCM, left/right splenius capitis, and left/right lumbar muscles (F=4.45, 9.84, 14.49, 26.44, 8.02, 18.34, P<0.01). Temporal analysis revealed varying fatigue onset times across postures:severe fatigue occurred earlier in lateral head tilt and forward trunk inclination, while excessive forward head tilt, lateral head tilt, and uneven shoulder postures predominantly induced mild to moderate fatigue.
Conclusions
Under different sitting postures, both the integrated IEMG of relevant muscles and subjective evaluations in schoolaged children increase with greater postural deviattion. Head tilt and trunkleaning postures require particular intervention, with emphasis on unevenshoulder alignment and trunk inclination control.
4.Dingchan Granule (定颤颗粒) for Paroxysmal Atrial Fibrillation with Syndrome of Qi Stagnation and Blood Stasis:A Randomized,Double-Blinded,Placebo-Controlled Clinical Trial
Xiaozhen CHENG ; Xingjuan CHEN ; Weina LI ; Lu XIAO ; Yunhan WANG ; Yun XU ; Yueyue NIU ; Ling FENG
Journal of Traditional Chinese Medicine 2025;66(12):1233-1240
ObjectiveTo observe the clinical effectiveness and safety of Dingchan Granule (定颤颗粒) for paroxysmal atrial fibrillation with syndrome of qi stagnation and blood stasis. MethodsUsing a randomised, double-blind, placebo controlled study method, 90 patients with paroxysmal atrial fibrillation with qi stagnation and blood stasis syndrome were divided into 45 cases each in the treatment group and the control group. Both groups were given conventional western medicine treatment, and the treatment group was additionally treated with Dingchan Granule, while the control group was treated with Dingchan Granule placebo, both of which were taken orally for 8 g each time twice a day. Both groups were treated for 8 weeks. We compared the clinical effectiveness, the improvement of traditional Chinese medicine (TCM) symptoms and the recovery rate of atrial fibrillation between the two groups. We compared the number and duration of atrial fibrillation episodes, TCM symptoms score, atrial fibrillation symptom classification, 24-hour average ventricular rate, Pittsburgh Sleep Quality Index (PSQI), anxiety index, depression index before and after treatment, and evaluated the safety of the two groups. ResultsThe total clinical effectiveness rate in the treatment group was 82.22% (37/45), which was better than 60.00% (27/45) in the control group (P<0.05). The total effective rate of TCM syndrome effectiveness in the treatment group was 88.89% (40/45), which was better than 66.67% (30/45) in the control group (P<0.05); and the rate of atrial fibrillation regression in the treatment group was 26.67% (12/45), better than 6.67% (3/45) in the control group (P<0.05). The number and duration of atrial fibrillation episodes in both groups were significantly decreased (P<0.01), and the number and duration of atrial fibrillation episodes in the treatment group were lower than those in the control group (P<0.01). The TCM syndrome scores of both groups after treatment were significantly lower than before treatment (P<0.01), and the scores of the treatment group was lower than those of the control group (P<0.05). The severity of atrial fibrillation symptoms and the grading of atrial fibrillation symptoms in both groups after treatment were improved (P<0.01), and the degree of symptom improvement in the treatment group was better than that in the control group (P<0.01). The 24-hour average ventricular rate of both groups after treatment was significantly lower (P<0.01). The PSQI, anxiety index and depression index of the treatment group were all lower than before treatment (P<0.01), while the PSQI and anxiety index of the control group were both lower than before treatment (P<0.01 or P<0.05), the PSQI, anxiety index and depression index of the treatment group being lower than those of the control group (P<0.05 or P<0.01). No adverse events occurred in both groups, and no abnormalities were observed in blood, urine, stool routine, liver and kidney function, and coagulation function indexes. ConclusionDingchan Granule for paroxysmal atrial fibrillation with qi stagnation and blood stasis syndrome can alleviate clinical symptom, improve TCM symptom scores, increase atrial fibrillation recovery rate, stabilise the average ventricular rate, and significantly improve the quality of sleep, alleviate the anxiety and depression, with a good safety profile.
5.Correlation between related carotid ultrasound parameters and severity of coronary atherosclerosis
Ying XU ; Yin-Ling NIU ; Xia LI
Chinese Journal of cardiovascular Rehabilitation Medicine 2024;33(1):75-79
Objective:To study correlation between related carotid ultrasound parameters and severity of coronary atherosclerosis(AS).Methods:According to number of diseased coronary arteries,a total of 116 patients with cor-onary heart disease diagnosed by coronary angiography in our hospital were divided into single vessel coronary dis-ease group(n=38,single group),double vessel coronary disease group(n=39,double group)and ≥3 vessel coro-nary disease group(n=39,multiple group).Another 41 healthy subjects were simultaneously regarded as healthy control group.General clinical data and carotid ultrasound parameters were compared among all groups,and corre-lation among them and AS severity was analyzed.Results:Compared with healthy control group,there were signifi-cant rise in levels of total cholesterol(TC),triglycerides(TG)and low density lipoprotein cholesterol(LDL-C),carotid intima-media thickness(IMT)and Crouse score in single,double and multiple groups,and significant re-ductions in plaque echo gray-scale median(GSM)in double and multiple groups.Compared with single group,there were significant rise in levels of TG and LDL-C,Gensini score and Crouse score in double and multiple groups and TC level in multiple group,and significant reduction in plaque echo GSM in multiple group.Compared with double group,there were significant rise in TC level,Gensini score and Crouse score,and significant reduction in plaque echo GSM in multiple group(P<0.05 or<0.01).Pearson correlation analysis indicated that Gensini score was significant positively correlated with Crouse score in these patients(r=0.580,P=0.001).Spearman correla-tion analysis indicated that IMT was significant positively correlated with number of diseased coronary arteries(r=0.582,P=0.001),and plaque echo GSM was significant inversely correlated with it(r=-0.518,P=0.001)in these patients.Conclusion:Related carotid ultrasound parameters are significantly correlated with severity of coro-nary atherosclerosis.
6.Influential factors of voriconazole trough concentration and AUC in pediatric patients with thalassemia undergoing hematopoietic stem cell transplantation
Yongjun LIU ; Yun WU ; Yayun LING ; Lulu NIU ; Tianmin HUANG ; Xin CHEN ; Yilin LUO ; Taotao LIU
China Pharmacy 2024;35(20):2499-2504
OBJECTIVE To analyze the influential factors on trough concentration (cmin) and area under the drug concentration time curve (AUC) of voriconazole (VRZ) in pediatric patients with thalassemia undergoing hematopoietic stem cell transplantation (HSCT). METHODS A total of 60 pediatric patients with thalassemia undergoing HSCT who used VRZ for prevention or treatment of invasive fungal infection were collected in our hospital from January 2021 to January 2024. The plasma concentration of VRZ was measured by high-performance liquid chromatography and the AUC was calculated. The factors affecting cmin and AUC of VRZ were analyzed using multiple linear regression. RESULTS A total of 120 cases of VRZ cmin in 60 pediatric patients was obtained and 27 cases of VRZ AUC in 26 pediatric patients were obtained. The median concentration of VRZ cmin was 0.31 mg/L; 46 cases had a cmin in 0.5-5 mg/L( 38.33%), 2 cases had a cmin>5 mg/L( 1.67%), and 72 cases had a cmin<0.5 mg/L. The median AUC of VRZ was 11.68 mg·h/L. The patient’s body weight, HSCT postoperative days, lymphocyte count, and combined use of phenytoin sodium, tacrolimus or cyclosporine had significant effects on VRZ cmin (P<0.05). Lymphocyte count and combined use of phenytoin sodium had significant effects on VRZ AUC (P<0.05). CONCLUSIONS The body weight, HSCT postoperative days, lymphocyte count, and combined use of phenytoin sodium, tacrolimus or cyclosporine are independent factors affecting VRZ cmin. Lymphocyte count and combined use of phenytoin sodium are independent factors affecting VRZ AUC.
7.Measurement and characterization of retinal vascular morphology parameters based on artificial intelligence automated analysis technology
Xuhan SHI ; Li DONG ; Lei SHAO ; Saiguang LING ; Zhou DONG ; Ying NIU ; Ruiheng ZHANG ; Wenda ZHOU ; Wenbin WEI
Chinese Journal of Experimental Ophthalmology 2024;42(1):38-46
Objective:To analyze retinal vascular parameters and distribution characteristics in Chinese population via the fully automated quantitative measurement of retinal vascular morphological parameters based on artificial intelligence technology.Methods:A cross-sectional study was performed.A total of 1 842 patients without fundus diseases who visited Beijing Tongren Hospital from January 2011 to December 2021 were included.Standardized questionnaires, blood draws and ophthalmologic examinations of enrolled subjects were conducted.Color fundus photographs centered on the optic disk of one eye of patients were collected, and a deep learning-based semantic segmentation network ResNet101-Unet was used to construct a vascular segmentation model for fully automated quantitative measurement of retinal vascular parameters.The main measurement indexes included retinal vascular branching angle, vascular fractal dimension, average vascular caliber, and average vascular tortuosity.To compare different retinal parameters between sexes, the correlation between the above parameters and ocular factors such as best corrected visual acuity, intraocular pressure, and axial length, as well as systemic factors such as sex, age, hypertension, diabetes mellitus, and cardiovascular disease was analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No.20001220). Written informed consent was obtained from each subject.Results:The model established in this study achieved an accuracy over 0.95 for both vascular and optic disk segmentation.The vascular branching angle, vascular fractal dimension, average vascular caliber, and average vascular tortuosity were (51.023±11.623)°, 1.573(1.542, 1.592), 64.124(60.814, 69.053)μm, (0.001 062±0.000 165)°, respectively.Compared with females, males had larger vascular branching angle, smaller average vascular caliber and smaller vascular tortuosity, and the differences were statistically significant (all at P<0.05). The average vascular caliber increased by 1.142 μm in people with cardiovascular disease compared to people without cardiovascular disease ( B=1.142, P=0.029, 95% CI: 0.116-2.167). The average vascular tortuosity was positively correlated with hypertension ( B=3.053×10 -5, P=0.002, 95% CI: 1.167×10 -5-4.934×10 -5) and alcohol consumption ( B=1.036×10 -5, P=0.014, 95% CI: 0.211×10 -5-1.860×10 -5) and negatively correlated with hyperlipidemia ( B=-2.422×10 -5, P=0.015, 95% CI: -4.382×10 -5-0.462×10 -5). For each 1-mm increase in axial length, there was a decrease of 0.004 in vessel fractal dimension ( B=-0.004, P<0.001, 95% CI: -0.006--0.002), a decrease of 0.266 μm in the average vessel caliber ( B=-0.266, P=0.037, 95% CI: -0.516--0.016), and a decrease of -2.45×10 -5° in the average vessel tortuosity ( B=-2.45×10 -5, P<0.001, 95% CI: -0.313×10 -5--0.177×10 -5). For each 1.0 increase in BCVA, there was an increase of 3.992° in the vascular branch angle ( B=3.992, P=0.004, 95% CI: 1.283-6.702), an increase of 0.090 in vascular fractal dimension ( B=0.090, P<0.001, 95% CI: 0.078-0.102) and a decrease of 14.813 μm in the average vascular diameter ( B=-14.813, P<0.001, 95% CI: -16.474--13.153). Conclusions:A model for retinal vascular segmentation is successfully constructed.Retinal vessel parameters are associated with sex, age, systemic diseases, and ocular factors.
8.Construction and practice of a "three progressions, four integrations, and five cocultivation" talent cultivation system for nursing professional groups under the 1+X certificate system
Jie NIU ; Guiying NAN ; Huan LI ; Zhaoxia MENG ; Ran ZHANG ; Qian ZHU ; Aijun ZHOU ; Ling YAN ; Xianghua LI
Chinese Journal of Practical Nursing 2024;40(19):1441-1446
Objective:To explore the talent cultivation model of nursing professional group under the 1+X certificate system, to build a talent cultivation system for nursing professional groups with "three progressions, four integrations, and five cocultivation"Methods:From 1 July 2021 to 31 December 2023, built a professional group course system of "mutual sharing of foundations, mutual generation of majors, mutual selection of positions, and progressive improvement of abilities". Aligned course content with X certificate content. Deepen the reform of the three education systems, create a "dual teacher" teaching team that combines full-time and part-time work, and build teaching resources that connect the cloud and the ground. The application effect of this model was evaluated in 2021 nursing majors in Cangzhou Medical College by cluster sampling.Results:There were 748 students majoring in nursing in class of 2021, 150 boys aged 19-22(20.00 ± 1.23), 598 girls, aged 19-21(19.00 ± 2.57). There were 118 students majoring in midwifery in class of 2021, all of them were girls, aged 18-20(18.00 ± 2.11). There were 128 students majoring in rehabilitation therapy technology in class of 2021, 66 boys aged 19-21(19.00 ± 2.11), 62 girls aged 19-21(19.00 ± 2.54). Nursing professional group completed the "Basic Nursing Technology Training Guidance", "Elderly Care" and other 5 self-compiled textbooks, 730 students had participated in the X certificate assessment, 729 students e passed the assessment, the passing rate was 99.9%.Conclusions:The talent cultivation model of "three progressions, four integrations, and five co cultivation" in the nursing professional group can cultivate students′ professional abilities, and cultivate a composite technical and skilled talent with multiple abilities and interconnections in one job.
9.Pharmacomechanical catheter-directed thrombolysis combined with Venovo venous stent implantation in treating iliac vein compression syndrome complicated by acute lower extremity deep venous thrombosis
Zhengzuo LV ; Bing WANG ; Xiaoyang NIU ; Ling WANG ; Haozhe ZHENG
Journal of Interventional Radiology 2024;33(6):627-632
Objective To investigate the short-term efficacy and clinical safety of pharmacomechanical catheter-directed thrombolysis(PCDT)combined with Venovo(Bard)venous stent implantation in treating iliac vein compression syndrome(IVCS)associated with acute lower extremity deep venous thrombosis(DVT).Methods The clinical data of 23 IVCS patients with acute DVT,who received PCDT combined with Venovo venous stent implantation at the Fifth Affiliated Hospital of Zhengzhou University of China between July 2022 and December 2022,were retrospective analyzed.The differences in preoperative and postoperative lower limb circumference and the postoperative thrombus clearance rate were evaluated.Outpatient follow-up was conducted at one,3,and 6 months after treatment,and the patient's venous clinical severity score(VCSS)was recorded and the stent patency was checked.Results Successful surgery was achieved in all 23 patients,and the target lesion thrombus was completely cleared(clearance ratio>95%).A total 23 Venovo iliac vein stents were implanted during the same period.During the follow-up period of 6 months,neither displacement,fracture or detachment of the stent nor death occurred.In the 23 patients,the circumference differences of thigh and calve between the affected and healthy lower limbs decreased from preoperative(5.59±0.93)cm and(3.52±0.85)cm respectively to postoperative(1.43±0.68)cm and(1.41±0.72)cm respectively,the differences were statistically significant(both P<0.05).Six months after treatment,the VCSS significantly decreased from preoperative(8.0±1.9)points to postoperative(5.4±1.1)points,the difference was statistically significant(P<0.05),the primary patency rate was 95.7%(22/23),and the surgical re-intervention rate was 4.3%.Conclusion For the treatment of IVCS complicated by acute lower extremity DVT,combination use of PCDT and Venovo venous stenting is clinically safe and effective,therefore,this technique carries good prospect of clinical application.(J Intervent Radiol,2024,33:627-632)
10.Euonymus alatus delays progression of diabetic kidney disease in mice by regulating EGFR tyrosine kinase inhibitor resistance signaling pathway
Jinjin WANG ; Wenfei CUI ; Xuewei DOU ; Binglei YIN ; Yuqi NIU ; Ling NIU ; Guoli YAN
Journal of Southern Medical University 2024;44(7):1243-1255
Objective To explore the therapeutic mechanism of Euonymus alatus for diabetic kidney disease(DKD).Methods TCMSP,PubChem and Swiss Target Prediction databases were used to obtain the active ingredients in Euonymus alatus and their targets.GEO database and R language were used to analyze the differentially expressed genes in DKD.The therapeutic targets of DKD were obtained using GeneCards,DisGeNet,OMIM and TTD databases.The protein-protein interaction network and the"drug-component-target-disease"network were constructed for analyzing the topological properties of the core targets,which were functionally annotated using GO and KEGG pathway enrichment analyses.Molecular docking was performed for the core targets and the main pharmacologically active components,and the results were verified in db/db mice.Results Analysis of GSE96804,GSE30528 and GSE30529 datasets(including 60 DKD patients and 45 normal samples)identified 111 differentially expressed genes in DKD.Network pharmacology analysis obtained 161 intersecting genes between the target genes of Euonymus alatus and DKD,including the key core target genes SRC,EGFR,and AKT1.The core active ingredients of Euonymus alatus were quercetin,kaempferol,diosmetin,and naringenin,which were associated with responses to xenobiotic stimulionus and protein phosphorylation and regulated EGFR tyrosine kinase inhibitor resistance pathways.Molecular docking suggested good binding activities of the core active components of Euonymus alatus with the core targets.In db/db mouse models of DKD,treatment with Euonymus alatus obviously ameliorated kidney pathologies,significantly inhibited renal expressions of SRC,EGFR and AKT1,and delayed the progression of DKD.Conclusion Euonymus alatus contains multiple active ingredients such as quercetin,kakaferol,diosmetin,naringenin,which regulate the expressions of SRC,EGFR,and AKT1 to affect the EGFR tyrosine kinase inhibitor resistance signaling pathway to delay the progression of DKD.


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