1.Research Progress in the Mechanism of TCM for Regulating JAK/STAT Signaling Pathway in Intervention of Myocardial Ischemia-reperfusion Injury
Xiaobin ZHAO ; Xinqiang WANG ; Hugang JIANG ; Jinyan HAN ; Xiaogang ZHANG ; Yingdong LI ; Xinke ZHAO
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(1):191-196
		                        		
		                        			
		                        			Acute myocardial infarction(AMI)is a common cardiovascular emergency in clinic.Early reperfusion is a typical and effective method for the treatment of AMI.However,the recovery of blood supply after reperfusion therapy will accelerate the damage of ischemic myocardium and cause myocardial ischemia-reperfusion injury(MI/RI).In recent years,studies have found that TCM has the unique advantages of multi-component,multi-channel and multi-target in the intervention of MI/RI.Janus tyrosine kinase/signal transducer and activator of transcription(JAK/STAT)signaling pathway is closely related to MI/RI,which can reduce MI/RI process by regulating inflammation,oxidative stress,cell proliferation,differentiation and apoptosis.This article reviewed the mechanism of JAK/STAT signaling pathway in MI/RI and the research of TCM targeting this pathway,in order to provide references for the prevention and treatment of MI/RI and further drug development.
		                        		
		                        		
		                        		
		                        	
2.Discussion on the Effects of Angelicae Sinensis Radix and Astragali Radix Extract on Coronary Microvascular Disease Based on NLRP3-mediated Pyroptosis
Chunyan YAN ; Hugang JIANG ; Xinqiang WANG ; Kai LIU ; Yingdong LI ; Xinke ZHAO
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(12):120-128
		                        		
		                        			
		                        			Objective To observe the effects of Angelica Sinensis Radix and Astragali Radix extract(ASR-AR)on HUVEC pyroptosis;To explore its mechanism of treating coronary microvascular disease.Methods HUVEC were divided into blank group,model group,MCC950 group,ASR-AR low-,medium-and high-dosage groups.After modeling and treatment with drug containing serum,cell viability was detected by CCK-8 method,and cell apoptosis was detected by flow cytometry,phalloidin staining was used to detect cytoskeletal morphology,immunofluorescence staining was used to detect the expressions of VEGF,eNOS,Ang-2,ROS,ET-1 and TXA2,ELISA was used to detect the contents of IL-1β and IL-18 in cell supernatant,Western blot was used to detect the expressions of NLRP3,ASC,Caspase-1 and GSDMD protein in cells.Results Compared with the blank group,the model group showed a decrease in HUVEC cell viability(P<0.01)and an increase in cell apoptosis rate(P<0.01),cellular microfilament structure was in disorder and knotting,the expressions of VEGF and eNOS decreased,and expressions of Ang-2,ROS,ET-1 and TXA2 increased,the contents of IL-1β and IL-18 in cell supernatant increased(P<0.01),and the expressions of NLRP3,ASC,Caspase-1 and GSDMD protein in cells increased(P<0.01).Compared with the model group,ASR-AR low-,medium-and high-dosage containing serum could increase cell viability(P<0.05),decrease cell apoptosis rate(P<0.05),improve cell microfilament structure,elevate VEGF and eNOS expressions,decrease Ang-2,ROS,ET-1,TXA2 expressions,reduce IL-1β and IL-18 contents in cell supernatant(P<0.05),and decrease NLRP3,ASC,Caspase-1 and GSDMD protein expressions(P<0.05).ASR-AR medium-dosage group was more obvious(P<0.05).Conclusion ASR-AR can inhibit pyroptosis of HUVEC induced by AngⅡ,attenuate endothelial cell dysfunction,thus treating coronary microvascular disease,and its mechanism may be related to the inhibition of the assembly of NLRP3 inflammasome.
		                        		
		                        		
		                        		
		                        	
3.Exploring the mechanism of Radix Angelica sinensis and Astragalus mongholicus extract therapy for radiationinduced myocardial fibrosis based on network pharmacology and experimental validation
Wen LI ; Hugang JIANG ; Xinqiang WANG ; Yingdong LI ; Kai LIU ; Xinke ZHAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(6):601-611
		                        		
		                        			
		                        			AIM:To explore the potential targets and mechanisms of Angelica sinensis and Astraga-lus membranaceus ultrafiltration(RAS-AM)in the treatment of radiation induced myocardial fibrosis(RIMF)through network pharmacology combined experimental validation.METHODS:Using the TC-MSP database TCM@TAIWAN The Taiwan Tradition-al Chinese Medicine Database and TCMID Tradition-al Chinese Medicine Database screen the compo-nents and targets of RAS-AM,and use the Swiss Target Prediction database for target prediction.Obtain RIMF disease targets from Gene Cards and OMIM databases,obtain intersection targets of dis-eases and drugs through Wayne's online tool,ob-tain protein interaction relationships(PPIs)through STRING database,and use Cytoscape 3.9.1 soft-ware to construct a visualized network topology di-agram of"drug component target disease".Con-duct GO and KEGG enrichment analysis on core tar-gets through the David database,and use the mi-crobiome platform for mapping.Experimental veri-fication:Sixty Wistar rats were randomly divided in-to a blank group,a model group,a positive drug group,a RAS-AM low-dose group,a RAS-AM medi-um dose group,and a RAS-AM high-dose group.A RIMF model was established using a 38Gy dose of radiation induction,and was administered orally for 4 weeks.The general condition of the rats was also observed.After blood and heart collection in rats,HE staining was used to observe the morpho-logical changes of myocardial tissue,and ELISA and Western blot methods were used to detect key tar-gets for network pharmacology prediction.RE-SULTS:Network pharmacology analysis revealed 34 active components and 705 targets of Angelica si-nensis and Astragalus membranaceus ultrafiltra-tion,with a total of 154 targets,with IL-6,VEGFA,MMP2,MMP9,and ACE as the top five core tar-gets;GO enrichment analysis screened a total of 153 entries,and KEGG enrichment had 25 path-ways.Experimental part:HE staining results showed that the degeneration and necrosis of myo-cardial cells improved in each medication group,the infiltration of inflammatory cells in the myocar-dial interstitium decreased,and the proliferation of fibrous connective tissue in the myocardial intersti-tium decreased.ELISA and Western blot results showed that compared with the normal group,the expression of IL-6,VEGFA,and MMP-9 in the mod-el group increased.Compared with the model groupthe expression of IL-6,VEGFA,and MMP-9 in each medication group decreased to varying de-grees,in a dose-dependent manner.CONCLUSION:RAS-AM may inhibit RIMF by downregulating core targets such as IL-6,VEGFA protein,MMP-9 pro-tein,and regulating inflammatory pathways,colla-gen degradation,and other processes.
		                        		
		                        		
		                        		
		                        	
4.Role of Nrf2/HO-1 Signaling Pathway in Myocardial Infarction and Traditional Chinese Medicine Intervention: A Review
Xiaobin ZHAO ; Hugang JIANG ; Xinqiang WANG ; Jinyan HAN ; Kai LIU ; Yingdong LI ; Xinke ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(14):248-255
		                        		
		                        			
		                        			Myocardial infarction (MI) is a common cardiovascular disease in clinical practice and one of the main causes of cardiovascular mortality. Its pathogenesis is complex and associated with oxidative stress reactions. Nuclear factor E2-related factor 2 (Nrf2) is a key factor in regulating oxidative stress reactions. It can regulate the expression of heme oxygenase-1 (HO-1), playing a role in maintaining the oxidative-reductive homeostasis in the body. During the course of MI, the biological activity and levels of Nrf2 and HO-1 decrease, leading to weakened tissue antioxidant and anti-inflammatory capabilities, endothelial damage in myocardial blood vessels, release of vascular cell adhesion factors, and impaired endothelial function. In recent years, many basic research studies have explored the role and mechanisms of traditional Chinese medicine (TCM) in treating MI by modulating the Nrf2/HO-1 signaling pathway. The results have indicated that the Nrf2/HO-1 signaling pathway is an important potential target for TCM in the treatment of MI. This article reviewed the mechanism of the Nrf2/HO-1 signaling pathway in MI and the research progress of TCM in targeting and regulating this pathway, aiming to provide a theoretical basis for the prevention and treatment of MI and further drug development. 
		                        		
		                        		
		                        		
		                        	
5. Effects and mechanism of Ginseng Yixin granules (QSYXG) for heart failure with preserved ejection fraction based on the network pharmacology and molecular docking strategy
Yulin CHEN ; Hugang JIANG ; Xinqiang WANG ; Kai LIU ; Yingdong LI ; Xinke ZHAO ; Xinke ZHAO ; Hugang JIANG ; Xinqiang WANG ; Kai LIU ; Yingdong LI ; Xinke ZHAO ; Tao AN
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(10):1081-1092
		                        		
		                        			
		                        			 AIM: To study the mechanism of Ginseng Yixin granules (QSYXG) in treating ejection fraction preserved heart failure (HFpEF) based on network pharmacology. METHODS: Effective chemical composition information of QSYXG particles was collected through TCMSP database; DisGeNET, GeneCards, OMIM database for obtaining HFpEF related targets; Metascape GO and KEGG enrichment analysis of the intersection targets of HFpEF; STRING Construction and analysis of the database PPI network; Cytoscape3.7.2 Software construction network diagram; Docking of the major active components to the core target with the AutoDock Vina software molecules, the results were visualized and analyzed with pymol. RESULTS: A total of 66 components and corresponding targets were obtained, HFpEF corresponds to 1 931 targets, The intersection of 127 targets, the main active ingredients are quercetin, kaempferol, β-sitosterol, etc.; TNF, AKT1, IL-6, P53 and JUN as the core targets, Good docking of the key components with the core targets; Mainly involving the positive regulation of gene expression, signal transduction, negative regulation of apoptotic process, positive regulation of cell proliferation and senescence, hypoxia response, negative regulation of gene expression, inflammatory response and so on, PI3K-Akt, AGE-RAG, MAPK, TNF, IL-17, and HIF-1 are the main associated signaling pathways. CONCLUSION: QSYXG may treat HFpEF by activating targets of TNF, AKT1, IL-6, P53, JUN, and regulating apoptotic process, cell proliferation, hypoxia response, and inflammatory response. 
		                        		
		                        		
		                        		
		                        	
6.Interventional Effect of Angelica Sinensis Ultrafiltrate on Radiation-Induced Myocardial Fibrosis by Inhibiting the Overexpression of Cardiac CILP1
Xiaobin ZHAO ; Hugang JIANG ; Xinqiang WANG ; Jinyan HAN ; Yulin CHEN ; Yingdong LI ; Xinke ZHAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(7):2612-2620
		                        		
		                        			
		                        			Objective To clarify the intervention effect of Angelica Radix Astragali ultrafiltrate(RAS-RH)on radiation-induced myocardial fibrosis by inhibiting the overexpression of cardiac CILP1.Methods Forty SPF Wistar male rats were randomly divided into normal group,model group,Benazepril hydrochloride group,RAS-RH group and Benazepril hydrochloride +RAS-RH group.Cardiomyocytes were induced by X-ray.The rat model of myocardial fibrosis was prepared by injury.The benazepril hydrochloride group was given benazepril hydrochloride 1.0 mg·kg-1 by gavage;the RAS-RH group was given RAS-RH 0.6 g·kg-1 by gavage;benazepril hydrochloride was given by gavage Pril + RAS-RH group was given benazepril hydrochloride 1.0 mg·kg-1 and RAS-RH 0.6 g·kg-1 by gavage;model group and normal group were given equal volume of normal saline by gavage,once a day,After 4 weeks of drug intervention,the serum NT-ProBNP,CTnⅠ and CTnT contents of the rats in each group were detected by ELISA method;HE staining was used to evaluate the pathological changes of myocardial tissue of the rats in each group;Masson staining was used to evaluate the myocardial collagen deposition of the rats in each group and calculated Collagen volume fraction(CVF);immunohistochemistry to detect the expression levels of α-SMA,Col-Ⅰ,Col-Ⅲ protein in myocardial tissue of rats in each group;Western blot method to detect TGF-β1 and smad3 in myocardial tissue of rats in each group,CILP1 protein expression.Results Compared with the blank group,the serum levels of NT-ProBNP,CTnⅠ and CTnT in the model group were significantly increased(P<0.01).Blue-stained fibrous tissue increased significantly,myocardial CVF increased significantly,and myocardial tissue α-SMA,Col-Ⅰ,Col-Ⅲ,TGF-β1,Smad3,CILP1 protein expression increased(P<0.01);Serum contents of NT-ProBNP,cTnⅠ and CTnT in rats in napril group,RAS-RH group and benazepril hydrochloride + RAS-RH group were significantly decreased(P<0.01).Sexual cell infiltration was improved,myocardial CVF was significantly decreased(P<0.01),and the protein expressions of α-SMA,Col-Ⅰ,Col-Ⅲ,TGF-β 1,Smad3 and CILP1 in myocardial tissue were significantly decreased(P<0.05).Conclusion Angelica sinensis ultrafiltrate can alleviate X-ray radiation-induced myocardial fibrosis in rats by inhibiting the overexpression of CILP 1 in the heart.
		                        		
		                        		
		                        		
		                        	
7. Effect of uncoupling protein 2 gene on radiation sensitivity of Siha cells
Cuihua LIU ; Xinyu DONG ; Yuanhang LI ; Xinqiang ZHANG ; Zhicheng WANG ; Gang ZHAO ; Yannan SHEN
Chinese Journal of Radiological Medicine and Protection 2020;40(2):88-93
		                        		
		                        			 Objective:
		                        			To investigate whether silencing UCP2 can sensitize cervical cancer cell line Siha to radiation.
		                        		
		                        			Methods:
		                        			Siha cells were transfected with UCP2 siRNA and then irradiated by X-ray. The radiosensitivity of Siha cells was verified by colony formation, CCK-8, apoptosis and immunofluorescence assays. The mitochondrial membrane potential and the production of reactive oxygen species (ROS) were detected to further explore the related mechanism.
		                        		
		                        			Results:
		                        			RT-PCR and Western blot assays showed that the expression of UCP2 in Siha cells was increased after irradiation and the UCP2 siRNA successfully silenced the expression of UCP in cells. According to the survival curves, the 
		                        		
		                        	
8. A new exploration and consideration of Type A fracture of distal femur based on finite element biomechanical analysis
Duo XU ; Ruijian SUN ; Tianyu WANG ; Xinqiang ZHAO ; Zhenggang BI ; Shuo GENG
Chinese Journal of Surgery 2019;57(11):812-817
		                        		
		                        			 Objective:
		                        			To investigate the changes of internal fixation stress under different angles of interior fracture line and different screw placement modes in the case of A-type distal femoral fracture.
		                        		
		                        			Methods:
		                        			A 24-year-old healthy male volunteer was recruited to collect the right femur data. CATIA V5R21 software produced a 10 mm fracture gap at the external side of the femur 6.5 cm proximal to the joint line and different angle fracture lines were generated on the internal of the femur at the same height. Based on the actual measured dimensions, the three-dimensional (3D) model of the locking plate and screw was reconstructed using CATIA V5R21 software, ignoring the screw surface threads and then the assembly of the internal fixation of the titanium plate, screws and femur was done. All models were meshed using Hypermesh 13.0 software. The assembled 3D model was input into ABAQUS 6.14 to generate a finite element model. Preliminary finite element biomechanical analysis was performed using the four medial fracture line angles and the stress distribution of the internal fixation under the three screw placement modes, and then the analysis was continued after the optimal screw placement method was re-determined.
		                        		
		                        			Results:
		                        			Under an axial loading of 700 N, with the increase of the angle of the fracture line, the stress of the lateral internal fixation gradually increased, and the displacement of the proximal end of the fracture gradually increased. The sequential screw placement method was superior to the leaping screw placement method. The placement of the first screw at the proximal end of the fracture was critical to the distribution of the internal fixation stress.
		                        		
		                        			Conclusions
		                        			The operation plan of the type A of distal femoral fracture needs to be confirmed according to the internal and external fracture′s condition. When the fracture line is at a excessive positive angle or a negative angle, a simple lateral fixation may not provide a stable fracture fixation so that other fixation methods are needed. 
		                        		
		                        		
		                        		
		                        	
9.Prevention and treatment of graft-carried carbapenem-resistant Klebsiella pneumoniae infection after kidney transplantation:a report of 13 cases
Lan ZHU ; Zhiqiang WANG ; Ke MA ; Hao FENG ; Guangyuan ZHAO ; Jindong JIA ; Xinqiang WANG ; Zhengbin LIN ; Gang CHEN
Chinese Journal of Organ Transplantation 2019;40(6):328-333
		                        		
		                        			
		                        			Objective To evaluate the efficacy of tigecycline plus prolonged high-dose meropenem infusion in the prevention and treatment of early carbapenem-resistant Klebsiella pneumoniae (CRKP) infection after renal transplantation .Methods From January 2016 to December 2018 ,clinical data were retrospectively analyzed for 13 renal transplant recipients with graft-carried CRKP .The relevant clinical data included treatments and outcomes of grafts and recipients .KPC-2 gene was the only resistance gene detectable in all isolates of CRKP . Among 13 CRKP positive recipients ,there were positive cultures of graft preservation solution ,recipient blood & urine (n=1) , positive cultures of graft preservation solution & urine (n=1) ,positive cultures of graft preservation solutions & peri-graft drainage (n=3) ,continuous positive cultures of peri-graft drainage more than twice (n= 3) and positive culture of graft preservation solution (n= 5).All patients received tigecycline plus prolonged high-dose meropenem infusion-based antibiotics .Results Five patients with CRKP positive in preservation solution were successfully prevented from infection after a treatment period of (12 .4 ± 2 .1)days .Among another 8 cases ,additional topical medications (n= 3) and surgical debridement (n= 1) were used .It took a median time of 16 (7~60) days until a negative culture and the total antibiotic treatment course was 20 (10~93) days .The average hospitalization duration was (50 ± 35) days .During a median follow-up period of 25 (6~28) months ,there was no onset of renal arterial rupture ,graft nephrectomy or death .The survival rate was 100% for recipients and 92 .3% for grafts .Conclusions For post-transplant infections due to graft-carried KPC-2 producing CRKP ,rapid diagnostics and tigecycline plus prolonged high-dose meropenem infusion may optimize clinical outcomes by decreasing the rate of graft nephrectomy and the recipient mortality .
		                        		
		                        		
		                        		
		                        	
10.A new exploration and consideration of Type A fracture of distal femur based on finite element biomechanical analysis
Duo XU ; Ruijian SUN ; Tianyu WANG ; Xinqiang ZHAO ; Zhenggang BI ; Shuo GENG
Chinese Journal of Surgery 2019;57(11):812-817
		                        		
		                        			
		                        			Objective To investigate the changes of internal fixation stress under different angles of interior fracture line and different screw placement modes in the case of A?type distal femoral fracture. Methods A 24?year?old healthy male volunteer was recruited to collect the right femur data. CATIA V5R21 software produced a 10 mm fracture gap at the external side of the femur 6.5 cm proximal to the joint line and different angle fracture lines were generated on the internal of the femur at the same height. Based on the actual measured dimensions, the three?dimensional (3D) model of the locking plate and screw was reconstructed using CATIA V5R21 software, ignoring the screw surface threads and then the assembly of the internal fixation of the titanium plate, screws and femur was done. All models were meshed using Hypermesh 13.0 software. The assembled 3D model was input into ABAQUS 6.14 to generate a finite element model. Preliminary finite element biomechanical analysis was performed using the four medial fracture line angles and the stress distribution of the internal fixation under the three screw placement modes, and then the analysis was continued after the optimal screw placement method was re?determined. Results Under an axial loading of 700 N, with the increase of the angle of the fracture line, the stress of the lateral internal fixation gradually increased, and the displacement of the proximal end of the fracture gradually increased. The sequential screw placement method was superior to the leaping screw placement method. The placement of the first screw at the proximal end of the fracture was critical to the distribution of the internal fixation stress. Conclusions The operation plan of the type A of distal femoral fracture needs to be confirmed according to the internal and external fracture′s condition. When the fracture line is at a excessive positive angle or a negative angle, a simple lateral fixation may not provide a stable fracture fixation so that other fixation methods are needed.
		                        		
		                        		
		                        		
		                        	
            
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