1.Danhong Injection Regulates Mitochondrial Dynamics in Rat Model of Chronic Heart Failure via AMPK/Drp1 Pathway
Jiahao YE ; Zizheng WU ; Yao ZHANG ; Lichong MENG ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):126-135
ObjectiveTo investigate the effects of Danhong injection on mitochondrial dynamics, morphology, and function in the rat model of chronic heart failure by mediating the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/dynamin-related protein 1 (Drp1) pathway. MethodsFrom 75 SD rats, 15 rats were randomly selected as the sham group, and the remaining 60 rats were used to prepare a rat model of chronic heart failure by abdominal aortic constriction (AAC). The modeled rats were randomly allocated into model, Danhong Injection (6 mL·kg-1), and captopril (8.8 mg·kg-1) groups and administrated with corresponding agents for 15 consecutive days. The levels of N-terminal pro-brain natriuretic peptide (NT-pro BNP), adenosine diphosphate (ADP), adenosine triphosphate (ATP), interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α and the activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ were determined by enzyme-linked immunosorbent assay. The changes in cardiac function were detected by echocardiography. The ultrastructural changes of myocardial mitochondria were observed by transmission electron microscopy. Western blot was employed to assess the protein levels of AMPK, p-AMPK, Drp1, p-Drp1, optic atrophy 1 (Opa1), mitofusin (Mfn2), and fission l (Fis1) in the myocardial tissue. Real-time PCR was performed to determine the mRNA levels of Opa1, Mfn2, and Fis1, and immunohistochemistry to detect the expression of p-AMPK. ResultsCompared with the sham group, the model group showed elevated levels of NT-pro BNP, ADP, TNF-α, IL-6, and IL-1β (P<0.01), declined ATP level (P<0.01), weakened activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ (P<0.01), decreased left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01), and increased left ventricular internal diameter at end-diastole (LVDd) and leaf ventricular internal diameter at end-systole (LVIDs) (P<0.01). Electron microscopy results showed that the model group presented heavily abnormal myocardial structure, with large areas of myofilament structure destroyed and dissolved, significantly enlarged residual structural gaps, and fragmented mitochondria. Western blot results showed that the model group demonstrated down-regulated protein levels of p-AMPK, Mfn2, and Opa1 (P<0.01) and up-regulated protein levels of p-Drp1 and Fis1 (P<0.01) in the myocardial tissue. Real-time PCR results showed that the model group presented up-regulated mRNA level of Fis1 (P<0.01) and down-regulated mRNA levels of Mfn2 and Opa1 (P<0.01). Immunohistochemistry results showed reduced expression of p-AMPK in the model group compared with sham group (P<0.01). Compared with the model group, Danhong injection lowered the levels of NT-pro BNP, ADP, TNF-α, IL-6, and IL-1β (P<0.01), raised the level of ATP (P<0.01), increased the activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ (P<0.05, P<0.01), increased the LVEF and LVFS (P<0.01), decreased the LVDd and LVIDs (P<0.05, P<0.01), alleviated mitochondrial damage, up-regulated the protein levels of p-AMPK, Mfn2, and Opa1 (P<0.05, P<0.01), down-regulated the protein levels of p-Drp1 and Fis1 (P<0.01), reduced the mRNA level of Fis1 (P<0.01), elevated the mRNA levels of Mfn2 and Opa1 (P<0.05, P<0.01), and promoted the expression of p-AMPK (P<0.05). ConclusionDanhong injection repairs the imbalance of mitochondrial dynamics, restores the mitochondrial function, improves the myocardial energy metabolism, and reduces the inflammatory response by regulating the AMPK/Drp1 pathway, thus improving the cardiac function.
2.Mechanism study on treatment of abnormal uterine bleeding by Taohong Siwu Tang based on lipidomics
Meng-Yu SU ; Yan-Yan ZHANG ; Rong HUANG ; Yao CHENG ; Shan-Shan QIAN ; Can PENG ; Dai-Yin PENG ; Xiao-Chuang LIU
Chinese Pharmacological Bulletin 2024;40(9):1649-1657
Aim To study the effects of Taohong Siwu Tang(TSD)on serum lipid metabolites in rats with abnormal uterine bleeding(AUB),and to analyze the mechanism of action of TSD in improving lipid metabo-lism disorders in AUB.Methods The rat model of AUB was replicated by the method of incomplete abor-tion with drugs,and the lipid metabolites of serum were detected by applying UPLC-Q-Exactive Orbitrap/MS technology,and combined with the principal com-ponent analysis and orthogonal partial least squares-discriminant analysis to screen for differential lipids,the changes of lipids in serum before and after the in-tervention of TSD were clarified.Results A total of 11 differential lipids were screened,mainly phosphati-dyl inositol,phosphatidic acid,phosphatidyl ethanola-mine,phosphatidyl serine,sterol lipids,ceramide,acrylolipids and fatty acids.The screened differential lipids all tended to regress to normal after the adminis-tration of TSD intervention.Conclusion Improvement of AUB by TSD may be related to lipid metabolism such as phosphatidic acid,phosphatidyl inositol,phos-phatidyl ethanolamine,phosphatidyl serine,and ce-ramide.
3.Progress in study of role of mitochondrial quality control in adriamycin myocardial injury
Shi-Yao LIU ; Meng-Xiao ZHANG ; Hao LIU
Chinese Pharmacological Bulletin 2024;40(10):1814-1818
Adriamycin/Doxorubicin(DOX)is a representative drug of anthracycline antitumor antibiotics and its main adverse reaction is cardiotoxicity,which seriously affects the clinical ap-plication of adriamycin and the quality of life of patients.Mito-chondrial dysfunction is an important pathologic mechanism of adriamycin-related cardiotoxicity.The heart is a highly energy-consuming organ,which contains abundant mitochondria to sup-port the energy needs of cardiomyocytes.The body maintains mi-tochondrial homeostasis through quality control mechanisms such as mitophagy,mitochondrial fusion/fission,mitochondrial bio-synthesis and mitochondrial unfolded protein response.Numer-ous studies have shown that adriamycin cardiotoxicity is associat-ed with the disruption of the mitochondrial quality control system in cardiomyocytes and that reconstruction of mitochondrial quali-ty control homeostasis can mitigate adriamycin-associated myo-cardial injury.This article addresses the role of disturbances in the myocardial mitochondrial quality control system in DOX myo-cardial injury and its underlying mechanisms and explores whether targeting mitochondrial quality control is a potential strategy for the treatment of DOX cardiomyopathy.
4.Study on inhibitory effect of alisol B on non-small cell lung cancer based on network pharmacology and its mechanism
Liu-Yan XIANG ; Wen-Xuan WANG ; Si-Meng GU ; Xiao-Qian ZHANG ; Lu-Yao LI ; Yu-Qian LI ; Yuan-Ru WANG ; Qi-Qi LEI ; Xue YANG ; Ya-Jun CAO ; Xue-Jun LI
Chinese Pharmacological Bulletin 2024;40(12):2375-2384
Aim To explore the potential genes and mechanism of alisol B in the treatment of non-small cell lung cancer(NSCLC).Methods The proliferation and migration of NSCLC cells were detected by CCK-8 and Transwell.Genes of NSCLC and alisol B were col-lected through TCGA and compound gene prediction database,and their intersection genes were obtained.The network of protein-protein interaction(PPI)was constructed by using String database,and the top 20 key nodes were screened out,and the prognosis-related proteins related to the prognosis of NSCLC were screened out by using R language,and the intersection of them was obtained.The potential mechanism of ali-sol B on NSCLC was explored by KEGG and GO en-richment analysis and the relationship between related genes and immune cells,which was verified by cell-lev-el experiments.Results Alisol B inhibited the cell activity and migration ability of NSCLC cells.Five im-portant genes were identified by network pharmacologi-cal analysis:CCNE1,CDK1,COL1A1,COL1A2 and COL3A1.The results of cell experiment showed that al-isol B down-regulated the expression of Cyclin E1,CDK1 and COL1A2 in NSCLC cells.In addition,alisol B could inhibit the expression of COL1A2 and M2 macrophage marker CD206 in macrophages.Conclu-sions Alisol B may inhibit the proliferation of tumor cells by down-regulating CDK1 and Cyclin E1,and may affect the function of macrophages by inhibiting COL1A2,thus regulating the tumor immune microenvi-ronment and inhibiting NSCLC.
5.Diammonium glycyrrhizinate negatively regulates LPS-induced neuroinflamma-tory responses in BV2 microglia via TLR4/NF-κB signaling pathway
Jizheng CUI ; Yao MENG ; Pingping TANG ; Xiaobao ZHANG ; Zhongyuan ZHOU
Chinese Journal of Immunology 2024;40(10):2135-2140
Objective:To evaluate effect of diammonium glycyrrhizinate(DG)on lipopolysaccharide(LPS)-induced TLR4/NF-κB inflammatory signaling pathway in BV2 microglial cells and to explore its potential regulatory mechanisms on ameliorating neu-roinflammation.Methods:BV2 microglia injury model was induced by LPS and treated with 20 and 60 μmol/L DG.MTS was used to determine vitality of cells.NO level secreted by cells was detected by Griess.Inflammatory factors TNF-α,IL-6,and IL-1β levels in cell supernatant were measured by ELISA.TNF-α,IL-6,IL-1β,TLR4 and MyD88 mRNA levels were detected by RT-qPCR.Western blot was used to determine expressions of TLR4,MyD88,NF-κB,p-NF-κB,IκB-α and p-IκB-α proteins of cells.Results:Compared with control group,LPS-treated BV2 microglia had significantly lower viability(P<0.05),significantly higher NO secretion(P<0.05),significantly up-regulation levels of inflammatory factors TNF-α,IL-6 and IL-1β(P<0.05),and significantly higher mRNA levels of TNF-α,IL-6,IL-1β,TLR4 and MyD88(P<0.05),TLR4,MyD88,NF-κB,p-NF-κB,IκB-α,and p-IκB-α protein expressions were significantly increased(P<0.05).Compared with LPS group,BV2 microglia intervened with different concentrations of DG had significantly higher viability(P<0.05),significantly lower NO secretion(P<0.05),significantly lower TNF-α,IL-6 and IL-1β inflammatory factors levels(P<0.05),significantly lower mRNA levels of TNF-α,IL-6,IL-1β,TLR4 and MyD88(P<0.05),and TLR4,MyD88,p-NF-κB and p-IκB-α protein expressions were significantly reduced(P<0.05).Conclusion:DG can inhibit LPS-induced neuroinflammatory responses in microglia,whose underlying mechanism is suppression of TLR4/NF-κB signaling pathway.
6.Analysis of medical reimbursement rate and influencing factors under the DIP payment method
Meng-Yuan ZHAO ; Kun-He LIN ; Ying-Bei XIONG ; Yi-Fan YAO ; Zhi-He CHEN ; Yu-Meng ZHANG ; Li XIANG
Chinese Journal of Health Policy 2024;17(6):40-46
Objective:Analyze the medical reimbursement rate and influencing factors under the DIP payment method to refine the DIP payment policy,promote the optimization of internal operations in medical institutions,and ensure reasonable compensation.Methods:Based on the 2022 DIP fund settlement data from 196 medical institutions in City A,the study used multiple linear regression to analyze the factors affecting medical reimbursement rate and conducted a heterogeneity analysis for medical institutions of different levels.Results:The medical reimbursement rate for medical institutions in City A in 2022 was 103.32%.Medical institutions with lower CMI standardized inpatient costs,lower rates of deviation cases,tertiary care institutions,lower proportion of level-four surgeries,and lower ratios of resident to employee medical insurance cases have higher medical reimbursement rate(P<0.05).Heterogeneity analysis reveals that therates of deviation cases,the proportion of primary care diseases,the ratio of resident to employee medical insurance cases,and the low-standard admission rate have different impacts on medical institutions of different levels.Conclusion:Medical insurance departments should improve policies for primary care diseases,dynamically adjust disease catalogs and payment standards,optimize funding levels and institutional coefficients,and increase penalties for violations to ensure effective use of funds.Medical institutions need to strengthen their understanding of policies,focus on refined internal management,promote standardized and rational diagnosis and treatment through performance assessment transformation,and leverage their own advantages in medical services to reasonably increase the medical reimbursement rate.
7.Human resource efficiency and spatial distribution characterization of district-level center for disease control and prevention in city N of Jiangsu Province
Yang LI ; Yu-Meng WEI ; Yu-Qi YANG ; Wen-Jie XU ; Ming-Yao GU ; Zi-Fa HUANG ; Zhi-Hao ZHANG ; Fang WU
Chinese Journal of Health Policy 2024;17(10):52-58
Objective:To analyze the efficiency of human resource allocation and its spatial distribution characteristics of district-level Center for Disease Control and Prevention(CDC)in city N of Jiangsu Province in 2020,in order to provide a strong decision-making reference for optimizing and strengthening the CDC talent team.Methods:The efficiency of human resources of district-level CDC of City N in2020 was measured using the Super-Efficiency SBM model,and the spatial association pattern was analyzed using the natural break point classification method and Moran's index,with the visualization presented through LISA maps.Results:The overall level of human resource efficiency in district-level CDC of City N is relatively high.However,spatially,there are significant differences among the regions,showing a trend of high efficiency in the central areas and low efficiency at the ends.Moran's index and LISA maps indicate a negative spatial correlation in efficiency,with a low-high(L-H)cluster centered on Area L and a high-low(H-L)cluster centered on Area J.The high-high(H-H)cluster pattern has not yet formed,exhibiting a characteristic of interspersed high and low efficiency.Conclusions:There are regional differences in the human resource efficiency of the Disease Control Center in City N,and the spatial cluster pattern needs to be optimized.It is recommended to focus on efficiency improvement in Areas P and L,formulate appropriate policies,and promote coordinated regional development.
8.Translation and psychometric properties test of the Eating Behaviors Assessment for Obesity
Lin YAO ; Xiaoqian ZHANG ; Xiaoxu DUAN ; Hua MENG ; Fang ZHAO
Chinese Journal of Nursing 2024;59(20):2509-2514
Objective To translate the Eating Behaviors Assessment for Obesity(EBA-O)and test its reliability and validity for providing an effective tool for brief and rapid clinical assessment of dietary behavior in obese patients.Methods The Chinese version of EBA-O was developed by Brislin's translation model for translation,back translation,cultural adaptation,and pilot investigation.Using convenience sampling method,200 obese patients who were admitted to the inpatient ward of the Weight Loss Center of a tertiary hospital in Beijing from April to June 2023 and planned to undergo weight loss metabolic surgery were selected as the research participants to test the reliability and validity of the Chinese version of EBA-O.Results The Chinese version of EBA-O includes 4 dimensions,with a total of 17 items.The Cronbach's α coefficient of the scale is 0.886;the Cronbach's αcoefficients of the dimensions are 0.770~0.866;the test-retest reliability of the scale is 0.881.The content validity index of the scale level is 0.980,and the content validity indexes of item level were 0.889~1.000.Totally 4 common factors were extracted through exploratory factor analysis,with a cumulative variance of 66.363%.Conclusion The Chinese version of EBA-O has good reliability and validity,and it can be used as a tool to evaluate the dietary behavior of obese patients undergoing weight loss metabolic surgery.
9.Consistency of chemical constituents between formula granules and standard decoction of Coptidis Rhizoma
Dai-Liang ZHANG ; Xin-Na DONG ; Lei SHI ; Xiao-Di DONG ; Yong-Qiang LIN ; Rong-Fei ZHANG ; Jing-Hua ZHANG ; Yuan-Cheng YAO ; Feng-Chao ZHANG ; Gui-Yun CAO ; Zhao-Qing MENG
Chinese Traditional Patent Medicine 2024;46(9):2851-2858
AIM To investigate the consistency of chemical constituents between formula granules and standard decoction of Coptidis Rhizoma.METHODS Eighteen batches of standard decoctions were prepared,after which the extraction rate and contents,transfer rates of magnolflorine,jatrorrhizine,columbamine,epiberberine,coptisine,palmatine,berberin were determined,HPLC characteristic chromatograms were established.RESULTS There were 11 common peaks in the characteristic chromatograms of 18 batches of standard decoctions and 24 batches of formula granules with the similarities of 0.861-1.000,which were clusterd into two categories.The formula granules and standard decoction demonstrated approximated extraction rate and contents,transfer rates of index constituents.CONCLUSION The chemical constituents between formula granules and standard decoction of Coptidis Rhizoma display good consistency,which can provide references for the quality control,process research and clinical application of the former.
10.Accurate determination of the whole genome sequencing and open reading frames composition of non-replicating Tiantan strain of vaccinia virus based on novel long read sequencing platform
Zhongxian ZHANG ; Changcheng WU ; Han LI ; Shuting HUO ; Li ZHAO ; Yao DENG ; Xin MENG ; Roujian LU ; Houwen TIAN ; Wenling WANG ; Baoying HUANG ; Wenjie TAN
Chinese Journal of Microbiology and Immunology 2024;44(6):502-509
Objective:To accurately ascertain the whole genome sequencing and the composition of open reading frames (ORFs) of non-replicating Tiantan strain of vaccinia virus (NTV) using next-generation long-read sequencing technology.Methods:NTV, obtained from our laboratory stock, was amplified and purified on chicken embryo fibroblast cells(CEFs), and the full-length genomic nucleic acid of NTV was extracted. The PacBio HiFi sequencing platform was utilized for de novo assembly to obtain the complete genomic sequence of NTV. Using a homology annotation strategy, we identified its ORF composition and compared it with known non-replicating vaccinia virus strains. Results:The total length of NTV′s genome was 171 729 bp, with a GC content of 33%. Its unique inverted terminal repeat (ITR) region comprised hairpin structures, two tandem repeat regions, and three non-repeat regions. NTV contained 166 ORFs, with major differences observed in the ITR and its surrounding regions when compared to MVA-BN and NYVAC. These three strains shared a common set of 138 ORFs. NTV encoded six unique ORFs related to virus evasion of host antiviral response.Conclusions:This study accurately determines the whole genome sequencing and ORFs composition of NTV, and reveals its similarities and differences with other replication-deficient vaccinia virus strains, which pave a way for the development and application of the next generation of monkeypox vaccines and novel viral vectors.

Result Analysis
Print
Save
E-mail