1.Liqi Huoxue Dripping Pill improves myocardial ischemia-reperfusion injury in rats by inhibiting apoptosis by regulating the HIF-1α/BNIP3 signaling pathway
Tianjing LIU ; Xiangyun CHEN ; Xiaofang TANG ; Yuxin LU ; Yaofeng LI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(6):802-810
Objective To explore the mechanism by which Liqi Huoxue Dripping Pill(LQHXDP)inhibits cardiomyocyte apoptosis in rats with myocardial ischemia-reperfusion injury(MIRI).Methods Male Sprague-Dawley(n=96)rats were randomly assigned to a normal,sham-operated,model,LQHXDP,adenovirus negative control(Ad-shNC),adenovirus-mediated HIF-1α knockdown(Ad-shHIF-1α),LQHXDP+Ad-shNC,or LQHXDP+Ad-shHIF-1α group using a random number table.LQHXDP was administered daily via oral gavage at 175.0 mg/(kg·d)for 10 consecutive days.On day 7,recombinant adenovirus was injected into the left ventricular wall of rats in the corresponding groups at multiple points.On day 10,the MIRI model was established by ligating the left anterior descending coronary artery.The sham-operated group underwent thoracotomy and suture placement without coronary ligation.Samples were collected after reperfusion was completed.Serum creatine kinase isoenzymes(CK-MB),cardiac troponin I(cTnI),and heart-type fatty acid binding protein(H-FABP)levels were measured using enzyme-linked immunosorbent assay.2,3,5-Triphenyltetrazolium chloride staining was used to measure the volume ratio of myocardial infarction.HE staining was performed to observe the morphology of myocardial tissue.Terminal transferase uridyl nick end labeling assay was conducted to analyze the apoptosis rate of cardiomyocytes,and Western blotting was used to detect the expression of key proteins in the apoptosis(B-cell lymphoma-2[Bcl-2],Bcl-2 associated X protein[Bax],and cleaved cysteinyl aspartate specific proteinase 3[Cleaved-Caspase-3]and HIF-1α/Bcl-2-adenovirus E1B 19 kDa interacting protein 3(BNIP3)signaling pathway(HIF-1α,heme oxygenase-1[HO-1],and BNIP3).Results LQHXDP pretreatment significantly reduced serum CK-MB,cTnI,and H-FABP levels,as well as the myocardial infarction volume ratio in rats with MIRI.LQHXDP also improved myocardial tissue morphology,decreased cardiomyocyte apoptosis,upregulated Bcl-2 protein expression,and downregulated Bax,Cleaved-Caspase-3,HIF-1α,HO-1,and BNIP3 protein expressions(P<0.05).However,adenovirus-mediated shRNA HIF-1α impaired the effects of LQHXDP pretreatment in attenuating myocardial injury and inhibiting apoptosis in MIRI rats(P<0.05).Conclusion LQHXDP reduces cardiomyocyte apoptosis and protects rat myocardium from MIRI by regulating the HIF-1α/BNIP3 signaling pathway.
2.Application value of quantitative indicators related to wide QRS complex in the differentiation of atrial fibrillation with wide QRS complex
Xiaojia YU ; Yaofeng CHEN ; Huani WU ; Shiyun TAN ; Lili DENG
Chinese Journal of Primary Medicine and Pharmacy 2025;32(2):184-189
Objective:To investigate the practicality and clinical significance of quantitative indicators related to wide QRS complex in the diagnosis of atrial fibrillation (AF) with wide QRS complex.Methods:A retrospective study was conducted to analyze the dynamic electrocardiogram data of 93 patients who visited Ankang People's Hospital from January 2021 to December 2023. Based on the type of arrhythmia, the patients were divided into two groups: AF with premature ventricular contraction (PVC) group ( n = 65) and AF with intraventricular conduction abnormality group ( n = 28). The traditional diagnostic indicators and newly introduced quantitative indicators were compared between the two groups to analyze the clinical significance of the new quantitative indicators in identifying AF with wide QRS complex. Results:There were statistically significant differences in the occurrence of cannon waves, QRS duration > 140 ms, QRS morphology in lead V1, the R wave or qR pattern, or the deepest point of R being greater than r or rS in lead V1 being > 60 ms, R/S ratio in lead V6 < 1 or displaying QS pattern, the presence of a notching, a slow decline, or a prominent R wave in the QRS beginning in lead aVR, Vi/Vt in lead aVR ≤ 1, and the data regarding the electrical axis in the no man's land between the two groups ( χ2 = 11.83, 37.59, 26.05, 27.33, 5.30, 49.46, 34.95, 4.90, all P < 0.05). The premature interval/coupling interval in the AF with PVC group was (1.38 ± 0.32), which was significantly lower than (1.84 ± 0.43) in the AF with intraventricular condection abnormality group ( t = -5.71, P < 0.001). The quasi-compensatory pause/coupling interval and quasi-compensatory pause/premature interval in the AF with PVC group were (1.71 ± 0.36) and (1.28 ± 0.25), respectively, which were significantly higher than those in the AF with intraventricular conduction abnormality group ( t = 5.48, 5.06, both P < 0.001). The areas under the curve for the premature interval/coupling interval, quasi-compensatory pause /coupling interval, and quasi-compensatory pause/premature interval, and the combined three indicators (using logistic regression) in distinguishing AF with wide QRS complex were 0.810, 0.788, 0.818, and 0.953, respectively. The area under the curve for the combined three indicators was significantly greater than that for each individual indicator ( Z = -3.10, -3.92, -3.09, all P < 0.05). Conclusions:Premature interval/coupling interval, quasi-compensatory pause/coupling interval, and quasi-compensatory pause/premature interval show good value in the diagnosis of AF with wide QRS complex, and the combined use of the three can significantly improve the diagnostic accuracy.
3.Liqi Huoxue Dripping Pill improves myocardial ischemia-reperfusion injury in rats by inhibiting apoptosis by regulating the HIF-1α/BNIP3 signaling pathway
Tianjing LIU ; Xiangyun CHEN ; Xiaofang TANG ; Yuxin LU ; Yaofeng LI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(6):802-810
Objective To explore the mechanism by which Liqi Huoxue Dripping Pill(LQHXDP)inhibits cardiomyocyte apoptosis in rats with myocardial ischemia-reperfusion injury(MIRI).Methods Male Sprague-Dawley(n=96)rats were randomly assigned to a normal,sham-operated,model,LQHXDP,adenovirus negative control(Ad-shNC),adenovirus-mediated HIF-1α knockdown(Ad-shHIF-1α),LQHXDP+Ad-shNC,or LQHXDP+Ad-shHIF-1α group using a random number table.LQHXDP was administered daily via oral gavage at 175.0 mg/(kg·d)for 10 consecutive days.On day 7,recombinant adenovirus was injected into the left ventricular wall of rats in the corresponding groups at multiple points.On day 10,the MIRI model was established by ligating the left anterior descending coronary artery.The sham-operated group underwent thoracotomy and suture placement without coronary ligation.Samples were collected after reperfusion was completed.Serum creatine kinase isoenzymes(CK-MB),cardiac troponin I(cTnI),and heart-type fatty acid binding protein(H-FABP)levels were measured using enzyme-linked immunosorbent assay.2,3,5-Triphenyltetrazolium chloride staining was used to measure the volume ratio of myocardial infarction.HE staining was performed to observe the morphology of myocardial tissue.Terminal transferase uridyl nick end labeling assay was conducted to analyze the apoptosis rate of cardiomyocytes,and Western blotting was used to detect the expression of key proteins in the apoptosis(B-cell lymphoma-2[Bcl-2],Bcl-2 associated X protein[Bax],and cleaved cysteinyl aspartate specific proteinase 3[Cleaved-Caspase-3]and HIF-1α/Bcl-2-adenovirus E1B 19 kDa interacting protein 3(BNIP3)signaling pathway(HIF-1α,heme oxygenase-1[HO-1],and BNIP3).Results LQHXDP pretreatment significantly reduced serum CK-MB,cTnI,and H-FABP levels,as well as the myocardial infarction volume ratio in rats with MIRI.LQHXDP also improved myocardial tissue morphology,decreased cardiomyocyte apoptosis,upregulated Bcl-2 protein expression,and downregulated Bax,Cleaved-Caspase-3,HIF-1α,HO-1,and BNIP3 protein expressions(P<0.05).However,adenovirus-mediated shRNA HIF-1α impaired the effects of LQHXDP pretreatment in attenuating myocardial injury and inhibiting apoptosis in MIRI rats(P<0.05).Conclusion LQHXDP reduces cardiomyocyte apoptosis and protects rat myocardium from MIRI by regulating the HIF-1α/BNIP3 signaling pathway.
4.Application value of quantitative indicators related to wide QRS complex in the differentiation of atrial fibrillation with wide QRS complex
Xiaojia YU ; Yaofeng CHEN ; Huani WU ; Shiyun TAN ; Lili DENG
Chinese Journal of Primary Medicine and Pharmacy 2025;32(2):184-189
Objective:To investigate the practicality and clinical significance of quantitative indicators related to wide QRS complex in the diagnosis of atrial fibrillation (AF) with wide QRS complex.Methods:A retrospective study was conducted to analyze the dynamic electrocardiogram data of 93 patients who visited Ankang People's Hospital from January 2021 to December 2023. Based on the type of arrhythmia, the patients were divided into two groups: AF with premature ventricular contraction (PVC) group ( n = 65) and AF with intraventricular conduction abnormality group ( n = 28). The traditional diagnostic indicators and newly introduced quantitative indicators were compared between the two groups to analyze the clinical significance of the new quantitative indicators in identifying AF with wide QRS complex. Results:There were statistically significant differences in the occurrence of cannon waves, QRS duration > 140 ms, QRS morphology in lead V1, the R wave or qR pattern, or the deepest point of R being greater than r or rS in lead V1 being > 60 ms, R/S ratio in lead V6 < 1 or displaying QS pattern, the presence of a notching, a slow decline, or a prominent R wave in the QRS beginning in lead aVR, Vi/Vt in lead aVR ≤ 1, and the data regarding the electrical axis in the no man's land between the two groups ( χ2 = 11.83, 37.59, 26.05, 27.33, 5.30, 49.46, 34.95, 4.90, all P < 0.05). The premature interval/coupling interval in the AF with PVC group was (1.38 ± 0.32), which was significantly lower than (1.84 ± 0.43) in the AF with intraventricular condection abnormality group ( t = -5.71, P < 0.001). The quasi-compensatory pause/coupling interval and quasi-compensatory pause/premature interval in the AF with PVC group were (1.71 ± 0.36) and (1.28 ± 0.25), respectively, which were significantly higher than those in the AF with intraventricular conduction abnormality group ( t = 5.48, 5.06, both P < 0.001). The areas under the curve for the premature interval/coupling interval, quasi-compensatory pause /coupling interval, and quasi-compensatory pause/premature interval, and the combined three indicators (using logistic regression) in distinguishing AF with wide QRS complex were 0.810, 0.788, 0.818, and 0.953, respectively. The area under the curve for the combined three indicators was significantly greater than that for each individual indicator ( Z = -3.10, -3.92, -3.09, all P < 0.05). Conclusions:Premature interval/coupling interval, quasi-compensatory pause/coupling interval, and quasi-compensatory pause/premature interval show good value in the diagnosis of AF with wide QRS complex, and the combined use of the three can significantly improve the diagnostic accuracy.
5.Efficacy and safety of rTMS combined with agomelatine in the treatment of depression:a Meta-analysis and trial sequential analysis
Ruihuan ZHANG ; Yaofeng YANG ; Tao HAO ; Jun CHEN
Chinese Journal of Pharmacoepidemiology 2024;33(10):1124-1136
Objective To systematically review the efficacy and safety of repetitive transcranial magnetic stimulation(rTMS)combined with agomelatine in the treatment of depression.Methods PubMed,Embase,Cochrane Library,Web of Science,CNKI,VIP,WanFang Data,SinoMed and Yiigle databases were electronically searched to collect randomized controlled trials(RCTs)of comparison between rTMS combined with agomelatine(combined group)and agomelatine or combined pseudostimulation(control group)in the treatment of depression from inception to May 10,2024.Meta-analysis was performed by using RevMan 5.4 software,GRADE grading system for evaluating the level of evidence for observational indicators,and TSA 0.9.5.lBeta software for trial sequential analysis.Results A total of 15 RCTs involving 1 196 patients were included.Meta-analysis showed that compared with control group,combination group had a higher effective rate(RR=1.24,95%CI 1.15 to 1.34,P<0.001),lower depression scale score(SMD=-2.95,95%CI-3.71 to-2.19,P<0.001),anxiety scale score(SMD=-2.21,95%CI-3.29 to-1.14,P<0.001),PSQI score(MD=-1.69,95%CI-2.79 to-0.59,P=0.003).There was no statistical difference between the two groups in terms of NE level,5-HT level and incidence of adverse reactions(P>0.05).GRADE quality grading of the evidence showed moderate-quality evidence for the effectiveness rate and incidence of adverse reactions,with the depression scale score and the NE level of the evidence being low-quality,and the level of evidence for the anxiety scale score,the PSQI score,and the 5-HT content was very low.The trial sequential analysis results showed that in terms of effective rate,the analysis results of combination group superior to control group were reliable,and the conclusion could exclude false positives.Conclusion The rTMS combined with agomelatine in the treatment of depression has advantages in improving effective rate,depression scale score,anxiety scale score and PSQI score compared with agomelatine alone or combined pseudostimulation,incidence of adverse reactions were equivalent to those of agomelatine aloneor or combined pseudostimulation.
6.Mechanism of Astragali Radix-Aconiti Lateralis Radix Praeparata in Treatment of Heart Failure Based on UPLC-Q-TOF-MS and Network Pharmacology
Xie ZHONG ; Yao ZHANG ; Jun LI ; Han MAO ; Xiangyun CHEN ; Yaofeng LI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(3):70-80
ObjectiveTo explore the mechanism of Astragali Radix-Aconiti Lateralis Radix Praeparata in the treatment of heart failure and substance basis based on ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) and network pharmacology. MethodThe chemical components of Astragali Radix-Aconiti Lateralis Radix Praeparata solution was analyzed by UPLC-Q-TOF-MS, and the active components and targets were screened out by the PubChem database. The targets related to heart failure disease were retrieved from Comparative Toxicogenomics Database(CTD), Online Mendelian Inheritance in Man (OMIM), and GeneCard databases, and the common targets were obtained by Venn analysis. The target protein-protein interactions (PPI) were analyzed using the STRING database. Gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed using the Metascape database, and molecular docking verification of key targets and active components was performed using SYBYL-X 2.1.1. Experimental validation of key targets was carried out using the rat model of heart failure. ResultThere were 202 chemical components identified in Astragali Radix-Aconiti Lateralis Radix Praeparata solution, of which 64 active components were predicted to act on 183 targets for the treatment of heart failure. The important active components were caffeic acid, L-arginine, biochanin A, adenine, nicotinic acid, trans-ferulic acid, p-coumaric acid, riboflavin, calycosin, etc. The main targets were interleukin (IL)-6, cysteine aspartic acid specific protease (Caspase)-3, vascular endothelial growth factor A (VEGFA), protein kinase B1 (Akt1), tumor necrosis factor (TNF), IL-1B, matrix metallopeptidase (MMP)-9, etc. The main signaling pathways involved hypoxia-inducible factor (HIF)-1 signaling pathway, TNF signaling pathway, phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, Toll-like receptor signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, forkhead box O (FoxO) signaling pathway, etc. The molecular docking results showed that the active components in Astragali Radix-Aconiti Lateralis Radix Praeparata solution had a good binding ability with HIF-1α, VEGFA, Akt1, Caspase-3, and IL-6, which were the key proteins in the HIF-1 signaling pathway. Animal experiments showed that Astragali Radix-Aconiti Lateralis Radix Praeparata solution significantly improved the hemodynamic indexes, reduced the serum atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and IL-6 levels, improved the myocardial histopathological changes, protected the mitochondrial morphology of cardiomyocytes, down-regulated the expression of HIF-1α, VEGFA and phosphorylation(p)-Akt, and reduced the activation of Caspase-3 in the myocardial tissue of rats with heart failure. ConclusionAstragali Radix-Aconiti Lateralis Radix Praeparata treats heart failure in a multi-component, multi-target, and multi-pathway manner. The experimental validation indicates that it treats heart failure by improving myocardial histopathological changes and regulating HIF-1 signaling pathway, which provides references for the subsequent pharmacodynamic substance research.
7.Progress in bipolar androgen therapy for castration resistant prostate cancer
Meikai ZHU ; Jian WANG ; Sifeng QU ; Qiujie ZHANG ; Shouzhen CHEN ; Wenfu WANG ; Shuo WANG ; Hu GUO ; Benkang SHI ; Yaofeng ZHU
Chinese Journal of Urology 2023;44(12):953-956
Bipolar androgen therapy (BAT), as a new therapy, can effectively reduce the serum prostate specific antigen (PSA) level of a part of patients with castration resistant prostate cancer (CRPC), delay tumor progression, improve their quality of life and restore the sensitivity to drug therapy. This paper will review the background, possible mechanism, clinical research progress and development prospect of BAT.
8.Abiraterone for treatment of germline mutation in BRCA1 gene with low age, high tumor burden and rapid progression of prostate cancer: a case report
Shuo WANG ; Shouzhen CHEN ; Yaofeng ZHU ; Hu GUO ; Benkang SHI
Chinese Journal of Urology 2021;42(Z1):27-29
The incidence of prostate cancer is increasing year by year in China. People with BRCA mutation are at high risk of prostate cancer. However, there is no clear and effective treatment for mHSPC with high metastatic load carrying BRCA mutation. In this study, we report a mHSPC patient with high metastatic burden and germline BRCA1 gene mutation who rapidly progressed to mCRPC after traditional CAB therapy and then received ADT combined with abiraterone and achieved significant PSA response, suggesting that ADT combined with abiraterone may be an effective therapy for mHSPC patients with BRCA1 germline mutation.
9.Clinical and imaging features of 27 cases of childhood Sturge-Weber syndrome
Di HAO ; Ruirui YIN ; Ping CHEN ; Yaofeng JI ; Wenqian CAI ; Xiangdong HAO ; Lina DONG ; Xiaoming LIU
Chinese Journal of Dermatology 2021;54(11):955-960
Objective:To analyze clinical and imaging features of Sturge-Weber syndrome in children.Methods:Clinical data were collected from 27 children with Sturge-Weber syndrome in Xuzhou Children′s Hospital, Xuzhou Medical University from July 2013 to December 2019, and analyzed retrospectively.Results:Among the 27 children, 17 were males and 10 were females. Their age at the clinic visit ranged from 2 days to 10 years and 7 months, and averaged 2.54 years. All the 27 patients presented with facial port-wine stains of varied color from light red to purple red, which were all distributed across the facial midline, including 21 with predominantly unilateral port-wine stains and 6 with bilateral symmetrical port-wine stains. There were 17 patients with ocular choroidal vascular malformations, including 14 with congenital glaucoma, 5 with high intraocular pressure, and 1 with optic nerve atrophy accompanied by transient blindness. Neurological impairment occurred in 12 patients, and all manifested as epilepsy. All the 27 children underwent imaging examination, and abnormalities were found in 20. Among the 10 patients with abnormal computed tomography images, local calcification was observed in 8, and local thickening of the skull on the side affected by skin lesions in 8; 13 of 14 patients with abnormal magnetic resonance imaging scan results had signs of brain atrophy, 9 showed enhanced gyrus-like blood vessel formation by enhanced magnetic resonance imaging, and 5 showed decreased branches of the anterior and middle cerebral artery on the affected facial side by magnetic resonance angiography.Conclusions:Children with Sturge-Weber syndrome are clinically characterized by predominantly unilateral port wine stains on the face, some of whom are accompanied by epilepsy, glaucoma or mental retardation, and imaging examinations mainly show local calcification, brain atrophy, local thickening of the skull plate, enhanced gyrus-like blood vessel formation, etc. Early definite diagnosis and comprehensive systemic treatment are needed to reduce disability and mortality rates in patients with Sturge-Weber syndrome, and long-term follow-up should be considered.
10.TCF-1 deficiency influences the composition of intestinal microbiota and enhances susceptibility to colonic inflammation.
Guotao YU ; Fang WANG ; Menghao YOU ; Tiansong XU ; Chunlei SHAO ; Yuning LIU ; Ruiqi LIU ; Min DENG ; Zhihong QI ; Zhao WANG ; Jingjing LIU ; Yingpeng YAO ; Jingjing CHEN ; Zhen SUN ; Shanshan HAO ; Wenhui GUO ; Tianyan ZHAO ; Zhengquan YU ; Qian ZHANG ; Yaofeng ZHAO ; Feng CHEN ; Shuyang YU
Protein & Cell 2020;11(5):380-386

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