1.Comprehensive Clinical Evaluation of Duliang Soft Capsules in Treatment of Migraine with Wind-cold Blood Stasis Syndrome
Xiaoxiao ZHAO ; Xuming ZHANG ; Junyu XI ; Zhenkai LU ; Fumei LIU ; Lianxin WANG ; Yuanyuan LI ; Yanming XIE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):223-232
ObjectiveTo comprehensively assess the clinical value of Duliang soft capsules in the treatment of migraine with wind-cold blood stasis syndrome, and to provide guidance for national medical decision-making, clinical drug promotion, and pharmaceutical services. MethodThe evaluation of Duliang soft capsules' clinical value was conducted in accordance with the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs (Trial Version, 2021) using a combination of qualitative and quantitative methods. Utilizing the CSC v2.0 software, this study conducted a comprehensive clinical evaluation of Duliang soft capsules across the "6+1" dimensions, including safety pre- and post-market launch, effectiveness in treating migraine, economy (cost-effectiveness), and innovation, suitability, accessibility, and traditional Chinese medicine (TCM) characteristics in both its technology and clinical applications. ResultSafety: Duliang soft capsules were found to have good safety based on evidence from known adverse reactions (spontaneous reporting system (SRS) data, literature data, etc.), pre-marketing toxicological research, and post-marketing drug monitoring. Effectiveness: A meta-analysis indicated that the combination of Duliang soft capsules and western medicine was more effective than Western medicine alone in the treatment of migraine. The product's effectiveness was rated as "Best" based on the quality and value of the evidence. Economy: Duliang soft capsules are moderately priced and categorized as a Type B medical insurance product. Economic research indicated that the combination of Western medicine and Duliang soft capsules was more cost-effective than Western medicine alone. The product's economy was rated as "Better". Innovation: Duliang soft capsules, with Angelicae Dahuricae Radix and Chuanxiong Rhizoma as the main components, hold one invention patent and have been awarded the China Patent Excellence Award. The pharmaceutical company has introduced innovative extraction (CO2 supercritical extraction technology) and formulation (soft capsule) processes. The product's innovation was rated as "Better". Suitability: A questionnaire survey on Duliang soft capsules showed that it was well-suited for both patients and healthcare professionals. The product received a comprehensive assessment of suitability through the "Evaluation of Chinese Patent Medicine Information Services". The product's suitability was rated as "Best". Accessibility: Duliang soft capsules are moderately priced, making them accessible and affordable. The product's accessibility was rated as "Good" based on evidence from these three aspects. TCM characteristics: The formulation of Duliang soft capsules can be traced back to WANG Qiu's Selected Formulas from the Praiseworthy Studio (Shi Zhai Bai Yi Xuan Fang) from the Song Dynasty, and it was documented in ZHANG Jiebin's The Complete Works of Zhang Jing-yue (Jing Yue Quan Shu) as "Duliangwan". The product has been extensively studied with over 2000 clinical cases since its market launch, and its TCM characteristics were rated as outstanding with sufficient evidence. ConclusionThe comprehensive clinical value evaluation of Duliang soft capsules demonstrated its high effectiveness, suitability, and accessibility, and outstanding TCM characteristics. The product's safety, economy, and innovation received good ratings. In summary, Duliang soft capsules exhibited significant clinical value and outstanding TCM characteristics, the evidence was sufficient, and the result was confirmed, providing crucial references for clinical decision-making and pharmaceutical management.
2.Research progress of nitroxide radical derivatives and their biological activities
Qili ZHANG ; Xue TIAN ; Jie WANG ; Lei ZHAO ; Pengfei XIA ; Yanli XU ; Fumei XU ; Yinqiang JIA
Journal of China Pharmaceutical University 2024;55(5):673-684
Nitroxide radicals are a kind of stable organic free radicals.Due to the presence of N-O·and unpaired electrons in its structure,it has many characteristics,and thus can be used as a spin marker to explore the mechanism of biological reactions;with its magnetic properties,it can be used for the development of multifunctional magnetic molecular materials and used as a polymerization inhibitor and catalyst in organic reactions.More importantly,it has a variety of biological activities such as anti-oxidation and anti-tumor,and so has attracted much attention in the research and development of new drugs.For example,the spin labeling of nitroxide radicals on anticancer drug podophyllotoxin can enhance the efficacy and reduce the toxicity,and can be easily to be absorbed by the body,thus obtaining a new anti-cancer drug 4-[4″-(2″,2″,6″,6″-tetramethyl-1″-piperidinyloxy nitroxide radical)amino]-4′-demethyl epipodophyllotoxin(GP-7).It is an effective way to seek new drugs by introducing pharmacophore to modify nitroxide radicals or it can be spin-labeled on active natural products to obtain new compounds with high efficiency and low toxicity.The research progress of derivatives and its biological activitives of nitroxide radicals are summarized,aiming to provide theoretical basis for the developing and utilizing of nitroxide radicals and searching for new drugs.
3.miR-509-3p promotes oxidized low-density lipoprotein-induced apoptosis in mouse aortic endothelial cells.
Rui ZHANG ; Yanqiu SONG ; Fumei ZHAO ; Ting LIU ; Hongliang CONG ; Hui ZHAO
Chinese Critical Care Medicine 2023;35(12):1291-1297
OBJECTIVE:
To investigate the effect of microRNA-509-3p (miR-509-3p) on the apoptosis of atherosclerotic vascular endothelial cells.
METHODS:
Mouse aortic endothelial cells (MAECs) were divided into normal control group, oxidized low-density lipoprotein (ox-LDL) group, miR-509-3p overexpression group, miR-509-3p overexpression control group, miR-509-3p inhibitor + ox-LDL group, and miR-509-3p inhibitor control + ox-LDL group. MAEC were induced with 100 mg/L ox-LDL for 24 hours, and then transfected with miR-509-3p overexpression/inhibitor and corresponding control for 48 hours. The miR-509-3p expression in MAECs exposed to ox-LDL was detected using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Flow cytometry was used to detect the level of apoptosis, and cell counting kit (CCK-8) was used to detect the proliferation activity of MAECs. The direct gene targets of miR-509-3p were predicted using bioinformatics analyses and confirmed using a dual luciferase reporter assay. The expression of Bcl-2 mRNA and protein was detected by RT-qPCR and Western blotting, respectively.
RESULTS:
Compared with the normal control group, miR-509-3p was significantly upregulated in ox-LDL-stimulated MAECs (1.68±0.85 vs. 1.00±0.30, t = 2.398, P < 0.05). After transfection of MAECs with miR-509-3p overexpression, the luciferase activity of the BCL2 3'UTR WT reporter gene was significantly lower than that of miR-509-3p overexpression control group (0.83±0.06 vs. 1.00±0.07, t = 4.531, P = 0.001). The luciferase activity of the BCL2 3'-UTR mutant (MUT) reporter gene was not significantly different from that of miR-509-3p overexpression control group (0.94±0.05 vs. 1.00±0.08, t = 1.414, P = 0.188). Compared with the normal control group and miR-509-3p mimics control group, the cell proliferation activity was decreased [(0.60±0.06)% vs. (1.00±0.09)%, (0.89±0.04)%, both P < 0.01], the percentage of apoptotic cells were increased [(23.46±2.02)% vs. (7.66±1.52)%, (10.40±0.78)%, both P < 0.05], and the mRNA and protein expression of Bcl-2 were significantly downregulated (Bcl-2 mRNA: 0.52±0.13 vs. 1.00±0.36, 1.10±0.19, Bcl-2 protein: 0.42±0.07 vs. 1.00±0.11, 0.93±0.10, both P < 0.01) in miR-509-3p overexpression group. Compared with the ox-LDL group, inhibition of miR-509-3p expression could increase the proliferation activity of MAECs induced by ox-LDL [(0.64±0.35)% vs. (0.34±0.20%)%, P < 0.05], and reduce the apoptosis rate [(13.59±2.22)% vs. (29.84±5.19)%, P < 0.01], and up-regulated the expression of Bcl-2 mRNA and protein in MAECs induced by ox-LDL (Bcl-2 mRNA relative expression: 0.82±0.09 vs. 0.52±0.10, Bcl-2 protein relative expression: 0.83±0.17 vs. 0.40±0.07, both P < 0.05).
CONCLUSIONS
Bcl-2 was one of the target genes of miR-509-3p. miR-509-3p can reduce the proliferation activity of endothelial cells, reduce the expression of Bcl-2, and promote cell apoptosis, thereby promoting the occurrence and development of atherosclerosis. Inhibition of miR-509-3p expression may be a potential therapeutic target for atherosclerosis.
Animals
;
Mice
;
Humans
;
Endothelial Cells
;
MicroRNAs/metabolism*
;
Signal Transduction
;
Lipoproteins, LDL/metabolism*
;
Apoptosis
;
RNA, Messenger/metabolism*
;
Proto-Oncogene Proteins c-bcl-2/pharmacology*
;
Atherosclerosis/metabolism*
;
Luciferases/pharmacology*
;
Cell Proliferation
;
Human Umbilical Vein Endothelial Cells
4.A single-center prospective study of a screening strategy for early gastric cancer under high-definition gastroscopy
Peng JIN ; Fumei YIN ; Hui SU ; Lang YANG ; Zilin KANG ; Yuqi HE ; Xiaojun ZHAO ; Jianqiu SHENG
Chinese Journal of Digestive Endoscopy 2022;39(6):464-471
Objective:To study the effectiveness of a strategy for detecting early gastric cancer using high-definition gastroscopy.Methods:A total of 849 patients over 35 years old who underwent gastroscopy in the Seventh Medical Center of PLA General Hospital from December 2018 to January 2019 were enrolled to a prospective study. During gastroscopy, biopsies were taken at any suspicious lesions in patients who had never been infected with Helicobacter pylori. In ulcer-type lesions, biopsies were taken at the edge of the ulcer. Outside the atrophic area, biopsies were taken at lesions in the cardia which were reddish under white light, or lesions in the non-cardiac area which were white or showed clear borders under white light. Inside the atrophic area, biopsies were taken at elevated lesions with clear borders or irregular depressions on the top, or flat/depressed lesions with irregular borders or being ocherous under narrow band imaging. In addition, biopsies were performed on any lesion that did not meet the above standard but was considered necessary. The high-risk patients were followed up by gastroscopy to observe the detection and missed diagnosis of neoplasm that meet the above standard, and to determine the sensitivity and positive predictive value of the strategy. Results:A total of 548 patients were biopsied (781 lesions). Among the 327 lesions that met the above standard, 16 lesions (4.9%) were diagnosed as epithelial neoplasm, of which 10 (3.1%) were high-grade neoplasm. Among the 454 lesions that did not meet the standard, only 1 (0.2%) epithelial neoplasm was diagnosed, and there was no high-grade neoplasm. The positive predictive value of this screening strategy for gastric epithelial neoplasm and high-grade neoplasm was higher than those who did not meet the standard (4.9% VS 0.2%, χ2=19.49, P<0.01; 3.1% VS 0, P<0.001). There were 146 patients (17.2%, 146/849) followed up by gastroscopy. During the follow-up, 2 high-grade intramucosal neoplasms were found. 84.2% (16/19) of epithelial tumors and 83.3% (10/12) of high-grade neoplasm were detected during the initial gastroscopy. Conclusion:This screening strategy can efficiently detect early gastric cancer under high-definition gastroscopy.
5.Investigation of relationship between mean platelet volume and saphenous vein graft restenosis after coronary artery bypass grafting
Rui ZHANG ; Yanqiu SONG ; Cun XIE ; Shan LIU ; Fumei ZHAO ; Hongliang CONG ; Gang WU
Chinese Journal of Geriatrics 2019;38(5):508-512
Objective To investigate the relationship between mean platelet volume(MPV)and saphenous vein graft restenosis in patients receiving coronary artery bypass grafting(CABG),and to analyze the clinical significance of MPV in the prediction of restenosis after CABG.Methods A total of 354 patients admitted into Tianjin chest hospital from September 2009 to September 2014 with suspected myocardial ischemic events 3 to 5 years after CABG treatment was enrolled for a retrospective analysis.According to the coronary angiography(CAG)results,patients were divided into the vein bridge vascular lesion group(saphenous vein graft diseases,SVGD)(n=233)and the venous bridge vascular patency group(saphenous vein graft,SVG)(n=121).Paired t test was used to analyze the relationship between different factors and the bridge vascular patency.The binary logistic regression was used to analyze the effects of MPV and other factors on bridge vascular patency.Venous bridge stenosis > 50% was considered to be clinically significant and to damage myocardial blood supply.Results The MPV was higher in the SVGD group than the SVG group [(10.2±1.5)fl vs.(9.6±1.5)fl,P<0.01].The logistic regression analysis showed that MPV(OR =1.268,95%CI:1.053-1.570,P=0.014),age(OR =1.007,95%CI:1.038-1.117,P=0.000),gender (OR=0.452,95%CI:0.250-0.816,P=0.008),diabetes mellitus(OR=2.319,95%CI:1.221-4.405,P =0.010)were the independent risk factors for venous bridge stenosis in the two groups,gender(OR=0.495,95%CI:0.251-0.976,P=0.042),diabetes mellitus(OR =2.237,95%CI:1.105-4.527,P =0.025),MPV(OR=1.334,95%CI;1.050 1.694,P=0.018),fibrinogen(OR=1.654,95%CI:1.020-2.682,P =0.041)were the independent risk factors for venous bridge stenosis in non-elderly patients,and age(OR =1.178,95%CI:1.116-1.244,P =1.178)was an independent risk factor for vein graft stenosis in elderly patients.The restenosis rate was higher in patients with MPV ≥ 12 fl(92.6% or 25/27) than in the patients with MPV < 12 fl(63.6% or 208/327).The receiver operating characteristics(ROC) curve showed that the areas under the curve of MPV,age,gender,diabetes,fibrinogen were 0.610,0.657,0.394,0.626,0.654,respectively,and the area under the curve of joint diagnosis was 0.796,showing that joint prediction value was higher than any single prediction value(P<0.01).Conclusions MPV level is an independent risk factor for vein graft stenosis,and has higher predictive value in combination with age,gender,diabetes and fibrinogen.
6.Relationship between serum levels of osteoproteins, inflammatory cytokines and coronary heart disease and disease severity
Fumei ZHAO ; Rui ZHANG ; Hui ZHAO ; Ting LIU ; Min REN ; Yanqiu SONG ; Shan LIU ; Hongliang CONG
Chinese Critical Care Medicine 2019;31(5):588-593
Objective To explore the relationship between serum levels of osteoprotein (OPG), soluble nuclear factor-κB receptor activator ligand (sRANKL), inflammatory factors and coronary heart disease (CHD) and its severity. Methods The patients who underwent coronary angiography (CAG) due to chest pain admitted to department of cardiology of Tianjin Chest Hospital from April 2017 to December 2018 were enrolled, and they were divided into CHD group and non-CHD group according to the CAG results. The gender, age, history of hypertension, smoking history, diabetes, the levels of cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apoAI), apolipoprotein B (apoB), lipoprotein (a) [Lp (a)], MB isoenzyme of creatine kinase (CK-MB) and other clinical data of patients were collected. The serum levels of OPG, sRANKL, matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1), insulin-like growth factor-1 (IGF-1) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). According to the results of CAG, the patients with CHD were divided into single-, double-, triple-branch coronary artery lesion groups, and the relationship between the levels of serum OPG, sRANKL, inflammatory factors and the degree of coronary artery lesions was observed. Multivariate Logistic regression was used to analyze the risk factors of CHD, and receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of main risk factors for CHD. Results A total of 472 patients were enrolled in the final analysis during the study period, including 264 patients in the CHD group, 208 patients in the non-CHD group, 79 patients in the CHD group with single-branch disease, 75 patients with double-branch disease, and 110 patients with three-branch disease. ① Compared with the non-CHD group, the CHD group had more older male patients, as well as higher proportion of hypertension and diabetes, the levels of serum Lp (a) and CK-MB were significantly increased, and the levels of serum HDL-C and apoAI were significantly lowered. There was no statistically significant difference in serum TC, LDL-C, or apoB between the two groups. The levels of serum OPG, MMP-9, MCP-1, IGF-1 and IL-6 in the CHD group were significantly higher than those in the non-CHD group [OPG (μg/L): 1.79±0.50 vs. 1.50±0.30, MMP-9 (μg/L): 57.91 (33.50, 130.46) vs. 38.33 (29.43, 109.78), MCP-1 (μg/L):298.30 (207.96, 537.16) vs. 252.73 (165.22, 476.01), IGF-1 (μg/L): 734.03±486.11 vs. 217.75±126.45, IL-6 (ng/L):64.76±40.25 vs. 48.60±15.80, all P < 0.05], and the levels of serum sRANKL was significantly lower than that in the non-CHD group (ng/L: 344.31±122.14 vs. 378.74±109.27, P < 0.05). ② The serum OPG level showed a slight upward tendency with the increase in the number of coronary artery lesions, and the sRANKL level showed a slight downward tendency [OPG (μg/L) in the single-, double-, triple-branch coronary artery lesion groups was 1.74±0.49, 1.76±0.50, 1.85±0.52, and sRANKL (ng/L) was 354.96±116.64, 340.05±124.24, 339.57±125.03, respectively) without statistically significant differences (all P > 0.05). The levels of IGF-1 and IL-6 were increased with the number of coronary artery lesions [IGF-1 (μg/L) in the single-, double- and triple-branch coronary artery lesions groups was 372.13±258.42, 676.06±350.29, 1 033.47±468.06, and IL-6 (ng/L) was 48.87±16.72, 65.36±18.84, 75.76±22.72, respectively], and the differences among different lesion groups were statistically significant (all P < 0.01). Correlation analysis showed that IGF-1 level was significantly positively correlated with the number of coronary artery lesions (r = 0.612, P < 0.01), while IL-6 was not correlated with the number of coronary artery lesions (r = 0.185, P > 0.05).③ Multivariate Logistic regression analysis showed that elevated serum OPG and IGF-1 levels were risk factors for CHD [OPG: odds ratio (OR) = 1.995, 95% confidence interval (95%CI) = 1.936-2.067, P = 0.012; IGF-1: OR = 1.009, 95%CI = 1.004-1.015, P = 0.001]. ④ ROC curve analysis showed that the area under ROC curve (AUC) of OPG and IGF-1 was 0.716 and 0.867, respectively. When the cut-off value of OPG was 1.13 μg/L, the sensitivity was 81.7%, the specificity was 58.1%; when the cut-off value of sRANKL was 401.20 μg/L, the sensitivity was 69.7%, the specificity was 95.7%. Conclusions CHD was associated with increased in OPG, related inflammatory cytokines including MMP-9, MCP-1, IGF-1 and IL-6, and decreased in sRANKL. The level of IGF-1 was positively correlated with the severity of CHD. The serum levels of OPG and IGF-1 were risk factors for CHD, which had good predictive value for CHD.
7.Polymorphisms of T149C and T950C genes in osteoprotegerin promoter sites and the relationship between serum osteoprotegerin levels and coronary heart disease.
Fumei ZHAO ; Hui ZHAO ; Rui ZHANG ; Min REN ; Chao LIU ; Shan LIU ; Jing MA ; Yanqiu SONG ; Ting LIU ; Xu ZHANG ; Hongliang CONG
Chinese Critical Care Medicine 2019;31(3):319-324
OBJECTIVE:
To explore the polymorphisms of T149C and T950C gene in osteoprotectin (OPG) promoter sites and the levels of serum OPG and soluble nuclear factor-ΚB receptor activator ligand (sRANKL) and the incidence of coronary heart disease (CHD).
METHODS:
528 patients in Tianjin suspected of CHD and underwent coronary angiography (CAG) who admitted to the department of cardiology of Tianjin Chest Hospital from April 2017 to December 2018 were enrolled. According to the CAG results, they were divided into two groups: CHD group (n = 302) and non-CHD group (n = 226). The gender, age, history of hypertension, family history of CHD, diabetes, levels of blood lipid parameters in serum and other clinical data of patients were recorded. The levels of serum OPG and sRANKL were measured by enzyme-linked immunosorbent assay (ELISA). T149C and T950C gene polymorphisms were analyzed by polymerase chain reaction-restriction endonuclease fragment length polymorphism (PCR-RFLP) methods. Hardy-Weinberg genetic balance test was performed for alleles. Binomial classification multivariate non-conditional Logistic regression method was used to analyze the relationship between T149C and T950C gene polymorphisms, serum levels of OPG and sRANKL and CHD.
RESULTS:
All patients were enrolled in the final analysis. The serum level of OPG in CHD group was significantly higher than that in non-CHD group (μg/L: 1.76±0.49 vs. 1.47±0.29, P < 0.01), the serum level of sRANKL was significantly lower than that in non-CHD group (ng/L: 342.14±121.38 vs. 376.63±108.66, P < 0.05). Logistic regression analysis showed that after adjusting for age, gender, blood lipid parameters, diabetes and other factors, the increase in serum OPG level was an independent risk factor for CHD [odds ratio (OR) = 1.995, 95% confidence interval (95%CI) = 1.935-2.066, P = 0.012]. PCR-RFLP results showed that TT, TC and CC genotypes were found in T149C and T950C of OPG promoter. According to Hardy-Weinberg equilibrium test, the polymorphisms of OPG T149C and T950C accorded with Hardy-Weinberg law, achieving genetic balance with representative of the population. The frequencies of TT, TC, CC and alleles T and C in T149C genotypes of non-CHD group were 53.5%, 42.9%, 3.6%, 75.0% and 25.0%, respectively, and they were 43.1%, 50.3%, 6.6%, 68.2% and 31.8%, respectively in CHD group. There were statistically significant differences in genotype and allele frequencies between the two groups (all P < 0.05). It was shown by Logistic regression analysis that the risk of CHD in TC+CC genotype of T149C was 1.86 of TT genotype (OR = 1.86, 95%CI = 1.24-2.78, P = 0.003). It was suggested that C allele might be a susceptible gene for CHD. In non-CHD group, the frequencies of TT, TC, CC, and alleles T and C in T950C genotypes were 39.8%, 46.5%, 13.7%, 63.1% and 36.9%, respectively. They were 39.4%, 43.4%, 17.2%, 61.1% and 38.9%, respectively in CHD group. There were no significant differences in genotype and allele frequencies between the two groups (all P > 0.05). Logistic regression analysis showed that TC+CC genotype of T950C was not related with CHD.
CONCLUSIONS
The increased level of serum OPG was closely related with CHD and could be used as a risk factor for CHD. The cases carried OPG T149C TC+CC genotype might have the risk suffering CHD. C allele is might be a susceptible gene.
China/epidemiology*
;
Coronary Disease/epidemiology*
;
Female
;
Humans
;
Male
;
Osteoprotegerin/genetics*
;
Polymorphism, Genetic
;
Promoter Regions, Genetic/genetics*
;
Risk Factors
8.Establishment and evaluation of mouse models of septic myocardial injury
Liya HU ; Peijun LI ; Chao CHANG ; Shan LIU ; Yanqiu SONG ; Fumei ZHAO ; Ting LIU
Chinese Critical Care Medicine 2018;30(4):342-345
Objective Mouse models of sepsis-induced myocardial injury by intraperitoneal injection of lipopolysaccharide (LPS) was established in order to provide a reliable method for the research of pathogenesis of sepsis-induced myocardial injury. Methods According to the method of random number table, a total of 150 male C57BL/6 mice were divided into five groups: NC group, sham group, and LPS 10, 12, 15 mg/kg groups, with 30 in each group. Septic myocardial injury was induced by intraperitoneal injection LPS in mice; sham group was injected with equal 0.9% saline; while there was no treatment in mice of NC group. Fifteen of the 30 mice in each group were used to observe the general status of mice before and after LPS or saline injection. Twenty-four hours after LPS or saline injection, the left ventricular function was assessed by echocardiography, serum level of cardiac troponin (cTnI) was determined by enzyme linked immunosorbent assays (ELISA), and the cardiac histomorphology and ultrastructure were observed; the other 15 mice were used to monitor the 7-day mortality after LPS or saline injection. Results The mice challenged to LPS displayed symptoms of sepsis, such as depression, ruffled fur, and diarrhea. Compared with NC group, left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS) were significantly decreased at 24 hours after LPS administration in LPS 10, 12, 15 mg/kg groups [LVEF: 0.459±0.044, 0.432±0.034, 0.348±0.064 vs. 0.588±0.019, LVFS: (22.36±2.60)%, (20.78±1.91)%, (16.27±3.31)% vs. (30.55±1.30)%, all P < 0.01], and cTnI levels were significantly increased (ng/L: 270.40±43.50, 281.14±41.79, 298.39±42.05 vs. 192.59±16.90, all P <0.01). Myocardium injury was observed in three LPS groups, myocardial fibrosis, interstitial edema, erythrocyte leakage and infiltrating inflammatory cells were observed under light-microscope; ultrastructural changes disorderly arranged in cardiac muscle fibers, mitochondrial swelling and even partly missing mitochondria cristae were found under transmission electron microscope (TEM), and the higher of the dose, the more sever of the damage. There was no significant difference between sham group and NC group. The 7-day mortality in LPS 10, 12, 15 mg/kg groups were 33.3%, 53.3% and 86.7%, respectively, while no death in the NC group and sham group. Conclusion For establishing the mouse model of sepsis-induced myocardial injury, intraperitoneal injection with 12 mg/kg LPS is a preferable choice in our research.
9.Protective effects of MicroRNA-214 on myocardial injury induced by myocardial ischemia and reperfusion and the regulation mechanism of its downstream protein kinase
Shan LIU ; Yanqiu SONG ; Fumei ZHAO ; Ting LIU ; Jie GENG
Chinese Journal of Geriatrics 2017;36(7):802-805
Objective To investigate the protective effects of MicroRNA-214 on myocardial injury induced by myocardial ischemia and reperfusion,as well as the regulation mechanism of PI3K and its downstream protein kinase B(AKT)and FoxO1(PI3K / AKT / FoxO1).Methods Wistar rats were randomly divided into 4 groups:sham operation group(Sham group),myocardial ischemia reperfusion injury(IRI)group(IRI group),microRNA-214+sham operation group(MS group),microRNA-214+IRI group(MI group),(n=10,each).The cardiac function was detected at 6 h after ischemia-reperfusion operation.And blood lactate dehydrogenase(LDH),creatine kinase(CK),creatine phosphate kinase isoforms MB(CK-MB),cardiac troponin T(cTnT),serum B natriuretic peptide(pro-BNP)in plasma were detected by enzyme-linked immunosorbent assay(ELISA).Interleukin 10(IL-10),Interleukin 6(IL-6)and tumor necrosis factor α(TNF-α)were assayed.Pathological changes of myocardial tissue were detected by HE and Masson.The expression of microRNA-214 was detected by RT-PCR.The expression of Bax,Caspase-3,BCl2,PI3K,Akt,FoxO1 was detected by Western Blot.Results Compared with Sham group,IRI group showed a significantly increases in myocardial injury parameters of LDH,CK,IL-6 and TNF concentration in plasma,and a significantly reduced concentration of IL-10(P<0.05).And compared with Sham group,MI group showed a significantly increased expression of microRNA-214(P<0.05)and showed a significantly increased myocardial parameters of Bax,Caspase-3,PI3K,Akt protein,and a decreased level of BCl2,FoxO1(P<0.05).Compared with IRI group,microRNA-21 group showed a reduced myocardial ischemia-reperfusion-induced myocardial injury in rats and a reduced plasma concentration of LDH,CK,IL-6 and TNF-alpha,a inhibited expression of caspase-3,Bax,myocardial PI3K and Akt,and a promoted expression of BCl2 and FoxO1 protein(P<0.05).Conclusions MicroRNA-214 reduces the myocardial injury induced by myocardial ischemia-reperfusion through PI3K/Akt signaling pathway.
10.Comparison of the treatment efficacy of pulmonary hypertension after mitral valve replacement
Fumei ZHAO ; Tongyun CHEN ; Jing SUN ; Jianshi LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2015;31(10):600-603
Objective To investigate the effect of rhBNP in treating pulmonary hypertension after mitral value replacement (MVR) compared with PGE1.Methods 60 patients with pulmonary hypertension after MVR were randomly divided into 3 groups(control group, PGE1 group and rhBNP group).Hemodynamic factors(MAP, CVP, mPAP, etc.) were monitored before and after taking medicine at 1 h, 6 h, 24 h, respectively including drug withdrawal 2 h.TXA2 and cGMP were analyzed by ELISA.To observe the levels of TXA2 and cGMP in plasma before and after treatment with rhBNP and PGE1 for three times (24 h, 1 week and 3 months).Information about patients'mechanical ventilation time was also recorded.Results Patients' mechanical ventilation time in PGE1 group was the shortest.MAP, mPAP, PRVI, PAWP were reduced after treatment by medicine 1 h for in PGE1 group.However, these indexes were rebound after drug withdrawal.mPAP, PRVI, PAWP in rhBNP group decreased after treatment by medicine at 6 h.The decreased level of mPAP was less than that in PGEI group.In control group, TXA2 went down and cGMP went up after operation.After taking medicine at 24 h, TXA2 decreased and cGMP increased in both PGE1 and rhBNP group.The increased level in rhBNP group was higher than that of control group.With medicine, the decreased level of TXA2 in PGE1 was also higher than that in rhBNP group.The going-up of cGMP in rhBNP was higher than that in PGE1.Conclusion Both rhBNP and PGE1 can reduce pulmonary artery pressure, PGE1 is more effective than that of rhBNP.

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