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Objective: To determine the impact of inflammatory reaction levels and the culprit plaque characteristics on preprocedural Thrombolysis in Myocardial Infarction (TIMI) flow grade in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: The is a retrospective study. A total of 1 268 STEMI patients who underwent pre-intervention optical coherence tomography (OCT) examination of culprit lesion during emergency PCI were divided into 2 groups by preprocedural TIMI flow grade (TIMI 0-1 group (n =964, 76.0%) and TIMI 2-3 group (n =304, 24.0%)). Baseline clinical data of the 2 groups were collected; blood samples were collected for the detection of inflammatory markers such as high sensitivity C-reactive protein (hsCRP), myocardial injury marker, blood lipid, etc.; echocardiography was used to determine left ventricular ejection fraction; coronary angiography and OCT were performed to define the lesion length, diameter stenosis degree of the infarct-related arteries, presence or absence of complex lesions, culprit lesion type, area stenosis degree and vulnerability of culprit plaques. Multivariable logistic regression analysis was performed to identify independent correlation factors. The receiver operating characteristic (ROC) curve of continuous independent correlation factors was analyzed, and the best cut-off value of TIMI 0-1 was respectively determined according to the maximum value of Youden index. Results: The mean age of 1 268 STEMI patients were (57.6±11.4) years old and 923 cases were males (72.8%). Compared with TIMI 2-3 group, the patients in TIMI 0-1 group were older and had higher N-terminal-pro-B-type natriuretic peptide level, lower cardiac troponin I (cTnI) level, lower left ventricular ejection fraction, and higher hsCRP level (5.16(2.06, 11.78) mg/L vs. 3.73(1.51, 10.46) mg/L). Moreover, the hsCRP level of patients in TIMI 0-1 group was higher in the plaque rupture subgroup (all P<0.05). Coronary angiography results showed that compared with TIMI 2-3 group, the proportion of right coronary artery (RCA) as the infarct-related artery was higher, the angiographical lesion length was longer, minimal lumen diameter was smaller, and diameter stenosis was larger in TIMI 0-1 group (all P<0.05). The prevalence of plaque rupture was higher (75.8% vs. 61.2%) in TIMI 0-1 group. Plaque vulnerability was significantly higher in TIMI 0-1 group than that in TIMI 2-3 group with larger mean lipid arc (241.27°±46.78° vs. 228.30°±46.32°), more thin-cap fibroatheroma (TCFA, 72.4% vs. 57.9%), more frequent appearance of macrophage accumulation (84.4% vs. 70.7%) and cholesterol crystals (39.1% vs. 25.7%). Minimal flow area was smaller [1.3(1.1-1.7)mm2 vs. 1.4(1.1-1.9)mm2, all P<0.05] and flow area stenosis was higher (78.2%±10.6% vs. 76.3%±12.3%) in TIMI 0-1 group. Multivariable analysis showed that mean lipid arc>255.55°, cholesterol crystals, angiographical lesion length>16.14 mm, and hsCRP>3.29 mg/L were the independent correlation factors of reduced preprocedural TIMI flow grade in STEMI patients. Conclusions: Plaque vulnerability and inflammation are closely related to reduced preprocedural TIMI flow grade in STEMI patients.
Subject(s)
Aged , Humans , Male , Middle Aged , Coronary Angiography , Inflammation , Myocardial Infarction/diagnostic imaging , Percutaneous Coronary Intervention , Plaque, Atherosclerotic/diagnostic imaging , Retrospective Studies , ST Elevation Myocardial Infarction/surgery , Stroke Volume , Thrombolytic Therapy , Ventricular Function, LeftABSTRACT
OBJECTIVE Gastric cancer is one of the most common malignant tumors,and the inci-dence rate is the highest in all kinds of tumors in China. However,it remains unclear that how signifi-cantly gastric cells are dependent on glycolysis,and which type of gastric cells are sensitive to glycolysis inhibition. In this study, several kind of gastric cancer cell lines were used as the research object, and the metabolic characteristics of different cell lines were systematically analyzed to provide theoretical support for the accurate treatment of gastric cancer. METHODS We examined the energy metabolism of four gastric cancer cell lines(MGC-803,SGC-7901,HGC-27 and BGC-823)by using glycolysis inhibitor, 2-deoxy-D-glucose(2-DG)and inhibitor of oxidative phosphorylation,oligomycin.Oxygen consumption rates(OCR)and L-lactate were also measured with an XF96 Analyzer(Seahorse Biosciences)to deter-mine the significance of metabolism of oxidative phosphorylation and aerobic glycolysisin gastric cells. In addition, western blot was used to detect the contribution of AMP-activated protein kinase (AMPK), and anti-apoptotic proteins(Bcl-2 and survivin)to clarify the mechanism of death or survival of gastric cancer cells treated by 2-DG or oligomycin. RESULTS In this study, it was shown that the growth of gastric cell lines were suppressed by 2-DG.However,the sensitivity to 2-DG was quite different among cell lines:IC 50 of 2-DG was from 3.28 mmol·L-1(MGC-803)to 15.57 mmol·L-1(BGC-823).MGC-803 was relatively sensitive to 2-DG (IC 50:3.28 mmol·L-1), consumed more glucose and produced more lactate (waste product of glycolysis) than the three other cell lines. Consequently, MGC-803 could be more dependent on glycolysis than other cell lines, which was further confirmed by the fact that glucose (+)FCS(-)medium showed more growth and survival than glucose(-)FCS(+)medium.Alternatively, BGC-823, most resistant to 2-DG (IC50: 15.57 mmol·L- 1), was most sensitive to oligomycin, and showed more growth and survival in glucose(-)FCS(+)medium than in glucose(+)FCS(-)medium. Thus,we had reasons to think BGC-823 cells depended on oxidative phosphorylation for energy production. In BGC-823,AMPK,which is activated when ATP becomes limiting,was rapidly phosphorylated by 2-DG, and expression of Bcl-2 was augmented,which might result in resistance to 2-DG.Interestingly,AMPK phosphorylation and augmentation of Bcl-2 expression by 2-DG were not observed in MGC-803,which is 2-DG sensitive. CONCLUSION There is a large metabolic difference between gastric cancer cell lines,which will facilitate the future gastric cancer therapy by targeting metabolic pathways.
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The unwanted immunogenicity of biopharmaceutical is an adverse reaction caused by long-term medication.The primary concerns of immunogenicity would be critical for the efficacy and safety of biopharmaceutical.The immunogenicity assessments include validation of methodology,detection of anti-drug antibodies,characterization antibodies and their subtypes against biopharmaceuticals,determination of antibody neutralization as well as the analyses of relationship of antibody formation to pharmacokinetics and pharmacodynamics parameter and toxicities of drugs.The optimization of detection methods,the predictability of immunogenicity with available animal models and the standardization of evaluation method are currently the major challenges in the assessment of immunogenicity for biopharmaceuticals.
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The unwanted immunogenicity of biopharmaceutical is an adverse reaction caused by long-term medication.The primary concerns of immunogenicity would be critical for the efficacy and safety of biopharmaceutical.The immunogenicity assessments include validation of methodology,detection of anti-drug antibodies,characterization antibodies and their subtypes against biopharmaceuticals,determination of antibody neutralization as well as the analyses of relationship of antibody formation to pharmacokinetics and pharmacodynamics parameter and toxicities of drugs.The optimization of detection methods,the predictability of immunogenicity with available animal models and the standardization of evaluation method are currently the major challenges in the assessment of immunogenicity for biopharmaceuticals.
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To compare the discriminatory ability of multilocus sequence typing and serotype of animal-derived Salmonella and find its distribution in Shandong Province,78 chicken-origin,56 duck-origin and 20 swine-origin Salmonella were separated from some regions of Shandong Province.Seven conserve sequences of Salmonella were PCR-amplified for MLST and slide agglutination test for serotyping.Results showed that by serotyping,6 serotypes were identified from chicken-origin Salmonella,including 88.5％0 S.enteritidis,5.1％ S.indiana,2.6％ S.thompson,1.3％ S.typhimurium,1.3％ S.senftenberg,1.3％ S.agama.Two serotypes were identified from duck-origin Salmonella,including 67.9％ S.enteritidis,32.1％ S.ty phimurium.Three serotypes were identified from swine-origin Salmonella,including 65％ S.typhimurium,20％ S.derby,and 15％ S.enteritidis.By MLST typing,seven ST types were identified from chicken-origin Salmonella:ST11,ST19,ST26,ST128,ST14,ST17 and Newl.Three ST types were identified form duck-origin Salmonella:ST11,ST19 and New2.Three ST types were identified from swine-origin Salmonella:ST34,ST40 and ST3007.Overall,the types identified with two methods were closed,so MLST and serotype have similar discriminatory ability.
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To compare the discriminatory ability of multilocus sequence typing and serotype of animal-derived Salmonella and find its distribution in Shandong Province,78 chicken-origin,56 duck-origin and 20 swine-origin Salmonella were separated from some regions of Shandong Province.Seven conserve sequences of Salmonella were PCR-amplified for MLST and slide agglutination test for serotyping.Results showed that by serotyping,6 serotypes were identified from chicken-origin Salmonella,including 88.5％0 S.enteritidis,5.1％ S.indiana,2.6％ S.thompson,1.3％ S.typhimurium,1.3％ S.senftenberg,1.3％ S.agama.Two serotypes were identified from duck-origin Salmonella,including 67.9％ S.enteritidis,32.1％ S.ty phimurium.Three serotypes were identified from swine-origin Salmonella,including 65％ S.typhimurium,20％ S.derby,and 15％ S.enteritidis.By MLST typing,seven ST types were identified from chicken-origin Salmonella:ST11,ST19,ST26,ST128,ST14,ST17 and Newl.Three ST types were identified form duck-origin Salmonella:ST11,ST19 and New2.Three ST types were identified from swine-origin Salmonella:ST34,ST40 and ST3007.Overall,the types identified with two methods were closed,so MLST and serotype have similar discriminatory ability.
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The study was designed to explore the effects of HS060098 on activation of peroxisome proliferator-activated receptors (PPARα, γ and δ) and in the down-regulation of hyperlipidemia in golden hamster. Luciferase gene reporters of PPARα, PPARγ and PPARδ were constructed in HepG2 cells and the green fluorescent protein (GFP) was used as an internal reference. Transfected cells were then cultured with various concentrations of HS060098 for 24 h. The peroxisome proliferator-response element luciferase activity was determined by the dual-luciferase reporter gene assay system. To investigate the lipid-lowering effect of HS060098, hyperlipidemic golden hamsters fed by high-diet were administered orally with HS060098 through prophylactic and therapeutic approaches respectively. The levels of blood lipids such as total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and fat index in hamsters were evaluated. The results showed that HS060098 was a potent activator of PPAR δ with a good selectivity and the median effective concentration (EC 50) is 0.01 μmol·L-1, while no obvious PPARα and PPARγ activation was observed. In the golden hamster, oral administration of HS060098 (5, 10, 20 mg·kg-1·d-1) for 2 weeks, led to a significant decrease the concentrations of plasma TC, TG, LDL-C and fat index (PPPPδ agonist with a significant activity in the prevention and therapy of hyperlipemia in golden hamster.
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<p><b>OBJECTIVE</b>To analyze the allergic status to common inhalant allergens and food allergens in clinical patients in Harbin in northeastern China and provide evidence to develop the prevention strategy of allergic disease.</p><p><b>METHODS</b>The data were collected from 5 473 patients with clinical suspected allergic diseases seeking medical care in the Second Affiliated Hospital of Harbin Medical University. Among these patients, 2 530 (46.2%) were males aged 0-86 years, the youngest was only 1 month old and 2 579 (47.1%) were young children and teenagers. The serum specific Immunoglobulin E (sIgE) to 14 kinds of common allergens and serum total IgE were detected by using AllergyScreen test (Mediwiss Analytic GmbH, Moers, Germany).</p><p><b>RESULTS</b>In 5 473 subjects the positive rate of sIgE was 33.1% (n=1 813). Cow milk (6.9%) and wheat (3.1%) were the most common food allergens, followed by house dust mite mix (12.5%) and mould mix (9.4%) and the age and gender specific differences in the positive rate were significant. For the children aged <7 years the positive rates to cow milk, beef-mutton, and egg white/egg yolk were high, but the positive rates to house dust mite mix, ragweed estragon, and mould mix were low (P<0.05). For the adults the positive rates to aeroallergens were high while the rates to food allergens were low.</p><p><b>CONCLUSION</b>The results from this study showed that the food allergens in Harbin had geographic characteristics, which support the viewpoint that the environment factors play an important role in the incidence of allergic diseases. Also, the detection of sIgE and total IgE are essential to identify relevant allergens for the purpose of early diagnosis, management and prevention of allergic disease.</p>
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Animals , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Young Adult , Age Factors , Allergens , China , Epidemiology , Cities , Food Hypersensitivity , Epidemiology , Allergy and Immunology , Incidence , Respiratory Hypersensitivity , Epidemiology , Allergy and Immunology , Sex FactorsABSTRACT
Erythropoientin (Epo), a glycoprotein hormone, plays an important role in erythropoiesis and neuroprotection. Recently,Epo is also considered to have protective effects against hyperoxic lung injury, retinopathy of prematurity and neonatal necrotizing enterocolitis. Recombinant human erythropietin (rhEpo) as Epo gene cloning drug has been widely used in neonatal clinical practice.
Subject(s)
Humans , Infant, Newborn , Enterocolitis, Necrotizing , Drug Therapy , Erythropoietin , Chemistry , Therapeutic Uses , Hypoxia-Ischemia, Brain , Drug Therapy , Infant, Newborn, Diseases , Drug Therapy , Recombinant Proteins , Therapeutic Uses , Retinopathy of Prematurity , Drug TherapyABSTRACT
Objective To investigate changes in CD_4~+ CD_(28)~(null)T cell numbers of peripheral blood and the expression of perforin in patients with coronary heart disease.Methods Sixty-eight patients with acute coronary syndromes,56 with stable angina and 65 healthy subjects were enrolled in the study.CD_4~+ CD_(28)~(null)T lymphocytes were measured by flow cytometric analysis.Results The numbers of CD_4~+ CD_(28)~(null)T lymphocytes in patients with acute coronary syndromes were higher than those in patients with stable angina and in the control subjects(11.6 % vs 2.84% and 0.59%,P