Objective: To explore influence of long-term oral valsartan-angiotensin II type 1 receptor blocker on ventricular arrhythmia after myocardial infarction (MI) in rabbits and its possible mechanism. Methods: A total of 24 New Zealand rabbits were randomly divided into sham operation group (n=8), MI group (n=8) and valsartan group (n=8) according to number table. Sham operation group only received thoracotomy without ligation of anterior descending branch of left coronary artery (LAD), while MI group and valsartan group received ligation of anterior descending branch of LAD. Valsartan group received valsartan gavage (10 mg•kg-1•d-1) since the second day after operation, three groups all were fed for 12 weeks. Mono active potential (MAP) of left ventricular myocardial cells of subendocardial myocardium（inner layer myocardium）, subepicardial myocardium（outer layer myocardium）and middle layer myocardium were recorded before MI and 12 weeks after MI, and times of provocative malignant arrhythmias were recorded on 12 weeks after MI in three groups. Results: 1. Ventricular tachycardia or fibrillation (VT/ VF) episodes were markedly decreased in VAL group than that in MI group on 12 weeks after MI [(3.1±0.8) vs. (12.7±1.5), P＜0.05]; 2. After MI 12 w, the action potential duration to 90% repolarization (APD90) of three-layer ventricular myocytes in MI group was prolonged than that before MI [（259.2±22.1）ms,（288.0±25.8）ms,（244.6±22.6）ms vs.（230.1±23.2）ms,（244.2±23.4）ms,（229.0±21.7）ms, P＜0.05 or＜0.01]；but there were no significant difference in APD90 of three layers ventricular myocytes between before and after MI in valsartan group (P>0.05 all); Compared with sham operation group and valsartan group, there was significant prolonged in transmural dispersion of repolarization (TDR) [(18.8±6.2) vs. (23.9±7.7) vs. (37.2±10.2), P<0.05 or＜0.01] in MI group; There was no significant difference in TDR between valsartan group and sham operation group (P>0.05). Conclusions: Long-term oral valsartan can significantly reduce malignant ventricular arrhythmia incidence in rabbits after MI, which may be related to improving TDR in rabbits after MI.

Cyclophilin A (CypA) is found to be highly expressed in different kinds of tumor cells,which could regulate the occurrence and development of many kinds of tumor through multiple signal transduction pathways such as inducing the formation of inflammatory carcinoma,accelerating the transcription cycle of tumor cells,promoting the invasion and metastasis of tumor cells,inhibiting the apoptosis of tumor cells and reducing the sensitivity of tumor cells to chemotherapy drugs.It suggests that CypA might be considered as a kind of oncogene,which is expected to be a novel target for tumor treatment.

OBJECTIVETo study the effects of low dose sodium selenite combined with all-trans retinoic acid (ATRA) on apoptosis and differentiation of human acute promyelocytic leukemia (APL) NB4 cells.

METHODSApo-ptosis was detected by translocation of phosphatidylserine (PS) with a Annexin-V kit and DNA fragmentation by agarose gel electrophoresis analysis, cell differentiation was studied by flow cytometry of CD(11b) expression and NBT reduction assay.

RESULTSFive micromol/L sodium selenite or 0.1 micromol/L ATRA alone could not induce apoptosis of NB4 cells within 48 hours. However, combination of the two drugs at the same doses as above could induce significant apoptosis in 48 hours characterized by increased PS translocation and DNA ladder. Sodium selenite at concentration of 2 micromol/L was not able to induce differentiation of NB4 cells, but when combined with 0.1 micromol/L ATRA, CD(11b) expression and NBT reduction were increased as compared with that of 0.1 micromol/L ATRA alone.

CONCLUSIONLow dose sodium selenite could enhance the effects of low dose ATRA in inducing apoptosis and differentiation of NB4 cells.

Apoptosis ; drug effects ; CD11b Antigen ; analysis ; Cell Differentiation ; drug effects ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Drug Synergism ; Flow Cytometry ; Humans ; Leukemia, Promyelocytic, Acute ; metabolism ; pathology ; Sodium Selenite ; pharmacology ; Tretinoin ; pharmacology

OBJECTIVETo study the separation, purification and ex vivo expansion of CD(34)(+) CD(59)(+) cells from patients with paroxysmal nocturnal hemoglobinuria (PNH), and explore the new treatment for the PNH patients.

METHODSCD(34)(+) CD(59)(+) cells were selected from the bone marrow mononuclear cells of PNH patients by means of immunomagnetic microbead-flow cytometry two step sorting method, followed by ex vivo expansion of the cells with combination of hematopoietic factors for two weeks.

RESULTSThe best combination for the ex vivo expansion was SCF + IL-3 + IL-6 + FL + Tpo + Epo, and the seventh day was the most suitable time for the best harvest when the CD(34)(+) CD(59)(+) cells were 22.42 +/- 3.73 fold expanded. After ex vivo expansion, the cells remained CD(59) positive and potent capacity of colony formation, but their potentialities to multilineage differentiation were decreased.

CONCLUSIONThe present study shows that ex vivo expansion of CD(34)(+) CD(59)(+) cells from PNH patients might promise the possibility of performing ABMT or APBSCT clinincally for the patients.

Antigens, CD34 ; analysis ; Bone Marrow Cells ; cytology ; immunology ; CD59 Antigens ; analysis ; Cell Differentiation ; immunology ; Cell Division ; immunology ; Cell Lineage ; Flow Cytometry ; Hemoglobinuria, Paroxysmal ; blood ; immunology ; Humans ; Immunophenotyping ; Time Factors

OBJECTIVESTo investigate the stroma-independent growth ability, multilineage differentiation and expansion of the single hematopoietic stem/progenitor cell from patients with paroxysmal nocturnal hematoglobinuria (PNH).

METHODThe CD(34)(+) CD(59)(+) and CD(34)(+) CD(59)(-) cells from PNH patients and CD(34)(+) CD(59)(+) cells from normal volunteers were sorted as each single cell into a well of 96 well culture plates containing culture medium supplemented with SCF, IL-3, Epo, GM-CSF, G-CSF, IL-6, Tpo and Flt-3 ligand.

RESULTS(1) Single PNH CD(34)(+) CD(59)(-) cell had a higher capacities for plating efficiency, colony (>/= 50 cells) formation and cell expansion than that of the PNH CD(34)(+) CD(59)(+) cells (P < 0.05); (2) Both the single CD(34)(+) CD(59)(-) cells from PNH patients and the single CD(34)(+) CD(59)(+) cells from normal controls had similar capacities for cell plating efficiency and colony and large colony formation. The PNH CD(34)(+) CD(59)(-) cells had a lower average cell production and cell expansion capacity. (3) The single CD(34)(+) CD(59)(+) cells from both PNH patients and normal controls showed the same capacities for cell plating efficiency and colony formation. The PNH CD(34)(+) CD(59)(+) cells exhibited much lower capacity for large colony formation, average cell production and total cell expansion. (4) A diminished secondary colony formation ability was also observed in the PNH CD(34)(+) CD(59)(+) and CD(34)(-) CD(59)(-) clones.

CONCLUSIONThe single PNH CD(34)(+) CD(59)(-) cells had growth advantage over the single PNH CD(34)(+) CD(59)(+) cells to some extent, but they both had impaired growth abilities as compared with CD(34)(+) cells from normal volunteers.

Antigens, CD34 ; immunology ; CD59 Antigens ; immunology ; Cell Culture Techniques ; Cell Division ; physiology ; Colony-Forming Units Assay ; Hematopoietic Stem Cells ; immunology ; pathology ; Hemoglobinuria, Paroxysmal ; physiopathology ; Humans

Before 131I-HAb18F(ab')2 administration, 24 cases of mid-term or advanced hepatocellular carcinoma(HCC) were given Lugol's Liquid to block the thyroid gland, and submitted to hepatic colloid imaging. The cases were randomly divided into 3 groups. Then 131I-HAb18F(ab')2 was injected into the target hepatic artery with doses of 0.5, 0.75, 1.0 mCi/kg, respectively. At the followed 10, 48, 96 and 192 hours, 131I-HAb18F(ab')2 distribution in human body was acquired by whole body dynamic image with Single photon emission computed tomography(SPECT). The results showsed that 131I-HAb18F(ab')2 in tumor tissue was significantly higher than that in normal liver tissue and other organs. This difference became obvious as time passed. 131I-HAb18F(ab')2 is stable in human body and it can combine with HCC tissue specifically. So it is a new medicine deserving further research for the treatment of HCC.
Adult ; Aged ; Antibodies, Monoclonal ; administration & dosage ; pharmacokinetics ; Carcinoma, Hepatocellular ; radiotherapy ; Female ; Humans ; Immunoglobulin Fab Fragments ; administration & dosage ; metabolism ; Iodine Radioisotopes ; administration & dosage ; pharmacokinetics ; Liver Neoplasms ; radiotherapy ; Male ; Middle Aged ; Radioimmunotherapy ; Radiopharmaceuticals ; administration & dosage ; pharmacokinetics ; Tissue Distribution

Objective: To investigate the early intervention effects of metoprolol on connexin 43(Cx43) and phosphorylated Cx43 (p-Cx43) expression in rabbits with post myocardial infarction. Methods: A total of 24 adult male New Zealand white rabbits were divided into sham group (n=6), early treatment group(n=6), routine treatment group(n=6), and myocardial infarction group(n=6) with a randomized block design blocked by weight. Myocardial infarction was induced by left anterior descending coronary artery (LAD) ligation. Rabbits in sham group received similar surgical procedure without LAD ligation. Metoprolol (12.5 mg/kg dissolved in 2 ml distilled water) was applied to rabbits in early treatment group and routine treatment group per gavage immediately after recovery from anesthesia and at 24 hours after myocardial infarction, respectively, then treated daily for 40 days. Rabbits in sham group and myocardial infarction group received 2 ml distilled water per gavage daily for 40 days. Plasma lactate dehydrogenase (LDH) and creatine kinase (CK) level were detected by automatic biochemistry analyzer after 6 hours in all rabbits. Ventricular fibrillation threshold (VFT) was measured in vivo by bipolar pacing electrodes at 40 days. Cx43 and p-Cx43 distribution in ventricular tissue was detected by immunofluorescence analyses. Cx43 and p-Cx43 protein level in ventricular tissue was determined by Western blot. Results: (1) Plasma LDH ((851.7±85.9)U/L vs. (332.3±39.6)U/L, P<0.01) and CK ((1 192.7±105.3)U/L vs. (462.3±65.6)U/L, P<0.01) were significantly higher in myocardial infarction group than in sham group (both P<0.01). (2) VFT was significantly lower in myocardial infarction group than that in sham group ((470.0±91.0) beats per minute vs. (683.3±60.9) beats per minute, P<0.05), and VFT was significantly higher in early treatment group ((633.3±43.2) beats per minute) and routine treatment group ((645.0±30.8) beats per minute) than in the myocardial infarction group (both P<0.05). (3) Immunofluorescence analyses showed that Cx43 was mainly localized in the intercalated disk, which was perpendicular to the cell long axis with linear arrangement, and less lateral distribution in sham group, early treatment group and routine treatment group, which was significantly different as the case in the myocardial infarction group. The expression of p-Cx43 in myocardial infarction group was less than in sham group, which was significantly upregulated in in early treatment group and routine treatment group when compared with myocardial infarction group, and expression of p-Cx43 was significantly higher in early treatment group than in routine treatment group. (4)The p-Cx43/Cx43 ratio of protein was significantly lower in myocardial infarction group than in sham group (0.165±0.011 vs. 0.363±0.046, P<0.05), and significantly higher in early treatment group (0.720±0.063) and routine treatment group (0.364±0.030) than in myocardial infarction group (both P<0.05), and this ratio was significantly higher in early treatment group than in routine treatment group (P<0.05). Conclusion Metoprolol treatment, especially the early metoprolol treatment (within 24 hours after LAD ligation), could significantly improve VFT by ameliorating the distribution and dephosphorylation of myocardial Cx43 in rabbits with experimental myocardial infarction.

Objective: To assess the efficacy and safety of thrombolytic treatment with reteplase in patients with intermediate-risk acute pulmonary embolism. Methods: Ten consecutive patients with intermediate-risk acute pulmonary embolism who received thrombolytic treatment with reteplase at Thrombosis and Vascular Medicine Center, Fuwai Hospital from March to November in 2016 were included.Vital signs, right ventricular diameter, systolic pulmonary artery pressure, and biochemical markers were assessed before and after thrombolytic therapy with reteplase, and bleeding complications were also observed during 3 months follow up. Results: (1) For the efficacy outcomes: at 48 hours after thrombolytic treatment with reteplase, echocardiography-derived diameter of right ventricular was significant reduced from (27.9±3.8) mm to (24.8±2.6) mm (P=0.03), systolic pulmonary artery pressure decreased from (63.9±21.6) mmHg(1 mmHg=0.133 kPa) to (34.4±19.8) mmHg (P=0.02). Heart rate and breathing rate were also decreased significantly (both P<0.05), blood pressure remained unchanged post therapy.Hypoxemia was quickly corrected with an significant elevation of PaO₂ and SaO₂ ((65.2±14.3) mmHg vs. (80.0±9.6) mmHg, P=0.006; (90.8±3.5)% vs. (95.2 ±1.6)%, P=0.002 respectively). PaCO₂ was also increased significantly (P<0.05). Serum NT-proBNP and cTnI were decreased significantly (both P<0.05). There was no recurrent pulmonary embolism or deep-vein thrombosis during the 3 months follow-up. (2) For the safety outcomes: a thrombolytic relevant hemoptysis (about 70 ml) occurred in 1 patient, and was controlled by PCC therapy.No other clinically relevant events were observed during thrombolytic treatment. Eight patients were followed more than 3 months, there was no major bleeding complication or death during the follow up period. Conclusion Treatment of intermediate-risk acute pulmonary embolism with reteplase is effective and safe and there are no obvious side effects.

OBJECTIVETo assess peak oxygen consumption (peak VO₂) derived from cardiopulmonary exercise testing (CPET), concentrations of NT-proBNP and echocardiographic changes in patients with chronic heart failure (CHF) and reduced left ventricular ejection fraction (LVEF, <40%).

METHODSSeventy patients were included and divided into two groups according to the New York Heart Association (NYHA) classification: NYHA II group (17 cases) and NYHA III-IV group (53 cases). The basic clinical information, plasma concentration of NT-proBNP at rest, echocardiographic parameters and peak VO₂from CPET were compared between two groups. Correlation among peak VO₂, NT-proBNP and echocardiographic parameters in this patient cohort was assessed and their abilities to discriminate the NYHA III-IV grade were analyzed through c-Statistic.

RESULTSLeft atrial diameter ((51.3 ± 7.2) mm vs. (44.0±7.4) mm, P<0.001) was larger, plasma concentration of NT-proBNP (1 379-4 399 pmol/L vs. 1 109-2 356 pmol/L, P<0.01) was higher and peak VO₂((13.4 ± 3.5) ml·kg⁻¹·min⁻¹ vs. (18.2 ± 3.7) ml·kg⁻¹·min⁻¹, P<0.001) were significantly lower in NYHA III-IV group than those in NYHA II group. However, left ventricular end-diastolic diameter (LVEDD) and LVEF were similar between two groups. Peak VO₂correlated significantly with NT-proBNP (r=-0.311, P<0.01), but neither peak VO₂nor NT-proBNP correlated with echocardiographic parameters (LA, LVEDD and LVEF). ROC analysis showed that peak VO₂had the strongest discriminatory power for detecting NYHA III-IV grade patients (AUC=0.835, P<0.001), followed by the NT-proBNP (AUC=0.723, P<0.01).

CONCLUSIONPeak VO₂is a more sensitive parameter to detect the disease aggravation (NYHA III-IV grade) of the CHF patients with reduced LVEF compared to plasma NT-proBNP and echocardiographic parameters (LA, LVEDD, LVEF).

Chronic Disease ; Echocardiography ; Exercise Test ; Heart ; Heart Failure ; Humans ; Natriuretic Peptide, Brain ; Oxygen Consumption ; Peptide Fragments ; ROC Curve ; Ventricular Function, Left

OBJECTIVETo assess the cardiopulmonary exercise testing (CPET) derived performance of oxygen uptake and ventilation efficiency parameters, including oxygen uptake efficiency plateau (OUEP) , oxygen uptake efficiency slope (OUES), V·E/V·CO2 slope and lowest V·E/V·CO2, in patients with end-stage chronic heart failure (CHF) and evaluate their clinical value on monitoring cardiac function and hemodynamic status.

METHODSA total of 26 end-stage CHF patients considered for heart transplantation were enrolled in this study. CPET, echocardiography and invasive hemodynamic examinations with Swan-Ganz flowing balloon catheter were performed. Correlation analysis was made between oxygen uptake and ventilation efficiency parameters from CPET and echocardiographic and hemodynamic parameters.

RESULTSOUEP and OUES showed good correlation with peak oxygen consumption (peak V·O2) (r = 0.535, P < 0.01;r = 0.840, P < 0.001). In end-stage CHF patients, the slope of OUEP with respect to peak V·O2 is about 32, but the slope of OUES with respect to peak V·O2 is only about 2. The difference was 16 times. The change of OUEP was more sensitive and significant than those of OUES and peak V·O2 (P < 0.05). OUEP, peak V·O2 (%pred), V·E/V·CO2 slope and lowest V·E/V·CO2 were all correlated well with non-invasive hemodynamic parameters peak cardiac output (r = 0.535, P < 0.01; r = 0.652, P < 0.001; r = -0.640, P < 0.001; r = -0.606, P = 0.001 respectively) and peak cardiac index (r = 0.556, P < 0.01;r = 0.772, P < 0.001; r = -0.641, P < 0.001; r = -0.620, P < 0.001 respectively) derived from CPET, but not correlated with invasive hemodynamic parameters cardiac output and cardiac index at rest (P > 0.05). Both peak V·O2 (%pred) and V·E/V·CO2 slope were significantly correlated with invasive hemodynamic parameters systolic pulmonary arterial pressure (r = -0.424, P < 0.05; r = 0.509, P < 0.01) and mean pulmonary arterial pressure (r = -0.479, P < 0.05; r = 0.405, P < 0.05). Peak V·O2 (%pred) was also significantly correlated with pulmonary capillary wedge pressure (r = -0.415, P < 0.05), and V·E/V·CO2 slope was significantly correlated with pulmonary vascular resistance (r = 0.429, P < 0.05).

CONCLUSIONSThe oxygen uptake and ventilation efficiency parameters derived from CPET, including peak V·O2, OUEP, lowest V·E/V·CO2 and V·E/V·CO2 slope etc, are objectively monitoring and evaluating cardiac function and hemodynamic status. And they are useful for optimizing clinical management of patients with end-stage CHF.

Cardiac Output ; Chronic Disease ; Exercise Test ; Heart Failure ; physiopathology ; Hemodynamics ; Humans ; Oxygen ; metabolism ; Oxygen Consumption ; Pulmonary Wedge Pressure