Congenital heart disease related pulmonary arterial hypertension (CHD—PAH) is a large class of PAH ,the patients possess pulmonary vascular disease as well as heart injury .When CHD complicated with PAH ,their progno—sis usually is poor .It is of important significance to understand natural course and influencing factors of prognosis of CHD—PAH for diagnosis and treatment of these patients .

Objective: To investigate the association between hyponatremia and hemodynamic and prognosis in patients with intermediate-risk acute pulmonary embolism. Methods: We retrospectively recruited 110 intermediate-risk acute pulmonary embolism patients (right ventricular dysfunction was confirmed by echocardiography and CT scan with or without the elevated levels of cardiac injury biomarkers) in the first and the second affiliated hospital of Harbin medical university from January 1,2011 to December 31, 2014. The patients were aged (58.4±14.9) years old.There were 49 males and 61 females.Patients were divided into 2 groups as non-hyponatremia group (plasma sodium>135 mmol/L, 93 cases) and hyponatremia group (plasma sodium≤135 mmol/L, 17 cases). Baseline clinical and hemodynamic parameters were obtained from these patients. All enrolled patients were followed up after discharge. Results: Heart rate ((106.7±21.9) beats per minute vs. (93.4±19.4) beats per minute, P=0.043),N-terminal pro B type natriuretic peptide (NT-proBNP, (5 561±1 593) ng/L vs. (1 738±589) ng/L, P=0.005), mean pulmonary arterial pressure((42.6±12.6)mmHg(1 mmHg=0.133 kPa) vs. (33.9±13.3)mmHg, P=0.046), mean right atria pressure ((20.6±8.1)mmHg vs. (10.2±5.4)mmHg, P=0.014), systolic right atria pressure ((27.3±9.0)mmHg vs. (15.6±6.1)mmHg,P=0.013) and diastolic right atria pressure(6.5(4.3,15.5)mmHg vs. 5.0(2.0,8.0)mmHg,P=0.016) were significantly higher in hyponatremia group than in non-hyponatremia group,and systolic blood pressure was significantly lower in hyponatremia group than in non-hyponatremia group ((113.5±21.9)mmHg vs.(129.5±28.9)mmHg, P=0.048). Pearson correlation analysis showed that hyponatremia was negatively correlated with heart rate (r=-0.262, P=0.043), NT-proBNP (r=-0.227, P=0.048), mean pulmonary arterial hypertension (r=-0.259, P=0.046), mean right ventricular pressure (r=-0.296, P=0.047), mean right atria pressure (r=-0.550, P=0.001), systolic right atria pressure (r=-0.552, P=0.001), and diastolic right atria pressure (r=-0.542, P=0.001). Kaplan-Meier survival analysis showed that the 1-year, 2-year and 3-year cumulative survival rates were 76.5%,70.6%,and 64.7% in the hyponatremia group, and 90.3%,86.0%,and 83.9% in the non-hyponatremia group(log-rank test, P=0.036).Multivariate Cox regression analysis showed that hyponatremia was an independent risk factor of death of intermediate-risk pulmonary embolism patient(HR=4.126, 95%CI 1.982-11.343, P=0.036). Conclusion Hyponatremia is associated with adverse hemodynamic and reduced survival in patients with intermediate-risk pulmonary embolism.

Objective To purify the anti-T cell immunoglobulin mucin ( TIM)-3 monoclonal antibody 4E8 and examine its biological function in vitro. Methods The mouse monoclonal antibody against human TIM-3, clone 4E8, was obtained by standard protocol for monoclonal antibody purification. The cell lines expressing human TIM-3 molecule were obtained by cell transfection technique. We ex-amined the ability of 4E8 binding to human TIM-3 by flow cytometry. The ability of 4E8 blocking the binding of fusion protein TIM-3 Ig-huFc with phosphatidylserine( PtdSer) , the apoptotic cell surface TIM-3 ligand, was also analyzed by flow cytometry. Mixed lympho-cyte reaction ( MLR) and ELISA assays were used to determine the effect of TIM-3 monoclonal antibody ( 4E8) on IFN-γsecretion in CD4+ T cells. Results 4E8 specifically bound to human TIM-3 but could not block the binding of TIM-3 to Ptdser. Compared with the negative control (IFN-γ secretion: 958.3±153.2), 4E8 enhanced the ability of CD4+ T cells to secrete IFN-γ in MLR (4E8 of 10μg/mL group:IFN-γ secretion 2563±150.3 and 4E8 of 3.33 μg/mL group:IFN-γ secretion 1981±211.5) with statistically signifi-cant difference ( P<0.05) . In addition, the combined application of 4E8 with the anti-programmed death-1 ( PD-1) monoclonal anti-body nivolumab showed synergistic effects for increasing IFN-γ secretion in MLR assay ( 4E8 of 10 μg/mL group: IFN-γ secretion 3049±80.5 and 4E8 of 0.33μg/mL group:IFN-γsecretion 1957±321.3) as compared with 4E8 alone (10μg /mL group:IFN-γse-cretion 2563±150.3 and 0.33 μg/mL group:IFN-γ secretion 844±76.2) with statistically significant difference (P<0.05). Conclu-sion We successfully obtained a 4E8 clone of monoclonal antibody to human TIM-3 which may enhance the capacity of IFN-γsecre-tion from CD4+ T cells. The effect of enhancing IFN-γ secretion of CD4+T cells by TIM-3 monoclonal antibody was independent from blocking the binding of TIM-3 with Ptdser.

Humans ; Atrial Fibrillation/surgery* ; Left Atrial Appendage Closure ; Heart Atria/surgery* ; Catheter Ablation/methods* ; Atrial Appendage/surgery* ; Treatment Outcome