USP10 exacerbates neointima formation by stabilizing Skp2 protein in vascular smooth muscle cells.

The underlying mechanism of neointima formation remains unclear. Ubiquitin-specific peptidase 10 (USP10) is a deubiquitinase that plays a major role in cancer development and progression. However, the function of USP10 in arterial restenosis is unknown. Herein, USP10 expression was detected in mouse arteries and increased after carotid ligation. The inhibition of USP10 exhibited thinner neointima in the model of mouse carotid ligation. In vitro data showed that USP10 deficiency reduced proliferation and migration of rat thoracic aorta smooth muscle cells (A7r5) and human aortic smooth muscle cells (HASMCs). Mechanically, USP10 can bind to Skp2 and stabilize its protein level by removing polyubiquitin on Skp2 in the cytoplasm. The overexpression of Skp2 abrogated cell cycle arrest induced by USP10 inhibition. Overall, the current study demonstrated that USP10 is involved in vascular remodeling by directly promoting VSMC proliferation and migration via stabilization of Skp2 protein expression.

[Coagulation and prothrombotic state parameters: clinical analysis in early pregnancy].

OBJECTIVE: To assess the changes in coagulation, thrombosis, anti-coagulation and fibrinolysis during early pregnancy. METHODS: A total of 105 gravidas with monocytic pregnancies between 10 and 12 weeks gestational age at Sun Yat-sen Memorial Hospital, Sun Yat-sen University during April 2005 to June 2009 were recruited for study group and another 82 non-pregnant women as control group. Coagulation parameters, including thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin (PT) and fibrinogen (Fg), were measured. We also tested the prothrombotic state parameters, including prothrombin fragment 1+2 (F1+2), thrombomodulin (TM), thrombin-antithrombin complex (TAT), antithrombin III(AT-III), GMP140, thromboxane B2 (TXB2), plasminogen activator inhibitor (PAI-2; performed by enzyme-linked immunosorbent assay) and D-dimer (D2; tested by latex turbidimetric immunoassay). RESULTS: Fg (4.00 vs 2.52 g/L), F1+2 (0.66 vs 0.31 nmol/L), TAT (179.95 vs 39.46 µg/L), GMP140 (9.42 vs 19.13 µg/L), D2 (201.51 vs 125.02 µg/L) and PAI-2 (0.047 vs 0.006 g/L) were statistically different between the study and control groups (P < 0.01). CONCLUSIONS: The coagulation, fibrinolysis and anti-fibrinolysis functions of healthy pregnant women become enhanced during early pregnancy while anti-coagulation function slightly increases. These four basic functions are balanced at a higher level so that the activation of platelets stays at a lower level.

[Clinical experience of using oxytocin antagonist atosiban in the rescue therapy of preterm labour].

OBJECTIVE: To investigate the effectiveness of oxytocin antagonist atosiban in the alternative rescue therapy of preterm labor. METHODS: Alternative tocolysis atosiban was given as rescue therapy to 35 women, who had received ritodrine or magnesium sulphate but failed, due to either progression of labour or intolerable adverse events. Atosiban was administered for up to 48 hours. Efficacy and tolerability were assessed based on the proportion of women who did not deliver and did not need alternative tocolytic therapy at 48 hours and 7 days after therapy initiation. The numbers of maternal adverse events and neonatal morbidity were also assessed. RESULTS: Efficacy and tolerability at 48 hours and 7 days after atosiban initiation were 77% (27/35) and 60% (21/35). One woman presented drug-related side effects with mild nausea and vomiting. Thirty-four women have delivered and one bigemina (28 weeks) is being followed-up. In 34 women, 11 delivered before 28 gestational weeks, 17 delivered after 28 gestational weeks, 3 delivered after 34 weeks and 3 had term delivery. Pregnancies were prolonged by 4 hours to 14(+2) weeks. There were nine neonatal deaths, with gestational ages less than 28 weeks at delivery. CONCLUSION: Oxytocin antagonist atosiban could be given as alternative rescue therapy if therapy with ritodrine or magnesium sulphate fails in the treatment of preterm labor, and it is safe and effective.