Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Objective To investigate the efficacy and safety of domestic exenatide injection versus imported exenatide injection in type 2 diabetic patients with inadequate glycemic control on monotherapy or combination therapy of metformin and insulin secretagogues. Methods A multicenter, randomized, parallel-controlled, and non-inferiority trial was carried out. A total of 240 subjects were randomized at a 1:1 ratio to add domestic exenatide injection (trial group) or imported exenatide injection (control group) on the background therapies. The primary endpoint of efficacy was HbA1C change from baseline to week 16. The secondary endpoints of efficacy were the proportion of HbA1C<7.0%, and the changes in fasting plasma glucose (FPG), 2 h plasma glucose after standard meal (2hPG), 7-point self monitoring of blood glucose (7P-SMBG), and body weight from baseline to week 16. Results Among subjects of per-protocol sets, adjusted mean HbA1C reduction was -1.07% in the trial group versus -1.06% in the control group after 16 weeks of treatment. The lower boundary of the two-sided 95% confidence intervals of the mean HbA1C reduction difference between the trial and control groups was -0.29%, which was more than -0.35%, suggesting that the predefined statistical criterion for non-inferiority was achieved. The proportions of subjects achieving HbA1C<7.0% at the end of the 16-week treatment were 56.19% and 54.08% in the trial and control groups, respectively (P>0.05). The changes in FPG, 2hPG, 7P-SMBG and body weight from baseline to week 16 were comparable between the two groups (all P>0.05). Moreover, the incidences of hypoglycemia and adverse events were similar between the two groups (both P>0.05). Conclusion In type 2 diabetic patients inadequately controlled by monotherapy or combination therapy of metformin and insulin secretagogues, the efficacy of cotreatment with domestic exenatide injection is not inferior to that of imported product ones, with a similar safety profile.

Objective To investigate the effects of Danshen Duofensuanyan on the blood coagulation,inflammatory and cardiac function in acute myocardial infarction(AMI) patients who did not accept emergency percutaneous coronary intervention.Methods One hundred and twenty patients,from January 2012 to November 2014 in the First Hospital of Qinhuangdao admission due to acute myocardial infarction frequent episodes of angina(Killip grade Ⅱ,grade m),were randomly divided into two groups:control group (n =60) and observation group (n =60).All patients suffered from severe angina after AMI and heart failure but without PCI.All included patients were gave antiplatelet drug,anticoagulants and Statins,etc.And the patients in observation group were additionally given 7-day Danshen Duofensuanyan injection 200 mg/d once daily intravenously.Platelet aggregation rate (PAG),fibrinogen (FIB),c-reaction protein (CRP),erythrocyte sedimentation rate (ESR),troponin Ⅰ (TNI),plasma brain natriuretic peptide (BNP) and left ventricular end diastolic dimension(LVEDD),left ventricular ejection fraction (LVEF) and cardiac output (CO) of two group were monitored before and after treatment.Results (1)Changes in coagulation,inflammatory cytokines and enzymes between the treatment group and the control group after treatment (Treatment Group:PAG (22.32 ±17.61) ％,FIB(3.58±0.74) g/L,CRP(9.34±1.82) mg/L,ESR(10.1±4.6) mm/1 h,TNI(4.51± 1.89) ng/ml);control group:PAG(31.32±21.62)％,FIB(3.84±0.62) g/L,CRP (14.32±1.79) mg/L,ESR(13.2 ± ±5.4) mm/1 h,TNI(5.32±2.31) μg/L) and before treatment(Treatment group:PAG(88.87± 18.21) ％,FIB (4.78±0.97) g/L,CRP(32.13±11.59) mg/L,ESR(28.5±6.1) mm/1 h,TNI (56.43 ± 21.87) μg/L);control group:PAG (89.53± 19.35) ％,FIB (4.66 ± 0.78) g/L,CRP (29.06± 12.47) mg/L,ESR (29.3 ± 3.2) mm/1 h,TNI (53.69± 18.76) μg/L) were significandy improved,and the differences were statistically significant (P＜0.01),and observation group had more significant improvements than the control group(P＜0.05 or P ＜0.01) after treatment.(2) All aboved indexes were improved after treatment except LVEDD.And Danshen Duofensuanyan can significantly improve PAG,FIB,CRP,ESR,TNI,BNP LVEF and CO(P＜0.05 or P ＜0.01).Conclusion Danshen Duofensuanyan can effectively improve the blood rheology and the frequency of angina,and then improve heart functions.

Objective To evaluate the effectiveness of combination technique in treating descending thoracic aortic dissection with coronary heart disease by endovascular graft exclusion (EVGE) and percutaneous coronary intervention(PCI). Methods From April, 2002 to October, 2013, a total of 40 in-hospital patients with descending thoracic aortic dissection and coronary heart disease who underwent EVGE and PCI were analyzed for outcomes. All patients were performed EVGE before they underwent PCI in 3~7days of time. Long-term treatment were observed. Results For dissection tears, 40 trunk tectorial membrane stents were used. The rate of success of EVGE implantation was 100%. No paraplegia, death and other complications. 59 stents were placed to 54 target vessels of 40 patients. The success rate of PCI procedure was 100%and no severe complication occurred. All patients were followed up for average 56±31 months. The rate of followed up was 92.5%(37/40). During follow-up, 3 patients died including two patients died of cerebral hemorrhage and one case of malignant tumor. The major adverse cardiac events (MACE) rate was 6.9% in the 29 cases of patients who underwent EVGE and PCI during the clinical follow-up. Conclusions It is safe and feasible that treating descending thoracic aortic dissection with coronary heart disease by combination technique of EVGE and PCI.

Objective Patients with aortic dissection have a significant incidence of coronary artery disease.The purpose of this study is to evaluate the safety and feasibility of percutaneous coronary stent in patients who have undergone endovascular stent,and to assess the effect of anti-coagulant and anti-platelet treatment on patients' thrombosis process.Methods From January 2005 to July 2007,8 patients who had undergone endovascular stent-graft during the past 1 to 7 months for type B aortic dissection repair,underwent percutaneous coronary intervention (PCI) because of coexisting coronary artery disease.Anti-coagulant and anti-platelet treatments were administrated after PCI according to the standard protocol.Patients were followed up for a mean period of 23 months.Clinical and false lumen status data were collected during the follow-up.Results PCI were technically successful in all 8 patients and no severe complications such as death,paraplegia,renal failure occurred during hospitalization.Complete false lumen thrombosis was observed in 5 patients and incomplete false lumen thrombosis in the remained 3 patients at the end of follow up.There were no major complications such as death,dissection rupture or aneurysm development occurred during the follow-up period.Conclusion Our data implied that PCI can be safely performed in patients with type B aortic dissection who have undergone endovascular stent-graft,without interrupting the thrombosis process.

Objective To compare the clinical therapeutic results of percutaneous transluminal stenting between patients with acute and chronic aortic dissections. Methods From May 2002 to October 2007,42 patients with acute type B aortic dissection and 40 patients with chronic aortic dissection underwent stenting. The clinical data of the patients were analyzed. Results Comparing with the chronic aortic dissection group,the acute aortic dissection group had higher percentage of pleural effusion(16.7% vs 0,P=0.01)and visceral /leg ischemia(23.8% vs 2.5%,P=0.01). The acute aortic dissection group had higher complications in early term(38.1% vs 15.0%,P=0.02). All patients were followed up for an average of(18.7 ± 17.3)months. The rate of complications were higher in the patients with acute aortic dissection than those with chronic aortic dissection(21.4% vs 5.0%,P=0.03). Kaplan-Meier analysis showed no difference of survival rate between the 2 groups during follow-up period(P=0.38). The 5-year survival rate was 90.0% in acute aortic dissection group years and 92.5% in chronic aortic dissection group,respectively. The event-free survival rate was higher in the patients with chronic dissection than that with in the patients acute aortic dissection(P=0.04). Conclusions Percutaneous transluminal stenting is effective in the treatment of type B aortic dissection,but there are more complications in acute than in chronic aortic dissection group.

Objectives To evaluate the safety and effect of transradial approach for coronary intervention. Methods A total of 165 cases of coronary artery disease in this hospital accepted coronary intervention by transradial approach. Three of them had acute myocardial infarction, 112 had unstable angina, and 67 failed by transfemoral approach. Results The proportion of multivessel diseases were 60 6% and C type lesions were 20 7%. The interventons were performed in totally 294 target vessels and 299 target lesions and 246 stents were implanted. Coronary intravescular ultrasound were performed in 14 cases and cutting balloon technique in 16 cases. During intervention 1 case had right coronary spiral dissection and was successfully treated by stenting. One case had subacute thrombosis after intervention and was successfully treated by re-intervention. There were no other severe complications in this group. The mean hospital stay was (2 1?0 6) days. The total success rate was 98 2%(162/165) for transradial approach. The interventions in two cases who had chronic total occlusion in circumflex artery failed by transradial but succeeded by transfemoral thereafter .Conclusions Transradial approach for coronary intervention is a safe and effective approach so long as standardized manipulation is practised.