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The primary objective of this study was to investigate if hepatic impairment alters the safety, pharmaThis was a clinical trial of HSK3486 in subjects with normal hepatic function (In total, 24 subjects were enrolled and completed the study. HSK3486 was generally well tolerated by all subjects. There were no serious AEs and no deaths reported during the study. The incidence of AEs was numerically highest in subjects with moderate hepatic impairment. The exposure (AUC) of HSK3486 increased gradually with the decrease in hepatic function; however, degree of hepatic impairment had little effect on HSK3486 PD (MOAA/S and BIS).Overall, there were no clinically relevant differences in HSK3486 exposure or PD in subjects with mild or moderate hepatic impairment compared to normal control. These data imply that HSK3486 dose adjustment is not warranted in subjects with mild or moderate hepatic impairment.The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04145596).Key MessageHSK3486 at an IV bolus dose of 0.4 mg/kg and a maintenance infusion of 0.4 mg/kg/h was safe and well tolerated by all mild or moderate hepatic impairment subjects and normal hepatic function subjects.There were no clinically relevant differences in HSK3486 exposure or PD in subjects with mild or moderate hepatic impairment compared to subjects with normal hepatic function.HSK3486 dose adjustment is not required in subjects with mild or moderate hepatic impairment.

Objective This study was performed to observe the occurrence of corrected QT (QTc) interval prolongation during anesthetic induction for laryngeal mask airway insertion and the effects of cisatracurium administration on the QTc interval. Methods Eighty-eight patients were assigned to two groups: the cisatracurium administration group (n = 45) and non-cisatracurium administration group (n = 43). The QTc interval was continuously recorded by a 12-lead Holter electrocardiogram beginning in the hospital ward and continuing until after anesthetic induction. Results In the cisatracurium administration group, the QTc interval significantly increased from 417.9 ± 27.9 to 451.6 ± 32.5 ms after arrival in the operating room and significantly decreased to 432.4 ± 32.5 ms after a 15-minute rest; it significantly increased to 459.7 ± 23.8 ms again after propofol and fentanyl injection. However, the QTc interval decreased after cisatracurium injection. In the non-cisatracurium administration group, the QTc interval initially showed changes similar to those in the cisatracurium group until fentanyl and propofol were injected. Conclusions The QTc interval was significantly prolonged on arrival in the operating room and after propofol and fentanyl injection. The QTc interval did not significantly change by laryngeal mask airway insertion regardless of the administration of cisatracurium.

BACKGROUND Increasing evidence indicates that GABAergic neurons in the nucleus of the solitary tract (NTS) play a significant role in the arterial baroreceptor reflex and control of cardiovascular homeostasis. However, the role of these neurons in the development of hypertension is not yet fully clear. METHODS AND RESULTS In the present study, we first confirmed that GABAB receptor (GBR) expression is enhanced in the NTS of SHR as compared with WKY rats using real-time RT-PCR and western blots. To study the functional consequence of upregulated GBR expression, GBR was overexpressed in the NTS by bilateral microinjection of the AAV2-GBR1 viral vector into the NTS of WKY rats. Immunofluorescence staining and western blots demonstrated that microinjection of AAV2-GBR1 into the NTS of WKY rats resulted in a significant increase in GBR1 expression in the NTS neurons. Overexpression of GBR in the NTS induced a chronic elevation in blood pressure and heart rate in the normotensive WKY rats. In an acute study, the pressor response to baclofen microinjected into the NTS was enhanced in SHR as compared with WKY rats. CONCLUSIONS GBR1 expression is enhanced in the NTS of SHR vs. WKY rats and overexpression of this gene in the NTS results in chronic elevation of blood pressure and heart rate in normotensive rats.

Background Refractory blood loss is a common problem in surgeries for acute type A aortic dissections. Significant evidence has supported the benefit of using recombinant activated factor VII (rFVIIa) to control of intractable bleeding in patients after cardiac surgery. In this prospective clinical study, we present a novel method to achieve intraoperative hemostasis by using a combination of platelets and rFVIIa during operations for acute type A aortic dissections. Methods Between May 2009 and August 2012, 71 patients with acute type A dissections who underwent emergency surgery were prospectively included and allocated to one of the following two intervention groups for hemostasis: 3 units platelets combined with 2.4 mg rFVIIa (n = 25), and conventional methods (n = 46). Results The patients who received the combination of platelets and rFVIIa required fewer transfusions of red blood cells (6.2 ± 3.1 units vs 9.8 ± 2.8 units; p < 0.05), fresh frozen plasma (736.9 ± 178.3 ml vs 1264.3 ± 245.2 ml, p < 0.05), platelet concentrates (3 units vs 5.0 ± 1.8 units, p < 0.001), and cryoprecipitate (2.8 ± 0.9 units vs 8.2 ± 2.3 units, p < 0.05). These patients also required less time for sternal closure (76.9 ± 17.2 min vs 102.3 ± 10.7 min, p < 0.05) compared with the conventional therapy patients. There was no statistically significant difference in the incidence of serious adverse events between these two groups. Conclusions Using a combination of platelets and rFVIIa is an effective strategy for achieving hemostasis during acute type A dissection surgery. This hemostatic strategy does not appear to be associated with an increase in postoperative adverse events. Electronic supplementary material The online version of this article (doi:10.1186/s13019-014-0156-y) contains supplementary material, which is available to authorized users.

Previous studies focusing on the association of PTGS2 polymorphism -765GC with coronary artery disease (CAD) have failed to reach the same conclusion. In the present study, we performed a meta-analysis to systematically summarize the possible association between PTGS2 polymorphism -765GC and the risk of CAD. We conducted a search of case-control studies on the associations of PTGS2 with susceptibility to CAD in PubMed, EMBASE, and Chinese National Knowledge Infrastructure databases. Data from eligible studies were extracted for meta-analysis. CAD risk associated with PTGS2 -765GC was estimated by pooled odds ratios (ORs) and 95% confidence intervals (95%CI) with the RevMan 5.2 software. Eleven independent case-control studies on PTGS2 -765GC were included in our meta-analysis. Our results showed that PTGS2 -765GC was associated with a decreased risk of CAD (OR = 0.66, 95%CI = 0.56-0.79; P0.001). This meta-analysis suggests that PTGS2 -765GC is associated with a decreased risk of CAD.

Aortoesophageal fistula is a rare disease with a high mortality rate. The disease is with high mortality due to aneurysm rupture, and thus successfully managed cases are rarely reported. Here, we report a case of aortoesophageal fistula caused by a huge descending aneurysm and another smaller aneurysm found in the aortic arch. Such case was relatively rare in the cardiovascular field. Due to the limited experience, it was difficult to determine the proper therapeutic strategy. For this case, for the dual aneurysm, we surgically inserted an aortic endovascular stent-graft to exclusive the aneurysm and simultaneously repair the other aortic arch aneurysm. The patient had an uneventful recovery and was discharged after 1 month antibiotics therapy for the palliative treatment of the esophageal fistula. She survived for 8 months at home before dying of massive hematemesis. Here, we present the operative method and our therapeutic experience for this extremely rare case.