Summary Background Seroprevalence data suggest that a third of the world's population has been infected with the hepatitis E virus. Our aim was to assess efficacy and safety of a recombinant ...hepatitis E vaccine, HEV 239 (Hecolin; Xiamen Innovax Biotech, Xiamen, China) in a randomised, double-blind, placebo-controlled, phase 3 trial. Methods Healthy adults aged 16–65 years in, Jiangsu Province, China were randomly assigned in a 1:1 ratio to receive three doses of HEV 239 (30 μg of purified recombinant hepatitis E antigen adsorbed to 0·8 mg aluminium hydroxide suspended in 0·5 mL buffered saline) or placebo (hepatitis B vaccine) given intramuscularly at 0, 1, and 6 months. Randomisation was done by computer-generated permuted blocks and stratified by age and sex. Participants were followed up for 19 months. The primary endpoint was prevention of hepatitis E during 12 months from the 31st day after the third dose. Analysis was based on participants who received all three doses per protocol. Study participants, care givers, and investigators were all masked to group and vaccine assignments. This trial is registered with ClinicalTrials.gov , number NCT01014845. Findings 11 165 of the trial participants were tested for hepatitis E virus IgG, of which 5285 (47%) were seropositive for hepatitis E virus. Participants were randomly assigned to vaccine (n=56 302) or placebo (n=56 302). 48 693 (86%) participants in the vaccine group and 48 663 participants (86%) in the placebo group received three vaccine doses and were included in the primary efficacy analysis. During the 12 months after 30 days from receipt of the third dose 15 per-protocol participants in the placebo group developed hepatitis E compared with none in the vaccine group. Vaccine efficacy after three doses was 100·0% (95% CI 72·1–100·0). Adverse effects attributable to the vaccine were few and mild. No vaccination-related serious adverse event was noted. Interpretation HEV 239 is well tolerated and effective in the prevention of hepatitis E in the general population in China, including both men and women age 16–65 years. Funding Chinese National High-tech R&D Programme (863 programme), Chinese National Key Technologies R&D Programme, Chinese National Science Fund for Distinguished Young Scholars, Fujian Provincial Department of Sciences and Technology, Xiamen Science and Technology Bureau, and Fujian Provincial Science Fund for Distinguished Young Scholars.
The incidence of atrial fibrillation (AF) is correlated with decreased levels of testosterone in elderly men. Late sodium current may exert a role in AF pathogenesis.
The purpose of this study was to ...explore the effect of testosterone deficiency on AF susceptibility and the therapeutic effect of late sodium current inhibitors in mice.
Male ICR mice (5 weeks old) were castrated to establish a testosterone deficiency model. One month after castration, dihydrotestosterone 5 mg/kg was administered subcutaneously for 2 months. Serum total testosterone level was assessed by enzyme-linked immunosorbent assay. High-frequency electrical stimulation was used to induce atrial arrhythmias. Whole-cell patch-clamp technique was used to for single-cell electrophysiologic study.
Serum dihydrotestosterone levels of castration mice declined significantly but recovered with administration of exogenous dihydrotestosterone. In comparison with sham mice, the number of AF episodes significantly increased by 13.5-fold, AF rate increased by 3.75-fold, and AF duration prolonged in castrated mice. Dihydrotestosterone administration alleviated the occurrence of AF. Action potential duration at both 50% and 90% repolarization were markedly increased in castrated mice compared to sham controls. The late sodium current was enhanced in castrated male mice. These alterations were alleviated by treatment with dihydrotestosterone. Systemic application of the I
inhibitors ranolazine, eleclazine, and GS967 inhibited the occurrence of AF in castrated mice.
Testosterone deficiency contributed to the increased late sodium current, prolonged action potential repolarization, and increased susceptibility to AF. Blocking of late sodium current is beneficial against the occurrence of AF in castrated mice.
Regarding susceptibility loci reported exclusively in GWASs of Asian populations, 5 loci (GLB1, CCDC80, ZNF365, OR10A/3/NLRP10, and CYP24A1/PFDN4) showed evidence for association in Europeans for the ...first time. ...21 of 23 reported AD risk loci could be confirmed.
To prospectively determine the feasibility of flat-detector (FD) computed tomography (CT) perfusion to measure hepatic blood volume (BV) in the angiography suite in patients with hepatocellular ...carcinoma (HCC).
Twenty patients with HCC were investigated with conventional multislice and FD CT perfusion. CT perfusion was carried out on a multislice CT scanner, and FD CT perfusion was performed on a C-arm angiographic system, before transarterial chemoembolization procedures. BV values of conventional and FD CT perfusion were measured within tumors and liver parenchyma. The arterial perfusion portion of CT perfusion BV was extracted from CT perfusion BV by multiplying it by a hepatic perfusion index. Relative values (RVs) for CT perfusion arterial BV and FD CT perfusion BV (FD BV) were defined by dividing BV of tumor by BV of parenchyma. Relationships between BV and RV values of these two techniques were analyzed.
In all patients, both perfusion procedures were technically successful, and all 33 HCCs larger than 10 mm were identified with both imaging methods. There were strong correlations between the absolute values of FD BV and CT perfusion arterial BV (tumor, r = 0.903; parenchyma, r = 0.920; both P < .001). Bland-Altman analysis showed a mean difference of -0.15 ± 0.24 between RVs for CT perfusion arterial BV and FD BV.
The feasibility of FD CT perfusion to assess BV values of liver tumor and surrounding parenchyma in the angiographic suite was demonstrated.
Abstract Purpose Cardiopulmonary bypass (CPB) during pediatric cardiac surgery often elicits a systemic inflammatory response followed by a compromised immune response, which has been attributed to ...the morbidity of postoperative infection; however, the underlying mechanism(s) has not yet been fully elucidated. We hypothesized that CPB inhibits the activation of Toll-like receptor (TLR) signal transduction pathways, thereby causing an immunosuppressive state after pediatric cardiac surgery. Methods We examined 20 children with congenital heart disease undergoing pediatric cardiac surgery. Results Cardiopulmonary bypass differentially affected lipopolysaccharide (LPS)- or bacterial lipoprotein (BLP)–stimulated ex vivo production of proinflammatory and anti-inflammatory cytokines, with significantly diminished tumor necrosis factor α , interleukin (IL) 1 β , IL-6, and IL-8, but substantially enhanced IL-10 production. Consistent with the reduced inflammatory response, CPB strongly inhibited LPS- or BLP-activated TLR signal transduction pathways in monocytes with down-regulated expression of CD14, TLR4, and TLR2 and with suppressed phosphorylation of nuclear factor κ B p65, p38, and extracellular signal-regulated kinase 1/2. Conclusions These results indicate that CPB during pediatric cardiac surgery causes substantially reduced production of inflammatory cytokines in response to bacterial component LPS or BLP stimulation, which is associated with CPB-induced suppression of TLR-mediated signal transduction pathways. This reduced inflammatory response after CPB in children with congenital heart disease may predispose them to an increased risk of postoperative infection.
