Immunogenicity and safety of an Escherichia coli-produced human papillomavirus (types 6/11/16/18/31/33/45/52/58) L1 virus-like-particle vaccine: a phase 2 double-blind, randomized, controlled trial.

The Escherichia coli-produced human papillomavirus (HPV) 16/18 bivalent vaccine (Cecolin) has received prequalification by the World Health Organization based on its high efficacy and good safety profile. We aimed to evaluate the immunogenicity and safety of the second-generation nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine (Cecolin 9) through the randomized, blinded phase 2 clinical trial. Eligible healthy women aged 18-45 years were randomly (1:1) allocated to receive three doses of 1.0 mL (270 µg) of Cecolin 9 or placebo with a 0-1-6-month schedule. The primary endpoint was the seroconversion rate and geometric mean titer of neutralizing antibodies (nAbs) one month after the full vaccination course (month 7). The secondary endpoint was the safety profile including solicited adverse reactions occurring within 7 d, adverse events (AEs) occurring within 30 d after each dose, and serious adverse events (SAEs) occurring during the 7-month follow-up period. In total, 627 volunteers were enrolled and randomly assigned to Cecolin 9 (n = 313) or placebo (n = 314) group in Jiangsu Province, China. Almost all participants in the per-protocol set for immunogenicity (PPS-I) seroconverted for nAbs against all the nine HPV types at month 7, while two failed to seroconvert for HPV 11 and one did not seroconvert for HPV 52. The incidence rates of total AEs in the Cecolin 9 and placebo groups were 80.8% and 72.9%, respectively, with the majority of them being mild and recovering shortly. None of the SAEs were considered related to vaccination. In conclusion, the E. coli-produced 9-valent HPV (9vHPV) vaccine candidate was well tolerated and immunogenic, which warrants further efficacy studies in larger populations.

Dexmedetomidine Attenuates Ischemia/Reperfusion-Induced Myocardial Inflammation and Apoptosis Through Inhibiting Endoplasmic Reticulum Stress Signaling.

BACKGROUND: Endoplasmic reticulum stress (ERS)-mediated myocardial inflammation and apoptosis plays an important role in myocardial ischemia/reperfusion (I/R) injury. Dexmedetomidine has been used clinically with sedative, analgesic, and anti-inflammatory properties. This study aimed to determine the effects of dexmedetomidine pretreatment on inflammation, apoptosis, and the expression of ERS signaling during myocardial I/R injury. METHODS: Rats underwent myocardial ischemia for 30 min and reperfusion for 6 h, and H9c2 cardiomyocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury (OGD for 12 h and reoxygenation for 3 h). Dexmedetomidine was administered prior to myocardial ischemia in rats or ODG in cardiomyocytes. In addition, the α2-adrenergic receptor antagonist (yohimbine) or the PERK activator (CCT020312) was given prior to dexmedetomidine treatment. RESULTS: Dexmedetomidine pretreatment decreased serum levels of cardiac troponin I, reduced myocardial infarct size, alleviated histological structure damage, and improved left ventricular function following myocardial I/R injury in rats. In addition, dexmedetomidine pretreatment increased cell viability and reduced cytotoxicity following OGD/R injury in cardiomyocytes. Mechanistically, the cardioprotection offered by dexmedetomidine was mediated via the inhibition of inflammation and apoptosis through downregulating the expression of the ERS signaling pathway, including glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), C/EBP homologous protein (CHOP), inositol-requiring protein 1 (IRE1), and activating transcription factor 6 (ATF6). Conversely, the protective effects of dexmedetomidine were diminished by blocking the α2 adrenergic receptors with yohimbine or promoting PERK phosphorylation with CCT020312. CONCLUSION: Dexmedetomidine pretreatment protects the hearts against I/R injury via inhibiting inflammation and apoptosis through downregulation of the ERS signaling pathway. Future clinical studies are needed to confirm the cardioprotective effects of dexmedetomidine in patients at risk of myocardial I/R injury.

Effects of Perioperative Dexmedetomidine on Postoperative Mortality and Morbidity: A Systematic Review and Meta-analysis.

PURPOSE: Major postoperative complications translate into increased health care resource utilization, prolonged hospital stays, and increased mortality. We aimed to assess the effects of perioperative dexmedetomidine use on postoperative mortality and the prevalence of major complications after cardiac and noncardiac surgery. METHODS: We searched the PubMed, EMBASE, and Cochrane databases to analyze all published evidence from randomized controlled trials (RCTs) and cohort studies comparing perioperative dexmedetomidine use versus no dexmedetomidine use in adult patients undergoing cardiac and noncardiac surgery. The primary outcome was postoperative mortality. Secondary outcomes were the durations of mechanical ventilation, intensive care unit (ICU) stay, and hospital stay, and the prevalence of major complications. FINDINGS: Twenty-three studies in cardiac surgery (n = 7635) and 8 studies in noncardiac surgery (n = 1805) were included. In cardiac surgery, dexmedetomidine use reduced postoperative 30-day mortality (risk ratio [RR], 0.35 [95% CI, 0.24 to 0.51]); durations of mechanical ventilation (mean difference [MD], -1.56 h [-2.52 to -0.60]), ICU stay (MD, -0.22 day [-0.35 to -0.08]), and hospital stay (MD, -0.65 day [-1.12 to -0.18]); and the prevalences of delirium (RR, 0.50 [0.36 to 0.69]), atrial fibrillation (RR, 0.74 [0.57 to 0.97]), and cardiac arrest (RR, 0.34 [0.13 to 0.87]). In noncardiac surgery, dexmedetomidine use was associated with decreases in the durations of mechanical ventilation and hospital stay, with a trend toward a lower prevalence of delirium (RR, 0.57 [0.32 to 1.01]). The prevalence of bradycardia was increased in dexmedetomidine-treated patients undergoing cardiac surgery (RR, 1.70 [1.19 to 2.44]) and noncardiac surgery (RR, 1.64 [1.05 to 2.58]). IMPLICATIONS: Dexmedetomidine use may help to reduce postoperative 30-day mortality, durations of mechanical ventilation, ICU stay, and hospital stay, and the prevalences of delirium, atrial fibrillation, and cardiac arrest in patients who undergo cardiac surgery. The majority of the benefits of dexmedetomidine were not significant in patients undergoing noncardiac surgery. An increased risk for bradycardia should be taken into consideration when prescribing dexmedetomidine. International Prospective Register of Systematic Reviews identifier: CRD42017070791.

The efficacy of bamboo charcoal in comparison with smectite to reduce the detrimental effect of aflatoxin B1 on in vitro rumen fermentation of a hay-rich feed mixture.

Two commercial materials, a bamboo charcoal (BC) and a smectite clay (SC), were assessed in vitro with aflatoxin B1 (AFB1) in an equilibrium adsorption test. The adsorption capacity and proportion adsorbed (0.381 µg/mg, 0.955) for BC were greater than for SC (0.372 µg/mg, 0.931). The effects of in vitro ruminal fermentation of hay-rich feed incubated with 1.0 µg/mL AFB1 for 0-10 g/L doses of BC and SC were measured at 39 °C for 72 h. The BC and SC binders increased AFB1 loss at dosages ≥1.0 g/L (p < 0.0001). Average AFB1 loss (p < 0.0001) was greater for SC (0.904) than BC (0.881). Both SC and SC addition increased in vitro dry matter loss, and the average dry matter losses were similar. Asymptotic gas volume and volatile fatty acid production were greater for BC than for SC (p < 0.0001). Thus, BC may be as effective as SC in removing aflatoxin B1's detrimental effects on rumen degradability and fermentation under the occurrence of microbial aflatoxin degradation.