[Show abstract][Hide abstract] ABSTRACT: The recent earthquakes in Nepal killed thousands, displaced tens of thousands, and destroyed much of the country's infrastructure. Thousands of Nepalis are living in makeshift camps, with limited or no access to clean drinking water. There is now considerable risk of infectious diseases in affected areas.
The Lancet 07/2015; DOI:10.1016/S0140-6736(15)61110-2 · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatitis E virus (HEV) is a leading cause of acute hepatitis. The long-term efficacy of a hepatitis E vaccine needs to be determined.
In an initial efficacy study, we randomly assigned healthy adults 16 to 65 years of age to receive three doses of either a hepatitis E vaccine (vaccine group; 56,302 participants) or a hepatitis B vaccine (control group; 56,302 participants). The vaccines were administered at 0, 1, and 6 months, and the participants were followed for 19 months. In this extended follow-up study, the treatment assignments of all participants remained double-blinded, and follow-up assessments of efficacy, immunogenicity, and safety were continued for up to 4.5 years.
During the 4.5-year study period, 60 cases of hepatitis E were identified; 7 cases were confirmed in the vaccine group (0.3 cases per 10,000 person-years), and 53 cases in the control group (2.1 cases per 10,000 person-years), representing a vaccine efficacy of 86.8% (95% confidence interval, 71 to 94) in the modified intention-to-treat analysis. Of the participants who were assessed for immunogenicity and were seronegative at baseline, 87% of those who received three doses of the hepatitis E vaccine maintained antibodies against HEV for at least 4.5 years; HEV antibody titers developed in 9% in the control group. The rate of adverse events was similar in the two groups.
Immunization with this hepatitis E vaccine induced antibodies against HEV and provided protection against hepatitis E for up to 4.5 years. (Funded by the Chinese Ministry of Science and Technology and others; ClinicalTrials.gov number, NCT01014845.).
New England Journal of Medicine 03/2015; 372(10):914-22. DOI:10.1056/NEJMoa1406011 · 54.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatitis E virus (HEV) infection is one of the main causes of acute hepatitis worldwide. A recombinant hepatitis E vaccine, HEV 239, has been licensed in China for immunizing adults of 16 year old and above. The vaccine antigen contains pORF2 aa 368 - 606 of the HEV genotype 1 expressed in E. coli. The quality of the vaccine is controlled through a combination of biophysical, biochemical and immunochemical methods. The vaccine is well tolerated in adults. The efficacy of the HEV 239 vaccine against symptomatic and asymptomatic infection had been proven to be high during a Phase III clinical trial and long-term follow up. The safety and efficacy of HEV 239 vaccine in certain high-risk populations remains to be further investigated.
Human Vaccines and Immunotherapeutics 02/2015; 11(4). DOI:10.1080/21645515.2015.1008870 · 3.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To establish a LC-MS/MS method for quantification of chlorogenic acid, caffeic acid, 3,4-DCQA, ferulic acid and cinnamic acid in rats plasma and study its pharmacokinetics after administration of Mailuoning injection at a single dose to rats. Plasma samples were acidified with hydrochloric acid and extracted with ethyl acetate. The analytes were determined by LC-MS-MS using a ZOBAX SB C18 column with a mobile phase of methanol-water (containing 2 mmol x L(-1) ammonium acetic) (60:40)at a flow rate of 0.5 mL x min(-1) and detected using ESI with negative ionization mode. Ions monitored in the multiple reaction monitoring (MRM) mode were m/z 353.1/191.0 [M-H]- for chlorogenic acid, m/z 178.9/134.9 [M-H]- for caffeic acid, m/z 515.2/353.0 [M-H]-for 3,4-DCQA, m/z 193.0/133.9 [M-H]-for ferulic acid, m/z 146.9/102.9 [M-H]- for cinnamic acid and m/z 246.0/125.8 [M-H]- for tinidazole (IS). After administration of Mailuoning injection at a single dose to eight Sprague-Dawley rats, the concentrations of chlorogenic acid, caffeic acid, 3,4-DCQA, ferulic acid and cinnamic acid in plasma were determined by LC-MS/MS method. The main pharmacokinetics parameters of measured data were caluculated by using DASver 1.0 software. The linear concentration ranges of the calibration curves for chlorogenic acid, caffeic acid, 3,4-DCQA and cinnamic acid were 2.006-1,027 microg x L(-1) (r = 0.999 6), 1.953-1,000 microg x L(-1) (r = 0.999 7), 28.51-1.459 x 10(4) microg x L(-1) (r = 0.998 9), 1.836-940.0, g x L(-1) (r = 0.997 7) and 4.780-2,447 microg x L(-1) (r = 0.998 6) respectively. The inner and inter-days relative standard deviations were both less than 5.0%, indicating legitimate precise and accuracy to the requirement of biological sample analysis. For chlorogenic acid, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (49.78 +/- 12.81) min, (123.55 +/- 14.82) mg x min x L(-1) and (0.004 3 +/- 0.000 5) L x min(-1), respectively. For caffeic acid, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (36.65 +/- 10.59) min, (91.67 +/- 11.77) mg x min L(-1) and (0.005 7 +/- 0.000 7) L x min(-1), respectively. For 3,4-DCQA, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (50.08 +/- 13.78) min, (278.34 +/- 31.82) mg x min x L-1 and (0.001 6 +/- 0.000 2) L x min(-1), respectively. For ferulic acid, the pharmacokinetic parameter t1/2, AUC0-t, and CL were (51.39 +/- 15.52) min, (34.72 +/- 4.67) mg x min x L(-1) and (0.000 4 +/- 0.0001) L x min(-1), respectively. For cinnamic acid, the pharmacokinetic parameter t1/2, AUCo-t, and CL were (74.42 +/- 18.32) min, (34.63 +/- 4.82) mg x min x L(-1) and (0.007 7 +/- 0.001 1) L x min-', respectively. The assay method is proved to be sensitive, accurate and convenient. It can be applied to the pharmacokinetic study of chlorogenic acid, caffeic acid, 3,4-DCQA, ferulic acid and cinnamic acid.
[Show abstract][Hide abstract] ABSTRACT: Introduction
Placental morphological and histopathological measures can be numerous and it is very time-consuming to collect all the information. When planning a large birth cohort study, researchers often face the dilemma as to whether and what information to collect in a placenta. The aim of this study was (1) to systematically select placental measures that have significant clinical implications, and (2) to assess the accuracy of these measures.
We used placental pathology information from the Collaborative Perinatal Project (CPP), in which 45,785 births had comprehensive information on placental morphology and pathology. We chose 20 major childhood diseases as outcomes. The statistical method of LASSO (least absolute shrinkage and selection operator) was used to select important placental measures that would have better predictability for outcomes.
LASSO selected 81 measures as candidates. After having consulted placental pathologists, we further narrowed down to the 38 and 23 most important measures to form two shortened evaluation systems that could be used in clinical practice and research. The sensitivity and specificity of these measures for composite child diseases were 68% and 34%, respectively, for the 38 measures and 48% and 53%, respectively, for the 23 measures.
We presented a potentially useful system for pathological characterization of the placenta. The use of these relatively simple and accessible characteristics as biomarkers may be considered in large birth cohort studies.
[Show abstract][Hide abstract] ABSTRACT: HEPATITIS E IS CAUSED BY TWO VIRAL GENOTYPE GROUPS: human types and zoonotic types. Current understanding of the epidemiology of the zoonotic hepatitis E disease is founded largely on hospital-based studies.
The epidemiology of hepatitis E was investigated in a community-based surveillance study conducted over one year in a rural city in eastern China with a registered population of 400,162.
The seroprevalence of hepatitis E in the cohort was 38%. The incidence of hepatitis E was 2.8/10,000 person-years. Totally 93.5% of the infections were attributed to genotype 4 and the rest, to genotype 1. Hepatitis E accounted for 28.4% (102/359) of the acute hepatitis cases and 68.9% (102/148) of the acute viral hepatitis cases in this area of China. The disease occurred sporadically with a higher prevalence during the cold season and in men, with the male-to-female ratio of 3∶1. Additionally, the incidence of hepatitis E increased with age. Hepatitis B virus carriers have an increased risk of contracting hepatitis E than the general population (OR = 2.5, 95%CI 1.5-4.2). Pre-existing immunity to hepatitis E lowered the risk (relative risk = 0.34, 95% CI 0.21-0.55) and reduced the severity of the disease.
Hepatitis E in the rural population of China is essentially that of a zoonosis due to the genotype 4 virus, the epidemiology of which is similar to that due to the other zoonotic genotype 3 virus.
PLoS ONE 01/2014; 9(1):e87154. DOI:10.1371/journal.pone.0087154 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A pseudovirion-based neutralisation assay has been considered the gold standard for measuring specific antibody responses against human papillomavirus (HPV). However, this assay is labor intensive and therefore very difficult to implement in large-scale studies. Previous studies have evaluated the agreement between virus-like particle (VLP)-based ELISA and pseudovirion-based neutralisation assays for measuring HPV vaccine-induced antibodies. However, the concordance of these assays to detect antibodies induced by natural infection has not yet been fully elucidated. In this study, the results of an Escherichia coli (E. coli)-expressed VLP-based ELISA were found to be highly concordant with those of a baculovirus-expressed VLP-based ELISA, as determined by assessing 90 human serum samples containing different levels of antibodies for HPV-16 and/or HPV-18. The correlation coefficients of the assay results were high (r = 0.98 and 0.97 for HPV-16 and HPV-18, respectively). The results of the E. coli expressed VLP-based ELISA correlated well with those of the pseudovirion-based neutralisation assay when testing 1020 post-vaccination human sera collected one month after the final vaccination with the E. coli expressed VLP-based bivalent HPV vaccine (r = 0.83 and 0.81 for HPV-16 and HPV-18). The agreement and correlation were moderate (kappa<0.3 for both HPV types 16 and 18, r = 0.59 and 0.68 for HPV-16 and HPV-18, respectively) when assessing 1600 serum samples from unvaccinated women of age 18-25 years. In conclusion, the VLP-based ELISA is an acceptable surrogate for the neutralizing antibody assay in measuring vaccine responses. However, the use of the VLP-based ELISA in epidemiological studies should be carefully considered.
[Show abstract][Hide abstract] ABSTRACT: A novel and compact tri-band microstrip-fed monopole antenna with dual-polarisation characteristics for wireless local area network (WLAN) and worldwide interoperability for microwave access (WiMAX) applications is proposed. The antenna is composed of a partial ground and a Y-shaped radiating patch that consists of two unequal monopole arms and a modified circle monopole. The antenna is able to generate three separate impedance bandwidths to cover the frequency bands of the WLAN (2.4-2.484 and 5.8 GHz) and the WiMAX (3.4-3.7 GHz). In addition, the antenna is circularly polarised in both the WLAN bands. Furthermore, the antenna structure is extremely simple, durable and occupies small space, making it suitable for practical applications.
[Show abstract][Hide abstract] ABSTRACT: Maternal obesity caused by overnutrition during pregnancy increases susceptibility to metabolic risks in adulthood, such as obesity, insulin resistance, and type 2 diabetes; however, whether and how it affects the cognitive system associated with the brain remains elusive. Here, we report that pregnant obesity induced by exposure to excessive high fatty or highly palatable food specifically impaired reversal learning, a kind of adaptive behavior, while leaving serum metabolic metrics intact in the offspring of rats, suggesting a much earlier functional and structural defects possibly occurred in the central nervous system than in the metabolic system in the offspring born in unfavorable intrauterine nutritional environment. Mechanically, we found that above mentioned cognitive inflexibility might be associated with significant striatal disturbance including impaired dopamine homeostasis and disrupted leptin signaling in the adult offspring. These collective data add a novel perspective of understanding the adverse postnatal sequelae in central nervous system induced by developmental programming and the related molecular mechanism through which priming of risk for developmental disorders may occur during early life.
PLoS ONE 11/2013; 8(11):e78876. DOI:10.1371/journal.pone.0078876 · 3.23 Impact Factor