Immunogenicity and safety of an E. coli-produced bivalent human papillomavirus (type 16 and 18) vaccine: A randomized controlled phase 2 clinical trial

BackgroundThis study aimed to investigate the dosage, immunogenicity and safety profile of a novel human papillomavirus (HPV) types 16 and 18 bivalent vaccine produced by E. coli.MethodsThis randomized, double-blinded, controlled phase 2 trial enrolled women aged 18–25 years in China. Totally 1600 eligible participants were randomized to receive 90 μg, 60 μg, or 30 μg of the recombinant HPV 16/18 bivalent vaccine or the control hepatitis B vaccine on a 0, 1 and 6 month schedule. The designated doses are the combined micrograms of HPV16 and 18 VLPs with dose ratio of 2:1. The immunogenicity of the vaccines was assessed by measuring anti-HPV 16 and 18 neutralizing antibodies and total IgG antibodies. Safety of the vaccine was assessed.ResultsAll but one of the seronegative participants who received 3 doses of the HPV vaccines seroconverted at month 7 for anti-HPV 16/18 neutralizing antibodies and IgG antibodies. For HPV 16, the geometric mean titers (GMTs) of the neutralizing antibodies were similar between the 60 μg (GMT = 10,548) and 90 μg (GMT = 12,505) HPV vaccine groups and were significantly higher than those in the 30 μg (GMT = 7596) group. For HPV 18, the GMTs of the neutralizing antibodies were similar among the 3 groups. The HPV vaccine was well tolerated. No vaccine-associated serious adverse events were identified.ConclusionThe prokaryotic-expressed HPV vaccine is safe and immunogenic in women aged 18–25 years. The 60 μg dosage formulation was selected for further investigation for efficacy.Clinical trials registration: NCT01356823.     

Association of STAT6 variants with asthma risk: A systematic review and meta-analysis

A large number of studies have reported that the genetic variants in STAT6 gene may be implicated in susceptibility to asthma, but with inconsistent results. Therefore, the aim of this meta-analysis was to determine the likelihood of developing asthma for the individuals with different STAT6 variants. The database including Pubmed, Embase and CNKI (Chinese National Knowledge Infrastructure) were searched to find the relevant papers. Data were extracted by two independent reviewers and the odds radios (ORs) were pooled with 95% confidence intervals (CIs), using random effect or fixed effect models as appropriate, to indicate the risk of asthma for different STAT6 variants. The heterogeneity and bias were tested for each pooled result. Data from 19 studies were pooled that reported associations of rs324015, rs71802646 and rs324011 in STAT6 gene with asthma risk. The results demonstrated that 13GT and short GT in rs71802646 were both associated with increased risk of asthma in overall analysis (OR = 1.26 for 13GT and 1.30 for short GT). Further, subgroup analysis showed an increased risk of asthma in Asian population with 13GT (OR = 1.21), 14GT (OR = 1.97) and short GT (OR = 1.27). Besides, 13GT, 14GT and short GT all contributed to higher risk of atopic asthma, with OR 1.50, 2.21 and 1.65 respectively. However, rs324015 (G>A) appeared to be associated with decreased risk for atopic asthma (with OR = 0.83, 0.68 and 0.79 for A, AA and AA+AG respectively). Both overall and subgroup analyses indicated no effect of rs324011 on asthma risk. In conclusion, our meta-analyses suggest that short GT repeats of rs71802646 in STAT6 contribute to higher risk for asthma, while rs324015 may have a protective effect on atopic asthma.     

Is asthma a protective factor for dengue fever? In vitro experiment and nationwide population-based cohort analysis

BackgroundDengue fever (DF) is the most rapidly spreading mosquito-borne viral disease. Practical vaccines or specific therapeutics are still expected. Environmental factors and genetic factors affect the susceptibility of Dengue virus (DV) infection. Asthma is a common allergic disease, with house dust mites (HDMs) being the most important allergens. Asthmatic patients are susceptible to several microorganism infections.MethodsA nationwide population-based cohort analysis was designed to assess whether to determine whether asthma can be a risk factor for DF.ResultsUnexpectedly, our data from a nationwide population-based cohort revealed asthmatic patients are at a decreased risk of DF. Compared to patients without asthma, the hazard ratio (HR) for DF in patients with asthma was 0.166 (95% CI: 0.118–0.233) after adjustment for possible confounding factors. In the age stratification, the adjusted HR for DF in young adult patients with asthma was 0.063. Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) of dendritic cells (DCs) is an important entry for DV. Through another in vitro experiment, we found that HDM can diminish surface expression of DC-SIGN in monocyte-derived DCs and further decrease the cellular entry of DV.ConclusionsDecreased DC-SIGN expression in DCs of allergic asthmatic patient may be one of many factors for them to be protected against DF. This could implicate the potential for DC-SIGN modulation as a candidate target for designing therapeutic strategies for DF.     

Diagnostic value of RASSF1A hypermethylation in colorectal cancer: a meta-analysis

Purpose

Ras association domain family 1 isoform A (RASSF1A), a member of Ras association domain family, plays an important role in tumorigenesis. The goal of our meta-analysis was to assess the diagnostic value of RASSF1A hypermethylation in colorectal cancer (CRC).

儿童人工耳蜗植入术后音乐能力发育研究

目的：探讨儿童人工耳蜗植入术后音乐能力的发展趋势,为人工耳蜗植入儿童音乐能力评估提供临床资料。方法：26例人工耳蜗植入儿童,手术年龄为11～68个月,平均35．6个月;以76例1～24月龄的听力正常婴幼儿作为对照组,平均月龄6．1个月。使用小龄人工耳蜗儿童音乐能力等级量表进行评估。人工耳蜗植入儿童评估分别在开机时,开机后1、3、6、9、12及24个月时进行;听力正常婴幼儿评估分别在1、3、6、9、12及24月龄时进行。结果：人工耳蜗植入儿童的音乐能力得分随人工耳蜗使用时间的延长而显著提高（P〈O．05）,听力正常婴幼儿的音乐能力得分亦随年龄的增长而显著提高（P〈O．05）。经两样本比较的秩和检验,人工耳蜗植入儿童与听力正常婴幼儿在听力年龄为1、3、6、9、12个月时音乐能力得分的差异无统计学意义（P〉O．05）,在听力年龄为24个月时音乐能力得分的差异有统计学意义（P〈O．05）。结论：人工耳蜗植入儿童开机后音乐能力随人工耳蜗使用时间的延长而显著提高,并在开机12个月内呈现快速增长趋势。     

Pulse pressure measured at the level of the femoral artery,but not at the level of the aorta,carotid and brachial arteries,is associated with the incidence of coronary heart disease events in a population with a high prevalence of type 2 diabetes and impaired glucose metabolism – The Hoorn study

IntroductionCentral (aortic or carotid) pulse pressure (PP) is more strongly associated with local organ damage and possibly mortality than brachial PP.AimTo investigate for the first time the association of femoral (f) PP with all-cause mortality, and incident cardiovascular disease (CVD), coronary heart disease (CHD) and cerebrovascular disease (CerVD) events, as well as with markers of renal function (estimated glomerular filtration rate, eGFR, and microalbuminuria).MethodsWe used data from a population-based study, by design including 50% type 2 diabetes and impaired glucose metabolism (IGM). The baseline examination included non-invasive PP assessment at the brachial, aorta (Sphygmocor device), carotid and femoral (ultrasound distention waves calibrated by brachial mean and diastolic pressure) arteries.ResultsAfter 7.8 years of follow-up (n = 449, age: 68.9 ± 6.0 males: 52%), 66 participants had died, 102 had a CVD event, 45 a CHD event, and 31 a CerVD event. PP at all sites was associated with incident all-cause mortality and CVD events. Only fPP was, however, associated with incident CHD events, even after adjustment for CVD risk factors (HRs 1.31 [1.07–1.61 95% CIs]). No association between PP and incident CerVD events was found – possibly due to the small number of events. fPP was associated with renal function but this was similar to other PP indices. No interaction between each any local PP index and glucose metabolism status or renal function was present.ConclusionBeyond anatomical topography, local fPP provide important information related to CVD events. This possibility and the underlying mechanisms should be further investigated.     

Impact of additional antibiotics on in-hospital mortality in tuberculosis isolated general bacteria: A propensity score analysis

Whether or not additional antibiotics with anti-tuberculosis agents are required to treat bacterial co-infection with pulmonary tuberculosis is unclear. We aimed to assess the impact of additional antibiotics on mortality in pulmonary tuberculosis patients whose sputum cultures were positive for general bacteria as a surrogate definition of bacterial pneumonia. This study was a single-center retrospective cohort using a propensity score analysis. We included patients who were admitted for pulmonary tuberculosis and whose sputum cultures were positive for general bacteria. The mortality of patients who received additional antibiotics was analyzed after adjusting for other variables, including the propensity score predicting treatment with additional antibiotics. We assessed 68 and 55 tuberculosis patients treated with and without general antibiotics, respectively. Additional antibiotics tended to be administered to patients with a high level of C-reactive protein and neutrophil count, poor performance status, hypoxemia and hypoalbuminemia (C-statistics of area under receiver operating characteristic curve to the propensity score; 0.884, p < 0.001). In the multivariate analysis, advanced age and not the use of additional antibiotics was associated with in-hospital mortality. Additional antibiotics with anti-tuberculosis agents may not improve the prognosis of pulmonary tuberculosis patients whose sputum cultures were positive for general bacteria. Isolation of general bacteria does not equate to complication with bacterial pneumonia, so physicians should not administer general antibiotics to TB patients based solely on the results of sputum culture for general bacteria. A prospective study is needed to verify these results using a more accurate definition of pulmonary tuberculosis complicated with bacterial pneumonia.     

Growth-differentiation factor-15 predicts adverse cardiac events in patients with acute coronary syndrome: A meta-analysis

BackgroundWe aimed to analyse the association between high-level growth-differentiation factor-15 (GDF-15) and mortality, recurrent MI and heart failure compared to low-level GDF-15 in patients with acute coronary syndrome (ACS).MethodsPubMed and EMBASE were searched from their commencement to December 2017 for qualified studies that evaluated the associations between GDF-15 and ACS. Risk ratios were synthesized with random effect meta-analysis. Publication bias and sensitivity analyses were also conducted.ResultsA total of thirteen studies and 43,547 participants were analyzed systematically in our meta-analysis. Our study showed a significant association between GDF-15 values and mortality (p = 0.000, RR = 6.75, 95% CI = 5.81–7.84) and recurrent MI (p = 0.000, RR = 1.95, 95% CI = 1.72–2.21) in the overall analyses. Subgroup analyses revealed similar results. However, there was evidence of heterogeneity in the study of heart failure, whose overall RR was 6.66, with an I² of 87.3%.ConclusionThere was a significant association between high-level GDF-15 and mortality, recurrent MI in patients with ACS. We need more data to research the risk stratification of heart failure in ACS patients in the future.