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Nowadays, nanotechnology environmental health and safety (nanoEHS) is gaining attention. We previously found that silica nanoparticles (SiNPs) could induce vascular endothelial damage. However, the subsequent toxicologic response to SiNPs-induced endothelial damage was still largely unknown. In this study, we explored the inflammation–coagulation response and thrombotic effects of SiNPs in endothelial cells and zebrafish embryos. For in vitro study, swollen mitochondria and autophagosome were observed in ultrastructural analysis. The cytoskeleton organization was disrupted by SiNPs in vascular endothelial cells. The release of proinflammatory and procoagulant cytokines including IL-6, IL-8, MCP-1, PECAM-1, TF and vWF, were markedly elevated in a dose-dependent manner. For in vivo study, based on the NOAEL for dosimetry selection, and using two transgenic zebrafish, Tg(mpo:GFP) and Tg(fli-1:EGFP), SiNPs-induced neutrophil-mediated inflammation and impaired vascular endothelial cells. With the dosage higher than NOAEL, SiNPs significantly decreased blood flow and velocity, exhibiting a blood hypercoagulable state in zebrafish embryos. The thrombotic effect was assessed by o-dianisidine staining, showed that an increasing of erythrocyte aggregation occurred in SiNPs-treated zebrafish. Microarray analysis was used to screen the possible genes for inflammation–coagulation response to SiNPs in zebrafish, and the JAK1/TF signaling pathway was further verified by qRT-PCR and Western blot assays. For in-deepth study, il6st was knocked down with specific morpholinos. The whole-mount in situ hybridization and qRT-PCR analysis showed that the expression jak1 and f3b were attenuated in il6st knockdown groups. In summary, our data demonstrated that SiNPs could induce inflammation–coagulation response and thrombotic effects via JAK1/TF signaling pathway.

BackgroundDifferent confounder adjustment strategies were used to estimate odds ratios (ORs) in case-control study, i.e. how many confounders original studies adjusted and what the variables are. This secondary data analysis is aimed to detect whether there are potential biases caused by difference of confounding factor adjustment strategies in case-control study, and whether such bias would impact the summary effect size of meta-analysis.MethodsWe included all meta-analyses that focused on the association between breast cancer and passive smoking among non-smoking women, as well as each original case-control studies included in these meta-analyses. The relative deviations (RDs) of each original study were calculated to detect how magnitude the adjustment would impact the estimation of ORs, compared with crude ORs. At the same time, a scatter diagram was sketched to describe the distribution of adjusted ORs with different number of adjusted confounders.ResultsSubstantial inconsistency existed in meta-analysis of case-control studies, which would influence the precision of the summary effect size. First, mixed unadjusted and adjusted ORs were used to combine individual OR in majority of meta-analysis. Second, original studies with different adjustment strategies of confounders were combined, i.e. the number of adjusted confounders and different factors being adjusted in each original study. Third, adjustment did not make the effect size of original studies trend to constringency, which suggested that model fitting might have failed to correct the systematic error caused by confounding.ConclusionsThe heterogeneity of confounder adjustment strategies in case-control studies may lead to further bias for summary effect size in meta-analyses, especially for weak or medium associations so that the direction of causal inference would be even reversed. Therefore, further methodological researches are needed, referring to the assessment of confounder adjustment strategies, as well as how to take this kind of bias into consideration when drawing conclusion based on summary estimation of meta-analyses.Electronic supplementary materialThe online version of this article (10.1186/s12874-017-0454-x) contains supplementary material, which is available to authorized users.

This study provides the evidence that the reporting quality of post-marketing safety evaluation studies conducted using routinely collected health data was often insufficient. Future stakeholders are encouraged to endorse the RECORD guidelines in pharmacovigilance.

Background Congenital heart defect (CHD) is the leading cause of birth defects globally, which results in a great disease burden. It is still imperative to detect the risk factors of CHD. This umbrella review aimed to comprehensively summarize the evidence and grade the evidence of the associations between non-genetic risk factors and CHD. Methods Databases including Medline, Embase, Web of Science, Cochrane Library, and four Chinese databases were searched from inception to 18 Jan 2022. The reference lists of systematic reviews (SR) and meta-analyses (MA) were screened, which aimed to explore the non-genetic risk factors of CHD. Subsequently, titles and abstracts of identified records and full texts of selected SR/MA were screened by two independent reviewers based on predefined eligibility criteria. A priori developed extraction form was used to abstract relative data following the PRISMA 2020 and MOOSE guidelines. The risk of bias was assessed with the AMSTAR2 instrument. Data were synthesized using fixed-effects and random-effects meta-analyses, respectively. Finally, the evidence on the association of non-genetic risk factors and CHD was graded using Ioannidis’s five-class evidence grade. Results A total of 56 SRs, encompassing 369 MAs, were identified. The risk factors included relative factors on air pollution, reproductive-related factors, parental age and BMI, parental life habits, working and dwelling environment, maternal drug exposure, and maternal disease. Based on AMSTAR2 criteria, only 16% (9/56) of SRs were classified as “Moderate”. One hundred and two traceable positive association MAs involving 949 component individual studies were included in further analysis and grading of evidence. Family genetic history, number of abortions, maternal obesity, especially moderate or severe obesity, decoration materials, harmful chemicals, noise during pregnancy, folic acid supplementation, SSRIs, SNRIs, any antidepressants in the first trimester, maternal DM (including both PGDM and GDM), and gestational hypertension were convincing and highly suggestive factors for CHD. After sensitivity analyses based on cohort studies, some grades of evidence changed. Conclusion The present umbrella review will provide evidence-based information for women of childbearing age before or during pregnancy to prevent CHD. In addition, sensitivity analysis based on cohort studies showed the changed evidence levels. Therefore, future SR/MA should concern the sensitivity analysis based on prospective birth cohort studies and case-control studies.

Accurate assessments of potassium intake in children are important for the early prevention of cardiovascular disease. Currently, there is no simple approach for accurate estimation of potassium intake in children. We aim to evaluate the accuracy of 24-hour urinary potassium excretion (24UKV) estimation in children using three common equations: the Kawasaki, Tanaka, and Mage formulas, in a hospital-based setting. A total of 151 participants aged 5˜18 years were initially enrolled, and spot urine samples were collected in the whole 24-hour duration to measure the concentrations of potassium and creatinine. We calculated the mean difference, absolute and relative difference, and misclassification rate between measured 24UKV and the predicted ones using Kawasaki, Tanaka, and Mage formulas in 129 participants. The mean measured 24UKV was 1193.3 mg/d in our study. Mean differences between estimated and measured 24UKV were 1215.6, −14.9, and 230.3 mg/d by the Kawasaki, Tanaka, and Mage formulas, respectively. All estimated 24UKV were significantly different from the measured values in all the timepoint (all P<0.05), except for the predicted values from Tanaka formula using morning, afternoon, and evening spot urine. The proportions with relative differences over 40% were 87.2%, 32.5%, and 47.3% for Kawasaki, Tanaka, and Mage formulas, respectively. Misclassification rates were 91.5% for Kawasaki, 44.4% for Tanaka, and 58.9% for Mage formula at the individual level. Our findings showed that misclassification could occur on the individual level when using Kawasaki, Tanaka, and Mage formulas to estimate 24UKV from spot urine in the child population.

Background Delirium is a common complication in ICU patients, and it can signi cantly increase the length of hospital stay and cost. Dexamethasone is widely used in various in ammatory diseases and is a glucocorticoid commonly used in critically ill patients. There are no studies on the effect of dexamethasone on the development of delirium in critically ill patients, therefore, this study aimed to con rm the effect of dexamethasone use and the dose on the incidence of delirium and patient prognosis in critically ill patients through a large cohort study. Methods A retrospective cohort study was conducted using data extracted from the MIMIC III database, and the primary outcome was the development of delirium, using multivariate logistic regression analysis to reveal the relationship between dexamethasone and delirium. Secondary endpoints were in-hospital mortality, total length of stay and length of ICU stay, and the relationship between dexamethasone and prognosis was assessed with Cox proportional hazards models. The Lowess smoothing technique was used to investigate the dose correlation between dexamethasone and outcomes, subgroup analysis was used to account for heterogeneity, and different correction models and propensity matching analysis were used to eliminate potential confounders. Results Finally, 38,509 patients were included, and 2,204 (5.7%) used dexamethasone. A signi cantly higher incidence of delirium (5.0% vs. 3.4%, P < 0.001), increased in-hospital mortality (15.0% vs. 11.3%, P < 0.001), and longer length of stay and ICU stay were observed in patients taking dexamethasone compared with those not taking dexamethasone. Multivariate logistic and Cox regression analyses con rmed that dexamethasone was signi cantly associated with delirium (adjusted OR = 1.45, 95% CI = 1.08-1.95, P = 0.014) and in-hospital mortality (adjusted HR = 1.19, 95% CI = 1.02-1.40, P = 0.032). The risk of delirium and in-hospital death was lower with dexamethasone less than 10 mg, and subjects with 10-14 mg had the shortest length of hospital stay. Conclusions This study demonstrated that the use of dexamethasone in critically ill patients exacerbated the occurrence of delirium, while increasing the risk of in-hospital death and length of stay, and the use of low-dose dexamethasone had a lower risk of delirium and death, which appeared to be safer. Key Points Question: Previous controversies have been inconclusive about the effect of dexamethasone on postoperative delirium, so in critically ill patients of ICU, does the use and dose of dexamethasone have an effect on the occurrence of delirium? Findings: The use of dexamethasone in critically ill patients exacerbates the development of delirium, while increasing the risk of inhospital mortality and length of stay, and low-dose dexamethasone had a lower risk of delirium and death. Meaning: To reduce the risk of delirium, it may be of interest to reduce the use of nonessential dexamethasone and control the intake level of dexamethasone in ICU patients.

Background Acute kidney injury (AKI) is a common postoperative complication with an incidence of nearly 15%. Relatively balanced fluid management, flexible use of vasoactive drugs, multimodal analgesia containing non-steroidal anti-inflammatory drugs are fundamental to ERAS protocols. However, these basic tenants may lead to an increased incidence of postoperative AKI. Methods A search was done in the PubMed, Embase, Cochrane Library and reference lists to identify relevant studies from inception until May 2020 to be included in this study. Effects were summarized using pooled risk ratios (RRs), mean differences (MDs) and corresponding 95% confidence intervals (Cls) with random effect model. Heterogeneity assessment, sensitivity analysis, and publication bias were performed. Results A systematic review of nineteen cohort studies covering 17,205 patients, comparing impact of ERAS with conventional care on postoperative AKI was performed. Notably, the ERAS regimen did not increase the incidence of postoperative AKI compared with standard care (RR: 1.21; 95% CI: 0.96 to 1.52; I2 = 53%). Both goal-directed fluid therapy (RR: 1.26; 95% CI: 0.99–1.61; I2 = 55%) and restrictive fluid management (RR: 1.06; 95% CI: 0.57–1.98; I2 = 60%) had no significant effect on the incidence of postoperative AKI. There was no significant statistical difference between different AKI diagnostic criteria (P = 0.43; I2 = 0%). ERAS group had significantly shorter hospital stay (MD: −1.54; 95% CI: −1.91 to −1.17; I2 = 66%). There was no statistical difference in 30-day readmission rate (RR: 0.98; 95% CI: 0.80 to 1.20; I2 = 42%), 30-day reoperation rate (RR: 0.98; 95% CI: 0.71 to 1.34; I2 = 42%) and mortality (RR: 0.81; 95% CI: 0.59 to 1.11; I2 = 0%) between the two groups. Conclusions This meta-analysis suggests that ERAS protocols do not increase readmission or reoperation rates and mortality while significantly reducing LOS. Most importantly, the ERAS protocol was shown to have no promoting effect on the incidence of postoperative AKI. Even GDFT and restrictive fluid management cannot avoid the occurrence of postoperative AKI, and the ERAS protocol is still worth recommending and its safety is further confirmed.