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Oral administration is a convenient drug delivery method in our daily lives. However, it remains a challenge to achieve precise target delivery and ensure the efficacy of medications in extreme environments within the digestive system with complex environments. This paper proposes an oral multilayer magnetic hydrogel microrobot for targeted delivery and on-demand release driven by a gradient magnetic field. The inner hydrogel shells enclose designated drugs and magnetic microparticles. The outer hydrogel shells enclose the inner hydrogel shells, magnetic microparticles, and pH neutralizers. The drug release procedure is remotely implemented layer-by-layer. When the required gradient magnetic field is applied, the outer hydrogel shells are destroyed to release their inclusions. The enclosed pH neutralizers scour the surrounding environment to avoid damaging drugs by the pH environment. Subsequently, the inner hydrogel shells are destroyed to release the drugs. A set of experiments are conducted to demonstrate the wirelessly controllable target delivery and release in a Petri dish and biological tissues. The results demonstrated attractive advantages of the reported microrobot in microcargo delivery with almost no loss, remote controllable release, and drug protection by the pH neutralizers. It is a promising approach to advance next-generation precision oral therapies in the digestive system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Xu, Wu, Xu and Xu.)

Drought stress is one of the most impactful abiotic stresses to global wheat production. Therefore, identifying key regulators such as the calcineurin B-like protein interacting protein kinase (CIPK) in the signaling cascades known to coordinate developmental cues and environmental stimuli represents a useful approach to improve drought tolerance. However, functional studies have been very limited partly due to the difficulties in prioritizing candidate genes from the large TaCIPK family. To address this issue, we demonstrate a straight-forward strategy by analyzing gene expression patterns in response to phytohormones or stresses and identified TaCIPK19 as a new regulator to improve drought tolerance. The effects of TaCIPK19 on drought tolerance were evaluated in both tobacco and wheat through transgenic approach. Ectopic expression of TaCIPK19 in tobacco greatly improves drought tolerance with enhanced ABA biosynthesis/signaling and ROS scavenging capacity. TaCIPK19 overexpression in wheat also confers the drought tolerance at both seedling and mature stages with enhanced ROS scavenging capacity. Additionally, potential CBL partners interacting with TaCIPK19 were investigated. Collectively, our finding exemplifies a straight-forward approach to facilitate reverse genetics related to abiotic stress improvement and demonstrates TaCIPK19 as a new candidate gene to improve ROS scavenging capacity and drought tolerance, which is useful for genetic improvement and breeding application in wheat., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The genus Pleuronema Dujardin, 1841, with nearly 40 morphospecies, is one of the largest genera in the well-known subclass Scuticociliatia. In the present study, two Pleuronema species were collected from subtropical coastal waters of the East China Sea. The morphology and molecular phylogeny were investigated using modern standard methods. Pleuronema ningboensis n. sp. is mainly characterized by an elliptical body in outline with the right ventrolateral side straight, 16-22 somatic kineties, 3-5 preoral kineties, and the posterior end of the membranelle 2a hook-like. An improved diagnosis of Pleuronema orientale Pan et al., 2015 was provided: body size in vivo usually 90-135 × 45-85 μm, right ventrolateral side convex, 36-51 somatic kineties, 1-5 preoral kineties, one to three spherical macronuclei, membranelle 2a arranged in a zig-zag pattern in middle portion, posterior region hook-like, both membranelle 1 and membranelle 3 composed of three rows of basal bodies. The small subunit ribosomal DNA (SSU rDNA) of two species is sequenced, and their molecular phylogeny is analyzed. The new species Pleuronema ningboensis n. sp. clusters with P. grolierei KF840519, P. setigerum JX310015, P. paucisaetosum KF206430, and P. cf. setigerum KF848875, basically in accord with the morphological characteristics.

Maintaining the completeness of cargo and achieving on-demand cargo release during long navigations in complex environments of the internal human body is crucial. Herein, we report a novel design of magnetic hydrogel soft capsule microrobots, which can be physically disintegrated to release microrobot swarms and diverse cargoes with almost no loss. CaCl 2 solution and magnetic powders are utilized to produce suspension droplets, which are put into sodium alginate solution to generate magnetic hydrogel membranes for enclosing microrobot swarms and cargos. Low-density rotating magnetic fields drive the microrobots. Strong gradient magnetic fields break the mechanical structure of the hydrogel shell to implement on-demand release. Under the guidance of ultrasound imaging, the microrobot is remotely controlled in acidic or alkaline environments, similar to those in the human digestion system. The proposed capsule microrobots provide a promising solution for targeted cargo delivery in the internal human body., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Anthropogenic input of nutrient has profoundly influenced water quality and aquatic organisms, however, large and unbalanced nitrogen (N) and phosphorus (P) inputs (decoupling) can lead to a range of ecological health problems such as eutrophication. Whether and how the decoupling varies along the aquatic food chain remains poorly addressed. Here we chose an urban river ecosystem in the cosmopolis region of Beijing, with reclaimed water as the entire replenishment water source over 20 years, to demonstrate the decoupling pattern of N vs P across trophic levels. Results showed that organism C, N and P concentration increased, but N:P ratio decreased upward along the food chains, suggesting that this decoupling of N and P increased as trophic level ascends. Compared with natural freshwater ecosystem, the decoupling of N and P was aggravated in the reclaimed water river. Moreover, the homeostasis of N and P were higher at higher relative to lower trophic levels, and higher in macro-food chain relative to planktonic food chain. This study, for the first time, revealed the increasing decoupling of N vs P upward along the major food chains in an urban aquatic ecosystem, and could improve the understanding of nutrient cycling at the food chain level under human disturbance, and provide useful information for ecological restoration and eutrophication control of urban wetlands replenished with reclaimed water., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wenxuan Han reports financial support was provided by Ministry of Science and Technologyof the People's Republic of China., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Rather than using longitudinal "muscle" as in biological inchworm, the existing magnetic active elastomer (MAE)-based inchworm robots utilize magnetic torque to pull and push the soft body, which hinders its locomotion mobility. In this paper, a new pre-strained MAE inchworm millirobot with micropillars is proposed. The pre-strained elastomer serves as a pre-load muscle to contract the soft body, and the micropillars act as tiny feet to anchor the body during the locomotion. The proposed magnetic inchworm robot features a simple fabrication process that does not require special magnetization equipment. For the first time, the pre-load muscle is introduced in the design of magnetic inchworm robots, making it more like a real inchworm in terms of locomotion mechanism. The locomotion principle and parametric design for the desired locomotion performance have been investigated. Experimental results show that the fabricated magnetic inchworm robot (size: 10 mm × 5 mm, micropillars length: 200 µm, and mass: 262 g) can locomote on a smooth acrylic surface (roughness of 0.3 µm) at the speed of 0.125 body lengths per second, which is comparable with the existing magnetic inchworm robots. Moreover, the locomotion capabilities of the inchworm robot on wet surfaces and inclined planes have been verified via experimental studies.

Accurate assessments of potassium intake in children are important for the early prevention of CVD. Currently, there is no simple approach for accurate estimation of potassium intake in children. We aim to evaluate the accuracy of 24-h 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-h 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 time point (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: 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., (© 2022. The Author(s).)

This paper presents the design and optimization of a new alternating electromagnetic-field-generation system, which is dedicated to actuating untethered magnetic microrobots under an inverted microscope. Its uniqueness is that the system parameters are optimally designed by considering both electric and geometry constraints for the target-driving application. The dominant parameters of the system are first determined by establishing analytical models. According to the requirements of targeted application, the optimization problem with certain constraints is formulated, which is solved via the multiobjective genetic algorithm method. A prototype system with the optimal parameters is developed for experimental testing. Experimental studies are carried out to characterize actual performance of the developed actuation system. For demonstration, a magnetic microball has been actuated for navigation by surface rolling in a petri dish filled with pure water. Results indicate that the reported electromagnetic-field-generation system meets the actuation requirements for potential applications.

Background: Delirium is a common complication in intensive care unit (ICU) patients, and it can significantly increase the length of hospital stay and cost. Dexamethasone is widely used in various inflammatory diseases and must be used with caution in critically ill patients. Previous studies have shown that the effect of corticosteroid use on the development of delirium in critically ill patients is still controversial, and there is inconclusive conclusion about the effect of dexamethasone on delirium in such patients. Therefore, this study aimed to confirm 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 Medical Information Mart for Intensive Care III database, which is a large and freely available database of all 46,476 patients who visited Beth Israel Deaconess Medical Center in Boston, Massachusetts, USA and were admitted to the ICU between 2001 and 2012. 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, ICU mortality, total length of stay, and length of ICU stay, and the relationship between dexamethasone and prognosis was assessed with Cox proportional hazards models. Propensity score matching with 1:1 grouping was used to eliminate the effect of confounders on both cohorts. The locally weighted scatter plot 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 2204 (5.7%) used dexamethasone. No significant statistical difference was observed in basic demographic information after propensity score matching between the two study groups. A significantly higher incidence of delirium (5.0% versus 3.4%, P < 0.001), increased in-hospital mortality (14.9% versus 10.3%, P < 0.001), ICU mortality (9.0% versus 7.5%, P = 0.008), 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 confirmed that dexamethasone was significantly associated with delirium (adjusted odds ratio = 1.48, 95% confidence interval [CI] = 1.09-2.00, P = 0.012), in-hospital mortality (adjusted hazard ratio = 1.19, 95% CI = 1.02-1.40, P = 0.032), and ICU mortality (adjusted hazard ratio = 1.62, 95% CI = 1.22-2.15, P = 0.001). Compared with critically ill patients using high-dose dexamethasone, the risk of delirium was lower in the dose less than the 10 mg group, and patients using 10-14 mg may be associated with a lower risk of in-hospital death and the least ICU mortality, length of hospital stay, and ICU 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, ICU death, and length of hospital stay, with a lower risk of delirium and a shorter total length of hospital stay with low-dose dexamethasone than with larger doses., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Regional anesthesia has been widely used in clinical practice. Over the past 30 years, various guidance techniques have been developed for regional anesthesia ranging from paresthesia progressing to neurostimulation and currently ultrasound guidance. Especially, the use of point-of-care ultrasound greatly enhances the success rate of regional anesthesia. However, the poor imaging quality of ultrasound in patients with obesity, fat infiltration, etc., limits the use of ultrasound. The combined use of ultrasound with neurostimulator, electromyography, pressure monitoring, etc. is advocated in order to facilitate regional anesthesia in this cohort of patients. The accumulated evidence has shown that the ultrasound combined with other techniques (UCOT) can help to solve the difficulties of puncture location caused by obesity, anatomical variation, and other factors when using ultrasound guidance alone. In recent years, with the development of medical image fusion and medical image artificial intelligence identification technology, guidance techniques for regional anesthesia have advanced considerably. To understand the advantages and disadvantages of the various guidance techniques for regional anesthesia developed in recent years and to guide their rational clinical application, this paper reviews these techniques, describing the progression from the early use of paresthesia to the latest UCOT, as well as the latest research on UCOT, and the prospects for the development of new guidance techniques for regional anesthesia., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Wu and Wang.)

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., Competing Interests: The authors have declared that no competing interests exist.

Adlayers have been one of the main concerns for controlled synthesis of graphene by the chemical vapor deposition (CVD) method. Here we investigate the CVD growth of graphene adlayers on copper (Cu) using isotope-labeling-based Raman spectroscopy and high-resolution atomic force microscopy (AFM). The results show that, besides conventional simultaneous growth for all the graphene layers, approximately 37% of the adlayers follow a sequential growth which can occur even hours after the nucleation of the first layer. The proportions of AB (Bernal)- and twisted (t)-stacked bilayer graphene (BLG) stacks formed by the two modes are not significantly different. Moreover, in those stacks with both AB- and t-BLG, evidence at the atomic scale demonstrates that they resulted from misoriented domains in their single-crystal-like top layers. We believe that this new understanding of the growth mechanism for graphene adlayers can help pave the way towards the synthesis of large-scale and high-quality graphene with controllable layer numbers., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

With the increasing production and application of engineered amorphous silica nanoparticles (aSiNPs), people have more opportunities to be exposed to aSiNPs. However, the knowledge of its adverse health effects and related mechanisms is still limited, compared with the well-studied crystalline micron-sized silica. Since small differences in the physical-chemical properties of nanoparticles could cause significant differences in the toxic effect, it is important to distinguish how these variations influence the outcoming toxicity. Notably, particle size, as one of the essential characterizations of aSiNPs, is relevant to its biological activities. Thus, the aim of this systematic review was to summarize the relationship between the particle size of aSiNPs and its adverse biological effects. In order to avoid the influence of complicated in vivo experimental conditions on the toxic outcome, only in vitro toxicity studies which reported on the cytotoxic effect of different sizes aSiNPs were included. After the systematic literature retrieval, selection, and quality assessment process, 76 eligible scientific papers were finally included in this review. There were 76% of the studies that concluded a size-dependent cytotoxicity of aSiNPs, in which smaller-sized aSiNPs possessed greater toxicity. However, this trend could be modified by certain influence factors, such as the synthetic method of aSiNPs, particle aggregation state in cell culture medium, toxicity endpoint detection method, and some other experimental conditions. The effects of these influence factors on the size-dependent cytotoxicity of aSiNPs were also discussed in detail in the present review., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Dong et al.)

This article presents the design and testing of a novel two-directional (2-D) piezoelectric stack-based energy harvester for capturing the mechanical energy from the human footstep. The uniqueness of the harvester lies in the fact that the energy of 2-D excitation is scavenged by a single piezoelectric stack transducer, which can reduce the loss of harvestable energy. The harvester is constructed by the integration of permanent magnets, position protection plates, and multistage force amplification frame. The input force and input displacement are restricted to guarantee the device's safety. The reported multistage force amplification frame with leverage mechanism and bridge-type amplifier enlarges the force acting on the piezoelectric stack, which further improves the power output. A linear guiding mechanism based on leaf flexure is applied to minimize the impact of input forces in other than moving directions. Through analytical modeling, the main architectural parameters of the device are determined. Simulation study with finite-element analysis is conducted to optimize the device parameters for achieving the largest force amplification ratio with a high safety factor. A prototype harvester is fabricated for experimental study. Results demonstrate the feasibility of the developed 2-D piezoelectric stack-based energy harvester.

Transfer acts as a crucial bridge between the chemical vapor deposition (CVD) synthesis of large-scale graphene and its applications, but the quality evolution of a graphene film during transfer remains unclear. Here we use scanning Raman spectroscopy to monitor as-grown graphene during each step of wet transfer including floating on etchant solution, loaded onto a target substrate, and with additional annealing. Results show that the etchant solution results in strong compressive strain and p-type doping to floating graphene, but both are significantly reduced after the sample is loaded and rinsed especially for the doping. An annealing treatment increases the compressive strain in graphene but hardly its doping level. Moreover, when a poly(methyl methacrylate) (PMMA) layer is used to assist the transfer, it does not only increase the p-type doping of floating graphene but also lowers the crystalline quality of annealed graphene. Therefore, to obtain graphene with better quality, besides the attempts of improving CVD synthesis for its larger domain sizes, universal and easy-to-use polymer-free transfer techniques must be developed as well., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Fracture behaves as one of the most fundamental issues for solid materials. As a one-atom-thick crystal, many aspects in fracture mechanics of graphene are of high significance, such as the crack propagation and its fracture toughness. Here we present a method to study the fracture characteristics of graphene using Raman spectroscopy and designed chemical-vapor-deposited monolayer graphene with preset cracks. The dynamic fracture process of graphene was experimentally observed, and its fracture toughness was obtained using Griffith's criterion based on the strain distribution derived from the frequency shifts of Raman bands. The fracture toughness of K c = 6.1 ± 0.6 MPa[Formula: see text] and G c = 37.4 ± 6.7 J/m 2 are comparable with the previously reported theoretical and experimental values, and we believe that this simple and easy-to-operate approach of characterizing the fracture of graphene using Raman spectroscopy can also be extended to other two-dimensional materials.

Large-scale applications of graphene require its high-efficiency transfer from growth metal substrates to any other substrates of interest. The wrinkles and folds generated during the transfer process of graphene by the well-known poly(methyl methacrylate) (PMMA)-assisted technique is a critical issue. Here, we report an improvement of this method by applying a directional etching process for the removal of the growth Cu substrates, using a pair of electrodes inserted into the etchant with a constant current to form an electrochemical system. The controlled redox reactions between the Cu and the solution environment result in the etching of Cu in a part-by-part manner strictly from one end to the other. The consistency of the Cu etching direction can avoid the formation of an easily destroyable Cu structure and release the stress concentration that is usually generated during the random etching process, and finally yield significantly improved quality of the transferred graphene film with a lowered density of wrinkles, cracks/folds, adlayers, reduced root-mean-square of surface roughness, and increased performance in sheet resistance and carrier mobility.

Objectives: To appraise the reporting quality of studies which concerned linezolid-related thrombocytopenia referring to REporting of studies Conducted using Observational Routinely collected health Data (RECORD) statement., Methods: Medline, Embase, Cochrane library and clinicaltrial.gov were searched for observational studies concerning linezolid-related thrombocytopenia using routinely collected health data from 2000 to 2017. Two reviewers screened potential eligible articles and extracted data independently. Finally, reporting quality assessment was performed by two senior researchers using RECORD statement., Results: Of 25 included studies, 11 (44.0%) mentioned the type of data in the title and/or abstract. In 38 items derived from RECORD statement, the median number of items reported in the included studies was 22 (inter-quartile range 18-27). Inadequate reporting issues were discovered in the following aspects: validation studies of the codes or algorithms, study size estimation, quantitative variables, subgroup statistical methods, missing data, follow-up/matching or sampling strategy, sensitivity analysis and cleaning methods, funding and role of funders and accessibility of protocol, raw data., Conclusion: 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.

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.

Background: Different 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., Methods: We 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., Results: Substantial 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., Conclusions: The 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.