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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. [ABSTRACT FROM AUTHOR]

Aiming at the problem of fault diagnosis and classification of rolling bearing and gear of gearboxes, a novel method based on matrix distance features of Gramian angular field (GAF) image is proposed based on sliding window compressible GAF transformation. The method converts the one-dimensional fault signal into a two-dimensional feature matrix and constructs the discrimination matrix of each fault category by establishing the mean value of the feature matrix of a priori samples. For the new sampled signal, after converting it into a two-dimensional feature matrix, the feature matrix is obtained. The fault classification is carried out by using the matrix distance between feature matrix and the discrimination matrix of each category. The method is validated by the test data of Case Western Reserve University and the acoustic emission data from a gearbox test bench. The classification accuracy is 99.17% and 95.71%, which presented the feasibility and effectiveness of the novel method proposed in this paper. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article reports that 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.

Magnetic mobile microrobots navigating biofluids with both upstream and downstream locomotion provide a promising solution to targeted drug delivery for precision medicine. However, the biofluid environment in blood vessels is complicated due to variations in flow rate and direction. It is still unknown how to make magnetic microrobots resist the variable flow rate in biofluids with both upstream and downstream locomotion. Herein, magnetic microrobots with various shapes and sizes have been controlled to navigate diverse biofluids under different flow rates and directions. Simulation and experimental studies have been conducted to analyze the influences of microrobot size and shape on translational velocity in confined microchannels filled with biofluids. A strategy is proposed to choose the optimized parameters of rotating magnetic field actuation for precise delivery of microrobots in a microfluidic chip, which contains a complex biofluid environment with variable flow rate and direction. The results are validated using various microrobots navigating the microfluidic chip and the yolks of zebrafish larvae in vivo. This work provides a guideline for selecting desirable microrobot dimensions and magnetic field actuation parameters for controllable navigation of magnetic mobile microrobots in complex biofluid flows. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In this letter, the angular jamming effect of electronically controlled corner reflectors after a maneuver aircraft is analyzed. Motion characteristics of the corner reflectors towed by a high‐speed aircraft are calculated through the Lagrange theory, and the angle measurement error of the jamming method for the monopulse angle measurement algorithm is analyzed based on the motion states and the electromagnetic states (scattering or penetration) of the corner reflectors. Results show that the automatic tracking process of a monopulse radar seeker can be effectively interfered by this method under complex maneuver motion. [ABSTRACT FROM AUTHOR]

This article presents the design, optimization, and testing of a new rotating electromagnetic field generation system for actuating magnetic microrobots. Its unique feature lies in that the proposed six-coil electromagnetic actuation system produces a uniform rotating magnetic field with a large 3-D workspace, which is enabled by conducting an architectural optimization of the system in consideration of both electric issues and geometry constraints. To maintain a low working temperature, each coil is fabricated with silicone grease for filling the gap among the copper wires and integrated with a water cooling fan for reducing the effect of coil heating. An analytical model is established to determine the dominant structural parameters, which are optimally tuned by resorting to genetic algorithm (GA) to achieve the best actuation performance. A prototype magnetic field generation system is developed for experimental testing. Experimental studies are carried out by driving various magnetic microrobots, including helical microswimmers and microparticles. Results indicate that the developed system can effectively actuate the microrobots with precision motion tracking, validating the effectiveness of the developed rotating magnetic field generation system. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This article presents the design, fabrication, and testing of a novel piezoelectric energy harvester. Its unique feature is that a single piezoelectric stack is used for harvesting the energy from two-directional excitation in vertical directions. To accept the input forces in two directions, a flexure-based two-stage force amplifier is integrated with a conical transmission mechanism and a sliding guiding mechanism. An analytical model is established to predict the force amplification ratio of the proposed energy harvester. In order to maximize the output performance of the energy harvester, the dominant parameters of the mechanism are determined, which are optimally designed by resorting to a genetic algorithm. A prototype energy harvester is fabricated for experimental testing. Experimental results indicate that the developed harvester exhibits the advantages of high safety factor, large force amplification ratio, and compact size. It can provide the maximum average output power density of over 286.70 kW $\cdot$ m $^{-3}$ from 10-N force excitation in two directions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A detailed solution to the remote monitoring and diagnosis system for a rolling mill is introduced. The hardware and software structure of remote monitoring and diagnosis system is presented. The structure of the system is made up of four subsystems, namely online monitoring subsystem, data servo subsystem, database service subsystem and www server subsystem. Software module of system includes seven parts, namely online monitoring module, data query module, fault information query module, trend analysis module, diagnosis analysis module, engineer station module and eigenvalue query module. The system adopts B/S model and integrates CORBA technology with SOAP/Web Service technology. It makes dynamic display and traversing for a great deal of on-line data and Firewall traversal possible. It has run a long time that proves that the system interface is friendly and easy to use. It has better security, good portability, expandability and stability. It can judge the running-condition of a rolling mill in real time. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic imposes an increasing demand for service robots as a substitute for humans to conduct various types of work in contaminated areas. Such work includes logistics, patient care, and disinfection, which can reduce the risk of human exposure to the highly contagious and deadly virus. This paper presents the design and development of Smart Cleaner, which is a new cost-effective autonomous indoor disinfection robot. It integrates a wheeled mobile robot platform and a hydrogen peroxide atomization device for automated disinfection operation in the complex indoor environment. Through the system integration of various hardware components and software programming, a prototype of the disinfection robot has been fabricated for experimental investigation. A simulation study of the drymist hydrogen peroxide disinfection model was carried out to understand the diffusion of disinfectant in a room environment. The effectiveness of the developed robot was verified in practical scenarios, such as hospital, hotel, office, and laboratory. The effect of disinfection was validated by a qualified third-party testing agency. Results demonstrate the high efficiency of the developed disinfection robot dedicated to autonomous indoor disinfection work. [ABSTRACT FROM AUTHOR]

This paper presents the design of a new flexure-based xy micropositioning stage with a large hollow platform, which is suitable for practical use with a microscope. The designed mechanism has a parallel-kinematic structure and is actuated by two voice coil motors. By employing multistage compound parallelogram flexures, the stage is designed as a four-layer structure, which produces a motion output platform with a large hollow space and large range of motion. Analytical modeling was carried out for parametric design of the stage. Evaluation results show that the designed xy stage exhibits a large safety factor and high natural frequency. Moreover, the large hollow platform is well-suited for practical applications with a microscope. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • The decoupling of N and P increased upward along the aquatic food chains. • N–P decoupling was aggravated in reclaimed water with unbalanced nutrient input. • Both N and P had higher homeostasis at higher relative to lower trophic levels. • Macro-food chain showed higher nutrient homeostasis than planktonic food chain. [ABSTRACT FROM AUTHOR]

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.)

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.

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.

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.