Unveiling the release mechanism of potentially toxic elements from Pb/Zn smelter contaminated soils under the coupled effects of freeze-thaw and acidification: Insights from mineralogical analysis.

Most Pb/Zn smelter contaminated sites in China are often encountered natural phenomenon known as freeze-thaw (F-T) cycles and acid rain. However, the coupled effects of F-T cycles and acidification on the release behavior of potentially toxic elements (PTEs) from soils remains unclear. A mechanistic study on PTEs release from soils was conducted by revealing the physicochemical weathering characteristics of minerals under F-T cycles combined with acidification. The results from F-T test indicated that among F-T parameters, F-T frequency were the more important factors influencing PTEs release, with the corresponding contribution ranges of 21.20-94.40 %. As pH decreased, the leaching concentrations of As, Cd, Cu, Mn, Pb and Zn did not increase under the same F-T frequency. As F-T frequency increased, the leaching concentrations of these studied PTEs also did not increase under the same pH condition. Microstructure characteristics revealed that the soils were a complex system with multi-mineral aggregates, which had experienced complex physicochemical weathering after F-T combined with acidification treatment. Combined with geochemical modeling results, PTEs release was found to be mainly influenced by the microstructure damage and proton corrosion of minerals, while little affected by their precipitation and dissolution. The mutual coupling relationships of mineral weathering and PTEs release were conducive to the better understanding of the migration behavior of PTEs in contaminated sites under complex environment scenarios. The present study results would provide theoretical instruction and technical support for the longevity evaluation of multi-metal stabilization remediation.

Quantitative Soil Characterization for Biochar-Cd Adsorption: Machine Learning Prediction Models for Cd Transformation and Immobilization.

Soil pollution with cadmium (Cd) poses serious health and environmental consequences. The study investigated the incubation of several soil samples and conducted quantitative soil characterization to assess the influence of biochar (BC) on Cd adsorption. The aim was to develop predictive models for Cd concentrations using statistical and modeling approaches dependent on soil characteristics. The potential risk linked to the transformation and immobilization of Cd adsorption by BC in the soil could be conservatively assessed by pH, clay, cation exchange capacity, organic carbon, and electrical conductivity. In this study, Long Short-Term Memory (LSTM), Bidirectional Gated Recurrent Unit (BiGRU), and 5-layer CNN Convolutional Neural Networks (CNNs) were applied for risk assessments to establish a framework for evaluating Cd risk in BC amended soils to predict Cd transformation. In the case of control soils (CK), the BiGRU model showed commendable performance, with an R2 value of 0.85, indicating an approximate 85.37% variance in the actual Cd. The LSTM model, which incorporates sequence data, produced less accurate results (R2=0.84), while the 5-layer CNN model had an R2 value of 0.91, indicating that the CNN model could account for over 91% of the variation in actual Cd levels. In the case of BC-applied soils, the BiGRU model demonstrated a strong correlation between predicted and actual values with R2 (0.93), indicating that the model explained 93.21% of the variance in Cd concentrations. Similarly, the LSTM model showed a notable increase in performance with BC-treated soil data. The R2 value for this model stands at a robust R2 (0.94), reflecting its enhanced ability to predict Cd levels with BC incorporation. Outperforming both recurrent models, the 5-layer CNN model attained the highest precision with an R2 value of 0.95, suggesting that 95.58% of the variance in the actual Cd data can be explained by the CNN model's predictions in BC-amended soils. Consequently, this study suggests developing ecological soil remediation strategies that can effectively manage heavy metal pollution in soils for environmental sustainability.

The Alfalfa-inpatient-CAT assessment model: a thrombotic risk assessment model for inpatient cancer patients.

PURPOSE: To construct a venous thromboembolism (VTE) risk assessment model specifically for inpatients with cancer. METHOD: Patients were included according to the inclusion criteria. Univariate and multivariate analyses of all variables were included to develop a VTE risk assessment model applicable to the derivation cohort. Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve were used to test the fit degree and identification validity of the model. The patient data from separate validation cohorts verified the external population. RESULT: A total of 944 cancer patients were included in this study. Alfalfa-inpatient-CAT model, a risk assessment model for VTE in hospitalized cancer patients, was established, which mainly includes hypertension, surgical history (nearly one month), history of VTE, peripherally inserted central venous catheters (PICC), chemotherapy, PT < 12.85 s, D-dimer ≥ 1.805 µg/mL, hemoglobin ≤ 114.5 g/L, CRP ≥ 7.575 mg/L. Hosmer-Lemeshow test results showed P = 0.353 > 0.05, (χ2 = 8.872, Df = 8). The area under ROC curve was 0.906 [95%CI (0.881-0.930), P < 0.001]. The authenticity evaluation in the model database showed that the risk of thrombosis in the high-risk group (score ≥ 3) was 72.63%, significantly higher than that in the low-risk group (score 0-2) (27.37%) [χ2 = 144.00, Df = 1, P < 0.001]. CONCLUSION: This study developed a new VTE risk assessment model - Alfalfa-inpatient-CAT model - for hospitalized cancer patients at high risk of thrombosis. This model has a good fitting degree and discriminant validity. It is expected to provide some reference for the clinical treatment of inpatients with cancer through continuous optimization.

Web-Based Warfarin Management (Alfalfa App) Versus Traditional Warfarin Management: Multicenter Prospective Cohort Study.

BACKGROUND: Poor anticoagulation management of warfarin may lead to patient admission, prolonged hospital stays, and even death due to anticoagulation-related adverse events. Traditional non-web-based outpatient clinics struggle to provide ideal anticoagulation management services for patients, and there is a need to explore a safer, more effective, and more convenient mode of warfarin management. OBJECTIVE: This study aimed to compare differences in the quality of anticoagulation management and clinical adverse events between a web-based management model (via a smartphone app) and the conventional non-web-based outpatient management model. METHODS: This study is a prospective cohort research that includes multiple national centers. Patients meeting the nadir criteria were split into a web-based management group using the Alfalfa app or a non-web-based management group with traditional outpatient management, and they were then monitored for a 6-month follow-up period to collect coagulation test results and clinical events. The effectiveness and safety of the 2 management models were assessed by the following indicators: time in therapeutic range (TTR), bleeding events, thromboembolic events, all-cause mortality events, cumulative event rates, and the distribution of the international normalized ratio (INR). RESULTS: This national multicenter cohort study enrolled 522 patients between June 2019 and May 2021, with 519 (99%) patients reaching the follow-up end point, including 260 (50%) in the non-web-based management group and 259 (50%) in the web-based management group. There were no observable differences in baseline characteristics between the 2 patient groups. The web-based management group had a significantly higher TTR than the non-web-based management group (82.4% vs 71.6%, P<.001), and a higher proportion of patients received effective anticoagulation management (81.2% vs 63.5%, P<.001). The incidence of minor bleeding events in the non-web-based management group was significantly higher than that in the web-based management group (12.1% vs 6.6%, P=.048). Between the 2 groups, there was no statistically significant difference in the incidence of severe bleeding and thromboembolic and all-cause death events. In addition, compared with the non-web-based management group, the web-based management group had a lower proportion of INR in the extreme subtreatment range (17.6% vs 21.3%) and severe supertreatment range (0% vs 0.8%) and a higher proportion in the treatment range (50.4% vs 43.1%), with statistical significance. CONCLUSIONS: Compared with traditional non-web-based outpatient management, web-based management via the Alfalfa app may be more beneficial because it can enhance patient anticoagulation management quality, lower the frequency of small bleeding events, and improve INR distribution.

Construction of warfarin population pharmacokinetics and pharmacodynamics model in Han population based on Bayesian method.

The purpose of this paper is to study the genetic polymorphisms of related gene loci (CYP2C9*3, VKORC1-1639G > A) based on demographic and clinical factors, and use the maximum a posterior Bayesian method to construct a warfarin individualized dose prediction model in line with the Chinese Han population. Finally, the built model is compared and analyzed with the widely used models at home and abroad. In this study, a total of 5467 INR measurements are collected from 646 eligible subjects in our hospital, and the maximum a posterior Bayesian method is used to construct a warfarin dose prediction that conforms to the Chinese Han population on the basis of the Hamberg model. The model is verified and compared with foreign models. This study finds that body weight and concomitant use of amiodarone have a significant effect on the anticoagulant effect of warfarin. The model can provide an effective basis for individualized and rational dosing of warfarin in Han population more accurately. In the performance of comparison with different warfarin dose prediction models, the new model has the highest prediction accuracy, and the prediction percentage is as high as 72.56%. The dose predicted by the Huang model is the closest to the actual dose of warfarin. The population pharmacokinetics and pharmacodynamics model established in this study can better reflect the distribution characteristics of INR values after warfarin administration in the Han population, and performs better than the models reported in the literature.

Impact of P2Y12 inhibitors on clinical outcomes in sepsis-3 patients receiving aspirin: a propensity score matched analysis.

BACKGROUND: Sepsis is a life-threatening disease accompanied by disorders of the coagulation and immune systems. P2Y12 inhibitors, widely used for arterial thrombosis prevention and treatment, possess recently discovered anti-inflammatory properties, raising potential for improved sepsis prognosis. METHOD: We conducted a retrospective analysis using the data from Medical Information Mart for Intensive Care-IV database. Patients were divided into an aspirin-alone group versus a combination group based on the use of a P2Y12 inhibitor or not. Differences in 30-day mortality, length of stay (LOS) in intensive care unit (ICU), LOS in hospital, bleeding events and thrombotic events were compared between the two groups. RESULT: A total of 1701 pairs of matched patients were obtained by propensity score matching. We found that no statistically significant difference in 30-day mortality in aspirin-alone group and combination group (15.3% vs. 13.7%, log-rank p = 0.154). In addition, patients received P2Y12 inhibitors had a higher incidence of gastrointestinal bleeding (0.5% vs. 1.6%, p = 0.004) and ischemic stroke (1.7% vs. 2.9%, p = 0.023), despite having a shorter LOS in hospital (11.1 vs. 10.3, days, p = 0.043). Cox regression showed that P2Y12 inhibitor was not associated with 30-day mortality (HR = 1.14, 95% CI 0.95-1.36, p = 0.154). CONCLUSION: P2Y12 inhibitors did not provide a survival benefit for patients with sepsis 3 and even led to additional adverse clinical outcomes.

Internet of Things (IoT)-enabled framework for a sustainable Vaccine cold chain management system.

Vaccines are a unique category of drugs sensitive to temperature and humidity and whose effectiveness directly impacts public health. There has been an increase in vaccine-related adverse events worldwide, particularly in developing countries, attributed to suboptimal temperatures during transport and storage. At the same time, the Internet of Things (IoT) has ushered in a paradigm shift in vaccine information and storage monitoring, enabling continuous 24/7 tracking. This further reduces the dependence on limited human resources and significantly reduces the associated errors and losses. This paper presents an IoT-driven framework that aims to improve the sustainability of medical cold chain management. The framework promotes trust and transparency in vaccine surveillance data by accessing and authenticating IoT devices. The proposed system aims to improve the safety and sustainability of vaccine management. Moreover, we provide detailed insights into the design and hardware components of the proposed framework. In addition, the specific use of the framework in a particular province is highlighted, covering the design of the software platform and the analysis of the hardware equipment.

nFeS Embedded into Cryogels for High-Efficiency Removal of Cr(VI): From Mechanism to for Treatment of Industrial Wastewater.

Most studies have focused on complex strategies for materials preparation instead of industrial wastewater treatment due to emergency treatment requirements for metal pollution. This study evaluated sodium polyacrylate (PSA) as a carbon skeleton and FeS as a functional material to synthesize PSA-nFeS material. The characteristics and interactions of PSA-nFeS composites treated with hexavalent chromium were analyzed by means of various techniques, such as scanning electron microscopy-energy dispersive X-ray spectrometry (SEM-EDS), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectrometry (FTIR), and atomic absorption spectroscopy (AAS). Adsorption-coupled reduction was observed to be the predominant mechanism of Cr(VI) removal. The feasibility of PSA-nFeS composites in reducing toxicity and removing of Cr(VI) from real effluents was investigated through column studies and material properties evaluation. The continuous column studies were conducted using tannery effluents to optimize feed flow rates, initial feed Cr(VI) concentration, and column bed height. The results revealed that PSA-nFeS composites are ideal for filling materials in portable filtration devices due to their lightweight and compact size.

Effects of BC on metal uptake by crops (availability) and the vertical migration behavior in soil: A 3-year field experiments of crop rotation.

Biochar (BC) has been substantiated to effectively reduce the available content of heavy metals (HMs) in soil-plant system; however, the risk of biochar (BC)derived dissolved organic matter (DOM) induced metal vertical migration has not been well documented, especially in the long-term field conditions. Therefore, this study investigated HM vertical migration ecological risks and the long-term effectiveness of the amendment of biochar in the three successive years of field trials during the rotation system. The results revealed that biochar application could increase soil pH and DOM with a decrease in soil CaCl2 extractable pool for Pb, Cu, and Cd. Furthermore, the results indicated a significant decrease in acid phosphatase activities and an increase in urease and catalase activities in the soil. Cucumber was shown to be safe during a three-year rotation system in the field. These results suggest that BC has the potential to enhance soil environment and crop yields. BC derived DOM-specific substances were identified using parallel factor analysis of excitation-emission matrix in deep soil (0-60 cm). The study incorporated HM concentration fluctuations in deep soils, providing an additional interpretation of DOM and co-migration of HMs.The environmental risk associated with the increase in DOM hydrophobicity should not be ignored by employing BC for soil HM remediation applications. The study enhances understanding of biochar-derived DOM's migration and stabilization mechanisms on heavy metals, providing guidelines for its use as a soil amendment.

High-performance magnetic metal microrobot prepared by a two-photon polymerization and sintering method.

Magnetically-actuated microrobots (MARs) exhibit great potential in biomedicine owing to their precise navigation, wireless actuation and remote operation in confined space. However, most previously explored MARs unfold the drawback of hypodynamic magnetic torque due to low magnetic content, leading to their limited applications in controlled locomotion in fast-flowing fluid and massive cargo carrying to the target position. Here, we report a high-performance pure-nickel magnetically-actuated microrobot (Ni-MAR), prepared by a femtosecond laser polymerization followed by sintering method. Our Ni-MAR possesses a high magnetic content (∼90 wt%), thus resulting in enhanced magnetic torque under low-strength rotating magnetic fields, which enables the microrobot to exhibit high-speed swimming and superior cargo carrying. The maximum velocity of our Ni-MAR, 12.5 body lengths per second, outperforms the velocity of traditional helical MARs. The high-speed Ni-MAR is capable of maintaining controlled locomotion in fast-flowing fluid. Moreover, the Ni-MAR with massive cargo carrying capability can push a 200-times heavier microcube with translation and rotation motion. A single cell and multiple cells can be transported facilely by a single Ni-MAR to the target position. This work provides a scheme for fabricating high-performance magnetic microrobots, which holds great promise for targeted therapy and drug delivery in vivo.

Three-year field experiments revealed the immobilization effect of natural aging biochar on typical heavy metals (Pb, Cu, Cd).

Biochar has been widely used for the remediation of heavy metal contaminated soil, while the long-term field aging on its properties and the performance in the ability of metal immobilization must not be overlooked. In this study, the stability of immobilized heavy metals (Cd, Cu, Pb) on biochar during a 3-year remediation for soil in the field was investigated through desorption experiments. The results indicated that the application of biochar and its aging in the field both remarkably increased the immobilization of the 3 metal ions in the field under 3-year remediation. The cumulative desorption of the 3 metals decreased with biochar aging, and the desorption rate of Pb2+, Cu2+ and Cd2+ in T3 (Application of 30 t·hm-2 of biochar) for the third year was 0.08 %, 0.20 % and 13.15 %. Meanwhile, both the desorption rates and extents exhibited significant difference with the order of Pb2+ < Cu2+ < Cd2+. The increased soil pH, the enhancement of O/C ratio (Increase from 0.30 for fresh BC to 0.61 for aged BC(S3)) and oxygen-containing functional groups in biochar, and the accretion of organo-mineral micro-agglomerates on biochar surfaces and in pores during field aging process jointly contributed the immobilization of metals in soils mainly through co-precipitation and complexation. Our results provide new insights into the practical application of biochar in soils contaminated with multiple heavy metals from the perspective of long-term effects, which suggests that the potential release risk of metals become slighter over time.

Water flow promoted charge separation in piezoelectric Bi4Ti3O12 for the enhanced photocatalytic degradation of antibiotic.

Addressing the issue of antibiotic residues in the environment is key to improving the quality of aquatic environments and reducing human health risks. In this study, piezoelectric bismuth titanate (Bi4Ti3O12) nanosheets are synthesized and employed to conduct antibiotic degradation. The piezoelectric potential induced by the water flow shear force is utilized to facilitate charge separation and migration in the photocatalytic process and enhance the catalytic degradation of antibiotic wastewater. As a result, 85% of tetracycline hydrochloride (TC) is degraded within 90 min. The piezo-photocatalytic process exhibits a 2.4 times faster reaction rate and a 15% higher mineralization rate than photocatalysis. Different environmental factors are investigated for their effects on the catalytic activity in piezo-photocatalysis. In situ electrochemical measurement and photoluminescence (PL) spectroscopy under stress demonstrated that the piezoelectric potential shifted the energy band of Bi4Ti3O12 and promoted the charge migration and separation, which produce more active species that favor the efficient catalytic degradation. Finally, the intermediate products of the tetracycline hydrochloride degradation process are analyzed and possible degradation pathways are suggested. This study elucidates the degradation mechanism of Bi4Ti3O12 as a piezo-photocatalyst for antibiotic pollutants, and meticulously investigates the charge transfer mechanism of the catalyst material in response to micro-stress. Hence, it provides an efficient solution for organic wastewater treatment and can potentially provide theoretical support for the development and performance optimization of catalyst materials applied in natural environments.

Magnetic Janus origami robot for cross-scale droplet omni-manipulation.

The versatile manipulation of cross-scale droplets is essential in many fields. Magnetic excitation is widely used for droplet manipulation due to its distinguishing merits. However, facile magnetic actuation strategies are still lacked to realize versatile multiscale droplet manipulation. Here, a type of magnetically actuated Janus origami robot is readily fabricated for versatile cross-scale droplet manipulation including three-dimensional transport, merging, splitting, dispensing and release of daughter droplets, stirring and remote heating. The robot allows untethered droplet manipulation from ~3.2 nL to ~51.14 µL. It enables splitting of droplet, precise dispensing (minimum of ~3.2 nL) and release (minimum of ~30.2 nL) of daughter droplets. The combination of magnetically controlled rotation and photothermal properties further endows the robot with the ability to stir and heat droplets remotely. Finally, the application of the robot in polymerase chain reaction (PCR) is explored. The extraction and purification of nucleic acids can be successfully achieved.

Enhanced nitrogen removal in immersed rotating self-aerated biofilm reactor: Nitrogen removal pathway and microbial mechanism.

To achieve energy-efficient treatment of the rural wastewater with satisfying performance, a novel immersed rotating self-aerated biofilm reactor (iRSABR) was proposed in this study. The iRSABR system showed better biofilm renewal performance and higher microbial activity. The effect of different regulation strategies on the iRSABR system was investigated in this study. The 70% immersion ratio and 4 r/min rotation speed (stage III) exhibited the best performance, with a total nitrogen removal efficiency of 86% and a simultaneous nitrification-denitrification (SND) rate of 76%, along with the highest electron transport system activity. The nitrogen removal pathway revealed that the SND was achieved through autotrophic/heterotrophic nitrification and aerobic/anoxic denitrification. The regulation strategy in the iRSABR system established a synergistic microbial community with main functional bacteria of nitrification (Nitrosomonas), anoxic denitrification (Flavobacterium, Pseudoxanthomonas), and aerobic denitrification (Thauera). This study highlighted the feasibility and adaptability of the iRSABR system toward energy-efficient rural wastewater treatment.

Geometry-Gradient Magnetocontrollable Lubricant-Infused Microwall Array for Passive/Active Hybrid Bidirectional Droplet Transport.

Manipulation of droplets has increasingly garnered global attention, owing to its multifarious potential applications, including microfluidics and medical diagnostic tests. To control the droplet motion, geometry-gradient-based passive transport has emerged as a well-established strategy, which induces a Laplace pressure difference based on the droplet radius differences in confined state and transport droplets with no consumption of external energy, whereas this transportation method has inevitably shown some critical limitations: unidirectionality, uncontrollability, short moving distance, and low velocity. Herein, a magnetocontrollable lubricant-infused microwall array (MLIMA) is designed as a key solution to this issue. In the absence of a magnetic field, droplets can spontaneously travel from the tip toward the root of the structure as a result of the geometry-gradient-induced Laplace pressure difference. When the subject of an external magnetic field, the microwalls bend and overlap sequentially, ultimately resulting in the formation of a continuous slippery meniscus surface. The formed meniscus surface can exert sufficient propulsive force to surmount the Laplace pressure difference of the droplet, thereby effectuating active transport. Through the continuous movement of the microwalls, droplets can be actively transported against the Laplace pressure difference from the root to the tip side of the MLIMA or continue to actively move to the root after finishing the passive self-transport. This work demonstrates passive/active hybrid bidirectional droplet transport capabilities, validates its feasibility in the accurate control of droplet manipulation, and exhibits great potential in chemical microreactions, bioassays, and the medical field.

Global burden of cardiovascular disease attributable to metabolic risk factors, 1990-2019: an analysis of observational data from a 2019 Global Burden of Disease study.

OBJECTIVES: An up-to-date, detailed global analysis of the current status of the metabolic-attributed cardiovascular disease (CVD) burden has not been reported. Therefore, we investigated the global burden of metabolic-attributed CVD and its association with socioeconomic development status over the past 30 years. METHODS: Data on the burden of metabolic-attributed CVD were taken from the 2019 Global Burden of Disease (GBD) study. Metabolic risk factors of CVD included high fasting plasma glucose, high low-density lipoprotein cholesterol (LDL-c), high systolic blood pressure (SBP), high body mass index (BMI) and kidney dysfunction. Numbers and age-standardised rates (ASR) of disability-adjusted life-years (DALYs) and deaths were extracted and stratified by sex, age, Socio-demographic Index (SDI) level, country and region. RESULTS: The ASR of metabolic-attributed CVD DALYs and deaths decreased by 28.0% (95% UI 23.8% to 32.5%) and 30.4% (95% UI 26.6% to 34.5%), respectively, from 1990 to 2019. The highest burden of metabolic-attributed total CVD and intracerebral haemorrhage was mainly in low SDI locations, while the highest burden of ischaemic heart disease and IS was mainly in high SDI locations. The burden of DALYs and deaths in CVD was higher in men than women. In addition, the number and ASR of DALYs and deaths were highest in those over 80 years old. CONCLUSION: Metabolic-attributed CVD threatens public health, especially in low-SDI locations and among the elderly. Low SDI location should strengthen the control of metabolic factors such as high SBP, high BMI, and high LDL-c and increase the knowledge of metabolic risk factors for CVD. Countries and regions should enhance screening and prevention of metabolic risk factors of CVD in the elderly. Policy-makers should use 2019 GBD data to guide cost-effective interventions and resource allocation.

High-performance Marangoni hydrogel rotors with asymmetric porosity and drag reduction profile.

Miniaturized rotors based on Marangoni effect have attracted great attentions due to their promising applications in propulsion and power generation. Despite intensive studies, the development of Marangoni rotors with high rotation output and fuel economy remains challenging. To address this challenge, we introduce an asymmetric porosity strategy to fabricate Marangoni rotor composed of thermoresponsive hydrogel and low surface tension anesthetic metabolite. Combining enhanced Marangoni propulsion of asymmetric porosity with drag reduction of well-designed profile, our rotor precedes previous studies in rotation output (~15 times) and fuel economy (~34% higher). Utilizing thermoresponsive hydrogel, the rotor realizes rapid refueling within 33 s. Moreover, iron-powder dopant further imparts the rotors with individual-specific locomotion in group under magnetic stimuli. Significantly, diverse functionalities including kinetic energy transmission, mini-generator and environmental remediation are demonstrated, which open new perspectives for designing miniaturized rotating machineries and inspire researchers in robotics, energy, and environment.

Severe Bleeding Risk of Direct Oral Anticoagulants Versus Vitamin K Antagonists for Stroke Prevention and Treatment in Patients with Atrial Fibrillation: A Systematic Review and Network Meta-Analysis.

PURPOSE: We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with atrial fibrillation (AF). METHODS: A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting severe bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. RESULTS: Twenty-three RCTs met the inclusion criteria, and a total of 87,616 patients were enrolled. The bleeding safety of DOACs for stroke prevention and treatment in patients with AF was ranked from highest to lowest as follows: fatal bleeding: edoxaban (SUCRA,80.2), rivaroxaban (SUCRA,68.3), apixaban (SUCRA,48.5), dabigatran (SUCRA,40.0), VKAs (SUCRA,12.9); major bleeding: dabigatran (SUCRA,74.0), apixaban (SUCRA,71.5), edoxaban (SUCRA,66.5), rivaroxaban (SUCRA,22.7), VKAs (SUCRA,15.4); gastrointestinal bleeding: apixaban (SUCRA,55.9), VKAs (SUCRA,53.7), edoxaban (SUCRA,50.5), rivaroxaban (SUCRA,50.4), dabigatran (SUCRA,39.5); intracranial hemorrhage: dabigatran (SUCRA,84.6), edoxaban (SUCRA,74.1), apixaban (SUCRA,65.8), rivaroxaban (SUCRA,24.4), VKAs (SUCRA,1.1). CONCLUSION: Based on current evidence, for stroke prevention and treatment in patients with AF, the most safe DOAC is edoxaban in terms of fatal bleeding; dabigatran in terms of major bleeding and intracranial hemorrhage and apixaban in terms of gastrointestinal bleeding. However, given the nature of indirect comparisons, more high-quality evidence from head-to-head comparisons is still needed to confirm them.