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2.
Environ Int ; 145: 106164, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33035894

RESUMO

Multiple antibiotics are widely used in clinic practice and livestock husbandry, but exposure data based on repeated measurements are scarce among pregnant women. Here, we biomonitored 41 antibiotics and their two metabolites in urine samples from 3235 pregnant women over three trimesters. Spearman's correlation coefficient, intraclass correlation coefficient (ICC), percentile analysis and linear mixed models were employed to evaluate the correlations, variability, co-exposure patterns and predictors of antibiotics, respectively. Pregnant urinary creatinine-adjusted concentrations of antibiotics were used to estimate daily exposure dose and assessed health risks. The target antibiotics were detected in more than 90% of urine samples, primarily as preferred as veterinary antibiotics (PVAs), and the 95th percentile urinary concentrations of each individual antibiotics were range from below the limits of detection to 5.74 ng/mL. We observed considerable within-subject variation (ICC: 0.05-0.63) of urinary antibiotics concentrations during pregnancy. More than half pregnant women were co-exposed to two or more antibiotics of different usage classes, while both co-exposure to high percentiles of three usage antibiotics at one trimester or exposure to single usage antibiotics at high-dose through three trimesters were infrequent in the study population, and most pregnant women were continuously exposed to low-dose PVAs across pregnancy. A total of 4.5% samples were showed hazard index values exceeding 1 during entire pregnancy. Urinary levels of antibiotics associated with residence, maternal age and education, pre-pregnancy BMI, household income and gestational week, especially vary by sampling seasons. Taken together, most pregnant women were frequently exposure to low-dose PVAs across pregnancy and some were in a health risk associated with the disturbance of gut microbiota. Multiple measurements of urinary antibiotic concentrations are essential to more accurate charactering the exposure levels during pregnancy. Several predictors of urinary antibiotics should be taken into consideration in future researches.

4.
Front Immunol ; 11: 2110, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042123

RESUMO

Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) are vital signaling adaptor proteins for the innate immune response and are involved in many important pathways, such as the NF-κB- and interferon regulatory factor (IRF)-activated signaling pathways. In this study, the TRAF3 ortholog from the shrimp Litopenaeus vannamei (LvTRAF3) was cloned and characterized. LvTRAF3 has a transcript of 3,865 bp, with an open reading frame (ORF) of 1,002 bp and encodes a polypeptide of 333 amino acids, including a conserved TRAF-C domain. The expression of LvTRAF3 in the intestine and hemocyte was up-regulated in response to poly (I:C) challenge and white spot syndrome virus (WSSV) infection. RNAi knockdown of LvTRAF3 in vivo significantly increased WSSV gene transcription, viral loads, and mortality in WSSV-infected shrimp. Next, we found that LvTRAF3 was not able to induce the activation of the NF-κB pathway, which was crucial for synthesis of antimicrobial peptides (AMPs), which mediate antiviral immunity. Specifically, in dual-luciferase reporter assays, LvTRAF3 could not activate several types of promoters with NF-κB binding sites, including those from WSSV genes (wsv069, wsv056, and wsv403), Drosophila AMPs or shrimp AMPs. Accordingly, the mRNA levels of shrimp AMPs did not significantly change when TRAF3 was knocked down during WSSV infection. Instead, we found that LvTRAF3 signaled through the IRF-Vago antiviral cascade. LvTRAF3 functioned upstream of LvIRF to regulate the expression of LvVago4 and LvVago5 during WSSV infection in vivo. Taken together, these data provide experimental evidence of the participation of LvTRAF3 in the host defense to WSSV through the activation of the IRF-Vago pathway but not the NF-κB pathway.

5.
Sci Rep ; 10(1): 16213, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004925

RESUMO

Italy was the first, among all the European countries, to be strongly hit by the COVID-19 pandemic outbreak caused by the severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2). The virus, proven to be very contagious, infected more than 9 million people worldwide (in June 2020). Nevertheless, it is not clear the role of air pollution and meteorological conditions on virus transmission. In this study, we quantitatively assessed how the meteorological and air quality parameters are correlated to the COVID-19 transmission in two large metropolitan areas in Northern Italy as Milan and Florence and in the autonomous province of Trento. Milan, capital of Lombardy region, it is considered the epicenter of the virus outbreak in Italy. Our main findings highlight that temperature and humidity related variables are negatively correlated to the virus transmission, whereas air pollution (PM2.5) shows a positive correlation (at lesser degree). In other words, COVID-19 pandemic transmission prefers dry and cool environmental conditions, as well as polluted air. For those reasons, the virus might easier spread in unfiltered air-conditioned indoor environments. Those results will be supporting decision makers to contain new possible outbreaks.


Assuntos
Poluição do Ar/estatística & dados numéricos , Infecções por Coronavirus/epidemiologia , Umidade , Pneumonia Viral/epidemiologia , Temperatura , Cidades/estatística & dados numéricos , Infecções por Coronavirus/transmissão , Humanos , Itália , Pandemias , Pneumonia Viral/transmissão , População Urbana/estatística & dados numéricos
6.
Life Sci ; 262: 118509, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33010280

RESUMO

Phosphoesterase complex (Pho), a major active component of barley malt, has been demonstrated to be clinically effective in relieving alcoholic fatty liver disease (AFLD), and several lines of evidence have suggested that microbial dysbiosis, caused by chronic alcohol overconsumption, plays a key role in the progression of AFLD. The current study aimed to investigate the modulatory effect of Pho on gut microflora. The microbiota diversity, determined via detection of the V4 region of 16S rDNA genes, was analyzed in rats fed the Lieber-Decarli diet. Gut permeability was evaluated via mucus layer staining. Dysbiosis-associated chronic inflammation was investigated by observing the expression of the following inflammatory molecules in the liver: tumor necrosis factor α (TNF-α), monocyte chemotactic protein 1 (MCP-1), chemokine (C-X-C motif) ligand 1 (CXCL-1) and interleukin 1 beta (IL-1ß). Pyrosequencing revealed that the gut microbiota in Pho-treated rats was different from that of AFLD rats at both the phylum and genus levels. In addition, Pho significantly alleviated dysbiosis-associated disruption of gut permeability and inflammation, increased mucus layer thickness and downregulated TNF-α, MCP-1, CXCL-1 and IL-1ß expression. In summary, the current results revealed that the microflora, gut barrier and chronic inflammation in AFLD may be modulated by Pho.

7.
Cell Rep ; 33(2): 108254, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33007239

RESUMO

Development of specific antiviral agents is an urgent unmet need for SARS-coronavirus 2 (SARS-CoV-2) infection. This study focuses on host proteases that proteolytically activate the SARS-CoV-2 spike protein, critical for its fusion after binding to angiotensin-converting enzyme 2 (ACE2), as antiviral targets. We first validate cleavage at a putative furin substrate motif at SARS-CoV-2 spikes by expressing it in VeroE6 cells and find prominent syncytium formation. Cleavage and the syncytium are abolished by treatment with the furin inhibitors decanoyl-RVKR-chloromethylketone (CMK) and naphthofluorescein, but not by the transmembrane protease serine 2 (TMPRSS2) inhibitor camostat. CMK and naphthofluorescein show antiviral effects on SARS-CoV-2-infected cells by decreasing virus production and cytopathic effects. Further analysis reveals that, similar to camostat, CMK blocks virus entry, but it further suppresses cleavage of spikes and the syncytium. Naphthofluorescein acts primarily by suppressing viral RNA transcription. Therefore, furin inhibitors may be promising antiviral agents for prevention and treatment of SARS-CoV-2 infection.

8.
Psychiatry Investig ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33059395

RESUMO

OBJECTIVE: Previous studies investigating association of alcohol intake and fracture risk in elderly yielded conflicting results. We first examined the association between alcohol intake and total fracture risk in elderly subjects and further analyzed whether the association varied by fracture locations. METHODS: This is a nationwide population-based cohort study which included all people aged 66 (n=1,431,539) receiving the National Screening Program during 2009-2014. Time-to-event were defined as duration from study recruitment, the day they received health screening, to the occurrence of fracture. RESULTS: Total fracture was significantly lower in mild drinkers [adjusted hazard ratio (aHR)=0.952; 95% confidence interval (95% CI) =0.931-0.973] and higher in heavy drinkers (aHR=1.246; 95% CI=1.201-1.294) than non-drinkers. Risk pattern of alcohol consumption and fracture differed according to affected bones. Similar J-shaped trends were observed for vertebra fractures, but risk of limb fracture showed a linear relationship with alcohol intake. For hip fracture, risk decrement was more pronounced in mild and moderate drinkers, and significant increment was noted only in very severe drinkers [≥60 g/day; (aHR)=1.446; 1.162-1.801]. CONCLUSION: Light to moderate drinking generally lowered risk of fractures, but association between alcohol and fracture risk varied depending on the affected bone lesions.

10.
Int Immunopharmacol ; 89(Pt A): 107067, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33039963

RESUMO

There are multiple causes of liver fibrosis, common ones include ethanol, toxins, and cholestasis. However, whether these different etiologies lead to the same pathological outcomes contain common genetic targets or signaling pathways, the current research has not attracted widespread attention. GSE40041 and GSE55747 were downloaded from the Gene Expression Omnibus (GEO) database. GSE40041 and GSE55747 represent the differential expression profiles in the liver of mice with bile duct ligation (BDL) and carbon tetrachloride (CCl4) induced liver fibrosis models, respectively. By using GEO2R, 701 differential expression genes (DEGs) in GSE40041 and 6540 DEGs in GSE55747 were identified. 260 co-DEGs were shared and extracted for gene ontology (GO) analysis. Through GO analysis, it was found that the regulation of cell migration in biological processes (BPs) was closely related to the pathogenesis of liver fibrosis, and the genes involved in this process include a key gene, chemokine (C-X-C motif) ligand 14 (CXCL14). Subsequently, further bioinformatic analysis showed that CXCL14 may be regulated by miR-122 to participate in the progression of liver fibrosis. Then real-time PCR and western blotting were performed to validate the expression of CXCL14 in liver tissue after liver fibrosis caused by different etiologies (ethanol, CCl4). The expression of CXCL4 in liver fibrosis induced by BDL was verified in another GEO dataset. Basically consistent with our bioinformatics results, our experimental results showed that the expression of CXCL14 was most significantly increased in alcoholic liver fibrosis model, followed by CCl4-induced liver fibrosis, which was also significantly increased in the BDL-induced model. Thus, CXCL14 can act as a common potential genetic target for different liver fibrosis diseases.

11.
Nat Methods ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077966

RESUMO

Although tremendous effort has been put into cell-type annotation, identification of previously uncharacterized cell types in heterogeneous single-cell RNA-seq data remains a challenge. Here we present MARS, a meta-learning approach for identifying and annotating known as well as new cell types. MARS overcomes the heterogeneity of cell types by transferring latent cell representations across multiple datasets. MARS uses deep learning to learn a cell embedding function as well as a set of landmarks in the cell embedding space. The method has a unique ability to discover cell types that have never been seen before and annotate experiments that are as yet unannotated. We apply MARS to a large mouse cell atlas and show its ability to accurately identify cell types, even when it has never seen them before. Further, MARS automatically generates interpretable names for new cell types by probabilistically defining a cell type in the embedding space.

12.
Biosens Bioelectron ; 170: 112677, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33032197

RESUMO

In recent years, imidacloprid and fipronil have been reported to harm beneficial insects, such as honey bees, and to potentially pose risks to mammals, including humans. Considering their widespread use and potential minimum toxic range from 10 ppb to 1 ppm (species dependent), a simple, rapid, sensitive, and reliable method for screening and detection is urgently needed. Here, we present a surface plasmon resonance (SPR)-based nanoplasmonic chip integrated with a multichannel spectral imaging system to detect ecosystem-harming pesticides. The pre-modification of the designed mercapto-haptens reduced detection time to 2.5 h. Moreover, owing to the multichannel configuration, it was possible to introduce an internal standard analytical method to effectively reduce matrix interference in real samples; thus, the concentration of the target pesticide could be determined more precisely. The strong linearity of the spiked sample test results indicated high accuracy in quantifying target pesticides. Considering the limit of detection (~10 ppb), the cutoffs for detection and quantification were set at 15 and 45 ppb, respectively, and were used as the detection criteria. The detection results of the blind tests of real samples were also compared with those of liquid chromatography electrospray ionization tandem mass spectrometry (standard method) and were highly consistent. The custom-made integrated SPR system allows much simpler, label-free, high-throughput, and reliable on-site identification and quantification of imidacloprid and fipronil. All test results validated the platform's capability in the on-site rapid screening and detection of pesticide residues at the parts per billion and parts per million levels.

13.
J Pharm Biomed Anal ; 192: 113657, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33053506

RESUMO

Montelukast is a potent and selective antagonist of the cysteinyl leukotriene receptor 1 subtype (CysLT1) and widely used in the form of oral tablets and granules for asthma prophylaxis and treatment. Recently, due to the pulmonary inhaled administration can limit montelukast distribution in the systemic circulation, avoid the first-pass metabolism and have better therapeutic effects in respiratory disease treatment, explore alternative routes of administration, like delivery of montelukast via an inhaled, is a new research trend for montelukast. The aim of the current study was to develop and validate a simple, accurate, highly sensitive and selective liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for determination of montelukast in an in vitro cell-based pulmonary pharmacokinetics system model, which can be used to be a better understanding the fate of inhaled montelukast in the lungs. In this study, montelukast was extracted by protein precipitation with acetonitrile containing labeled montelukast. The chromatography was performed on an Agilent Eclipse plus C8 column (4.6 mm × 100 mm, 3.5 µm, Darmstadt, Germany) operating at 35 ◦C. The mobile phase consisted of acetonitrile: 20 mM ammonium formate buffer (80: 20, v/v), was delivered at a flow rate of 0.5 mL/min. montelukast and the internal standard were both eluted at 4.2 min. A linear (1/x2) relationship was used to perform the calibration over an analytical range from 0.5 to 600 ng/mL. The intra- and inter-batch precision expressed as CV for four QC samples including LLOQ range from 1.14 % to 6.25 %. The intra- and inter-batch accuracy for four concentrations of montelukast were in the range of 95.19%-104.1%. All the values for accuracy and precision were within the acceptance range. The method met all the bioanalytical method validation requirements by ICH and was suitable for the assay of montelukast which in the in vitro cell-based pulmonary pharmacokinetics system model.

14.
J Chromatogr A ; 1631: 461526, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-33002705

RESUMO

A self-separating, analyte-compatible, and efficient clean-up method for QuEChERS extracts was designed and developed based on dispersive solid-phase extraction using a branched polyethylenimine and nanoscale CaSO4 functionalized carboxylated multi-walled carbon nanotubes (MWCNTs) nanohybrids as sorbent. The feasibility of using a self-separating strategy based on the functionalization of sorbent in a purification procedure was analyzed for the first time in this study. Compared to the traditional QuEChERS method, the proposed method is rapid and convenient without centrifugation of numerous samples in the clean-up process. The use of nanohybrids overcame the issue of low recoveries for planar pesticides, which are easily adsorbed using MWCNTs. A better clean-up capability of the nanohybrids to remove matrix interferences and reduce matrix effect was demonstrated compared with that of traditional clean-up sorbent primary secondary amine. The method was validated by determining twenty-eight pesticides in cucumber, cabbage, apple, and orange. Limits of detections were in the range of 0.0001-0.0026 mg/kg. Spike recoveries of pesticides were within 75.3 - 113.6%, with relative standard deviations less than 14.3% at levels 0.01 mg/kg and 0.1 mg/kg. The developed method was successfully applied to monitor the multi-residues.

15.
J Colloid Interface Sci ; 583: 470-486, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33011414

RESUMO

Temperature/pH dual-stimuli-responsive phase-change microcapsules (Dual-SR-MEPCM) were designed that can form the basis of smart drug delivery systems. They employed n-eicosane as a phase change material (PCM) microencapsulated in an acrylate-functionalized silica shell via emulsion-templated interfacial polycondensation. A poly(N-isopropylacrylamide-co-acrylate acid) functional layer was then fabricated on the surface of the silica shell through surfactant-assisted radical polymerization. The combination of phase-change microcapsules and stimuli-responsive material results in a system that synchronously implements thermal self-regulation by its PCM core together with controllable drug release through its polymeric functional layer. The resultant Dual-SR-MEPCM exhibits regularly spherical morphology, uniform particle-size distribution and well-defined core-shell microstructure, which indicates successful construction according to our design principle. This system has been further evaluated for multipurpose applications in thermal regulation and drug delivery with independent temperature and pH triggering. The Dual-SR-MEPCM not only shows a high thermal energy-storage capacity of over 160 J/g, but also good anti-leakage performance, thermal cycle stability and high-temperature shape stability. Our studies also reveal independent stimuli-responsive behaviors for temperature and pH when using bovine serum albumin and doxorubicin hydrochloride as model drugs. All of these features indicate that the Dual-SR-MEPCM designed in this study can serve as a promising candidate for smart drug delivery systems, with great potential for future multipurpose applications in advanced pharmaceutical areas.

16.
Science ; 370(6514): 346-350, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33060360

RESUMO

Mutualisms, or reciprocally beneficial interspecific interactions, constitute the foundation of many ecological communities and agricultural systems. Mutualisms come in different forms, from pairwise interactions to extremely diverse communities, and they are continually challenged with exploitation by nonmutualistic community members (exploiters). Thus, understanding how mutualisms persist remains an essential question in ecology. Theory suggests that high species richness and functional redundancy could promote mutualism persistence in complex mutualistic communities. Using a yeast system (Saccharomyces cerevisiae), we experimentally show that communities with the greatest mutualist richness and functional redundancy are nearly two times more likely to survive exploitation than are simple communities. Persistence increased because diverse communities were better able to mitigate the negative effects of competition with exploiters. Thus, large mutualistic networks may be inherently buffered from exploitation.

17.
Toxicol Ind Health ; 36(8): 580-590, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33064063

RESUMO

Nickel (Ni) is a known human carcinogen that has an adverse effect on various human organs in occupational workers during Ni refinement and smelting. In the present study, we used real-time polymerase chain reactions, Western blot analysis, and a lactate production assay to investigate whether an increase in the NLRP3 inflammasome induced by Ni-refining fumes was associated with the Warburg effect in BEAS-2B cells, a nonmalignant pulmonary epithelial line. Exposure to Ni-refining fumes suppressed cell proliferation and increased lactate production compared with those in an untreated control group in a dose- and time-dependent manner. Ni-refining fumes induced the Warburg effect, which was observed based on increases in the levels of hypoxia-inducible factor-1α, hexokinase 2, pyruvate kinase isozyme type M2, and lactate dehydrogenase A. In addition, Ni-refining fumes promoted increased expression of NLRP3 at both the gene and protein levels. Furthermore, inhibition of the Warburg effect by 2-Deoxy-d-glucose reversed the increased expression of NLRP3 induced by Ni-refining fumes. Collectively, our data demonstrated that the Warburg effect can promote the expression of the NLRP3 inflammasome induced by the Ni-refining fumes in BEAS-2B cells. This indicates a new phenomenon in which alterations in energy production in human cells induced by Ni-refining fumes regulate the inflammatory response.

18.
Cardiovasc Res ; 2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33070195

RESUMO

AIMS: Previous studies have shown the intake of omega-3 polyunsaturated fatty acids are associated with low rates of obesity and ischemic pathologies. Omega-3 also have anti-inflammatory and plaque-stabilization effects and regulate vasodilation and constriction. However, there are few studies of the role of omega-3 in flow-induced vasodilation involving Ca2+-permeable ion channel TRPV4 in high-fat diet-induced obese (DIO) mouse. Here, we determined whether omega-3 protect against vascular dysfunction induced by high-fat diet by enhancing TRPV4 activity and subsequently improving flow-mediated vasodilation. METHODS AND RESULTS: Flow-mediated vasodilation in 2nd-order mesenteric arteries from mice was measured using a pressure myograph. The intracellular Ca2+ concentration in response to flow and GSK1016790A (a TRPV4 agonist) was measured by Fluo-4 fluorescence. Whole-cell current was measured by patch clamp. Cell membrane tether force was measured by atomic force microscopy. Impairment of flow-mediated vasodilation in arteries and Ca2+ influx in endothelial cells from DIO mice was restored by omega-3 treatment. The improved flow-induced vasodilation was inhibited by the TRPV4 antagonist HC067047 and in TRPV4-/- mice. Omega-3 treatment enhanced endothelial TRPV4 activity and altered cell membrane mechanic property, as indicated by enhanced GSK1016790A-induced Ca2+ influx and whole-cell current and altered membrane mean tether force in endothelial cells from DIO mice. CONCLUSION: Omega-3 improve vascular function by improving flow-induced vasodilation via enhancing TRPV4 activity in the endothelium of obese mice which may be related to improved cell membrane physical property. Activation of TRPV4 in endothelium plays an important role in the protective mechanisms of omega-3 against vascular dysfunction in obesity by improving flow-mediated vasodilation. TRANSLATIONAL PERSPECTIVE: Omega-3 improve the endothelial function via enhancing TRPV4 activity and augmenting the endothelial-dependent flow-induced vasodilation in DIO mice resistance arteries. This study provides a strategy of improving vascular function under obesity, namely, by targeting TRPV4 via the usage of omega-3.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32985008

RESUMO

Quasi-1D metal halide perovskite nanorods (NRs) are emerging as a type of materials with remarkable optical and electronic properties. Research into this field is rapidly expanding and growing in the past several years, with significant advances in both mechanistic studies of their growth and widespread possible applications. Here, the recent advances in 1D metal halide perovskite nanocrystals (NCs) are reviewed, with a particular emphasis on NRs. At first, the crystal structures of perovskites are elaborated, which is followed by a review of the major synthetic approaches toward perovskite NRs, such as wet-chemical synthesis, substrate-assisted growth, and anion exchange reactions, and discussion of the growth mechanisms associated with each synthetic method. Then, thermal and aqueous stability and the linear polarized luminescence of perovskite NRs are considered, followed by highlighting their applications in solar cells, light-emitting diodes, photodetectors/phototransistors, and lasers. Finally, challenges and future opportunities in this rapidly developing research area are summarized.

20.
Trials ; 21(1): 817, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993731

RESUMO

BACKGROUND: Endoscopic ultrasound-guided biliary drainage (EUS-BD) is used after failed endoscopic retrograde cholangiopancreatography. Based on existing studies, intrahepatic (IH) approaches are preferred in patients with dilated IH bile ducts. Both ultrasound-guided hepaticogastrostomy (EUS-HGS) and ultrasound-guided antegrade treatment (EUS-AG) are appropriate for patients with unreachable papillae. Nevertheless, there have been no direct comparisons between these two approaches. Therefore, we aim to evaluate and compare the safety and efficiency of EUS-HGS and EUS-AG in patients with an unreachable papilla. METHODS: This is a prospective, randomised, controlled, multicentre study with two parallel groups without masking. One hundred forty-eight patients from three hospitals who met the inclusion criteria will be randomly assigned (1:1) to undergo either EUS-HGS or EUS-AG for relief of malignant biliary obstruction. The final study follow-up is scheduled at 1 year postoperatively. The primary endpoint is efficiency, described by technical and clinical success rates of EUS-HGS and EUS-AG in patients with unreachable papillae. The secondary endpoints include stent patency, overall survival rates, complication rates, length of hospital stays, and hospitalisation expenses. The chi-square test, Kaplan-Meier methods, log-rank test, and Cox regression analysis will be used to analyse the data. DISCUSSION: To our knowledge, this is the first study to compare these two EUS-BD approaches directly using a multicentre, randomised, controlled trial design. The clinical economic indexes will also be compared, as they may also affect the patient's choice. The result may contribute to establishing a strategic guideline for choosing IH EUS-BD approaches. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) ChiCTR1900020737 . Registered on 15 January 2019.

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