Nitrogen deposition further increases Ambrosia trifida root exudate invasiveness under global warming.

Invasive plants can change the soil ecological environment in the invasion area to adapt to their growth and reproduction through root exudates. Root exudates are the most direct manifestation of plant responses to external environmental changes, but there is a lack of studies on root exudates of invasive plants in the context of inevitable global warming and nitrogen deposition. In this research, we used widely targeted metabolomics to investigate Ambrosia trifida root exudates during seedling and maturity under warming and nitrogen deposition to reveal the possible mechanisms of A. trifida adaptation to climate change. The results showed that the organic acids increased under warming condition but decreased after nitrogen addition in the seedling stage. Phenolic acids increased greatly after nitrogen addition in the mature stage. Most phenolic acids were annotated in the phenylpropane metabolic pathway and tyrosine metabolism. Therefore, nitrogen deposition may increase the adaptability of A. trifida through root exudates, making it more invasive under global warming. The results provide new ideas for preventing and controlling the invasion of A. trifida under climate change.

Aptamer-Integrated Scaffolds for Biologically Functional DNA Origami Structures.

The manufacture of DNA origami nanostructures with highly ordered functional motifs is of great significance for biomedical applications. Here, we present a robust strategy to produce customized scaffolds with integrated aptamer sequences, which enables direct construction of functional DNA origami structures. As we demonstrated, aptamers of various numbers and types were efficiently and stably integrated in user-defined positions of the scaffolds. Specifically, two different thrombin aptamer sequences were simultaneously inserted into the M13mp18 phage genome. The assembled functional DNA origami structures from this aptamer-integrated scaffold exhibited increased binding efficiency to thrombin and displayed more than 10-fold stronger resistance to exonuclease degradation than that produced using the traditional staple extension method. Additionally, a scaffold integrated with the platelet-derived growth factor aptamer was produced, and the assembled DNA origami structures showed significant inhibitory effect on breast cancer cells MDA-MB-231. This scalable method of creating design-specific scaffolds opens up a new way to construct more stable and functionally robust DNA origami structures and thus provides an important basis for their broader applications.

Moderate DNA hypomethylation suppresses intestinal tumorigenesis by promoting caspase-3 expression and apoptosis.

Global DNA hypomethylation is a most common epigenetic alteration in human neoplasia. However, accumulative evidence shows that global DNA hypomethylation impacts tumorigenesis in a tissue-specific manner, promoting tumorigenesis in some but suppressing tumorigenesis in others including colorectal cancer. The underlying mechanisms, especially how DNA hypomethylation suppresses tumorigenesis, remain largely unknown. Here, we investigate how DNA hypomethylation affects intestinal tumorigenesis by using an Uhrf1 tandem tudor domain knockin mutant mouse model (Uhrf1ki/ki) that exhibits a moderate ~10% reduction of global DNA methylation. We found that both chemical-induced colorectal carcinogenesis and Apc loss of heterozygosity (LOH)-induced intestinal tumorigenesis are substantially suppressed in the Uhrf1 mutant mice. Furthermore, unlike Dnmt1 hypomorphic mice in which DNA hypomethylation suppresses the incidence of macroscopic intestinal tumors but promotes the formation of microadenoma in ApcMin/+ background, Uhrf1ki/ki/ApcMin/+ mice have markedly reduced incidence of both microadenoma and macroadenoma. DNA hypomethylation does not appear to affect Apc LOH, activation of the Wnt or Hippo pathway, or tumor cell proliferation, but acts cooperatively with activated Wnt pathway to enhance the caspase-3 gene expression, activation, and apoptosis. Furthermore, increased caspase-3 expression correlates with DNA hypomethylation within the caspase-3 enhancer regions. Taken together, we present a new mouse model for investigating the role of and the molecular mechanisms by which DNA hypomethylation suppresses intestinal tumorigenesis. Our finding that a moderate DNA hypomethylation is sufficient to suppress intestinal tumorigenesis by promoting caspase-3 expression and apoptosis sheds new light on DNA-methylation inhibitor-based colorectal cancer therapeutics.

2'-Fluoroarabinonucleic Acid Nanostructures as Stable Carriers for Cellular Delivery in the Strongly Acidic Environment.

DNA nanotechnology is powerful in constructing programmable nanostructures with distinct dimensions, sizes, and shapes. However, natural DNA molecules are prone to nuclease degradation, thus limiting the in vivo applications of such DNA nanostructures. 2'-Fluoroarabinonucleic acid (FANA) is a chemically modified oligonucleotide with similar base pairing properties to DNA and exhibits superior physical and chemical stabilities. In this work, FANA molecules were used to construct double crossover nanostructures, and it was demonstrated that incorporation of FANA conferred nucleic acid nanostructures with increased thermal stability and stronger nuclease resistance. More importantly, FANA nanostructures were able to maintain the structural integrity in the strongly acidic environment (pH 1.2). Last, such FANA nanostructures functioned well in acting as stable carriers of small-molecule cargoes for cellular delivery in simulated gastric fluid, while the DNA counterparts were mostly degraded. Collectively, these results demonstrated that FANA self-assembly was not only a substantial complement to the structural DNA nanotechnology but also an appealing molecular tool for in vivo biomedical applications.

The coronavirus diseases 2019 (COVID-19) pneumonia with spontaneous pneumothorax: a case report.

BACKGROUND: The outbreak of the novel coronavirus (COVID-19) that was firstly reported in Wuhan, China, with cases now confirmed in more than 100 countries. However, COVID-19 pneumonia with spontaneous pneumothorax is unknown. CASE PRESENTATION: We reported a case of 66-year-old man infected with COVID-19, presenting with fever, cough and myalgia; The patient received supportive and empirical treatment including antiviral treatment, anti-inflammatory treatment, oxygen supply and inhalation therapy; The symptoms, CT images, laboratory results got improved after the treatments, and a throat swab was negative for COVID-19 PCR test; However, on the hospital day 30, the patient presented with a sudden chest pain and dyspnea. CT showed a 30-40% left-sided pneumothorax. Immediate thoracic closed drainage was performed and his dyspnea was rapidly improved. With five more times negative PCR tests for SARS-CoV-2 virus, the patient was discharged and home quarantine. CONCLUSION: This case highlights the importance for clinicians to pay attention to the appearance of spontaneous pneumothorax, especially patients with severe pulmonary damage for a long course, as well as the need for early image diagnose CT and effective treatment once pneumothorax occurs.

Reduced glutathione ameliorates liver function, oxidative stress and inflammation after interventional therapy for hepatocellular carcinoma.

PURPOSE: To investigate the influence of reduced glutathione (GSH) in liver function, oxidative stress, inflammatory response, immune function and quality of life of patients after an interventional therapy for hepatocellular carcinoma. METHODS: 96 hepatocellular carcinoma patients undergoing hepatic arterial intervention chemotherapy were selected and randomly divided into the control group (n=48) and the observation group (n=48). The patients in the control group were given conventional treatment after operation, while those in the observation group were treated with GSH based on the treatment in the control group. The liver function, oxidative stress, inflammation, quality of life and adverse reactions were compared before and after treatment between the two groups. RESULTS: The levels of superoxide dismutase (SOD), cluster of differentiation (CD)3+, CD4+ and CD4+/CD8+ as well as physical, emotion and social function scores after treatment were higher in the observation group than in the control group. The observation group had lower levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBiL), malondialdehyde (MDA), advanced oxidation protein product (AOPP), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and CD8+ as well as pain score than the control group (p<0.05). The total effective rate in the observation group was remarkably higher than in the control group (p<0.05), while there were no significant differences in disease control rate and clinical adverse reactions between the two groups (p>0.05). CONCLUSIONS: GSH can evidently ameliorate the liver function and immune function, reduce oxidative stress and inflammatory response and improve the postoperative quality of life of the patients after the interventional therapy for hepatocellular carcinoma, with satisfactory clinical therapeutic effects, so it is worthy of further application and generalization.

Case Report: The Coronavirus Disease 2019 (COVID-19) Pneumonia With Multiple Thromboembolism.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan, China, in late December 2019 and has since spread rapidly around the world. Severe coronavirus disease 2019 (COVID-19) pneumonia patients have abnormal blood coagulation function, but their thromboembolism prevalence is still unknown. We reported a case of a 49-year-old man infected with COVID-19, presenting with fever, chest pain, limb weakness, myalgia, and dyspnea. The patient was diagnosed with severe COVID-19 pneumonia, pulmonary thromboembolism (PTE), deep vein thrombosis (DVT), and cerebral infarction. He received supportive and empirical treatment including anticoagulant treatment, anti-inflammatory treatment, oxygen supply, and inhalation therapy. The patient's symptoms, CT images, and laboratory results improved after treatment, and a throat swab was reported to be negative for SARS-CoV-2 virus by polymerase chain reaction (PCR) test. However, on day 51 of illness onset, CT reexamination demonstrated hemorrhagic infarction. Anticoagulant therapy was discontinued temporarily. After the patient tested negative for SARS-CoV-2 virus by PCR test six more times, he was discharged and remained in home quarantine. This case highlights the importance of clinician attentiveness to the appearance of multiple thromboembolism, especially in patients with severe pulmonary damage. It also emphasizes the diagnostic value of early CT imaging and the need for effective treatment once thrombotic events occur.

Isolated gastric varices secondary to abdominal tuberculosis mimicking lymphoma: a case report.

BACKGROUND: Abdominal tuberculosis (TB) rarely presents with abdominal masses and rarely causes isolated gastric varices. CASE PRESENTATION: We report a case of isolated gastric varices secondary to abdominal TB mimicking lymphoma. A 42-year-old woman without any history of liver disease presented with melena and mild abdominal pain. Upon admission to the hospital, laboratory investigations revealed a hemoglobin level of 76 g/L. Gastroduodenoscopic examination showed isolated gastric fundal varices with red color signs. Abdominal contrast-enhanced computed tomography (CECT) revealed non-enhanced masses of soft-tissue density in the lesser omental and the retropancreatic areas, multiple para-aortic lymph nodes, and multiple small hypodense splenic lesions. Positron emission tomography-CT showed hypermetabolic [F-18]2-fluoro-2-deoxyglucose activity involving multiple regional lymph nodes and the bone marrow, suggestive of lymphoma. Bone marrow biopsy revealed no abnormality. Histopathological examination of a CT-guided biopsy specimen showed granulomatous inflammation with necrosis and microorganisms that stained positive with acid-fast stains. Abdominal CECT showed a decrease in the size of the lesser omental and peripancreatic masses, as well as the para-aortic lymph nodes after 4-month anti-TB therapy. CONCLUSIONS: TB should be considered among the differential diagnoses in patients with abdominal masses, isolated gastric varices, and regional lymphadenopathy. Prompt and definitive diagnosis of abdominal TB requires a coordinated approach involving laboratory tests, radiological examination, and invasive procedures for optimal decision making and management.

Inhibition of myeloid differentiation 1 specifically in colon with antisense oligonucleotide exacerbates dextran sodium sulfate-induced colitis.

Myeloid differentiation 1 (MD-1), also known as lymphocyte antigen 86 (Ly86), is a soluble protein homologous to MD-2 and forms a complex with radioprotective 105 (RP105). RP105/MD-1 complex negatively regulates toll-like receptor 4 (TLR4) signaling and is involved in several immune disorders. However, the precise role of MD-1 in inflammatory bowel diseases (IBD) remains poorly understood. To further investigate the involvement of MD-1 in IBD, we inhibited MD-1 in colon with antisense oligonucleotide (AS-ODN) and assessed the effect of MD-1 inhibition on dextran sodium sulfate (DSS)-induced colitis. We discovered that MD-1 protein expression was remarkably decreased in both patients with ulcerative colitis and mice with DSS-induced colitis. For the first time, we showed that oral administration of MD-1 AS-ODN to mice significantly suppressed the MD-1 protein levels in colon rather than systemic tissues. Subsequently, we found that MD-1 AS-ODN treated mice were more susceptible to DSS-induced colitis based on loss of body weight, colon length, histological scores, and disease activity index. MD-1 inhibition also significantly enhanced inflammatory cytokines production such as IL-6 and IL-1ß in colons. Finally, mice treated with MD-1 AS-ODN exhibited increased messenger RNA levels of TLR4 and MyD88 after DSS exposure and showed enhanced nuclear factor (NF)-κB activation compared with the control. Taken together, specifically suppression of MD-1 in colon tissues with AS-ODN exacerbates DSS-induced experimental colitis in mice, which is possibly related to activation of TLR4/NF-κB signaling.

Vaginal cuff length during radical hysterectomy is a prognostic factor for stage IB-IIA cervical cancer: a retrospective study.

PURPOSE: The aim of this study was to investigate the impact of vaginal cuff length (VCL) resected during radical hysterectomy (RH) on the long-term survival outcomes of patients with cervical cancer (International Federation of Gynecology and Obstetrics [FIGO] stage IB-IIA) and to explore whether VCL is a prognostic factor for cervical cancer. METHODS: A total of 435 eligible patients with stage IB and IIA cervical cancer who underwent RH in Zhongnan Hospital of Wuhan University (Wuhan, People's Republic of China) from January 2007 to February 2017 were retrospectively analyzed. These patients were divided into two groups (VCL ≤2.0 cm and >2.0 cm) for further analysis according to the VCL during RH. The Kaplan-Meier method was adopted to calculate the survival rates. Univariate and multivariate Cox regression models were used to analyze independent prognosis factors for survival. RESULTS: Of the 435 identified patients, 196 had VCL ≤2.0 cm and 239 had VCL >2.0 cm after RH. The 5-year disease-free survival (DFS) for the group who had VCL ≤2.0 cm vs the group who had VCL >2.0 cm was 68.1% vs 87.5% (P<0.001). Correspondingly, the overall survival (OS) for the two groups was 71.4% vs 89.2% (P<0.001). More interestingly, the VCL was significantly associated with the 5-year local recurrence rate, but not associated with the distant metastasis rate. In addition to the VCL, FIGO stage and lymph node involvement were also identified as significant prognostic factors for cervical cancer. CONCLUSION: Resection of VCL >2.0 cm in RH has a more favorable long-term outcome than VCL ≤2.0 cm among patients with cervical cancer (FIGO stage IB-IIA); shorter VCL resection was significantly associated with local recurrence, DFS, and OS; thus, it can be considered as a prognostic factor for cervical cancer.

Self-Assembly of Large DNA Origami with Custom-Designed Scaffolds.

As a milestone in DNA self-assembly, DNA origami has demonstrated powerful applications in many fields. However, the scarce availability of long single-stranded DNA (ssDNA) limits the size and sequences of DNA origami nanostructures, which in turn impedes the further development. In this study, we present a robust strategy to produce long circular ssDNA scaffold strands with custom-tailored lengths and sequences. These ssDNA products were then used as scaffolds for constructing various DNA origami nanostructures. This scalable method produces ssDNA at low cost with high purity and high yield, which can enable production of custom-designed DNA origami for various applications.

Profiles of differentially expressed genes and overexpression of NEBL indicates a positive prognosis in patients with colorectal cancer.

The present study aimed to identify differentially expressed genes (DEGs) in colorectal cancer (CRC) and provide novel prognostic biomarkers for CRC. The microarray dataset GSE41258 was used to screen DEGs of CRC. Subsequently, a protein­protein interaction network of DEGs and Gene Ontology analysis were performed to identify hub genes and associated biological processes. Nebulette (NEBL) and complement C1q like 1 (C1QL1) were validated using reverse transcription­quantitative polymerase chain reaction in patients with CRC. Survival analysis was performed for the two hub genes. GSE41258 dataset included 182 CRC samples and 54 normal tissues. A total of 759 DEGs, including 279 upregulated and 480 downregulated were screened between both groups. NEBL and C1QL1 were identified as the two hub genes and upregulated genes involved in various biological processes, including 'regulation of biological quality' and 'response to stimulus', respectively. Additionally, the overexpression of NEBL and C1QL1 in experimental validation was consistent with the aforementioned bioinformatics analysis results. Survival analysis suggested that overexpressed NEBL in patients with CRC was associated with a positive prognosis for overall survival. In conclusion, CRC was associated with a large group of DEGs. From the upregulated genes, overexpressed NEBL in patients CRC indicated a positive prognosis for overall survival and may be used as a prognostic biomarker for patients with CRC.

Transition radiation from graphene plasmons by a bunch beam in the terahertz regime.

The terahertz band is an increasingly important spectrum in a wide range of applications from bioimaging and medical diagnostics to security and wireless communications. We propose a tunable terahertz coherent radiation source based on graphene plasmon-induced transition radiation. The transition radiation in terahertz regime arises from the graphene plasmons, which are excited by a normally incident bunched electron beam. We analyze the field-intensities and spectral-angular distributions of the transition radiation with respect to Fermi energy, substrate dielectric permittivity, and electron bunch energy for both the coherent and incoherent radiation. The effect of electron bunching on the radiation pattern is discussed. The mechanism of plasmon frequency-selective transition radiation is discovered.

A magnetite/PMAA nanospheres-targeting SERS aptasensor for tetracycline sensing using mercapto molecules embedded core/shell nanoparticles for signal amplification.

Surface-enhanced Raman scattering (SERS) biosensors have promising potential in the field of antibiotics detection because of their ultrahigh detection sensitivity. This paper reports a rapid and sensitive SERS-based magnetic nanospheres-targeting strategy for sensing tetracycline (TTC) using aptamer-conjugated magnetite colloid nanocrystal clusters (MCNCs)-polymethacrylic acid (PMAA) magnetic nanospheres (MNs) as the recognition and the Au/PATP/SiO2 (APS) as the labels. Initially, MNs were fabricated and conjugated with the aptamers through condensation reaction. MNs possessed high saturation magnetization (Ms) value of 71.5emu/g and excellent biocompatibility, which facilitated the rapid and easy magnetic separation. Then, complementary DNA (cDNA) were loaded on the APS nanocarrier to produce a large amplification factor of Raman signals. The MNs-targeting aptasensor was thus fabricated by immobilizing the APS to the MNs' surfaces via the hybrid reaction between cDNA and aptamers. Sequel, TTC bound successfully to the aptamer upon its addition with the subsequent release of some cDNA-APS into the bulk solution. Under magnet attraction, the nanospheres were deposited together. Consequently, a display of strong SERS signals by supernatants of the resulting mixtures with increasing TTC concentrations was observed. The proposed aptasensor showed excellent performances for TTC detection along with wide linear range of 0.001-100ng/mL, low detection limit 0.001ng/mL, high sensitivity, and good selectivity to the general coexisted interferences.

Manometric Measurement of the Sphincter of Oddi in Patients with Common Bile Duct Stones: A Consecutive Study of the Han Population of China.

Objective. Role of dysfunction of the sphincter of Oddi (SO) in choledocholithiasis is controversial. This study was to evaluate SO motor activity in patients with common bile duct (CBD) stones in the Han population of China. Patients and Methods. In this study, 76 patients with CBD stones were enrolled in a single tertiary endoscopy center. Data of SO motor activities was prospectively evaluated by endoscopic manometry. Mean basal SO pressure, amplitude, and frequency were collected and analyzed. Results. The mean basal SO pressure, amplitude, and frequency were 52.7 ± 40.0 (1.60-171.1) mmHg, 39.9 ± 19.7 (14.9-115.5) mmHg, and 5.7 ± 3.2 (1.3-13.8)/min, respectively. The basal SO pressure was higher in patients with CBD stones < 10 mm in diameter than that in those with CBD stones larger than 10 mm in diameter (60.7 ± 41.0 mmHg versus 36.8 ± 29.4 mmHg, P = 0.043). There was no significant difference in the basal SO pressure, amplitude, and frequency when compared with the CBD diameter, CBD stone number, prior cholecystectomy, periampullary diverticula, and symptoms. Levels of alanine aminotransferase, aspartate transaminase, γ-glutamyl transpeptidase, and alkaline phosphatase showed no significant difference in patients with normal or elevated basal SO pressure. Conclusion. These results identify that, in Chinese Han population, abnormalities of SO motor activity are associated with CBD stones.

Plasmon modes of circular cylindrical double-layer graphene.

In this paper, a theoretical investigation on plasmon modes in a circular cylindrical double-layer graphene structure is presented. Due to the interlayer electromagnetic interaction, there exist two branches of plasmon modes, the optical plasmon mode and the acoustic plasmon mode. The characteristics of these two modes, such as mode pattern, effective mode index and propagation loss, are analyzed. The modal behaviors can be effectively tuned by changing the distance between two graphene layers, the chemical potential of graphene and the permittivity of interlayer dielectric. Importantly, the breakup of tradeoff between mode confinement and propagation loss is discovered in the distance-dependent modal behavior, which originates from the unique dispersion properties of a double-layer graphene system. As a consequence, both strong mode confinement and longer propagation length can be achieved. Our results may provide good opportunities for developing applications based on graphene plasmonics in circular cylindrical structure.

Coherent and Tunable Terahertz Radiation from Graphene Surface Plasmon Polarirons Excited by Cyclotron Electron Beam.

Terahertz (THz) radiation can revolutionize modern science and technology. To this date, it remains big challenges to develop intense, coherent and tunable THz radiation sources that can cover the whole THz frequency region either by means of only electronics (both vacuum electronics and semiconductor electronics) or of only photonics (lasers, for example, quantum cascade laser). Here we present a mechanism which can overcome these difficulties in THz radiation generation. Due to the natural periodicity of 2π of both the circular cylindrical graphene structure and cyclotron electron beam (CEB), the surface plasmon polaritions (SPPs) dispersion can cross the light line of dielectric, making transformation of SPPs into radiation immediately possible. The dual natural periodicity also brings significant excellences to the excitation and the transformation. The fundamental and hybrid SPPs modes can be excited and transformed into radiation. The excited SPPs propagate along the cyclotron trajectory together with the beam and gain energy from the beam continuously. The radiation density is enhanced over 300 times, up to 10(5) W/cm(2). The radiation frequency can be widely tuned by adjusting the beam energy or chemical potential. This mechanism opens a way for developing desired THz radiation sources to cover the whole THz frequency regime.

Peptide-induced affinity binding of carbonic anhydrase to carbon nanotubes.

Although affinity binding between short chain peptides and carbon nanotube (CNT) has been reported, little is known for the study of proteins with CNT recognition and specific binding capabilities. Herein, carbonic anhydrase (CA) was functionalized via protein fusion with a single-walled carbon nanotube (SWNTs)-binding peptide, thereby forming a bioactive protein with high affinity binding capability. TEM and AFM analyses showed that the fusion CA could firmly coat to SWNTs with a surface coverage over 51%, while the enzyme maintained its catalytic activity. Structural analysis revealed that slight conformation changes were induced as a result of the fusion; however, the affinity binding of CA to the hydrophobic surface of SWNTs restored the native structure of the protein, with the conformation of the SWNT-bound CA largely resembling that of the native parent enzyme. Interfacial interactions between the fusion CA and SWNT were further investigated with Raman spectrometry and microscopic analysis. The results suggested that such peptide-induced CNT-protein binding allows the development of bioactive hybrid materials with the native structures of the protein moieties largely undisrupted.

Electron beam excitation of surface plasmon polaritons.

In this paper, the excitations of surface plasmon polaritons (SPPs) by both perpendicular and parallel electron beam are investigated. The results of analytical theory and numerical calculation show that the mechanisms of these two excitations are essentially different, and the behavior and properties of SPPs in metal structures strongly depend on the methods of excitation. For the perpendicular excitation, SPPs contain plenty of frequency components, propagate with attenuation and are always accompanied with the transition radiation. Whereas for parallel excitation, SPPs waves are coherent, tunable, propagating without attenuation and the transition radiation does not occur. We also show that there are two modes for the parallel excited SPPs on the metal films and they all can be excited efficiently by the parallel moving electron beam. And the operating frequency of SPPs can be tuned in a large frequency range by adjusting the beam energy.

Comparison of endoscopic papillary large balloon dilation and endoscopic sphincterotomy for retrieval of choledocholithiasis: a meta-analysis of randomized controlled trials.

BACKGROUND: Endoscopic sphincterotomy (EST) is the most frequently used technique for removal of stones from the bile duct. In recent years, endoscopic papillary large balloon dilation (EPLBD) has been shown to be a safe and effective technique for the removal of large or difficult common bile duct stones. However, comparison of EPLBD and EST for effectiveness in bile duct stone removal has given inconsistent results. The present meta-analysis was carried out to compare the effect of EPLBD and EST in retrieval of choledocholithiasis. METHODS: A literature search was performed using Medline, PubMed, EMBase and the Cochrane Central Register of Controlled Trials (CENTRAL) for relevant articles published in English. A meta-analysis was performed on the retrieved studies. RESULTS: Seven randomized controlled trials and 790 patients were involved. EPLBD compared with EST resulted in similar outcomes for overall successful clearance rates of bile duct stones (97.35 vs. 96.35%, OR 1.28, 95% CI 0.58-2.82, P = 0.54), stone clearance in the first ERCP session (87.87 vs. 84.15%, OR 1.31, 95% CI 0.81-2.11, P = 0.21) and removal of large sized stones (OR 1.08, 95% CI 0.21-5.64, P = 0.49). EPLBD performed with either a short or a long ballooning time did not increase the bile duct stone clearance rate. EPLBD decreased overall usage of mechanical lithotripsy in the bile duct stone removal process (OR 0.51, 95% CI 0.30-0.86, P = 0.01). However, no significant difference was found between EPLBD and EST in the use of mechanical lithotripsy for the removal of large sized stones (OR 0.67, 95% CI 0.34-1.28, P = 0.22). Compared with EST, EPLBD did not show a short ERCP duration (WMD -0.75, 95% CI -1.57 to 0.08, P = 0.08). EPLBD was associated with fewer overall complications than EST (5.8 vs. 13.1%, OR 0.41, 95% CI 0.24-0.68, P = 0.0007). Hemorrhage occurred less frequently with EPLBD than with EST (OR 0.15, 95% CI 0.04-0.50, P = 0.002). There was no significant difference in post-ERCP pancreatitis, perforation and cholangitis. CONCLUSIONS: EPLBD is an effective and safe method for the removal of large or difficult common bile stones. EPLBD should be considered as an alternative to EST for patients in whom EST could not be routinely performed. Based on EPLBD causing fewer cases of hemorrhaging, EPLBD is also recommended for removal of large or difficult common bile duct stones in patients with an underlying coagulopathy or need for anticoagulation following ERCP. The long-term prognosis of EPLBD need to be further investigated.