Exhausted intratumoral Vδ2- γδ T cells in human kidney cancer retain effector function.

Gamma delta (γδ) T cells reside within human tissues including tumors, but their function in mediating antitumor responses to immune checkpoint inhibition is unknown. Here we show that kidney cancers are infiltrated by Vδ2- γδ T cells, with equivalent representation of Vδ1+ and Vδ1- cells, that are distinct from γδ T cells found in normal human tissues. These tumor-resident Vδ2- T cells can express the transcriptional program of exhausted αß CD8+ T cells as well as canonical markers of terminal T-cell exhaustion including PD-1, TIGIT and TIM-3. Although Vδ2- γδ T cells have reduced IL-2 production, they retain expression of cytolytic effector molecules and co-stimulatory receptors such as 4-1BB. Exhausted Vδ2- γδ T cells are composed of three distinct populations that lack TCF7, are clonally expanded and express cytotoxic molecules and multiple Vδ2- T-cell receptors. Human tumor-derived Vδ2- γδ T cells maintain cytotoxic function and pro-inflammatory cytokine secretion in vitro. The transcriptional program of Vδ2- T cells in pretreatment tumor biopsies was used to predict subsequent clinical responses to PD-1 blockade in patients with cancer. Thus, Vδ2- γδ T cells within the tumor microenvironment can contribute to antitumor efficacy.

A ring-like accretion structure in M87 connecting its black hole and jet.

The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation1,2. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of [Formula: see text] Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at 3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring indicates a substantial contribution from the accretion flow with absorption effects, in addition to the gravitationally lensed ring-like emission. The images show that the edge-brightened jet connects to the accretion flow of the black hole. Close to the black hole, the emission profile of the jet-launching region is wider than the expected profile of a black-hole-driven jet, suggesting the possible presence of a wind associated with the accretion flow.

Innovative ochre processing and tool use in China 40,000 years ago.

Homo sapiens was present in northern Asia by around 40,000 years ago, having replaced archaic populations across Eurasia after episodes of earlier population expansions and interbreeding1-4. Cultural adaptations of the last Neanderthals, the Denisovans and the incoming populations of H. sapiens into Asia remain unknown1,5-7. Here we describe Xiamabei, a well-preserved, approximately 40,000-year-old archaeological site in northern China, which includes the earliest known ochre-processing feature in east Asia, a distinctive miniaturized lithic assemblage with bladelet-like tools bearing traces of hafting, and a bone tool. The cultural assembly of traits at Xiamabei is unique for Eastern Asia and does not correspond with those found at other archaeological site assemblages inhabited by archaic populations or those generally associated with the expansion of H. sapiens, such as the Initial Upper Palaeolithic8-10. The record of northern Asia supports a process of technological innovations and cultural diversification emerging in a period of hominin hybridization and admixture2,3,6,11.

InDEP: an interpretable machine learning approach to predict cancer driver genes from multi-omics data.

Cancer driver genes are critical in driving tumor cell growth, and precisely identifying these genes is crucial in advancing our understanding of cancer pathogenesis and developing targeted cancer drugs. Despite the current methods for discovering cancer driver genes that mainly rely on integrating multi-omics data, many existing models are overly complex, and it is difficult to interpret the results accurately. This study aims to address this issue by introducing InDEP, an interpretable machine learning framework based on cascade forests. InDEP is designed with easy-to-interpret features, cascade forests based on decision trees and a KernelSHAP module that enables fine-grained post-hoc interpretation. Integrating multi-omics data, InDEP can identify essential features of classified driver genes at both the gene and cancer-type levels. The framework accurately identifies driver genes, discovers new patterns that make genes as driver genes and refines the cancer driver gene catalog. In comparison with state-of-the-art methods, InDEP proved to be more accurate on the test set and identified reliable candidate driver genes. Mutational features were the primary drivers for InDEP's identifying driver genes, with other omics features also contributing. At the gene level, the framework concluded that substitution-type mutations were the main reason most genes were identified as driver genes. InDEP's ability to identify reliable candidate driver genes opens up new avenues for precision oncology and discovering new biomedical knowledge. This framework can help advance cancer research by providing an interpretable method for identifying cancer driver genes and their contribution to cancer pathogenesis, facilitating the development of targeted cancer drugs.

From multi-omics data to the cancer druggable gene discovery: a novel machine learning-based approach.

The development of targeted drugs allows precision medicine in cancer treatment and optimal targeted therapies. Accurate identification of cancer druggable genes helps strengthen the understanding of targeted cancer therapy and promotes precise cancer treatment. However, rare cancer-druggable genes have been found due to the multi-omics data's diversity and complexity. This study proposes deep forest for cancer druggable genes discovery (DF-CAGE), a novel machine learning-based method for cancer-druggable gene discovery. DF-CAGE integrated the somatic mutations, copy number variants, DNA methylation and RNA-Seq data across ˜10 000 TCGA profiles to identify the landscape of the cancer-druggable genes. We found that DF-CAGE discovers the commonalities of currently known cancer-druggable genes from the perspective of multi-omics data and achieved excellent performance on OncoKB, Target and Drugbank data sets. Among the ˜20 000 protein-coding genes, DF-CAGE pinpointed 465 potential cancer-druggable genes. We found that the candidate cancer druggable genes (CDG) are clinically meaningful and divided the CDG into known, reliable and potential gene sets. Finally, we analyzed the omics data's contribution to identifying druggable genes. We found that DF-CAGE reports druggable genes mainly based on the copy number variations (CNVs) data, the gene rearrangements and the mutation rates in the population. These findings may enlighten the future study and development of new drugs.

Intestinal Lymphatic Dysfunction in Kidney Disease.

Kidney disease is associated with adverse consequences in many organs beyond the kidney, including the heart, lungs, brain, and intestines. The kidney-intestinal cross talk involves intestinal epithelial damage, dysbiosis, and generation of uremic toxins. Recent studies reveal that kidney injury expands the intestinal lymphatics, increases lymphatic flow, and alters the composition of mesenteric lymph. The intestinal lymphatics, like blood vessels, are a route for transporting potentially harmful substances generated by the intestines. The lymphatic architecture and actions are uniquely suited to take up and transport large macromolecules, functions that differentiate them from blood vessels, allowing them to play a distinct role in a variety of physiological and pathological processes. Here, we focus on the mechanisms by which kidney diseases result in deleterious changes in intestinal lymphatics and consider a novel paradigm of a vicious cycle of detrimental organ cross talk. This concept involves kidney injury-induced modulation of intestinal lymphatics that promotes production and distribution of harmful factors, which in turn contributes to disease progression in distant organ systems.

Supramolecular cage-mediated cargo transport.

A steady stream of material transport based on carriers and channels in living systems plays an extremely important role in normal life activities. Inspired by nature, researchers have extensively applied supramolecular cages in cargo transport because of their unique three-dimensional structures and excellent physicochemical properties. In this review, we will focus on the development of supramolecular cages as carriers and channels for cargo transport in abiotic and biological systems over the past fifteen years. In addition, we will discuss future challenges and potential applications of supramolecular cages in substance transport.

Effects of Dipeptidyl Peptidase-4 Inhibitor and Angiotensin-Converting Enzyme Inhibitor on Experimental Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease in the United States and worldwide. Proteinuria is a major marker of the severity of injury. Dipeptidyl peptidase-4 inhibitor (DPP-4I) increases incretin-related insulin production and is, therefore, used to treat diabetes. We investigated whether DPP4I could have direct effect on kidney independent of its hypoglycemic activity. We, therefore, tested the effects of DPP4I with or without angiotensin-converting enzyme inhibitor (ACEI) on the progression of diabetic nephropathy and albuminuria in a murine model of DKD. eNOS-/-db/db mice were randomized to the following groups at age 10 weeks and treated until sacrifice: baseline (sacrificed at week 10), untreated control, ACEI, DPP4I, and combination of DPP4I and ACEI (Combo, sacrificed at week 18). Systemic parameters and urine albumin-creatinine ratio were assessed at baseline, weeks 14, and 18. Kidney morphology, glomerular filtration rate (GFR), WT-1, a marker for differentiated podocytes, podoplanin, a marker of foot process integrity, glomerular collagen IV, and alpha-smooth muscle actin were assessed at the end of the study. All mice had hyperglycemia and proteinuria at study entry at week 10. Untreated control mice had increased albuminuria, progression of glomerular injury, and reduced GFR at week 18 compared with baseline. DPP4I alone reduced blood glucose and kidney DPP-4 activity but failed to protect against kidney injury compared with untreated control. ACEI alone and combination groups showed significantly reduced albuminuria and glomerular injury, and maintained GFR and WT-1+ cells. Only the combination group had significantly less glomerular collagen IV deposition and more podoplanin preservation than the untreated control. DPP-4I alone does not decrease the progression of kidney injury in the eNOS-/-db/db mouse model, suggesting that targeting only hyperglycemia is not an optimal treatment strategy for DKD. Combined DPP-4I with ACEI added more benefit to reducing the glomerular matrix.

Inhibition of transcriptional coactivator YAP Impairs the expression and function of transcription factor WT1 in diabetic podocyte injury.

Podocyte injury and loss are hallmarks of diabetic nephropathy (DN). However, the molecular mechanisms underlying these phenomena remain poorly understood. YAP (Yes-associated protein) is an important transcriptional coactivator that binds with various other transcription factors, including the TEAD family members (nuclear effectors of the Hippo pathway), that regulate cell proliferation, differentiation, and apoptosis. The present study found an increase in YAP phosphorylation at S127 of YAP and a reduction of nuclear YAP localization in podocytes of diabetic mouse and human kidneys, suggesting dysregulation of YAP may play a role in diabetic podocyte injury. Tamoxifen-inducible podocyte-specific Yap gene knockout mice (YappodKO) exhibited accelerated and worsened diabetic kidney injury. YAP inactivation decreased transcription factor WT1 expression with subsequent reduction of Tead1 and other well-known targets of WT1 in diabetic podocytes. Thus, our study not only sheds light on the pathophysiological roles of the Hippo pathway in diabetic podocyte injury but may also lead to the development of new therapeutic strategies to prevent and/or treat DN by targeting the Hippo signaling pathway.

N-glycosylation Regulates Intrinsic IFN-γ Resistance in Colorectal Cancer: Implications for Immunotherapy.

BACKGROUND & AIMS: Advanced colorectal carcinoma (CRC) is characterized by a high frequency of primary immune evasion and refractoriness to immunotherapy. Given the importance of interferon (IFN)-γ in CRC immunosurveillance, we investigated whether and how acquired IFN-γ resistance in tumor cells would promote tumor growth, and whether IFN-γ sensitivity could be restored. METHODS: Spontaneous and colitis-associated CRC development was induced in mice with a specific IFN-γ pathway inhibition in intestinal epithelial cells. The influence of IFN-γ pathway gene status and expression on survival was assessed in patients with CRC. The mechanisms underlying IFN-γ resistance were investigated in CRC cell lines. RESULTS: The conditional knockout of the IFN-γ receptor in intestinal epithelial cells enhanced spontaneous and colitis-associated colon tumorigenesis in mice, and the loss of IFN-γ receptor α (IFNγRα) expression by tumor cells predicted poor prognosis in patients with CRC. IFNγRα expression was repressed in human CRC cells through changes in N-glycosylation, which decreased protein stability via proteasome-dependent degradation, inhibiting IFNγR-signaling. Downregulation of the bisecting N-acetylglucosaminyltransferase III (MGAT3) expression was associated with IFN-γ resistance in all IFN-γ-resistant cells, and highly correlated with low IFNγRα expression in CRC tissues. Both ectopic and pharmacological reconstitution of MGAT3 expression with all-trans retinoic acid increased bisecting N-glycosylation, as well as IFNγRα protein stability and signaling. CONCLUSIONS: Together, our results demonstrated that tumor-associated changes in N-glycosylation destabilize IFNγRα, causing IFN-γ resistance in CRC. IFN-γ sensitivity could be reestablished through the increase in MGAT3 expression, notably via all-trans retinoic acid treatment, providing new prospects for the treatment of immune-resistant CRC.

Chiral Brønsted Acid-Catalyzed Asymmetric Reaction via Vinylidene ortho-Quinone Methides.

Vinylidene ortho-quinone methides (VQMs) have been proven to be versatile and crucial intermediates in the catalytic asymmetric reaction in last decade, and thus have drawn considerable concentrations on account of the practical application in the construction of enantiomerically pure functional organic molecules. However, in comparison to the well established chiral Brønsted base-catalyzed asymmetric reaction via VQMs, chiral Brønsted acid-catalyzed reaction is rarely studied and there is no systematic summary to date. In this review, we summarize the recent advances in the chiral Brønsted acid-catalyzed asymmetric reaction via VQMs according to three types of reactions: a) intermolecular asymmetric nucleophilic addition to VQMs; b) intermolecular asymmetric cycloaddition of VQMs; c) intramolecular asymmetric cyclization of VQMs. Finally, we put forward the remained challenges and opportunities for potential breakthroughs in this area.

Faecalibacterium prausnitzii as a potential Antiatherosclerotic microbe.

BACKGROUND: The gut microbiota plays a crucial role in coronary artery disease (CAD) development, but limited attention has been given to the role of the microbiota in preventing this disease. This study aimed to identify key biomarkers using metagenomics and untargeted metabolomics and verify their associations with atherosclerosis. METHODS: A total of 371 participants, including individuals with various CAD types and CAD-free controls, were enrolled. Subsequently, significant markers were identified in the stool samples through gut metagenomic sequencing and untargeted metabolomics. In vivo and in vitro experiments were performed to investigate the mechanisms underlying the association between these markers and atherosclerosis. RESULTS: Faecal omics sequencing revealed that individuals with a substantial presence of Faecalibacterium prausnitzii had the lowest incidence of CAD across diverse CAD groups and control subjects. A random forest model confirmed the significant relationship between F. prausnitzii and CAD incidence. Notably, F. prausnitzii emerged as a robust, independent CAD predictor. Furthermore, our findings indicated the potential of the gut microbiota and gut metabolites to predict CAD occurrence and progression, potentially impacting amino acid and vitamin metabolism. F. prausnitzii mitigated inflammation and exhibited an antiatherosclerotic effect on ApoE-/- mice after gavage. This effect was attributed to reduced intestinal LPS synthesis and reinforced mechanical and mucosal barriers, leading to decreased plasma LPS levels and an antiatherosclerotic outcome. CONCLUSIONS: Sequencing of the samples revealed a previously unknown link between specific gut microbiota and atherosclerosis. Treatment with F. prausnitzii may help prevent CAD by inhibiting atherosclerosis.

Effect of Penetration Enhancer on the Structure of Stratum Corneum: On-Site Study by Confocal Polarized Raman Imaging.

Keratin and lipid structures in the stratum corneum (SC) are closely related to the SC barrier function. The application of penetration enhancers (PEs) disrupts the structure of SC, thereby promoting infiltration. To quantify these PE-induced structural changes in SC, we used confocal Raman imaging (CRI) and polarized Raman imaging (PRI) to explore the integrity and continuity of keratin and lipid structures in SC. The results showed that water is the safest PE and that oleic acid (OA), sodium dodecyl sulfate (SDS), and low molecular weight protamine (LMWP) disrupted the ordered structure of keratin, while azone and liposomes had less of an effect on keratin. Azone, OA, and SDS also led to significant changes in lipid structure, while LMWP and liposomes had less of an effect. Establishing this non-invasive and efficient strategy will provide new insights into transdermal drug delivery and skin health management.

Inflammatory cell death PANoptosis is induced by the anti-cancer curaxin CBL0137 via eliciting the assembly of ZBP1-associated PANoptosome.

OBJECTIVE: PANoptosis, a new form of regulated cell death, concomitantly manifests hallmarks for pyroptosis, apoptosis, and necroptosis. It has been usually observed in macrophages, a class of widely distributed innate immune cells in various tissues, upon pathogenic infections. The second-generation curaxin, CBL0137, can trigger necroptosis and apoptosis in cancer-associated fibroblasts. This study aimed to explore whether CBL0137 induces PANoptosis in macrophages in vitro and in mouse tissues in vivo. METHODS: Bone marrow-derived macrophages and J774A.1 cells were treated with CBL0137 or its combination with LPS for indicated time periods. Cell death was assayed by propidium iodide staining and immunoblotting. Immunofluorescence microscopy was used to detect cellular protein distribution. Mice were administered with CBL0137 plus LPS and their serum and tissues were collected for biochemical and histopathological analyses, respectively. RESULTS: The results showed that CBL0137 alone or in combination with LPS induced time- and dose-dependent cell death in macrophages, which was inhibited by a combination of multiple forms of cell death inhibitors but not each alone. This cell death was independent of NLRP3 expression. CBL0137 or CBL0137 + LPS-induced cell death was characterized by simultaneously increased hallmarks for pyroptosis, apoptosis and necroptosis, indicating that this is PANoptosis. Induction of PANoptosis was associated with Z-DNA formation in the nucleus and likely assembly of PANoptosome. ZBP1 was critical in mediating CBL0137 + LPS-induced cell death likely by sensing Z-DNA. Moreover, intraperitoneal administration of CBL0137 plus LPS induced systemic inflammatory responses and caused multi-organ (including the liver, kidney and lung) injury in mice due to induction of PANoptosis in these organs. CONCLUSIONS: CBL0137 alone or plus inflammatory stimulation induces PANoptosis both in vitro and in vivo, which is associated with systemic inflammatory responses in mice.

Metabolomics unveil key pathways underlying the synergistic activities of aztreonam and avibactam against multidrug-resistant Escherichia coli.

PURPOSE: Aztreonam/avibactam is effective against serious infections caused by Gram-negative bacteria including Enterobacterales harboring metallo-ß-lactamases. While the utility of this combination has been established in vitro and in clinical trials, the purpose of this study is to enhance our understanding of the underlying mechanism responsible for their activities through metabolomic profiling of a multidrug-resistant Escherichia coli clinical isolate. METHODS: Metabolomic analyses of time-dependent changes in endogenous bacterial metabolites in a clinical isolate of a multidrug-resistant E. coli treated with aztreonam and avibactam were performed. E. coli metabolomes were compared at 15 min, 1 h and 24 h following treatments with either avibactam (4 mg/L), aztreonam (4 mg/L), or aztreonam (4 mg/L) + avibactam (4 mg/L). RESULTS: Drug treatment affected 326 metabolites with magnitude changes of at least 2-fold, most of which are involved primarily in peptidoglycan biosynthesis, nucleotide metabolism, and lipid metabolism. The feedstocks for peptidoglycan synthesis were depleted by aztreonam/avibactam combination; a significant downstream increase in nucleotide metabolites and a release of lipids were observed at the three timepoints. CONCLUSION: The findings indicate that the aztreonam/avibactam combination accelerates structural damage to the bacterial membrane structure and their actions were immediate and sustained compared to aztreonam or avibactam alone. By inhibiting the production of crucial cell wall precursors, the combination may have inflicted damages on bacterial DNA.

A Visible Light Responsive Smart Covalent Organic Framework with a Bridged Azobenzene Backbone.

Condensation of 3,3'-diamino-2,2'-ethylene-bridged azobenzene with 1,2,4,5-tetrakis-(4-formylphenyl) benzene produces a visible light responsive porous 2D covalent organic framework, COF-bAzo-TFPB, with a large surface area, good crystallinity, and thermal and chemical stability. The results demonstrate that the elaborated designed linker can make azo unit on the COF-bAzo-TFPB skeleton undergo reversible photoisomerization. This work expands the application scope of covalent organic frameworks in photo-controlled release, uptake of guest molecules, dynamic photoswitching, and UV-sensitive functions.

Topological phases, local magnetic moments, and spin polarization triggered by C558-line defects in armchair graphene nanoribbons.

The topological and magnetic properties induced by topological defects in graphene have attracted attention. Here, we study a novel topological defect structure for graphene nanoribbons interspersed with C558-line defects along the armchair boundary, which possesses topological properties and is tritopic. Using strain engineering to regulate the magnitude of hopping at defects, the position of the energy level can be easily changed to achieve a topological phase transition. We also discuss the local magnetic moment and the ferromagnetic ground state in the context of line defects. This leads to spin polarization of the whole system. Finally, when C558 graphene nanoribbons are controlled by a nonlocal exchange magnetic field, spin-polarized quantum conductivity occurs near the Fermi level. Consequently, spin filtering can be achieved by varying the incident energy of the electrons. Our results provide new insights into realizing topological and spin electronics in low-dimensional quantum devices.

Adverse effects of acute tubular injury on the glomerulus: contributing factors and mechanisms.

The intricate relationship between tubular injury and glomerular dysfunction in kidney diseases has been a subject of extensive research. While the impact of glomerular injury on downstream tubules has been well-studied, the reverse influence of tubular injury on the glomerulus remains less explored. This paper provides a comprehensive review of recent advances in the field, focusing on key pathways and players implicated in the pathogenesis of tubular injury on glomerular dysfunction. Anatomical and physiological evidence supports the possibility of crosstalk from the tubule to the glomerulus, whereby various mechanisms contribute to glomerular injury following tubular injury. These mechanisms include tubular backleak, dysfunctional tubuloglomerular feedback, capillary rarefaction, atubular glomeruli, and the secretion of factors from damaged tubular epithelial cells. Clinical evidence further supports the association between even mild or recovered acute kidney injury and an increased risk of chronic kidney disease, including glomerular diseases. We also discuss potential therapeutic interventions aimed at mitigating acute tubular injury, thereby reducing the detrimental effects on glomerular function. By unraveling the complex interplay from tubular injury to glomerular dysfunction, we aim to provide insights that can enhance clinical management strategies and improve outcomes for patients with kidney disease.

Silencing EIF3A ameliorates pulmonary arterial hypertension through HDAC1 and PTEN/PI3K/AKT pathway in vitro and in vivo.

Pulmonary vascular remodeling caused by the excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) is the hallmark feature of pulmonary arterial hypertension (PAH). Eukaryotic initiation factor 3 subunit A (EIF3A) exhibited proliferative activity in multiple cell types. The present study investigated the role of EIF3A in the progression of PAH. A monocrotaline (MCT)-induced PAH rat model was constructed, and adeno-associated virus type 1 (AAV1) carrying EIF3A shRNA was intratracheally delivered to PAH rats to block EIF3A expression. PASMCs were isolated from rats and treated with PDGF-BB to simulate PASMC proliferation, and shRNA for EIF3 was conducted to investigate the mechanism behind the role of EIF3A in PASMC function in vitro. EIF3A expression was upregulated in pulmonary arteries, and EIF3A inhibition effectively improved pulmonary hypertension and right ventricular hypertrophy and suppressed MCT-induced vascular remodeling in vivo. In addition, we found that genetic knockdown of EIF3A reduced PDGF-triggered proliferation and arrested cell cycle, accompanied by downregulated proliferation-related protein expression in PASMCs. Mechanistically, the histone deacetylase 1 (HDAC1)-mediated PTEN/PI3K/AKT pathway was recognized as a primary mechanism in PAH progression. Silencing EIF3A decreased HDAC1 expression, and further inhibited the excessive proliferation of PASMCs by increasing the phosphatase and tension homolog (PTEN) expression and suppressing the AKT phosphorylation. Notably, HDAC1 expression reversed the effect of silencing EIF3A on PAH and PTEN/PI3K/AKT pathway. Collectively, silencing EIF3A improved PAH by decreasing PASMC proliferation through the HDAC1-mediated PTEN/PI3K/AKT pathway. These findings suggest that targeting EIF3A may represent a potential approach for the treatment of PAH.

A nomogram for prediction of ERCP success in patients with bile duct leaks: a multicenter study.

BACKGROUND: Bile duct leaks (BDLs) are serious complications that occurs after hepatobiliary surgery and trauma, leading to rapid clinical deterioration. Endoscopic retrograde cholangiopancreatography (ERCP) is the first-line treatment for BDLs, but it is not clear which patients will respond to this therapy and which patients will require additional surgical intervention. The aim of our study was to explore the predictors of successful ERCP for BDLs. METHODS: A retrospective analysis was conducted using data from six centers' databases. All consecutive patients who were clinically confirmed as BDLs were included in the study. Collected data were demographics, disease severity, and ERCP procedure characteristics. Univariate and multivariate analysis were used to select independent predictive factors that affect the outcome of ERCP for BDLs, and a nomogram was established. Calibration and ROC curves were used to evaluate the models. RESULTS: Four hundred and forty-eight consecutive patients were clinically confirmed as BDLs and 347 were excluded. In the 101 patients included patients, clinical success was achieved in 78 patients (77.2%). In logistic multivariable regression, two independent factors were negatively associated with the success of ERCP: SIRS (OR, 0.183; 95% CI 0.039-0.864; P = 0.032) and high-grade leak (OR 0.073; 95% CI 0.010-0.539; P = 0.010). Two independent factors were positively associated with the success of ERCP: leak-bridging drainage (OR 4.792; 95% CI 1.08-21.21; P = 0.039) and cystic duct leak (OR 6.193; 95% CI 1.03-37.17; P = 0.046). The prediction model with these four factors was evaluated using a receiver-operating characteristic (ROC) curve, which demonstrated an area under the curve of 0.9351. The calibration curve showed that the model had good predictive accuracy. CONCLUSION: Leak-bridging drainage and cystic duct leak are positive predictors for the success of ERCP, while SIRS and high-grade leak are negative predictors. This prediction model with nomogram has good predictive ability and practical clinical value, and may be helpful in clinical decision-making and prognostication.