Sequence classification facilitates a fundamental understanding of the structure of microbial communities. Binary metagenomic sequence classifiers are insufficient because environmental metagenomes are typically derived from multiple sequence sources. Here we introduce a deep-learning based sequence classifier, DeepMicroClass, that classifies metagenomic contigs into five sequence classes, i.e. viruses infecting prokaryotic or eukaryotic hosts, eukaryotic or prokaryotic chromosomes, and prokaryotic plasmids. DeepMicroClass achieved high performance for all sequence classes at various tested sequence lengths ranging from 500 bp to 100 kbps. By benchmarking on a synthetic dataset with variable sequence class composition, we showed that DeepMicroClass obtained better performance for eukaryotic, plasmid and viral contig classification than other state-of-the-art predictors. DeepMicroClass achieved comparable performance on viral sequence classification with geNomad and VirSorter2 when benchmarked on the CAMI II marine dataset. Using a coastal daily time-series metagenomic dataset as a case study, we showed that microbial eukaryotes and prokaryotic viruses are integral to microbial communities. By analyzing monthly metagenomes collected at HOT and BATS, we found relatively higher viral read proportions in the subsurface layer in late summer, consistent with the seasonal viral infection patterns prevalent in these areas. We expect DeepMicroClass will promote metagenomic studies of under-appreciated sequence types.
Peptidyl arginine deiminase 4 (PAD4) plays a pivotal role in infection and inflammatory diseases by facilitating the formation of neutrophil extracellular traps (NETs). However, the substrates of PAD4 and its exact role in inflammatory bowel disease (IBD) remain unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) and substrate citrullination mapping to decipher the role of PAD4 in intestinal inflammation associated with IBD. Our results demonstrated that PAD4 deficiency alleviated colonic inflammation and restored intestinal barrier function in a dextran sulfate sodium (DSS)-induced colitis mouse model. scRNA-seq analysis revealed significant alterations in intestinal cell populations, with reduced neutrophil numbers and changes in epithelial subsets upon PAD4 deletion. Gene expression analysis highlighted pathways related to inflammation and epithelial cell function. Furthermore, we found that neutrophil-derived extracellular vesicles (EVs) carrying PAD4 were secreted into intestinal epithelial cells (IECs). Within IECs, PAD4 citrullinates mitochondrial creatine kinase 1 (CKMT1) at the R242 site, leading to reduced CKMT1 protein stability via the autophagy pathway. This action compromises mitochondrial homeostasis, impairs intestinal barrier integrity, and induces IECs apoptosis. IEC-specific depletion of CKMT1 exacerbated intestinal inflammation and apoptosis in mice with colitis. Clinical analysis of IBD patients revealed elevated levels of PAD4, increased CKMT1 citrullination, and decreased CKMT1 expression. In summary, our findings highlight the crucial role of PAD4 in IBD, where it modulates IECs plasticity via CKMT1 citrullination, suggesting that PAD4 may be a potential therapeutic target for IBD.
AIM: Increased corpus cavernosum smooth muscle cells (CCSMCs) apoptosis in the penis due to cavernous nerve injury (CNI) is a crucial contributor to erectile dysfunction (ED). Caveolin-1 scaffolding domain (CSD)-derived peptide has been found to exert potential antiapoptotic properties. However, whether CSD peptide can alleviate CCSMCs apoptosis and ED in CNI rats remains unknown. The study aimed to determine whether CSD peptide can improve bilateral CNI-induced ED (BCNI-ED) by enhancing the antiapoptotic processes of CCSMCs. MAIN METHODS: Fifteen 10-week-old male Sprague-Dawley (SD) rats were randomly classified into three groups: sham surgery (Sham) group and BCNI groups that underwent saline or CSD peptide treatment respectively. At 3 weeks postoperatively, erectile function was assessed and the penis tissue was histologically examined. Furthermore, an in vitro model of CCSMCs apoptosis was established using transforming growth factor-beta 1 (TGF-ß1) to investigate the mechanism of CSD peptide in treating BCNI-ED. KEY FINDINGS: In BCNI rats, CSD peptide significantly prevented ED and decreased oxidative stress, the Bax/Bcl-2 ratio, and the levels of caspase3. TGF-ß1-treated CCSMCs exhibited severe oxidative stress, mitochondrial dysfunction, and apoptosis. However, CSD peptide partially reversed these alterations. SIGNIFICANCE: Exogenous CSD peptide could improve BCNI-ED by inhibiting oxidative stress, the Bax/Bcl-2 ratio, and caspase3 expression in penile tissue. The underlying mechanism might involve the regulatory effects of CSD peptide on oxidative stress, mitochondrial dysfunction, and apoptosis of CCSMCs following CNI. This study highlights CSD peptide as an effective therapy for post-radical prostatectomy ED (pRP-ED).
The prediction of affinity between TCRs and peptides is crucial for the further development of TIL (Tumor-Infiltrating Lymphocytes) immunotherapy. Inspired by the broader research of drug-protein interaction (DPI), we propose an atom-level peptide-TCR interaction (PTI) affinity prediction model APTAnet using natural language processing methods. APTAnet model achieved an average ROC-AUC and PR-AUC of 0.893 and 0.877, respectively, in ten-fold cross-validation on 25,675 pairs of PTI data. Furthermore, experimental results on an independent test set from the McPAS database showed that APTAnet outperformed the current mainstream models. Finally, through the validation on 11 cases of real tumor patient data, we found that the APTAnet model can effectively identify tumor peptides and screen tumor-specific TCRs.
Cuprous thiocyanate (CuSCN) emerges as a prime candidate among inorganic hole-transport materials, particularly suitable for the fabrication of perovskite solar cells. Nonetheless, there is an Ohmic contact degradation between the perovskite and CuSCN layers. This is induced by polar solvents and undesired purities, which reduce device efficiency and operational stability. In this work, we introduce amidinothiourea (ASU) as an intermediate layer between perovskites and CuSCN to overcome the above obstacles. The characterization results confirm that ASU-modified perovskites have eliminated trap-induced defects by strong chemical bonding between -NH- and CâS from ASU and under-coordinated ions in perovskites. The interfacial engineering based on the ASU also reduces the potential barrier between the perovskite and CuSCN layers. The ASU-treated perovskite solar cells (PSC) with a gold electrode obtains an improved power conversion efficiency (PCE) from 16.36 to 18.03%. Furthermore, after being stored for 1800 h in ambient air (relative humidity (RH) = 45%), the related device without encapsulation maintains over 90% of its initial efficiency. The further combination of ASU and carbon-tape electrodes demonstrates its potential to fabricate low-cost but stable carbon-based PSCs. This work finds a universal approach for the fabrication of efficient and stable PSCs with different device structures.
Developing cost-effective and sustainable catalysts with exceptional activity and selectivity is essential for the practical implementation of on-site H2O2 electrosynthesis, yet it remains a formidable challenge. Metal phosphide core-shell heterostructures anchored in carbon nanosheets (denoted as Ni@Ni2P/C NSs) are designed and synthesized via carbonization and phosphidation of the 2D Ni-BDC precursor. This core-shell nanostructure provides more accessible active sites and enhanced durability, while the 2D carbon nanosheet substrate prevents heterostructure aggregation and facilitates mass transfer. Theoretical calculations further reveal that the Ni/Ni2P heterostructure-induced optimization of geometric and electronic structures enables the favored adsorption of OOH* intermediate. All these features endow the Ni@Ni2P/C NSs with remarkable performance in 2e ORR for H2O2 synthesis, achieving a top yield rate of 95.6 mg L-1 h-1 with both selectivity and Faradaic efficiency exceeding 90% under a wide range of applied potentials. Furthermore, when utilized as the anode of an assembled gas diffusion electrode (GDE) device, the Ni@Ni2P/C NSs achieve in situ H2O2 production with excellent long-term durability (>32 h). Evidently, this work provides a unique insight into the origin of 2e ORR and proposes optimization of H2O2 production through nano-interface manipulation.
Dihydromyricetin (DHM) is a natural flavonoid compound with multiple antitumour effects, including inhibition of proliferation, promotion of apoptosis, inhibition of invasion and migration, clearance of reactive oxygen species (ROS) and induction of autophagy. For example, DHM can effectively block the progression of the tumour cell cycle and inhibit cell proliferation. In different types of cancer cells, DHM can regulate the PI3K/Akt pathway, mTOR, and NF-κB pathway components, such as p53, and endoplasmic reticulum stress can alter the accumulation of ROS or induce autophagy to promote the apoptosis of tumour cells. In addition, when DHM is used in combination with various known chemotherapy drugs, such as paclitaxel, nedaplatin, doxorubicin, oxaliplatin and vinblastine, it can increase the sensitivity of tumour cells to DHM and increase the therapeutic effect of chemotherapy drugs. In the present review, the multiple molecular and cellular mechanisms underlying the antitumour effect of DHM, as well as its ability to increase the effects of various traditional antitumour drugs were summarized. Through the present review, it is expected by the authors to draw attention to the potential of DHM as an antitumour drug and provide valuable references for the clinical translation of DHM research and the development of related treatment strategies.
Objective: To introduce a locating device for the entry point of intramedullary nail based on the inertial navigation technology, which utilizes multi-dimensional angle information to assist in rapid and accurate positioning of the ideal direction of femoral anterograde intramedullary nails' entry point, and to verify its clinical value through clinical tests. Methods: After matching the locating module with the developing board, which are the two components of the locating device, they were placed on the skin surface of the proximal femur of the affected side. Anteroposterior fluoroscopy was performed. The developing angle corresponding to the ideal direction of entry point was selected based on the X-ray image, and then the yaw angle of the locating module was reset to zero. After resetting, the locating module was combined with the surgical instrument to guide the insertion angle of the guide wire. The ideal direction of entry point was accurately located based on the angle guidance. By setting up an experimental group and a control group for clinical surgical operations, the number of guide wire insertion times, surgical time, fluoroscopy frequency, and intraoperative blood loss with or without the locating device was recorded. Results: Compared to the control group, the experimental group showed significant improvement in the number of guide wire insertion times, surgical time, fluoroscopy frequency, and intraoperative blood loss, with a statistically significant difference (P<0.01). Conclusion: The locating device can assist doctors in quickly locating the entry point of intramedullary nail, effectively reducing the fluoroscopy frequency and surgical time by improving the success rate of the guide wire insertion with one shot, improving surgical efficiency, and possessing certain clinical value.
Fracture Fixation, Intramedullary , Surgery, Computer-Assisted , Humans , Bone Nails , Blood Loss, Surgical , Fluoroscopy/methods , Fracture Fixation, Intramedullary/methods , Surgery, Computer-Assisted/methods
Tuning the interfacial Schottky barrier with van der Waals (vdW) contacts is an important solution for two-dimensional (2D) electronics. Here we report that the interlayer dipoles of 2D vdW superlattices (vdWSLs) can be used to engineer vdW contacts to 2D semiconductors. A bipolar WSe2 with Ba6Ta11S28 (BTS) vdW contact was employed to exhibit this strategy. Strong interlayer dipoles can be formed due to charge transfer between the Ba3TaS5 and TaS2 layers. Mechanical exfoliation breaks the superlattice and produces two distinguished surfaces with TaS2 and Ba3TaS5 terminations. The surfaces thus have opposite surface dipoles and consequently different work functions. Therefore, all the devices fall into two categories in accordance with the rectifying direction, which were verified by electrical measurements and scanning photocurrent microscopy. The growing vdWSL family along with the addition surface dipoles enables prospective vdW contact designs and have practical application in nanoelectronics and nano optoelectronics.
Tuberculosis (TB) remains a prevalent global infectious disease caused by genetically closely related tubercle bacilli in Mycobacterium tuberculosis complex (MTBC). For a century, the Bacillus Calmette-Guérin (BCG) vaccine has been the primary preventive measure against TB. While it effectively protects against extrapulmonary forms of pediatric TB, it lacks consistent efficacy in providing protection against pulmonary TB in adults. Consequently, the exploration and development of novel TB vaccines, capable of providing broad protection to populations, have consistently constituted a prominent area of interest in medical research. This article presents a concise overview of the novel TB vaccines currently undergoing clinical trials, discussing their classification, protective efficacy, immunogenicity, advantages, and limitations. In vaccine development, the careful selection of antigens that can induce strong and diverse specific immune responses is essential. Therefore, we have summarized the molecular characteristics, biological function, immunogenicity, and relevant studies associated with the chosen antigens for TB vaccines. These insights gained from vaccines and immunogenic proteins will inform the development of novel mycobacterial vaccines, particularly mRNA vaccines, for effective TB control.
Industrial-level hydrogen production from the water electrolysis requires reducing the overpotential (η) as much as possible at high current density, which is closely related to intrinsic activity of the electrocatalysts. Herein, A-site cation deficiency engineering is proposed to screen high-performance catalysts, demonstrating effective Pr0.5- xLa0.5BaCo2O5+ δ (P0.5- xLBC) perovskites toward alkaline hydrogen evolution reaction (HER). Among all perovskite compositions, Pr0.4La0.5BaCo2O5+ δ (P0.4LBC) exhibits superior HER performance along with unique operating stability at large current densities (J = 500-2000 mA cm-2 geo). The overpotential of ≈636 mV is achieved in P0.4LBC at 2000 mA cm-2 geo, which outperforms commercial Pt/C benchmark (≈974 mV). Furthermore, the Tafel slope of P0.4LBC (34.1 mV dec-1) is close to that of Pt/C (35.6 mV dec-1), reflecting fast HER kinetics on the P0.4LBC catalyst. Combined with experimental and theoretical results, such catalytic activity may benefit from enhanced electrical conductivity, enlarged Co-O covalency, and decreased desorption energy of H* species. This results highlight effective A-site cation-deficient strategy for promoting electrochemical properties of perovskites, highlighting potential water electrolysis at ampere-level current density.
The recognition of cytosolic nucleic acid triggers the DNA/RNA sensor-IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingly, indomethacin also prohibits the nuclear translocation of IRF3 following cytosolic nucleic acid recognition. Importantly, in cell lines and a mouse model of Aicardi-Goutières syndrome, indomethacin administration blunts self-DNA-induced autoimmune responses. Thus, our study reveals a previously unknown function of indomethacin and provides a potential treatment for cytosolic nucleic acid-stimulated autoimmunity.
Background: Bridging repair has emerged as a promising and reliable treatment strategy for the massive rotator cuff tears (MRCTs). However, there remains a lack of evidence on which bridging graft provides the better repair results, and a dearth of animal studies comparing bridging repairs with different grafts. The purpose of this study was to evaluate the histological and biomechanical outcomes of commonly used grafts (autologous fascia lata (FL), acellular dermal matrix graft (ADM), and polyethylene terephthalate (PET) patch). Methods: A total of 66 male New Zealand White Rabbits were used to mimic a model of unilateral chronic MRCTs. The rabbits were randomly divided into three groups: (1) FL group, which underwent bridging repair with autologous FL; (2) ADM group, which underwent bridging with ADM; and (3) PET group, which underwent bridging with PET patch. Tissue samples were collected and subjected to histological analysis using Hematoxylin and eosin, Picrosirius red, Safranin O/Fast green staining, and Immunostaining. Collagen diameter and fibril density in the regenerated tendon was analyzed with transmission electron microscopy (TEM). Additionally, biomechanical tests were performed at 6 and 12 weeks after repair. Results: The regenerated tendon successfully reattached to the footprint in all experimental groups. At 6 weeks after repair, the FL group had a significantly higher Modified Tendon Histological Evaluation (MTHE) score at the regenerated tendon than the PET group (13.2 ± 1.64 vs 9.6 ± 1.95, respectively; P = 0.038). The picrosirius red staining results showed that the FL group had a significantly higher type I collagen content than the ADM and PET groups at 6 weeks, and this difference was sustained with the PET group at 12 weeks (P < 0.05). Immunofluorescence analysis against CD68 indicated that the number of macrophage infiltrates was significantly lower in the FL group than in the ADM and PET groups (P < 0.05). At 12 weeks after repair, the area of Safranin O metachromasia was significant greater in ADM group than that in the PET group (P = 0.01). The FL group showed a significantly larger collagen diameter in the regenerated tendon than the PET group (P < 0.05), as indicated by TEM results. Furthermore, the FL group resulted in a greater failure load (at 6 weeks; 118.40 ± 16.70 N vs 93.75 ± 9.06 N, respectively; P = 0.019) and elastic modulus (at 6 weeks; 12.28 ± 1.94 MPa vs 9.58 ± 0.79 MPa, respectively; P = 0.024; at 12 weeks; 15.02 ± 2.36 MPa vs 11.63 ± 1.20 MPa, respectively; P = 0.032) than the ADM group. Conclusions: This study demonstrated that all three grafts could successfully bridging chronic MRCTs in a rabbit model. However, autologous FL promoted tendon regeneration and maturation, and enhanced the tensile properties of the tendon-to-bone complex when compared with ADM and PET grafts.
Conventional plate electrodes were commonly used in electrochemical flow injection analysis and only part of molecules diffused to the plane of electrodes could be detected, which would limit the performance of electrochemical detection. In this study, a low-cost native stainless steel wire mesh (SSWM) electrode was integrated into a 3D-printed device for electrochemical flow injection analysis with a pass-through mode, which is different compared with previous flow-through mode. This strategy was applied for sensitive analysis of hydrogen peroxide (H2O2) released from cells. Under the optimal conditions (the applied potentials, the flow rate and the sample volume), the device exhibits high sensitivity toward H2O2. Linear relationships could be achieved between electrochemical responses and the concentration of H2O2 ranging from 1 nM to 1 mM. The excellent analytical performance of the SSWM-based device could be attributed to the pass-through mode based on the mesh microstructure and intrinsic catalytic properties for H2O2 by stainless steel. This approach could be further successfully extended for screening of H2O2 released from HeLa cells with electrochemical responses linear to the number of cells in a range of 3 - 1.35 × 104 cells with an injection volume of 30 µL. This study revealed the potential of mesh electrodes in electrochemical flow injection analysis for cellular function and pathology and its possible extension in cell counting and on-line analysis.
Flow Injection Analysis , Hydrogen Peroxide , Humans , HeLa Cells , Hydrogen Peroxide/analysis , Stainless Steel , Electrochemical Techniques , Electrodes
The discovery of room-temperature ferromagnetism in van der Waals (vdW) materials opens new avenues for exploring low-dimensional magnetism and its applications in spintronics. Recently, the observation of the room-temperature topological Hall effect in the vdW ferromagnet Fe3GaTe2 suggests the possible existence of room-temperature skyrmions, yet skyrmions have not been directly observed. In this study, real-space imaging was employed to investigate the domain evolution of the labyrinth and skyrmion structure. First, Néel-type skyrmions can be created at room temperature. In addition, the influence of flake thickness and external magnetic field (during field cooling) on both labyrinth domains and the skyrmion lattice is unveiled. Due to the competition between magnetic anisotropy and dipole interactions, the specimen thickness significantly influences the density of skyrmions. These findings demonstrate that Fe3GaTe2 can host room-temperature skyrmions of various sizes, opening up avenues for further study of magnetic topological textures at room temperature.
ABSTRACT: Multiple myeloma (MM) cells are addicted to MYC and its direct transactivation targets IRF4 for proliferation and survival. MYC and IRF4 are still considered "undruggable," as most small-molecule inhibitors suffer from low potency, suboptimal pharmacokinetic properties, and undesirable off-target effects. Indirect inhibition of MYC/IRF4 emerges as a therapeutic vulnerability in MM. Here, we uncovered an unappreciated tumor-suppressive role of C-terminal binding protein 2 (CTBP2) in MM via strong inhibition of the MYC-IRF4 axis. In contrast to epithelial cancers, CTBP2 is frequently downregulated in MM, in association with shortened survival, hyperproliferative features, and adverse clinical outcomes. Restoration of CTBP2 exhibited potent antitumor effects against MM in vitro and in vivo, with marked repression of the MYC-IRF4 network genes. Mechanistically, CTBP2 impeded the transcription of MYC and IRF4 by histone H3 lysine 27 deacetylation (H3K27ac) and indirectly via activation of the MYC repressor IFIT3. In addition, activation of the interferon gene signature by CTBP2 suggested its concomitant immunomodulatory role in MM. Epigenetic studies have revealed the contribution of polycomb-mediated silencing and DNA methylation to CTBP2 inactivation in MM. Notably, inhibitors of Enhance of zeste homolog 2, histone deacetylase, and DNA methyltransferase, currently under evaluation in clinical trials, were effective in restoring CTBP2 expression in MM. Our findings indicated that the loss of CTBP2 plays an essential role in myelomagenesis and deciphers an additional mechanistic link to MYC-IRF4 dysregulation in MM. We envision that the identification of novel critical regulators will facilitate the development of selective and effective approaches for treating this MYC/IRF4-addicted malignancy.
Alcohol Oxidoreductases , Interferon Regulatory Factors , Multiple Myeloma , Proto-Oncogene Proteins c-myc , Multiple Myeloma/metabolism , Multiple Myeloma/drug therapy , Multiple Myeloma/pathology , Humans , Interferon Regulatory Factors/metabolism , Interferon Regulatory Factors/genetics , Proto-Oncogene Proteins c-myc/metabolism , Mice , Animals , Alcohol Oxidoreductases/metabolism , Alcohol Oxidoreductases/antagonists & inhibitors , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , Tumor Suppressor Proteins/metabolism , Signal Transduction/drug effects
Central nervous system lymphoma (CNSL) is a type of hematological tumor. Treatment of CNSL is difficult due to the existence of the blood-brain barrier (BBB). Here, we used exosomes (Exos), a type of extracellular vesicle, and iRGD to construct a new drug carrier system and use it to load doxorubicin (DOX). The results of in vitro and in vivo experiments showed that the iRGD-Exo-DOX system can efficiently and securely transport DOX through the BBB and target tumor cells. The results suggest that iRGD-Exo-DOX may cross the BBB through brain microvascular endothelial cell-mediated endocytosis. Together, our study indicates an impactful treatment of central nervous system tumors.
Central Nervous System Neoplasms , Lymphoma , Humans , Blood-Brain Barrier , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Drug Carriers , Central Nervous System Neoplasms/drug therapy , Lymphoma/drug therapy , Cell Line, Tumor
The presence of endotoxemia is strongly linked to the development of endothelial dysfunction and disruption of myocardial microvascular reactivity. These factors play a crucial role in the progression of endotoxemic cardiomyopathy. Sepsis-related multiorgan damage involves the participation of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). However, whether DNA-PKcs contributes to endothelial dysfunction and myocardial microvascular dysfunction during endotoxemia remains unclear. Hence, we conducted experiments in mice subjected to lipopolysaccharide (LPS)-induced endotoxemic cardiomyopathy, as well as assays in primary mouse cardiac microvascular endothelial cells. Results showed that endothelial-cell-specific DNA-PKcs ablation markedly attenuated DNA damage, sustained microvessel perfusion, improved endothelial barrier function, inhibited capillary inflammation, restored endothelium-dependent vasodilation, and improved heart function under endotoxemic conditions. Furthermore, we show that upon LPS stress, DNA-PKcs recognizes a TQ motif in cofilin2 and consequently induces its phosphorylation at Thr25. Phosphorylated cofilin2 shows increased affinity for F-actin and promotes F-actin depolymerization, resulting into disruption of the endothelial barrier integrity, microvascular inflammation, and defective eNOS-dependent vasodilation. Accordingly, cofilin2-knockin mice expressing a phospho-defective (T25A) cofilin2 mutant protein showed improved endothelial integrity and myocardial microvascular function upon induction of endotoxemic cardiomyopathy. These findings highlight a novel mechanism whereby DNA-PKcs mediates cofilin2Thr25 phosphorylation and subsequent F-actin depolymerization to contribute to endotoxemia-related cardiac microvascular dysfunction.
OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.
Capsule Endoscopy , Esophageal and Gastric Varices , Varicose Veins , Adult , Humans , Esophageal and Gastric Varices/diagnosis , Esophageal and Gastric Varices/etiology , Liver Cirrhosis/complications , Prospective Studies
