Gut virome-wide association analysis identifies cross-population viral signatures for inflammatory bowel disease.

BACKGROUND: The gut virome has been implicated in inflammatory bowel disease (IBD), yet a full understanding of the gut virome in IBD patients, especially across diverse geographic populations, is lacking. RESULTS: In this study, we conducted a comprehensive gut virome-wide association study in a Chinese cohort of 71 IBD patients (15 with Crohn's disease and 56 with ulcerative colitis) and 77 healthy controls via viral-like particle (VLP) and bulk virome sequencing of their feces. By utilizing an integrated gut virus catalog tailored to the IBD virome, we revealed fundamental alterations in the gut virome in IBD patients. These characterized 139 differentially abundant viral signatures, including elevated phages predicted to infect Escherichia, Klebsiella, Enterococcus_B, Streptococcus, and Veillonella species, as well as IBD-depleted phages targeting Prevotella, Ruminococcus_E, Bifidobacterium, and Blautia species. Remarkably, these viral signatures demonstrated high consistency across diverse populations such as those in Europe and the USA, emphasizing their significance and broad relevance in the disease context. Furthermore, fecal virome transplantation experiments verified that the colonization of these IBD-characterized viruses can modulate experimental colitis in mouse models. CONCLUSIONS: Building upon these insights into the IBD gut virome, we identified potential biomarkers for prognosis and therapy in IBD patients, laying the foundation for further exploration of viromes in related conditions. Video Abstract.

Artificial intelligence-based automatic nidus segmentation of cerebral arteriovenous malformation on time-of-flight magnetic resonance angiography.

OBJECTIVE: Accurate nidus segmentation and quantification have long been challenging but important tasks in the clinical management of Cerebral Arteriovenous Malformation (CAVM). However, there are still dilemmas in nidus segmentation, such as difficulty defining the demarcation of the nidus, observer-dependent variation and time consumption. The aim of this study isto develop an artificial intelligence model to automatically segment the nidus on Time-Of-Flight Magnetic Resonance Angiography (TOF-MRA) images. METHODS: A total of 92patients with CAVM who underwent both TOF-MRA and DSA examinations were enrolled. Two neurosurgeonsmanually segmented the nidusonTOF-MRA images,which were regarded as theground-truth reference. AU-Net-basedAImodelwascreatedfor automatic nidus detectionand segmentationonTOF-MRA images. RESULTS: The meannidus volumes of the AI segmentationmodeland the ground truthwere 5.427 ± 4.996 and 4.824 ± 4.567 mL,respectively. The meandifference in the nidus volume between the two groups was0.603 ± 1.514 mL,which wasnot statisticallysignificant (P = 0.693). The DSC,precision and recallofthe testset were 0.754 ± 0.074, 0.713 ± 0.102 and 0.816 ± 0.098, respectively. The linear correlation coefficient of the nidus volume betweenthesetwo groupswas 0.988, p < 0.001. CONCLUSION: The performance of the AI segmentationmodel is moderate consistent with that of manual segmentation. This AI model has great potential in clinical settings, such as preoperative planning, treatment efficacy evaluation, riskstratification and follow-up.

Drug-eluting bead transarterial chemoembolization (DEB-TACE) versus conventional transarterial chemoembolization (cTACE) in colorectal liver metastasis: Efficacy, safety, and prognostic factors.

OBJECTIVE: To comparatively evaluate drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (cTACE) for efficacy, safety, and related prognostic factors in the treatment of colorectal liver metastasis (CRLM). MATERIALS AND METHODS: This study retrospectively analyzed 75 patients with CRLM-administered DEB-TACE (n = 36) or cTACE (n = 39) between January 2016 and December 2017. Local control, survival outcome, and complications were compared between the two groups. Univariate and multivariate analyses of prognostic factors affecting progression-free survival (PFS) and overall survival (OS) were performed. RESULTS: The median follow-up in the two groups was 10.5 months (range, 0.5-22). Median PFS and OS in the DEB-TACE group were 10.0 and 13.0 months, respectively, and 6.0 and 8.5 months in the cTACE group, respectively (P = 0.009 and P = 0.008). The 3-, 6-, and 12-month OS rates in the DEB-TACE group were 100.0%, 94.4%, and 55.6%, respectively, and 92.3%, 71.8%, and 35.9% in the cTACE group, respectively. The 3-month OS rate (P = 0.083) showed no significant difference between the two groups, but significant differences were found in the 6- and 12-month OS rates (P = 0.008 and P = 0.030). Univariate and multivariate survival analyses showed that treatment method, tumor size, and tumor number were independent prognostic factors affecting PFS and OS. CONCLUSION: DEB-TACE has advantages over cTACE in prolonging PFS and OS in patients with CRLM. Treatment method, tumor number, and tumor size are important prognostic factors affecting PFS and OS. However, further multicenter and prospective trials are needed to confirm a deeper comparison between DEB-TACE and cTACE in patients with CRLM.

Klotho activation of Nrf2 inhibits the ferroptosis signaling pathway to ameliorate sepsis-associated acute kidney injury.

Background: Sepsis-associated acute kidney injury (SA-AKI) is a common complication of sepsis and greatly increases patient mortality. Recombinant human Klotho protein (Klotho) is a protective protein that can be secreted by the kidney. The aim of this study was to explore the protective effect of Klotho on SA-AKI and its molecular mechanism. Methods: In vivo, a mouse SA-AKI model was constructed by cecum ligation perforation (CLP). In vitro, a human renal tubular cell epithelial cell line (HK2) was induced with lipopolysaccharide (LPS) in the SA-AKI model. Determine renal injury markers, inflammatory factors, oxidative stress and molecular proteins related to the ferroptosis signaling pathway. Results: Klotho reduced the release of renal injury markers and inflammatory cytokines, decreased oxidative stress, improved renal histopathological changes, ameliorated mitochondrial damage in mouse renal tubular epithelial cells, increased HK2 cell viability and reduced reactive oxygen species (ROS) accumulation. Exogenous supplementation with Klotho increased the Klotho content in circulating blood, renal tissue and HK2 cells. Conclusions: In the SA-AKI model, Klotho attenuated renal tissue injury, increased HK2 cell viability, decreased inflammatory factor expression and oxidative stress, restored tubular epithelial mitochondrial function, and increased its level in circulating blood, renal tissue and HK2 cells. Klotho probably exerts its protective effects by activating Nrf2 to inhibit the ferroptosis signaling pathway.