Background: Intestinal barrier integrity in the pathogenesis of sepsis is critical. Despite an abundance of evidence, the molecular mechanism of the intestinal barrier in sepsis pathology remains unclear. Here, we report a protective role of polo-like kinase 1 (PLK1) in intestinal barrier integrity during sepsis.Methods: Mice with PLK1 overexpression (CAG-PLK1 mice) or PLK1 inhibition (BI2536-treated mice) underwent caecal ligation and puncture (CLP) to establish a sepsis model. The intestinal barrier function, apoptosis in the intestinal epithelium, mitochondrial function and NF-κB signalling activity were evaluated. To suppress the activation of NF-κB signalling, the NF-κB inhibitor PDTC, was administered. The Caco-2 cell line was chosen to establish an intestinal epithelial injury model in vitro.Results: Sepsis destroyed intestinal barrier function, induced excessive apoptosis in the intestinal epithelium, and disrupted the balance of mitochondrial dynamics in wild-type mice. PLK1 overexpression alleviated sepsis-induced damage to the intestinal epithelium by inhibiting the activation of NF-κB signalling. PLK1 colocalized and interacted with TANK in Caco-2 cells. Transfecting Caco-2 cells with TANK-SiRNA suppressed NF-κB signalling and ameliorated mitochondrial dysfunction, apoptosis and the high permeability of cells induced by lipopolysaccharide (LPS). Furthermore, TANK overexpression impaired the protective effect of PLK1 on LPS-induced injuries in Caco-2 cells.Conclusion: Our findings reveal that the PLK1/TANK/NF-κB axis plays a crucial role in sepsis-induced intestinal barrier dysfunction by regulating mitochondrial dynamics and apoptosis in the intestinal epithelium and might be a potential therapeutic target in the clinic.

Background: Peritoneal and intra-abdominal infections (IAIs) are a major cause of morbidity and mortality in surgical patients, with rising antimicrobial resistance (AMR) threatening surgical safety. This study mapped global and regional patterns in IAI burden and resistant pathogens to inform evidence-based surgical practice. Methods: Global IAI deaths, disability-adjusted life years, and distributions of key AMR pathogens were analyzed from 1990 to 2021 across 21 Global Burden of Disease regions using the Measuring Infectious Causes and Resistance Outcomes for Burden Estimation (MICROBE) database, with future projections through 2050. Results: IAI-related deaths rose from 394 500 [95% uncertainty intervals (UIs) 361 200–427 800] in 1990 to 646 359 (95% UIs 585 349–707 369) in 2021, with mortality rates increasing from 7.4 (95% UIs 6.8–8.0) to 8.2 (95% UIs 7.4–9.0) per 100 000 population. By 2050, global deaths are projected to decrease slightly by 0.6% to 642 485 (95% UIs 552 824–750 367). However, this decrease is not seen in all regions. The death count is predicted to rise in Latin America and the Caribbean, while substantial declines are projected for South Asia, Central/Eastern Europe, and Central Asia. Escherichia coli was the leading global pathogen, with regional variation: Klebsiella pneumoniae predominated in sub-Saharan Africa, while Staphylococcus aureus was most frequent in high-income regions. In 2021, AMR-related deaths approached 329 000 worldwide, with the death rate rising from 3.79 to 4.17 per 100 000. Carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae showed the most rapid increases. Methicillin-resistant S. aureus mortality remained stable, while efforts to control vancomycin-resistant Enterococcus faecium were less effective. Conclusion: The rising and regionally diverse burden of IAIs, exacerbated by increasing AMR, demands robust surgical antimicrobial stewardship and targeted infection control strategies. Tailoring perioperative antibiotics to local resistance patterns and prioritizing effective source control are essential to optimizing surgical outcomes worldwide.

Sepsis and its related complications are very challenging in the intensive care unit, among which intestinal barrier injury is a general manifestation. Polo-like kinase 1 (PLK1) is widely studied in cancer, while its role in sepsis is poorly understood. In this study, the efficiency of PLK1 as a marker of intestinal barrier function as well as a predictor of mortality in sepsis was evaluated. The level of serum PLK1 was measured in septic patients (n = 51) and controls (n = 20); subsequently, its correlation with serum diamine oxidase (DAO), d-lactate, and endotoxin levels and its ability topredict mortality were analysed. The survival rate and barrier injury degree were also assessed in septic mice. Serum PLK1 levels were elevated in septic patients, were negatively correlated with serum DAO, d-lactate, and endotoxin levels, and had a high predictive value for 28-day mortality in patients. The serum PLK1 level in non-survivors was lower. The expression of PLK1 in the intestine was decreased in septic mice, and overexpression or inhibition of PLK1 alleviated or aggravated intestinal barrier injury, respectively, as evaluated by Chiu's score, serum levels of DAO and d-lactate, and expression of tight junction proteins. Overexpressing PLK1 also decreased the 72-hour death rate of septic mice. Further study also revealed the negative correlation of PLK1 and IL-6 in patients, and increasing or interfering with PLK1 expression reduced or increased the serum IL-6 level in mice. PLK1 plays a critical role in intestinal barrier function during sepsis, providing a novel perspective for sepsis therapy in the clinic.