Sepsis, an infection-induced systemic disease, leads to pathological, physiological, and biochemical abnormalities in the body. Organ dysfunction is caused by a dysregulated host response to infection during sepsis which is a major contributing factor to acute kidney injury (AKI) and the mortality rate for sepsis doubles due to coincidence of AKI. Sepsis-induced AKI is strongly associated with increased mortality and other adverse outcomes. More timely diagnosis would allow for earlier intervention and could improve patient outcomes. Sepsis-induced AKI is characterized by a distinct pathophysiology compared with other diseases and may also have unique patterns of plasma and urinary biomarkers. This concise review summarizes properties and perspectives of the biomarkers for their individual clinical utilization.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to an infection. It is a disease with a high incidence, mortality, and recurrence rate and frequently results in its survivors requiring readmission into hospitals. The readmission is mainly due to recurrent sepsis. Patients with recurrent sepsis are more susceptible to secondary infections partly due to immune dysfunction, leading to a higher mortality in the long term. However, there remains a gap in the understanding of immunological characteristics and underlying mechanisms of recurrent sepsis. In this study, we used mouse models of acute and recurrent sepsis to investigate their different immunological characteristics. And then we subjected the two mouse models to a secondary influenza A virus (H1N1) infection and characterized the different immune responses. Here, we demonstrated that CD4+ T cells present an exacerbated exhaustion phenotype in response to recurrent sepsis as illustrated by the decreased frequency of CD4+ T cells, reduced co-stimulatory CD28 and increased inhibitory PD-1 and Tim-3 expression on CD4+ T cells, increased frequency of regulatory T cells, and reduced MHC-II expression on antigen-presenting cells. Moreover, we showed that antiviral immune responses decrease in the recurrent sepsis mouse model subjected to a secondary infection as illustrated by the reduced pathogen clearance and inflammatory response. This may be a consequence of the exacerbated CD4+ T cell exhaustion. In summary, recurrent sepsis exacerbates CD4+ T cell exhaustion and decreases antiviral immune responses, contributing to significant morbidity, increased late mortality, and increased health care burden in recurrent sepsis patients.

Summary Objective To assess the diagnostic value of serum Candida mannan antigen (MN) and anti‐mannan IgG and IgM antibodies for candidiasis. Methods This study was a prospective cohort study. Clinical data and venous blood samples from 23 medical centres in Beijing, China were collected between 1 January 2017 and 31 December 2018. All collected specimens were tested within one week for serum Candida MN and IgG and IgM antibodies using an ELISA kit. Results A total of 452 patients were enrolled, including 188 patients in the Candida exposure groups (56 patients with Candida bloodstream infection, 69 patients with Candida‐positive tracheal aspirate cultures and 63 patients with Candida‐positive urine cultures) and 264 patients in the control groups (212 healthy controls and 52 patients with bacteraemia). The receiver operating characteristic (ROC) curve of the 56 patients with Candida bloodstream infection and 212 healthy controls showed that serum MN and IgG had good diagnostic value. The area under the ROC curve (AUC) values were 0.812 (95% CI, 0.750‐0.873) and 0.866 (95% CI, 0.808‐0.924), respectively, wherein the MN specificity and sensitivity were 86.79% and 60.71%, and the IgG were 84.43% and 80.36%, respectively. The AUC of the combination of serum MN and IgG was 0.871(95% CI, 0.813‐0.929), and the specificity and sensitivity were 93.87% and 57.14%. Conclusions The serum levels of Candida MN and its IgG antibody have diagnostic value for Candida bloodstream infection, and combination of MN and IgG can improve diagnostic specificity and may provide a new approach for diagnosis of candidaemia.

The aim of the study was to investigate the mechanism of arsenic trioxide (As2O3) in the treatment of malignant pleural effusion (MPE) caused by pleural metastasis of lung cancer. A mouse model of MPE caused by pleural metastasis of lung cancer was first established, and As2O3 was then intraperitoneally injected to treat the MPE. Mice treated with bevacizumab and bleomycin were included as positive controls, and placebo equivalents were also used as negative controls. The effects of As2O3 on MPE volume, pleural vessel density, vascular permeability, expression of angiogenic function-related factors, including vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-α), as well as nuclear factor-κB (NF-κB) activity in pleural carcinomatosis, were observed. Intraperitoneal injection of As2O3 reduced the volume of MPE and decreased vascular density and permeability in pleural metastatic nodules in a dose-dependent manner. Moreover, dose-dependent decreases in VEGF and TNF-α expression in MPE, and NF-κB activity in pleural carcinomatosis, were also found after As2O3 treatment. We showed that As2O3 can down-regulate VEGF expression via inhibition of NF-κB, and decrease vascular density and permeability in pleural metastatic nodules, thereby eliciting its effects on MPE caused by pleural metastasis of lung cancer. Our results provide a foundation for an As2O3-based clinical treatment program.