microRNAs (miRNAs) are a new class of small non-coding RNAs that function as tumor suppressors or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNA may contribute to cancer development. We hypothesized that genetic variations of the miRNA could be associated with the risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A total of 100 patients with HCC, 100 cases of chronic hepatitis B and 100 health adults were enrolled in this present study. Two common polymorphisms in pre-miRNAs: Homo sapiens miRNA-146a (hsa-mir-146a) (rs291016, guanine to cytosine [G-C]) and hsa-mir-499 (rs3746444; adenine to guanine [C-T]) were genotyped by PCR-Restriction Fragment Length Polymorphism and confirmed by bidirectional DNA sequencing. Significant differences were found in frequency and distribution of the genotypes of miRNA-499 between the HCC and the control group. Compared with miRNA-499 T/T, the odds ratio (OR) of patients with miRNA-499 C/C for developing HCC was 3.630 (95% CI: 1.545-8.532), and OR for developing HBV-related HCC was 3.133 (95% CI: 1.248-7.861). There was no significant association between miRNA-146a polymorphism and the risk of HCC in all subjects. Our results suggested that hsa-mir-499 polymorphism was associated with susceptibility to HBV-related HCC in Chinese population. Further characterization of miRNA SNPs may open new avenue for the study of cancer and therapeutic interventions.

Sepsis is a common complication of combat injuries and trauma, and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is also one of the significant causes of death and increased health care costs in modern intensive care units. The use of antibiotics, fluid resuscitation, and organ support therapy have limited prognostic impact in patients with sepsis. Although its pathophysiology remains elusive, immunosuppression is now recognized as one of the major causes of septic death. Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis. It is characterized by the release of anti-inflammatory cytokines, abnormal death of immune effector cells, hyperproliferation of immune suppressor cells, and expression of immune checkpoints. By targeting immunosuppression, especially with immune checkpoint inhibitors, preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance. Here, we comprehensively discuss recent findings on the mechanisms, regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.

Postinfluenza pneumococcal pneumonia is a common cause of death in humans. However, the role of IL-27 in the pathogenesis of secondary pneumococcal pneumonia after influenza is unknown. We now report that influenza infection induced pulmonary IL-27 production in a type I IFN-α/β receptor (IFNAR) signalling-dependent manner, which sensitized mice to secondary pneumococcal infection downstream of IFNAR pathway. Mice deficient in IL-27 receptor were resistant to secondary pneumococcal infection and generated more IL-17A-producing γδ T cells but not αβ T cells, thereby leading to enhanced neutrophil response during the early phase of host defence. IL-27 treatment could suppress the development of IL-17A-producing γδ T cells activated by Streptococcus pneumoniae and dendritic cells. This suppressive activity of IL-27 on γδ T cells was dependent on transcription factor STAT1. Finally, neutralization of IL-27 or administration of IL-17A restored the role of γδ T cells in combating secondary pneumococcal infection. Our study defines what we believe to be a novel role of IL-27 in impairing host innate immunity against pneumococcal infection.

Although candidemia has been reported globally, little is known about the differences in candidemia episodes between ICU and surgical wards or the correlation between serum biomarkers and mortality from candidemia. A retrospective study of hospitalized patients with candidemia was conducted in southwest China. A total of 198 non-duplicate candidemia episodes were identified between January 2011 and December 2016. Candida albicans was the leading species causing candidemia (34.9%), and 78.8% of these isolates were susceptible to fluconazole. More than half of candidemic patients were hospitalized in surgical wards, but the incidence of these surgical patients was much lower than that of ICU patients. Compared with surgical patients, patients admitted to ICU were more frequently subjected to extensive invasive procedures, severe clinical presentations, and heavy exposure to antibiotics. In addition, the mortality in ICU was significantly higher than that in surgical wards. Multivariable analysis revealed that ascites, catheter-related candidemia, ICU admission, septic shock, and concomitant bacterial infection were independent factors associated with mortality. Moreover, we observed that high PCT and BDG levels as well as low PLT counts were also associated with mortality from candidemia. Better understanding of the specific predictors in different wards could facilitate the identification of high-risk candidates to receive early antifungal therapy, thus improving the outcomes of critically ill patients with candidemia.

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