BackgroundSepsis is now the leading cause of death in the non-cardiovascular intensive care unit (ICU). Recent research suggests that sepsis is likely to be due to an interaction between genetic and environmental factors. Genetic mutations of toll-like receptor 4 (TLR4) and cluster of differentiation 14 (CD14) genes are involved in the immune and (or) inflammatory response. These may contribute to the susceptibility to sepsis in patients. This study was designed to evaluate whether the TLR4 and cluster CD14 gene polymorphisms are associated with susceptibility to sepsis.MethodsThe single nucleotide polymorphisms (SNPs) of TLR4 (rs10759932, rs11536889, rs7873784, rs12377632, rs1927907, rs1153879) and CD14 (rs2569190 and rs2563298) in patients with sepsis and control subjects in the Guangxi Province were analyzed by using the polymerase chain reaction-single base extension (PCR-SBE) and DNA sequencing methods.ResultsThe rs11536889 polymorphism in TLR4 and rs2563298 polymorphism in CD14 were significantly associated with the risk of sepsis when compared to the control group. The frequencies of rs11536889 and rs2563298 polymorphisms in the group with sepsis were higher than that in the control group (OR = 1.430, 95% CI, 1.032-1.981, P<0.05; OR = 2.454, 95% CI, 1.458-4.130, P<0.05, respectively). Followed up haplotype analysis suggested that there were two haplotypes in which increased risk factors for sepsis were indicated.ConclusionsThe rs11536889 polymorphism in TLR4 and rs2563298 polymorphism in CD14, and two haplotypes were associated with increased susceptibility to sepsis.

Background: LncRNA is a key factor influencing tumor development. The present study aimed to investigate the effect of a novel lncRNA on the progression of hepatocellular carcinoma (HCC). Methods: A candidate lncRNA in The Cancer Genome Atlas database was identified using limma and survival R packages. The effect of lncRNA AC099850.3 on cell proliferation, apoptosis, migration, and invasion, as well as its association with immune cells in HCC were investigated. Furthermore, the functional mechanisms of lncRNA AC099850.3 in HCC were elucidated. Results:The aberrant expression of lncRNA AC099850.3 was identified in tumor tissues and its prognostic relevance in HCC was determined. The results revealed that AC099850.3 was highly expressed in HCC tissues and cell lines, and it predicted poor prognosis in patients with HCC. Furthermore, knockdown of AC099850.3 significantly suppressed the proliferation and metastatic potential of HCC cells, and promoted cell apoptosis in HCC cells. The results of gene set enrichment analysis revealed that the PI3K/AKT pathway was associated with the biological function of AC099850.3, which was further validated by western blotting. PRR11 was identified as the target gene of AC099850.3 and we established that AC099850.3 acted as an oncogene in the PRR11/PI3K/AKT axis. Immune cell infiltration analyses results revealed that AC099850.3 was positively correlated with T follicular helper cells, M0 macrophages, CD4 + memory T cells, and memory B cells. Conversely, AC099850.3 was negatively correlated with M2 macrophages, monocytes, natural killer cells, and CD8 + T cells, which could be responsible for its oncogenic effect. Of note, a significantly positive correlation was observed between AC099850.3 and key immune checkpoint molecules (PD-1, PD-L1, PD-L2, and CTLA4) in the present study, making AC099850.3 a potential immune therapeutic target for HCC. Conclusion: AC099850.3 can promote malignant biological behavior of HCC cells, and could be a potential biomarker and therapeutic target for HCC.

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