BackgroundThe mortality rate due to severe sepsis is approximately 30–60%. Sepsis readily progresses to septic shock and multiple organ dysfunction, representing a significant problem in the pediatric intensive care unit (PICU). The aim of this study was to explore the value of plasma mitochondrial DNA (mtDNA) for early diagnosis and prognosis in children with sepsis.MethodsA total of 123 children with sepsis who were hospitalized in the Hunan Children’s Hospital PICU from July 2013 to December 2014 were divided into the general sepsis group (n = 70) and severe sepsis group (n = 53) based on diagnostic standards. An additional 30 children with non-sepsis infection and 30 healthy children were randomly selected as a control group. Patients’ plasma was collected during admission to the PICU. A pediatric critical illness score (PCIS) was also calculated. The plasma mtDNA level was examined using real-time polymerase chain reaction technology, and other parameters including routine laboratory values; blood lactate, procalcitonin (PCT), and C-reactive protein (CRP) levels; and data on survival were collected and compared among the groups.ResultsThe plasma mtDNA level in the sepsis group than that in the non-sepsis infection and healthy groups. The plasma mtDNA level was significantly higher in the severe sepsis than in the general sepsis group (p < 0.001). A lower PCIS was associated with a higher plasma mtDNA level (p < 0.001). A higher number of organs with dysfunction was associated with higher plasma mtDNA levels (p < 0.001). Plasma mtDNA levels were higher among patients with elevated alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, lactate dehydrogenase, creatine kinase, myoglobin, creatine kinase MB, and troponin than in those with values within the normal range. The mtDNA level was higher among non-survivors than among survivors, and this difference was significant. mtDNA showed a prognostic prediction value similar to that of lactate, PCT, and CRP.ConclusionsPlasma mtDNA levels may be a suitable biomarker for diagnosis and prognosis in children with sepsis.

BACKGROUND mTOR gene is a key component of the PI3K/Akt/mTOR signaling pathway, and its dysregulation is associated with various diseases. Several studies have demonstrated that tea drinking is a protective factor against tuberculosis (TB). This study was designed to explore five single nucleotide polymorphisms (SNPs) of mTOR in the Han population of China to determine how their interactions with tea drinking affect susceptibility to TB. AIM To investigate if the polymorphisms of mTOR gene and the gene-tea interaction are associated with susceptibility to TB. METHODS In this case-control study, 503 patients with TB and 494 healthy controls were enrolled by a stratified sampling method. The cases were newly registered TB patients from the county-level centers for disease control and prevention, and the healthy controls were permanent residents from Xin’ansi Community, Changsha city. Demographic data and environmental exposure information including tea drinking were obtained from the study participants. We genotyped five potentially functional SNP sites (rs2295080, rs2024627, rs1057079, rs12137958, and rs7525957) of mTOR gene and assessed their associations with the risk of TB using logistic regression analysis, and marginal structural linear odds models were used to estimate the gene-environment interactions. RESULTS The frequencies of four SNPs (rs2295080, rs2024627, rs1057079, and rs7525957) were found to be associated with susceptibility to TB ( P < 0.05). Genotypes GT (OR 1.334), GG (OR 2.224), and GT + GG (OR 1.403) at rs2295080; genotypes CT (OR 1.562) and CT + TT (OR 1.578) at rs2024627, genotypes CT (OR 1.597), CC (OR 2.858), and CT + CC (OR 1.682) at rs1057079; and genotypes CT (OR 1.559) and CT + CC (OR 1.568) at rs7525957 of mTOR gene were significantly more prevalent in TB patients than in healthy controls. The relative excess risk of interaction between the four SNPs (rs2295080, rs2024627, rs1057079, and rs7525957) of mTOR genes and tea drinking were found to be -1.5187 (95%CI: -1.9826, -1.0547, P < 0.05), -1.8270 (95%CI: -2.3587, -1.2952, P < 0.05), -2.3246 (95%CI: -2.9417, -1.7076, P < 0.05) and -0.4235 (95%CI: -0.7756, -0.0714, P < 0.05), respectively, which suggest negative interactions. CONCLUSION The polymorphisms of mTOR (rs2295080, rs2024627, rs1057079, and rs7525957) are associated with susceptibility to TB, and there is a negative interaction between each of the four SNPs and tea drinking.

Background. Sepsis can lead to multiple organ damage, of which the heart is one of the most vulnerable organs. Vagal nerve stimulation can reduce myocardial injury in sepsis and improve survival rates. However, the potential impact of low-level tragus stimulation and disparate cell populations on sepsis-induced myocardial dysfunction remains undetermined. Methods. A cardiac single-cell transcriptomic approach was used for characterizing cardiac cell populations that form the heart. Single-cell mRNA sequencing data were used for selecting all cardiac macrophages from CD45+ cells. Then, echocardiography, western blot, flow cytometry, immunofluorescence, and immunohistochemistry were performed to verify the single-cell mRNA sequencing results. Results. Using single-cell mRNA sequencing data, we uncovered the multiple cell populations contributing to myocardial injury in sepsis under low-level tragus stimulation, thereby illustrating a comprehensive map of the cardiac cellular landscape. Pseudotiming analysis in single-cell sequencing showed that low-level vagal nerve stimulation played an anti-inflammatory role by promoting cardiac monocytes into M2 macrophages, which significantly increased α7nAChR expression in heart tissues. Echocardiography assessment indicated that low-level vagal nerve stimulation could also improve cardiac functions in mice with sepsis-induced myocardial dysfunction. In addition, the heart tissues of mice from the sepsis group with low-level tragus stimulation had significantly lower interleukin-1β expression levels than those from the sepsis group. Flow cytometry analysis showed that different acetylcholine concentrations promoted cardiac monocytes into M2 macrophages in in vitro experiments. Conclusion. Low-level tragus stimulation could improve sepsis-induced myocardial dysfunction by promoting cardiac monocytes to M2 macrophages.

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