Monocyte HLA-DR level on admission predicting in-hospital mortality rate in exertional heatstroke: A 12-year retrospective study.

BACKGROUND: Exertional heatstroke (EHS), a fatal illness, pronounces multiple organ dysfunction syndrome (MODS) and high mortality rate. Currently, no ideal factor prognoses EHS. Decreased monocyte human leukocyte-DR antigen (mHLA-DR) has been observed in critically ill individuals, particularly in those with sepsis. While most research focus on the pro-inflammatory response exploration in EHS, there are few studies related to immunosuppression, and no report targeted on mHLA-DR in EHS. The present study tried to explore the prognostic value of mHLA-DR levels in EHS patients. METHODS: This was a single-center retrospective study. Clinical data of EHS patients admitted to the intensive care unit of the General Hospital of Southern Theatre Command between January 1, 2008, and December 31, 2020, were recorded and analyzed. RESULTS: Seventy patients with 54 survivors and 16 nonsurvivors were ultimately enrolled. Levels of mHLA-DR in the nonsurvivors (41.8% [38.1-68.1]%) were significantly lower than those in the survivors (83.1% [67.6-89.4]%, p < 0.001). Multivariate logistic regression indicated that mHLA-DR (odds ratio [OR] = 0.939; 95% confidence interval [CI]: 0.892-0.988; p = 0.016) and Glasgow coma scale (GCS) scores (OR = 0.726; 95% CI: 0.591-0.892; p = 0.002) were independent risk factors related with in-hospital mortality rate in EHS. A nomogram incorporated mHLA-DR with GCS demonstrated excellent discrimination and calibration abilities. Compared to the traditional scoring systems, the prediction model incorporated mHLA-DR with GCS had the highest area under the curve (0.947, 95% CI: [0.865-0.986]) and Youden index (0.8333), with sensitivity of 100% and specificity of 83.33%, and a greater clinical net benefit. CONCLUSION: Patients with EHS were at a risk of early experiencing decreased mHLA-DR early. A nomogram based on mHLA-DR with GCS was developed to facilitate early identification and timely treatment of individuals with potentially poor prognosis.

Netrin-1 mitigates acute lung injury by preventing the activation of the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling.

Acute lung injury (ALI) is one of the most common high-risk diseases associated with a high mortality rate and is still a challenge to treat effectively. Netrin-1 (NT-1) is a novel peptide with a wide range of biological functions, however, its effects on ALI have not been reported before. In this study, an ALI model was constructed using lipopolysaccharide (LPS) and treated with NT-1. Pulmonary function and lung wet to dry weight ratio (W/D) were detected. The expressions of pro-inflammatory cytokines and chemokines interleukin-8 (IL-8), interleukin-1ß (IL-1ß), and chemokine (C-X-C motif) ligand 2 (CXCL2) were measured using real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). We found that the levels of NT-1 were reduced in the LPS-induced ALI mice model. Administration of NT-1 improved histopathological changes of lung tissues and lung function in LPS-challenged ALI mice. We also report that NT-1 decreased Myeloperoxidase (MPO) activity and ameliorated pulmonary edema. Additionally, treatment with NT-1 reduced the levels of pro-inflammatory cytokines and chemokines such as IL-8, IL-1ß, and CXCL2 in lung tissues of LPS-challenged ALI mice. Importantly, NT-1 reduced cell count in BALF and mitigated oxidative stress (OS) by reducing the levels of MDA and increasing the levels of GSH. Mechanistically, it is shown that NT-1 reduced the levels of Toll-like receptor 4 (TLR4) and prevented nuclear translocation of nuclear factor-κB (NF-κB) p65. Our findings indicate that NT-1 is a promising agent for the treatment of ALI through inhibiting TLR4/NF-κB signaling.