Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma.

Pyroptosis is a recently identified form of programmed cell death; however, its role in lung adenocarcinoma (LUAD) remains unclear. Therefore, we set out to explore the prognostic potential of pyroptosis-related genes in LUAD. The pyroptosis-related risk score (PRRS) was developed by least absolute shrinkage and selection operator Cox regression and multivariate Cox regression. We found that PRRS was an independent prognostic factor for LUAD. LUAD patients in the high-PRRS group showed a significantly shorter overall survival (OS) and enriched in cell proliferation-related pathways. Then pathway enrichment analyses, mutation profile, tumor microenvironment, and drug sensitivity analysis were further studied in PRRS stratified LUAD patients. Tumor purity (TP) analyses revealed that L-PRRS LUAD patients had a lower TP, and patients in L-TP + L-PRRS subgroup had the most prolonged OS. Mutation analyses suggested that the L-PRRS LUAD patients had a lower tumor mutation burden (TMB), and patients in H-TMB + L-PRRS subgroup had the most prolonged OS. Drug sensitivity analyses showed that PRRS was significantly negatively correlated with the sensitivity of cisplatin, besarotene, etc., while it was significantly positively correlated with the sensitivity of kin001-135. Eventually, a nomogram was constructed based on PRRS and clinical characters of LUAD. Overall, the pyroptosis-related signature is helpful for prognostic prediction and in guiding treatment for LUAD patients.

Instantaneous death risk, conditional survival and optimal surgery timing in cervical fracture patients with ankylosing spondylitis: A national multicentre retrospective study.

Background: The mortality rate in patients with ankylosing spondylitis (AS) and cervical fracture is relatively high. Objectives: This study aimed to investigate the instantaneous death risk and conditional survival (CS) in patients with AS and cervical fracture. We also studied the relationship between surgical timing and the incidence of complications. Methods: This national multicentre retrospective study included 459 patients with AS and cervical fractures between 2003 and 2019. The hazard function was used to determine the risk of instantaneous death. The five-year CS was calculated to show the dynamic changes in prognosis. Results: The instantaneous death risk was relatively high in the first 6 months and gradually decreased over time in patients with AS and cervical fracture. For patients who did not undergo surgery, the instantaneous risk of death was relatively high in the first 15 months and gradually decreased over time. For patients with American Spinal Injury Association impairment scale (ASIA) A and B, the 5-year CS was 55.3% at baseline, and improved steadily to 88.4% at 2 years. Odds ratios (ORs) for pneumonia, electrolyte disturbance, respiratory insufficiency, and phlebothrombosis decreased as the surgery timing increased. Conclusion: Deaths occurred mainly in the first 6 months after injury and gradually decreased over time. Our study highlights the need for continued surveillance and care in patients with AS with cervical fractures and provides useful survival estimates for both surgeons and patients. We also observed that early surgery can significantly increase functional recovery, and decrease the incidence of complications and rehospitalisation.

Temporal kinetics of CD8+ CD28+ and CD8+ CD28- T lymphocytes in the injured rat spinal cord.

This study aims to explore the temporal changes of cytotoxic CD8+ CD28+ and regulatory CD8+ CD28- T-cell subsets in the lesion microenvironment after spinal cord injury (SCI) in rats, by combination of immunohistochemistry (IHC) and flow cytometry (FCM). In the sham-opened spinal cord, few CD8+ T cells were found. After SCI, the CD8+ T cells were detected at one day post-injury (dpi), then markedly increased and were significantly higher at 3, 7, and 14 dpi compared with one dpi (p < 0.01), the highest being seven dpi. In CD8+ T cells, more than 90% were CD28+ , and there were only small part of CD28- ( < 10%). After 14 days, the infiltrated CD8+ T cells were significantly decreased, and few could be found in good condition at 21 and 28 dpi. Annexin V and propidium iodide (PI) staining showed that the percentages of apoptotic/necrotic CD8+ cells at 14 dpi and 21 dpi were significantly higher than those of the other early time-points (p < 0.01). These results indicate that CD8+ T cells could rapidly infiltrate into the injured spinal cords and survive two weeks, however, cytotoxic CD8+ T cells were dominant. Therefore, two weeks after injury might be the "time window" for treating SCI by prolonging survival times and increasing the fraction of CD8+ regulatory T-cells. © 2016 Wiley Periodicals, Inc.

Differential effects of myelin basic protein-activated Th1 and Th2 cells on the local immune microenvironment of injured spinal cord.

Myelin basic protein (MBP) activated T cells (MBP-T) play an important role in the damage and repair process of the central nervous system (CNS). However, whether these cells play a beneficial or detrimental role is still a matter of debate. Although some studies showed that MBP-T cells are mainly helper T (Th) cells, their subtypes are still not very clear. One possible explanation for MBP-T immunization leading to conflicting results may be the different subtypes of T cells are responsible for distinct effects. In this study, the Th1 and Th2 type MBP-T cells (MBP-Th1 and -Th2) were polarized in vitro, and their effects on the local immune microenvironment and tissue repair of spinal cord injury (SCI) after adoptive immunization were investigated. In MBP-Th1 cell transferred rats, the high levels of pro-inflammatory cells (Th1 cells and M1 macrophages) and cytokines (IFN-γ, TNF-α, -ß, IL-1ß) were detected in the injured spinal cord; however, the anti-inflammatory cells (Th2 cells, regulatory T cells, and M2 macrophages) and cytokines (IL-4, -10, and -13) were found in MBP-Th2 cell transferred animals. MBP-Th2 cell transfer resulted in decreased lesion volume, increased myelination of axons, and preservation of neurons. This was accompanied by significant locomotor improvement. These results indicate that MBP-Th2 adoptive transfer has beneficial effects on the injured spinal cord, in which the increased number of Th2 cells may alter the local microenvironment from one primarily populated by Th1 and M1 cells to another dominated by Th2, Treg, and M2 cells and is conducive for SCI repair.