The prognostic value of tumor-associated macrophages in glioma patients.

Glioma is a complex tumor composed of both neoplastic and non-neoplastic cells, including tumor-infiltrating leukocytes (TILs), and each cell type contributes to tumor formation and malignant progression. Among TILs, tumor-associated macrophages (TAMs) are of great importance and play a key role in the immune response to cancer. In this study, 22 types of adaptive and innate TILs were evaluated in gliomas. TAMs, which account for 38.7% of all these cells, are the most abundant immune infiltrates in the tumor microenvironment. In addition, we observed different immune cell patterns in low-grade glioma and glioblastoma. Our research indicated that there was a connection between TILs, and 13 of 22 TILs were significantly associated with patient outcomes. Finally, the prognosis and diagnostic value of TAMs were revealed using Kaplan-Meier analysis. We identified the optimal cutoff point of TAMs at an infiltrating level of 0.47 to predict patient prognosis, with a median overall survival of 448 days in patients with higher TAM infiltration levels and 2660 days in patients with lower TAM infiltration levels. These findings provide a new idea for glioma to regulate tumor-specific immunity, clarify the potential effects of TAMs on disease pathology, and provide a theoretical basis for immune intervention treatment of gliomas.

Effects and mechanism of the etanercept on pancreatic encephalopathy.

Pancreatic encephalopathy (PE) is a common fatal complication of acute pancreatitis (AP). Proinflammatory cytokines such as tumor necrosis factor (TNF)­α and interleukin (IL)­6 are generated during AP, and act synergistically to promote PE and multisystem failure. Caerulein­induced AP provides a convenient model to explore the role of proinflammatory cytokines in PE. The aim of the present study was to examine the effect of the TNF­α inhibitor etanercept in PE models and elucidate the regulatory mechanisms. To model PE in vitro, rat hippocampal H19­7/IGF­IR neuronal cells were treated with 10 nmol/ml caerulein alone or in combination with etanercept (1, 10 or 100 µmol/ml). To model PE in vivo, rats were injected with 50 µg/kg caerulein alone or combined with 10 mg/kg etanercept. At 6 h after administration, it was noted that etanercept downregulated expression of TNF­α, IL­1ß and IL­6 by negatively regulating NF­κB (a master regulator of cytokine expression) signaling, and prevented the accumulation of reactive oxygen species. Conversely, etanercept promoted the expression of the neurotrophic and anti­inflammatory hypoxia­inducible factor 1 α (HIF­1α). In rat hippocampus, etanercept also reduced the levels of TNF­α, IL­1ß and IL­6, upregulated HIF­1α expression and inhibited the inflammatory response to reduce edema and neural necrosis. Together, these data suggested that etanercept could attenuate caerulein­induced PE, at least in part via suppression of NF­κB signaling and alleviation of oxidative stress.

Mild hypothermia for treatment of diffuse axonal injury: a quantitative analysis of diffusion tensor imaging.

Fractional anisotropy values in diffusion tensor imaging can quantitatively reflect the consistency of nerve fibers after brain damage, where higher values generally indicate less damage to nerve fibers. Therefore, we hypothesized that diffusion tensor imaging could be used to evaluate the effect of mild hypothermia on diffuse axonal injury. A total of 102 patients with diffuse axonal injury were randomly divided into two groups: normothermic and mild hypothermic treatment groups. Patient's modified Rankin scale scores 2 months after mild hypothermia were significantly lower than those for the normothermia group. The difference in average fractional anisotropy value for each region of interest before and after mild hypothermia was 1.32-1.36 times higher than the value in the normothermia group. Quantitative assessment of diffusion tensor imaging indicates that mild hypothermia therapy may be beneficial for patients with diffuse axonal injury.

Occludin and connexin 43 expression contribute to the pathogenesis of traumatic brain edema.

The experimental model of traumatic brain injury was established in Sprague-Dawley rats according to Feeney's free falling method. The brains were harvested at 2, 6 and 24 hours, and at 3 and 5 days after injury. Changes in brain water content were determined using the wet and dry weights. Our results showed that water content of tissue significantly increased after traumatic brain injury, and reached minimum at 24 hours. Hematoxylin-eosin staining revealed pathological impairment of brain tissue at each time point after injury, particularly at 3 days, with nerve cell edema, degenera-tion, and necrosis observed, and the apoptotic rate significantly increased. Immunohistochemistry and western blot analysis revealed that the expression of occludin at the injured site gradually de-creased as injury time advanced and reached a minimum at 3 days after injury; the expression of connexin 43 gradually increased as injury time advanced and reached a peak at 24 hours after in-jury. The experimental findings indicate that changes in occludin and connexin 43 expression were consistent with the development of brain edema, and may reflect the pathogenesis of brain injury.