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.

Calponin 3 Acts as a Potential Diagnostic and Prognostic Marker and Promotes Glioma Cell Proliferation, Migration, and Invasion.

BACKGROUND: Calponin 3 (CNN3) is involved in the proliferation and invasion of cervical cancer and osteosarcoma cells. However, the role of CNN3 in glioma tumorigenesis remains to be elucidated. METHODS: CNN3 mRNA expression in normal brain tissue and gliomas, including glioblastoma multiforme and lower-grade glioma, was analyzed using GEPIA 2 and Oncomine. CNN3 levels in glioma tissues were identified using immunohistochemical data provided by the Human Protein Atlas website. The relationship between CNN3 mRNA expression and clinical characteristics of patients with glioma was analyzed using the Oncomine database and The Cancer Genome Atlas. The diagnostic value of CNN3 expression in glioma was analyzed using receiver operating characteristic analysis according to The Cancer Genome Atlas and Genotype-Tissue Expression data. The relationship between CNN3 and prognosis was analyzed using GEPIA 2. The function of CNN3 knockdown in glioma cell lines was analyzed using cell proliferation, Transwell, and Western blot assays. RESULTS: Both mRNA and protein levels of CNN3 were distinctly higher in lower-grade glioma and glioblastoma multiforme tissues than those in normal brain tissues, particularly glioblastoma. A higher CNN3 mRNA level had significant relationship with higher World Health Organization grade, isocitrate dehydrogenase wild-type status, and 1p/19q noncodeletion. CNN3 mRNA expression is a highly accurate marker for the diagnosis of glioma. Patients with glioma in the high-CNN3 group had significantly lower disease-free survival and survival rates. In addition, CNN3 silencing significantly inhibited cell proliferation, migration, invasion, and the phosphorylation of P65 NF-κB. CONCLUSIONS: CNN3 expression is increased in glioma, particularly glioblastoma. Silencing CNN3 expression inhibited the proliferation, migration, and invasion of glioma cell lines.

Acute Glycemic Variability and Functional Outcome in Patients with Acute Ischemic Stroke: A Meta-Analysis.

Dysglycemia are involved in the development of functional impairment after acute ischemic stroke (AIS). The aim of the study was to evaluate the association between acute glycemic variability and functional outcome in patients with AIS. Cohort studies were obtained by search Medline, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure databases from inception to November, 2021. A random-effect model which incorporates the intra-study heterogeneity was chosen to pool the results. Ten cohort studies including 3038 patients were included, and 1319 (43.4%) had poor functional outcome (modified Rankin Scale >2) up to three months after disease onset. Pooled results showed that higher acute GV was associated with an increased risk of poor functional outcome, as evidenced by GV evaluated by the standard deviation of blood glucose (SDBG, OR: 1.91, 95% CI: 1.38 to 2.65, I2=60%, p<0.001), the coefficient of variation of blood glucose (OR: 2.03, 95% CI: 1.15 to 3.58, I2=17%, p=0.02), the range of glucose (OR: 1.43, 95% CI: 1.11 to 1.83, I2=22%, p=0.005), and the mean amplitude of glycemic excursion (OR: 1.59, 95% CI: 1.10 to 2.31, I2=0%, p=0.01). Subgroup analyses did not support that difference in study design, treatments for AIS, mean age of the patients, duration for GV measuring, or study quality would significantly affect the association between SDBG and functional outcome after AIS. In conclusion, higher acute glycemic variability may predict poor functional outcome within 3 months after AIS.

Acute glycemic variability and mortality of patients with acute stroke: a meta-analysis.

BACKGROUND: Increased glucose fluctuation has been related to poor prognosis in patients with critical illnesses, while its prognostic role in patients with acute stroke remains unknown. The meta-analysis aimed to evaluate the association between the acute glycemic variation (GV) and mortality risk in patients with acute stroke. METHODS: Cohort studies were obtained by searching Medline, Web of Science, Embase, Wanfang and CNKI databases. A random-effect model which incorporates the intra-study heterogeneity was chosen to pool the results. RESULTS: Ten cohort studies with 1433 patients were included, and 280 (19.5%) of them died within 90 days of disease onset. Results of the meta-analyses showed that a higher acute GV was associated with an increased risk of early mortality in patients with acute stroke, as indicated by GV measured with the coefficient of variation of blood glucose (CVBG, odds ratio [OR]: 2.24, 95% CI 1.40 to 3.58, p < 0.001, I2 = 73%), the standard deviation of blood glucose (SDBG, OR: 2.31, 95% CI 1.70 to 3.13, p < 0.001, I2 = 50%), and the mean amplitude of glycemic excursion (OR: 3.57, 95% CI 1.44 to 8.85, p = 0.006, I2 = 23%). For acute GV measured with CVBG and SDBG, subgroup analyses showed consistent results in patients with acute ischemic and hemorrhagic stroke, and for studies reporting 28-day and 90-day all-cause mortality (p for subgroup analysis all > 0.05). CONCLUSIONS: Higher acute GV may be an independent risk factor of early mortality in patients with acute stroke.

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.