Identification of T-cell exhaustion-related gene signature for predicting prognosis in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a highly malignant primary brain tumour with a poor prognosis in adults. Identifying biomarkers that can aid in the molecular classification and risk stratification of GBM is critical. Here, we conducted a transcriptional profiling analysis of T-cell immunity in the tumour microenvironment of GBM patients and identified two novel T cell exhaustion (TEX)-related GBM subtypes (termed TEX-C1 and TEX-C2) using the consensus clustering. Our multi-omics analysis revealed distinct immunological, molecular and clinical characteristics for these two subtypes. Specifically, the TEX-C1 subtype had higher infiltration levels of immune cells and expressed higher levels of immune checkpoint molecules than the TEX-C2 subtype. Functional analysis revealed that upregulated genes in the TEX-C1 subtype were significantly enriched in immune response and signal transduction pathways, and upregulated genes in the TEX-C2 subtype were predominantly associated with cell fate and nervous system development pathways. Notably, patients with activated T-cell activity status in the TEX-C1 subgroup demonstrated a significantly worse prognosis than those with severe T cell exhaustion status in the TEX-C2 subgroup. Finally, we proposed a machine-learning-derived novel gene signature comprising 12 TEX-related genes (12TexSig) to indicate tumour subtyping. In the TCGA cohort, the 12TexSig demonstrated the ability to accurately predict the prognosis of GBM patients, and this prognostic value was further confirmed in two independent external cohorts. Taken together, our results suggest that the TEX-derived subtyping and gene signature has the potential to serve as a clinically helpful biomarker for guiding the management of GBM patients, pending further prospective validation.

Dexmededomidine in pediatric unilateral internal inguinal ring ligation.

BACKGROUND: Safe and effective analgesia strategy remains one of the priorities for pediatric inguinal hernia treatment. AIM: To explore safety and efficacy of dexmededomidine monotherapy for postoperative analgesia in children who received laparoscopic unilateral internal inguinal ring ligation. METHODS: This randomized single-center controlled trial included 390 children (aged 1-3 years, ASA grade I-II), randomly divided into a dexmededomidine group (D group), a dexmededomidine + sufentanil group (DS group), and a sufentanil group (S group). The primary endpoint was percentage of children with the Face, Legs, Activity, Cry, and Consolability (FLACC) score ≤ 3 points 2 h after surgery. RESULTS: The comparisons of the FLACC scores at 2, 4, 6, 8, 12, and 24 h were not significantly different among the three groups (P > 0.05). The sedative effects in the D group were significantly better than those in the S group (P > 0.05), but not significantly different from those in the DS group. The incidence of nausea and vomiting was significantly lower in the D group than in the S group and DS group (P > 0.05). CONCLUSION: Analgesic effects of dexmededomidine monotherapy are comparable to those of sufentanil alone or in combination with dexmededomidine for children who underwent laparoscopic unilateral internal inguinal ring ligation, with better sedative effects and a lower incidence of adverse events.