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Simple Summary: Perineural invasion (PNI) as the fourth way for solid tumor metastasis and invasion has attracted a lot of attention, and axon growth and possible nerve "invasion" to tumors has also become an important component of PNI. We aim to summarize the current theories on the molecular mediators and pathogenesis of PNI, add the latest scientific research progress, and especially explore the use of single-cell spatial transcriptomics in this invasion way, to obtain a better understanding of PNI. Perineural invasion (PNI) as the fourth way for solid tumors metastasis and invasion has attracted a lot of attention, recent research reported a new point that PNI starts to include axon growth and possible nerve "invasion" to tumors as the component. More and more tumor–nerve crosstalk has been explored to explain the internal mechanism for tumor microenvironment (TME) of some types of tumors tends to observe nerve infiltration. As is well known, the interaction of tumor cells, peripheral blood vessels, extracellular matrix, other non-malignant cells, and signal molecules in TME plays a key role in the occurrence, development, and metastasis of cancer, as to the occurrence and development of PNI. We aim to summarize the current theories on the molecular mediators and pathogenesis of PNI, add the latest scientific research progress, and explore the use of single-cell spatial transcriptomics in this invasion way. A better understanding of PNI may help to understand tumor metastasis and recurrence and will be beneficial for improving staging strategies, new treatment methods, and even paradigm shifts in our treatment of patients. [ABSTRACT FROM AUTHOR]

(1) Background: To explore the correlation between the blood urea nitrogen to creatinine ratio (UCR) and in-hospital mortality in non-traumatic subarachnoid hemorrhage patients. (2) Methods: Specific clinical information was collected from the Medical Information Mart for Intensive Ⅳ (MIMIC-Ⅳ) database. The optimal cut-off value of the UCR was calculated with ROC curve analysis conducted using the maximum Youden index for the prediction of survival status. Univariable and multivariable logistic regression analyses were also carried out to assess the prognostic significance of UCR, and the Kaplan–Meier (K–M) analysis was conducted to draw the survival curves. Then, the 1:1 propensity score matching (PSM) method was applied to improve the reliability of the research results while balancing the unintended influence of underlying confounders. (3) Results: This retrospective cohort study included 961 patients. The optimal cut-off value of the UCR for in-hospital mortality was 27.208. The PSM was performed to identify 92 pairs of score-matched patients, with balanced differences exhibited for nearly all variables. According to the K–M analysis, those patients with a UCR of more than 27.208 showed a significantly higher level of in-hospital mortality compared to the patients with a UCR of less than 27.208 (p < 0.05). After the adjustment for possible confounders, those patients whose UCR was more than 27.208 still had a significantly higher level of in-hospital mortality than the patients whose UCR was less than 27.208, as revealed by the multivariable logistic regression analysis (OR = 3.783, 95% CI: 1.959~7.305, p < 0.001). Similarly, the in-hospital mortality remained substantially higher for those patients in the higher UCR group than for the patients in the lower UCR group after PSM. (4) Conclusion: A higher level of the UCR was evidently associated with an increased risk of in-hospital mortality, which made the ratio useful as a prognostic predictor of clinical outcomes for those patients with non-traumatic subarachnoid hemorrhage. [ABSTRACT FROM AUTHOR]

Diffuse intrinsic pontine glioma (DIPG) is the most lethal tumor involving the pediatric central nervous system. The median survival of children that are diagnosed with DIPG is only 9 to 11 months. More than 200 clinical trials have failed to increase the survival outcomes using conventional cytotoxic or myeloablative chemotherapy. Immunotherapy presents exciting therapeutic opportunities against DIPG that is characterized by unique and heterogeneous features. However, the non-inflammatory DIPG microenvironment greatly limits the role of immunotherapy in DIPG. Encouragingly, the induction of immunogenic cell death, accompanied by the release of damage-associated molecular patterns (DAMPs) shows satisfactory efficacy of immune stimulation and antitumor strategies. This review dwells on the dilemma and advances in immunotherapy for DIPG, and the potential efficacy of immunogenic cell death (ICD) in the immunotherapy of DIPG. [ABSTRACT FROM AUTHOR]

Simple Summary: Diffuse intrinsic pontine gliomas are malignant brain tumors which arise from the pons in children. These tumors are incurable and nearly all the patients die within a year after diagnosis. To identify effective therapeutics, the molecular mechanisms of tumorigenesis need be comprehensively understood and advanced mouse DIPG models have to be developed for further therapeutic assessment. Over the past decade, remarkable research progress has been made, leading to several ongoing clinical trials. In this review, we update the molecular findings and summarize innovative mouse models generated in the past few years, that are used to understand DIPG and help identify potential treatments. We also prospect future directions for the development of next generation DIPG mouse models. Diffuse intrinsic pontine gliomas (DIPGs) account for ~15% of pediatric brain tumors, which invariably present with poor survival regardless of treatment mode. Several seminal studies have revealed that 80% of DIPGs harbor H3K27M mutation coded by HIST1H3B, HIST1H3C and H3F3A genes. The H3K27M mutation has broad effects on gene expression and is considered a tumor driver. Determination of the effects of H3K27M on posttranslational histone modifications and gene regulations in DIPG is critical for identifying effective therapeutic targets. Advanced animal models play critical roles in translating these cutting-edge findings into clinical trial development. Here, we review current molecular research progress associated with DIPG. We also summarize DIPG animal models, highlighting novel genomic engineered mouse models (GEMMs) and innovative humanized DIPG mouse models. These models will pave the way towards personalized precision medicine for the treatment of DIPGs. [ABSTRACT FROM AUTHOR]