Jun Huang

Aims: Post‐hemorrhagic hydrocephalus (PHH) is a devastating complication. This study aims to elucidate how the acute post‐hemorrhagic adrenergic storm drives neutrophil extracellular traps (NETs) formation, blocks the glymphatic system (GS), and causes an imbalance in intracranial fluid homeostasis, leading to PHH. It is necessary to explore whether pan‐adrenergic inhibition as non‐surgical intervention strategies can rescue this neuro‐immune dysregulation. Methods: Single‐cell RNA sequencing (scRNA‐seq) was used to draw the immune infiltration map. Utilizing a rat PHH model, ventricular volumes and glymphatic fluid dynamics were assessed via MRI and fluorescent tracer tracking. Multiple behavioral analyses were used to observe the neurological dysfunction. The structural integrity of the GS was assessed using IF staining and TEM. The formation of NETs was detected using ELISA, WB, and IF. In vitro, flow cytometry and molecular assays were used to explore the changes in molecular pathways in epinephrine‐stimulated primary neutrophils, and NETs were used to treat astrocytes to study the interaction between them. A pharmacological intervention using pan‐adrenergic inhibitor cocktail PPA (prazosin, propranolol, atipamezole), NETs agonist, NETs inhibitor, and AKT activator was conducted to explore the mechanism. Results: scRNA‐seq identified a pathogenic neutrophil subset presented as a transcriptional phenotype consistent with NETs, which dominated hemorrhagic stroke. Structurally, adrenergic storm‐driven NETs extrusion occluded perivascular spaces and stripped aquaporin‐4 (AQP4) polarization at astrocytic endfeet, precipitating glymphatic stasis and severe ventricular dilation. Molecular analysis revealed that epinephrine might promote the formation of NETs by activating the PI3K/AKT/mTOR cascade. PPA blocked this pathological axis, inhibited NETs, polarized AQP4 distribution, restored the fluid dynamics of the GS, and relieved cognitive deficits after intraventricular hemorrhage and alleviated hydrocephalus. Conclusion: After PHH, targeted pan‐adrenergic inhibition can block the adrenergic storm and inhibit NET formation, protect the clearance function and structural integrity of the GS, stabilize the intracranial fluid homeostasis, and alleviate hydrocephalus in the acute phase. The molecular mechanism may involve the PI3K/AKT/mTOR cascade. This mechanism provides a potential therapeutic strategy for neuro‐immune‐based drug protection.

In recent years, accumulating evidence has established mechanistic connections between the microbiota and the efficacy of anticancer treatments, encompassing microbial communities residing in the gut, within tumors, and across other tissue sites. Across diverse malignancies, distinct compositional and functional profiles of these microbial ecosystems have been associated with differential responses to chemotherapy, immunotherapy, and targeted agents, as observed in both clinical settings and experimental systems. It is now understood that microbial communities exert influence on drug activity through multiple pathways: they may compromise therapeutic efficacy by metabolic inactivation or structural modification of anticancer compounds, or, conversely, potentiate responses by enhancing tumor cell susceptibility. Furthermore, these communities modulate the tumor immune microenvironment, fostering antitumor immunity through augmented antigen presentation and effector cell function, or constraining immune responses via regulatory networks and immunosuppressive myeloid polarization. The crosstalk between microbial cues and signaling networks in malignant and surrounding stromal tissues is widely thought to influence therapeutic outcomes. Key challenges ahead involve proving causation, elucidating context-dependent mechanisms, and translating patient heterogeneity into robust biomarkers and targeted therapies. Anticancer interventions can reportedly alter microbial community structure and function, with therapy-associated dysbiosis potentially contributing to primary or acquired resistance. Microbiota-directed strategies, including transplantation, defined microbial consortia, targeted delivery systems, and lifestyle interventions, are under investigation, yet challenges remain in establishing causality, ensuring safety, and enabling patient stratification. Collectively, these insights establish a translational framework for rationally designed microbiota‒drug combination strategies aimed at enhancing anticancer therapeutic outcomes.

Aims: Intraventricular hemorrhage (IVH) has a high mortality and disability rate and poses significant clinical challenges, which often leads to hydrocephalus and neurological dysfunction. Emerging evidence implicates dysfunction of the glymphatic‐meningeal lymphatic‐deep cervical lymphatic system in the pathogenesis of post‐IVH hydrocephalus. Therapeutic hypothermia (TH) holds promise for mitigating these sequelae. This study investigates the potential of TH to ameliorate IVH‐induced hydrocephalus and neurological dysfunction, while elucidating its underlying mechanisms. Methods: Rat models of IVH are established by intraventricular injection of autologous blood. TH, deep cervical lymph nodes (dCLNs) ligation, and intraperitoneal injection of AMPK inhibitor are used to intervene. Results: In rat models of IVH, TH alleviates neurological dysfunction and attenuates hydrocephalus and pathology damage. TH protects physiological function and maintains normal structure of the glymphatic system. TH improves function and structure of the meningeal lymphatic system and promotes drainage of the deep cervical lymphatic system. TH upregulates RTN3, facilitates phosphorylation of AMPK, and suppresses ERS. All the above effects are reversed by ligation of dCLNs and AMPK inhibitor. Conclusion: TH alleviates hydrocephalus and neurological dysfunction post IVH by enhancing drainage of the glymphatic‐meningeal lymphatic‐deep cervical lymphatic system. The RTN3/AMPK/ERS pathway may be the proposed mechanism mediating this effect. TH is expected to become a novel therapeutic strategy for IVH.

Background Glioma is a type of malignant cancer that affect the central nervous system. New predictive biomarkers have been investigated in recent years, but the clinical prognosis for glioma remains poor. The function of CPLX2 in glioma and the probable molecular mechanism of tumor suppression were the focus of this investigation. Methods The glioma transcriptome profile was downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases for analysis of CPLX2 expression in glioma. RT-qPCR was performed to detect the expression of CPLX2 in 68 glioma subjects who have been followed up. Kaplan-Meier survival analyses were conducted to assess the effect of CPLX2 on the prognosis of glioma patients. The knockdown and overexpressed cell lines of CPLX2 were constructed to investigate the impact of CPLX2 on glioma. The cell growth, colony formation, and tumor formation in xenograft were performed. Results The expression of CPLX2 was downregulated in glioma and was negatively correlated with the grade of glioma. The higher expression of CPLX2 predicted a longer survival, as indicated by the analysis of Kaplan-Meier survival curves. Overexpressed CPLX2 impaired tumorigenesis in glioma progression both in vivo and in vitro. Knocking down CPLX2 promoted the proliferation of glioma cells. The analysis of GSEA and co-expression analysis revealed that CPLX2 may affect the malignancy of glioma by regulating the hypoxia and inflammation pathways. Conclusions Our data indicated that CPLX2 functions as a tumor suppressor and could be used as a potential prognostic marker in glioma.

Background: Glioma is a type of malignant cancer in the central nervous system. New predictive biomarkers have been investigated in recent years, but the clinical prognosis in glioma remains poor. The function of CPLX2 in glioma and the probable molecular mechanism of tumor suppression was the focus of this investigation. Methods: The glioma transcriptome profile is downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases were performed to analyze the expression of CPLX2 in glioma. RT-qPCR was performed to detect the expression of CPLX2 in 68 glioma subjects, these patients who have been followed up. Kaplan-Meier survival analyses were done to evaluate the effect of CPLX2 on the prognosis of glioma patients. The CPLX2 knockdown and overexpressed cell lines were constructed to investigate the effect of CPLX2 on glioma. The cell growth, colony formation, and tumor formation in xenograft were performed. Results: The expression of CPLX2 was downregulated in glioma and negatively correlated to the grade of glioma. The higher expression of CPLX2 predicted a longer survival through the analysis of Kaplan-Meier survival curves. Overexpressed CPLX2 impaired tumorigenesis in glioma progression both in vivo and in vitro. Knocking down of CPLX2 promoted the proliferation of the glioma cells. The analysis of GSEA and co-expression analysis revealed that CPLX2 may affect the malignancy of glioma by regulating hypoxia and inflammation pathway. Conclusions: Our data indicated that CPLX2 functioned as a tumor suppressor and could be used as a potential prognostic marker in glioma.

Glioma, the most common of malignant tumors in the brain, is responsible for the majority of deaths from primary brain tumors. The regulation of long noncoding RNAs (lncRNAs) in HIF‐1α‐driven tumor development remains unclear. LINC02774 is a nuclear lncRNA and that it is being reported for the first time in this study. We found the downregulation of LINC02774 in glioma and decreased with the degree of malignant, with its expression showing a negative correlation with the relative index of enhanced magnetic resonance (RIEMR). RIEMR‐associated LINC02774 was found to inhibit glycolysis by modulating the hypoxia pathway rather than the hypoxia response itself. LINC02774 interacted with its neighboring gene, RP58 (ZBTB18), to enhance the expression of PHD3, which catalyzed HIF‐1α hydroxylase and ubiquitination, leading to the downregulation of HIF‐1α expression. We also found that the function of LINC02774, dependent on PHD3, was diminished upon RP58 depletion. Notably, higher expression of RIEMR‐associated LINC02774 was associated with a favorable prognosis. In conclusion, these findings reveal the role of RIEMR‐associated LINC02774, which relies on its neighbor gene, RP58, to regulate the hypoxia pathway as a novel tumor suppressor, suggesting its potential to be a prognostic marker and a molecular target for the therapy of glioma.

Objective: This study aims to investigate the inducing factors that cause ischemic events and summarize the clinical features between TIA and infarction in pediatrics with ischemic MMD. Methods: A retrospective analysis was conducted from September 2015 to September 2021 in-patients and out-patients admitted to Xiangya Hospital of Central South University. Results: The results indicated that 74.1% (63/85) of patients had obvious inducing factors before the ischemic attack, among which fever accounted for 41.3% (26/63). TIA patients with obvious inducing factors accounted for 83.3% (25/30) cases, and cerebral infarction patients with obvious inducing factors accounted for 69.1% (38/55). The inducing factorof fever is significantly higher in patients with infarction than in those with TIA (p=0.0023). The inducing factors of crying (p=0.0006) and consumption of irritating foods (p=0.0018) are significantly higher in patients with TIA than infarction. The age was younger in patients with infarction than TIA (8.8 ± 0.7 vs 5.8 ± 0.5, p=0.0011). The infarctions were more common in patients with PCA involvement than in patients present with TIA (p=0.0044). Multivariate analysis revealed that crying (p= 0.002) was independently associated with TIA. Conclusions: The occurrence of ischemic events in children with ischemic MMD tends to be associated with a clear inducing factor. Fever is more common in causing cerebral infarction, while crying and eating irritating foods are easy to cause TIA. Crying was identified as an independent risk factor for inducing TIA. The patients present with infarction are associated with younger age and PCA involvement in pediatric ischemic MMD.

胶质瘤是中枢神经系统最常见的恶性肿瘤，低氧微环境在实体肿瘤中普遍存在。本研究旨在探讨在低氧环境中发生上调的相关基因及其对胶质瘤生长和预后的影响。 在基因表达数据库(Gene Expression Omnibus，GEO)中筛选胶质瘤与低氧相关的数据集，通过生物信息学分析低氧处理与非低氧处理之间的差异表达基因，并在低氧处理后的细胞中通过real-time PCR和蛋白质印迹法来验证并筛选出C10orf10(chromosome 10 open reading frame 10)基因。下载癌症基因组图谱(The Cancer Genome Atlas，TCGA)以及中国脑胶质瘤图谱(Chinese Glioma Genome Atlas，CGGA)数据库中胶质瘤样本数据集，分析在不同级别胶质瘤中C10orf10 mRNA的表达及其对胶质瘤预后的影响。收集2017年3月至2021年1月在中南大学湘雅医院行手术治疗的68例胶质瘤患者的瘤组织标本及随访数据，采用real-time PCR检测不同级别胶质瘤中C10orf10 mRNA的表达，再结合Kaplan-Meier法分析C10orf10与胶质瘤预后之间的关系。构建干扰C10orf10表达的胶质瘤细胞系，采用细胞计数试剂盒-8(cell counting kit-8，CCK-8)及克隆形成实验评估C10orf10对胶质瘤细胞增殖的影响。 与常氧条件下相比，在低氧环境下胶质瘤细胞系能够显著上调C10orf10 mRNA和蛋白质水平(均PC10orf10 mRNA表达水平随着WHO分级的增高而上调(PC10orf10 mRNA表达水平越高，患者的生存期则越短(PC10orf10 mRNA表达水平在复发胶质瘤中较原发胶质瘤中表达高(PC10orf10的表达后，在常氧和低氧环境下均能够显著抑制胶质瘤细胞的生长(均PC10orf10的表达水平与胶质瘤的生长和预后相关，并有望成为胶质瘤的一个预后标志物及治疗靶点。