Background: Age is associated with the prognosis of glioma patients, but there is no uniform standard of age-group classification to evaluate the prognosis of glioma patients. In this study, we aimed to establish an age group classification for risk stratification in glioma patients. Methods: 1502 patients diagnosed with gliomas at Nanfang Hospital between 2000 and 2018 were enrolled. The WHO grade of glioma was used as a dependent variable to evaluate the effect of age on risk stratification. The evaluation model was established by logistic regression, and the Akaike information criterion (AIC) value of the model was used to determine the optimal cutoff points for age-classification. The differences in gender, WHO grade, pathological subtype, tumor cell differentiation, tumor size, tumor location, and molecular markers between different age groups were analyzed. The molecular markers included GFAP, EMA, MGMT, P53, NeuN, Oligo2, EGFR, VEGF, IDH1, Ki-67, PR, CD3, H3K27M, TS, and 1p/19q status. Results: The proportion of men with glioma was higher than that of women with glioma (58.3% vs 41.7%). Analysis of age showed that appropriate classifications of age group were 0–14 years old (pediatric group), 15–47 years old (youth group), 48–63 years old (middle-aged group), and ≥ 64 years old (elderly group).The proportions of glioblastoma and large tumor size (4–6 cm) increased with age (p = 0.000, p = 0.018, respectively). Analysis of the pathological molecular markers across the four age groups showed that the proportion of patients with larger than 10% area of Ki-67 expression or positive PR expression increased with age (p = 0.000, p = 0.017, respectively). Conclusions: Appropriate classifications of the age group for risk stratification are 0–14 years old (pediatric group), 15–47 years old (young group), 48–63 years old (middle age group) and ≥ 64 years old (elderly group). This age group classification is effective in evaluating the risk of glioblastoma in glioma patients.

Background: Temozolomide (TMZ) treatment efficacy in glioblastoma (GBM) patients has been limited by resistance in the clinic. Currently, there are no clinically proven therapeutic options available to restore TMZ treatment sensitivity. Here, we investigated the potential of albumin-bound paclitaxel (ABX), a novel microtubule targeting agent, in sensitizing GBM cells to TMZ and elucidated its underlying molecular mechanism. Methods: A series of in vivo and in vitro experiments based on two GBM cell lines and two primary GBM cells were designed to evaluate the efficacy of ABX in sensitizing GBM cells to TMZ. Further proteomic analysis and validation experiments were performed to explore the underlying molecular mechanism. Finally, the efficacy and mechanism were validated in GBM patients derived organoids (PDOs) models. Results: ABX exhibited a synergistic inhibitory effect on GBM cells when combined with TMZ in vitro. Combination treatment of TMZ and ABX was highly effective in suppressing GBM progression and significantly prolonged the survival oforthotopic xenograft nude mice, with negligible side effects. Further proteomic analysis and experimental validation demonstrated that the combined treatment of ABX and TMZ can induce sustained DNA damage by disrupting XPC and ERCC1 expression and nuclear localization. Additionally, the combination treatment can enhance ferroptosis through regulating HOXM1 and GPX4 expression. Preclinical drug-sensitivity testing based on GBM PDOs models confirmed that combination therapy was significantly more effective than conventional TMZ monotherapy. Conclusion: Our findings suggest that ABX has the potential to enhance TMZ treatment sensitivity in GBM, which provides a promising therapeutic strategy for GBM patients.

Objective. To evaluate the efficacy of Xuefu Zhuyu Tang (XFZYT) for treating angina pectoris (AP). Methods. Six databases were searched (up to December, 2013). Eligible randomized controlled trials (RCTs) evaluating the efficiency of XFZYT plus traditional antianginal medications (TAMs) compared with TAMs alone in patients with AP were included. The outcomes were relief of anginal symptoms (RAS) and improvement of electrocardiogram (ECG) and blood high‐density lipoprotein cholesterol (HDL‐C) level. Result. Finally 14 RCTs were included. There were evidences that XFZYT combined with TAMs was more effective in improving RAS (RR = 1.29; 95% CI = [1.20, 1.38]), ECG (RR = 1.37; 95% CI = [1.22, 1.54]), and blood HDL‐C level (MD = 0.29 mmol/L; 95% CI = [0.23, 0.35]) compared with TAMs alone. Our meta‐analysis also showed the pooled number needed to treat (NNT) of the group with stable angina pectoris (SAP) was smaller in improving RAS (4.2 versus 5.7) and ECG (3.1 versus 5.5) compared with the group with both SAP and unstable angina pectoris (UAP). Conclusion. Combination therapy with XFZYT and TAMs is more effective in treating AP compared with TAMs alone. And XFZYT may be a more suitable choice for the treatment of SAP. However, the findings should be interpreted with caution due to the mediocre methodological quality of the included RCTs.

Pleomorphic xanthoastrocytoma (PXA), anaplastic pleomorphic xanthoastrocytoma (A-PXA), and epithelioid glioblastoma (E-GBM) show overlapping features. However, little is known about their clinical characteristics, molecular features and relationship with progression. Fourteen patients diagnosed at Nanfang Hospital from 2016 to 2019 were enroled, including eleven PXA patients, two A-PXA patients, and one E-GBM patient. All tumour tissue samples of the fourteen patients were examined by immunohistochemical staining (MGMT, VEGF, BRAF-V600E, etc.). The mean age of 13 patients with PXA or A-PXA was 25.4 years; twelve of these patients had tumours at supratentorial regions. VEGF positivity was detected in the tumour samples of 13 patients, MGMT positivity in 10 patients, and BRAF-V600E positivity in 7 patients. The recurrent tumour tissue of the patient with E-GBM arising from A-PXA was screened to detect 11 glioma markers (MGMT, BRAF-V600E, etc.) and chromosome 1p/19q by next-generation sequencing (NGS). For the tumour sample of the E-GBM patient who survived for up to 11 years after the fourth resection, BRAF V600E was wild type in the sample obtained from the first surgery, while it was mutant in the second, third, and fourth surgeries. In contrast, the promoter status of MGMT in the four surgeries was unmethylated. The NGS results showed that the mutation frequencies of BRAF V600E in the second, third and fourth surgeries were 14.06%, 9.13% and 48.29%, respectively. Collectively, the results suggest that patients with A-PXA may relapse multiple times and eventually progress to E-GBM with the BRAF-V600E mutation.

Lactylation, a type of post-translational modification (PTM) of proteins driven by cancer metabolic reprogramming, not only offers new perspectives on the Warburg effect but also has drawn increasing attention due to its critical roles in tumorigenesis and therapeutic resistance. Given its significant potential for precision cancer therapy, this review first integrates recent advancements in lactylation research by systematically summarizing newly identified lactylation writers, readers, and erasers, as well as their involvement in feedback loops and crosstalk with other modifications. Subsequently, we elaborate on how histone and non-histone lactylation contribute to both intrinsic and acquired resistance to radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Key mechanisms encompass maintaining cancer stemness, enhancing DNA damage repair, reprogramming metabolic pathways, inhibiting ferroptosis, and promoting an immunosuppressive tumor microenvironment. Finally, we evaluate preclinical strategies targeting lactylation, including inhibition of lactate metabolic pathways and direct modulation of lactylation-modifying enzymes or lactylated proteins, while critically assessing mechanistic challenges and early-phase clinical trial outcomes. Our analysis establishes a theoretical framework and actionable roadmap for the development of lactylation-based precision therapies in oncology.

Background: The clinical efficacy of temozolomide (TMZ) in glioblastoma (GBM) patients is often limited by the development of resistance. To date, no clinically validated therapeutic strategies exist to restore sensitivity to TMZ treatment. In this study, we investigated the potential of FR054, a hexosamine biosynthesis pathway (HBP) inhibitor, to sensitize GBM cells to TMZ and elucidated its underlying molecular mechanism.Methods: TMZ‐resistant U87‐MG and A172 cell lines were generated through stepwise exposure to increasing concentrations of TMZ. Proteomics and bioinformatics analyses revealed HBP activation in these resistant cells. The effects of FR054 alone or in combination with TMZ were assessed using cell line models, GBM organoid models, and intracranial xenograft models. Transcriptomic analysis and validation experiments were further conducted to explore the molecular mechanisms involved.Results: Long‐term exposure to TMZ induced resistance in U87‐MG and A172 GBM cells, which was associated with the activation of the HBP pathway. PGM3, a key enzyme in the HBP, was found to correlate with poor prognosis in GBM patients. The combination of FR054, a specific PGM3 inhibitor, with TMZ exhibited synergistic inhibitory effects in vitro and superior inhibitory efficacy in GBM organoid models. In vivo, this combination significantly suppressed tumor progression and prolonged survival in orthotopic xenograft mice with minimal side effects. Mechanistically, FR054 enhanced TMZ sensitivity by inhibiting protein O‐GlcNAcylation and promoting ferroptosis via the upregulation of HMOX1 and downregulation of GPX4.Conclusion: Our findings demonstrate that targeting the HBP pathway with FR054 can overcome TMZ resistance in GBM by reducing O‐GlcNAc modification and inducing ferroptosis. This novel approach enhances the efficacy of TMZ, offering a promising therapeutic strategy for GBM patients with limited treatment options.