Background: Gliomas are the most common primary malignant tumors of the central nervous system. Accurate preoperative grading is essential for individualized surgical planning and treatment selection; however, reliable non-invasive prediction tools integrating multimodal preoperative data remain limited. This study aimed to develop and internally validate an interpretable machine-learning model for non-invasive glioma grading. Methods: Clinical and imaging data from 400 patients with pathologically confirmed gliomas were retrospectively collected. Twenty-four preoperative variables were analyzed. The dataset was randomly divided into training and validation cohorts (7:3). Feature selection was performed using a combination of the Boruta algorithm and logistic regression analyses, followed by correlation filtering. Seventeen machine-learning algorithms were benchmarked using five-fold cross-validation, and the optimal model was evaluated in the independent validation cohort using ROC analysis, calibration assessment, precision-recall curves, and decision curve analysis. Model interpretability was examined using SHAP. Results: Eight key predictors were identified, including age, focal neurological deficits, midline shift, tumor laterality, tumor lobar location, enhancing tumor volume, and MRS-derived Cho/NAA and Cho/Cr ratios. The Random Forest model achieved an area under the ROC curve of 0.946 (95% CI: 0.902-0.989) in the validation cohort. Calibration analysis demonstrated reasonable agreement between predicted and observed outcomes, and the precision-recall curve yielded an average precision of 0.98. Decision curve analysis indicated net clinical benefit across relevant probability thresholds. Conclusions: A multimodal machine-learning model integrating clinical, structural imaging, and MRS-derived metabolic features was developed and internally validated for non-invasive preoperative glioma grading. The model showed good discrimination and calibration and provided individualized probability estimates, suggesting potential value for preoperative risk stratification. However, clinical deployment remains premature, and further external validation is required.

Objective: Meningiomas and schwannomas are the most commonly encountered intradural extramedullary (IDEM) spinal cord tumors, which can lead to spinal cord compression and limb dysfunction. Due to the unique anatomical barrier provided by the arachnoid or pia mater, complete excision of these tumors is achievable through surgical intervention. While some studies have suggested the feasibility of using the posterior approach for ventral IDEM tumors, there is a lack of research on surgical management strategies and functional outcomes for these tumors. Methods: This study composed of 58 consecutive patients who underwent complete resection of IDEM tumors. Ventral IDEM tumors were removed through a narrow space between the dura and the spinal cord, without retracting or rotating the spinal cord, using the posterior approach. The baseline characteristics of the patients, including sex, age, tumor position at the spinal level, histopathological type, percentage of tumor occupying the intradural space, duration of surgery, perioperative neurological complications, neurological outcomes, and recurrence, were retrospectively analyzed. Results: The study included 28 cases of meningiomas and 30 cases of schwannomas. Among these, 24 patients had ventral IDEM tumors, while 34 had dorsal IDEM tumors. There was no statistically significant difference in operative time between the two groups. Importantly, the comparison of preoperative and postoperative McCormick scores or KPS changes showed no statistically significant difference (p = 0.063), indicating similar improvements in neurological function post-surgery. Each group had one case of cerebrospinal fluid leakage identified, and no recurrences were observed in either group during the follow-up period. Conclusion: Complete resection of ventral IDEM tumors can be achieved with clinical outcomes comparable to dorsal IDEM tumors through a posterior approach. Therefore, a thorough understanding of the anatomical and growth characteristics of IDEM tumors is essential for safe excision. However, the posterior approach should be used cautiously and with a full understanding of its limitations.

Background: Glioma is the most common malignant brain tumor of the central nervous system. Despite of the improvement of therapeutic strategy, the prognosis of malignant glioma patients underwent by STUPP strategy is still unexpected. Previous studies have suggested that ticagrelor exerted chemotherapeutic effects by inhibition of epithelial-mesenchymal transition (EMT) in various diseases including tumors. However, whether ticagrelor can exhibit the antitumor efficiency in glioma by affecting the EMT process is still unclear. In this study, we investigated the cancer-fighting role of ticagrelor and demonstrated its chemotherapeutic mechanism in glioma. Materials and methods: The MTT assay was performed to detect the cytotoxicity of ticagrelor in glioma cells. We evaluated the expression of Ki67 in glioma cells by immunofluorescence assay after ticagrelor treatment. We conducted wound healing assay and transwell assay to determine the effects of ticagrelor on the migration and invasion of glioma cells. RNA-seq analysis was conducted to examine potential target genes and alternative signaling pathways for ticagrelor treatment. The expression levels of key EMT -related proteins were examined by Western blot experiment. Results: Ticagrelor inhibited the proliferation, migration and invasion of glioma cells with a favorable toxicity profile in vitro. Ticagrelor downregulated the expression of GTSE1 in glioma cells. RNA-seq analysis explored that GTSE1 acted as the potential target gene for ticagrelor treatment. Upregulation of GTSE1 antagonized the inhibitory effect of ticagrelor on the invasion of glioma and EMT progression by regulation of PI3K/Akt/NF-kappa B signaling pathway. And ticagrelor also exhibited the similar chemotherapeutic effect of glioma in vivo. Conclusions: Ticagrelor as a potential chemotherapeutic option induced the inhibition of the GTSE1-induced EMT progression by regulation of PI3K/AKT/NF-kappa B signaling pathway.

Verbascum thapsus (VT) is a medicinal plant that is used in folk medicine to treat a variety of ailments. For this study, the biological functions of VT methanol extract were determined in vitro. The plant's methanol extract was created through the maceration process. The phytochemical composition of plant extracts was investigated using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The antioxidant capacity of the extract was determined using the DPPH (2,2-diphenyl-1-picrylhydrazil) and ABTS (2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) tests and its cytotoxicity was assessed using the MTT ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole)) assay on the Caco-2 (human colorectal adenocarcinoma cells), LNCaP (Lymph Node Carcinoma of the Prostate), and HEK293 cell lines (Human embryonic kidney 293 cells) used to model colon, prostate, and non-cancerous cells. VT extract showed low DPPH and ABTS radical scavenging activities compared to standard antioxidants at 30 mg/ml concentration. In addition, it was determined that VT extract inhibited acetylcholinesterase enzyme.

Abstract Background  Spinal cord hemangioblastomas are rare benign and highly vascular tumors that develop either sporadically or as part of von Hippel–Lindau (VHL) disease. Generally, complete resection without significant neurologic deficit remains considerably challenging due to the risk of massive bleeding. The current study therefore aimed to describe en bloc resection of spinal cord hemangioblastomas according to the typical anatomical structures of peripheral lesions and evaluate the neurofunctional prognosis of this technique. Methods  A total of 39 spinal cord hemangioblastomas from a series of 19 patients who underwent en bloc resection were retrospectively analyzed. In all cases, clinical and radiologic characteristics, as well as surgical tenets, were retrospectively determined and analyzed. Short- and long-term outcomes were analyzed using the McCormick grade and Odom's criteria. Factors significantly associated with poor neurologic function after en bloc resection were also determined. Results  All 39 spinal cord hemangioblastomas, including 28 intramedullary, 2 intramedullary–extramedullary, and 9 extramedullary lesions, were located dorsally or dorsolaterally (100.0%). The most common lesion location was the thoracic segment (53.8%), with most of the lesions being accompanied by syringomyelia (94.7%). Long-term follow-up (mean: 103 ± 50.4 months) for prognosis determination revealed that 88.2% (15/17) of all cases had stable or improved neurofunctional outcomes according to the McCormick grade and Odom's criteria. Only one case with VHL disease developed recurrence 4 years after surgery. Additionally, statistical analysis showed that VHL disease was an independent prognostic factor associated with deteriorating neurologic function ( p  = 0.015). Conclusions  En bloc resection facilitated satisfactory long-term functional outcomes in patients with spinal cord hemangioblastomas. Given that VHL disease was identified as a predictor of poor long-term outcomes, regular long-term follow-up of patients with VHL-associated spinal cord hemangioblastoma seems necessary.

目前在线教学成为各医学高校授课的主要形式.基于新的教学形式,医学院校更应该探索一些更匹配的教学模式以提升教学成效,这些新的教学模式对于医药学教育的影响也需进一步的验证.为满足新形势下药学发展的需要,培养满足临床需求的药学生,哈尔滨医科大学附属第一医院对临床药学生课程教学模式进行改革,包括优化理论课程教学模式、临床浸入式课程教学模式以及临床实践教学模式,以期提高学生的理论知识掌握与应用能力,更好地进行临床实践.最终,根据该院临床药学教学模式改革效果,研究发现利用在线教学模式将理论知识与案例研究相结合,可以在短时间内提高学生的理论考试成绩,更能够激发学生的学习兴趣,带领学生进行探索和深度研究.这为未来的理论课程教学带来了新的方向.

BACKGROUND: Spinal meningiomas are the common benign tumors in intradural extramedullary spinal tumors. Simpson grade I resection is recommended to avoid tumor recurrence. However, the dura reconstruction increases a risk of cerebrospinal fluid leakage after this surgical resection. To address this concern, the inner dura layer resection and long-term surgical outcomes of this technique were designed and examined after total tumor resection to preserve the outer dura layer. METHODS: This study included 40 spinal meningioma patients undergoing the outer dura layer resection between 2002 and 2019. Clinical characteristics, radiologic features, preoperative and postoperative functional states, tumor recurrence, and perioperative complications were described and evaluated. RESULTS: A total of 40 spinal meningioma cases with the median age of 63 years (36-81 years) were enrolled in this study. The median postoperative follow-up period of all 40 cases was 96 months (34-193 months). About 82.5% of cases were located in the thoracic spine, while 16.5% of cases were located in the cervical spine. Of the symptomatic cases, 87.5% of cases follow with satisfactory outcomes and 12.5% of cases follow with unexpected outcomes. The local spinal meningioma recurrence rate was 2.5% (1 of 40 cases). No postoperative cerebrospinal fluid leak occurred in the 40 spinal meningioma cases. CONCLUSIONS: A long-term postoperative follow-up indicated that this modified spinal dura preservation technique caused good neurologic improvement with rare recurrence. Therefore we recommend this improved technique may be an alternative surgical option for total resection of spinal meningiomas with favorable prognosis.

Abstract Objective Human immunodeficiency virus type 1 (HIV-1) infection disturbs the balance of CD4+ T cells and monocytes in the immune system. In the early stage of infection, the virus stimulates the activation and proliferation of immune cells, induces the release of cytokines, destroys CD4+ T cells, and accelerates HIV-1 replication and AIDS progression. It is essential to explore cytokine changes after HIV-1 infection and further understand the underlying mechanism of HIV infection. Materials and methods In this study, we enrolled 38 HIV-infected subjects and 30 healthy subjects. We measured and compared CD4+ T cell counts, the tropism of HIV and the serum cytokine levels in different groups. Results Our results showed significantly higher serum levels of IL-1β, IL-2, IL-4, IL-7, IL-10, IL-17, IFN-γ, and TNF-α in HIV-infected patients. Higher levels of IL-6 and IL-17 were observed in the < 200/mL CD4+ T cell count group, and higher levels of IL-2 were observed in the CCR5-tropic HIV strain group. Conclusion In conclusion, we found that HIV infection-induced activation of the immune system. IL-6 and IL-17 may predict the severity of HIV disease and regulate HIV infection. The level of IL-2 depended on the type of virus strain.

Photodynamic therapy (PDT) is a novel therapy that achieves therapeutic effects by exciting photosensitizers accumulated in tumour tissues with specific wavelengths of light. Among the various photosensitizers, 5-aminoketovaleric acid (5-ALA) has been used in the treatment of basal cell carcinoma, glioma, bladder cancer, and other tumours owing to its safety and economy. However, the efficacy of PDT is limited by the poor permeability and targeting of 5-ALA, and favourable nano-delivery systems would provide ideal platforms to solve this problem. Researchers have developed a variety of 5-ALA nano-delivery systems, such as nanoparticles, liposomes, and gels, and have achieved good efficacy in the treatment of various tumours. In this review, we present the progress of 5-ALA nano-delivery systems in different oncology fields and discuss the current challenges and future research prospects.

Background Glioma is the most common primary brain tumor in adults with poor prognosis. The glioma patients benefit from STUPP strategy, including maximum and safe resection and adjuvant radiotherapy and chemotherapy. Arsenic trioxide could inhibit various tumors. However, it is a challenge to evaluate the efficiency and safety of srsenic trioxide in glioma patients. Objective The arsenic trioxide has the potent therapeutic effect on glioma. However, the safety and efficacy of local interstitial chemotherapy with arsenic trioxide in newly diagnosed glioma patients is unclear. Methods All patients received partial or complete tumor resection and intraoperative implantation of Ommaya reservoirs followed by standard radiotherapy. Arsenic trioxide with the starting dose 0.3 mg was administered via an Ommaya reservoir catheter inserted into the tumor cavity for 5 consecutive days every 3 months for a total of eight cycles unless tumor progression or excessive toxicity was observed. Results No hematological or grade 4 non-hematological toxicity was observed in any patient during arsenic trioxide treatment. The maximum tolerated dose of 1.5 mg of arsenic trioxide was safe and well tolerated. The median overall survival for WHO grade 3 glioma was 33.6 months, and for glioblastoma was 13.9 months. The median progression-free survival for WHO grade 2 glioma was 40.3 months, for grade 3 glioma was 21.5 months, and for glioblastoma was 9.5 months. Conclusion These results suggest that arsenic trioxide is safe and well tolerated with local delivery into the tumor cavity of the brain, and the dose recommended for a phase II trial is 1.5 mg.

Glioblastoma (GBM) is the most common and aggressive tumor of the central nervous system, which has a highly invasive growth pattern, which creates poor prospects for patient survival. Chemotherapy and tumor surgery are limited by anticancer drug resistance and tumor invasion. Evidence suggests that combinations of treatments may be more effective than single drugs alone. Natural polyphenolic compounds have potential as drugs for the treatment of glioblastoma and are considered as potential anticancer drugs. Although these beneficial effects are promising, the efficacy of natural polyphenolic compounds in GBM is limited by their bioavailability and blood-brain barrier permeability. Many of them have a significant effect on reducing the progression of glioblastoma through mechanisms such as reduced migration and cell invasion or chemosensitization. Various chemical formulations have been proposed to improve their pharmacological properties. This review summarizes natural polyphenolic compounds and their physiological effects in glioblastoma models by modulating signaling pathways involved in angiogenesis, apoptosis, chemoresistance, and cell invasion. Polyphenolic compounds are emerging as promising agents for combating the progression of glioblastoma. However, clinical trials are still needed to confirm the properties of these compounds in vitro and in vivo.

The tumor microenvironment plays an important role in tumor progression. Hyaluronic acid (HA), an important component of the extracellular matrix in the tumor microenvironment, abnormally accumulates in a variety of tumors. However, the role of abnormal HA accumulation in glioma remains unclear. The present study indicated that HA, hyaluronic acid synthase 3 (HAS3), and a receptor of HA named CD44 were expressed at high levels in human glioma tissues and negatively correlated with the prognosis of patients with glioma. Silencing HAS3 expression or blocking CD44 inhibited glioma cell proliferation in vitro and in vivo. The underlying mechanism was attributed to the inhibition of autophagy flux and maintaining glioma cell cycle arrest in G1 phase. More importantly, 4-methylumbelliferone (4-MU), a small competitive inhibitor of Uridine diphosphate (UDP) with the ability to penetrate the blood-brain barrier (BBB), also inhibited glioma cell proliferation in vitro and in vivo. Thus, approaches that interfere with HA metabolism by altering the expression of HAS3 and CD44 and the administration of 4-MU potentially represent effective strategies for glioma treatment.

High-grade glioma is the most common and aggressive primary brain tumor in adults with poor therapeutic efficiency and survival prognosis. Cell division cycle associated 8 (CDCA8) has been well known as a cell cycle regulator and tumor promotor in various malignant tumors. However, its biological role in glioma still remains unclear. Our results showed that high level of CDCA8 was significantly correlated with advanced WHO grade and poor overall survival and disease-free survival prognosis. In vitro and in vivo investigations demonstrated that CDCA8 promoted the glioma malignancy by promoting cell proliferation, cell migration, and inhibiting cell apoptosis. Moreover, we found its synergetic biological protein-E2F1 by the gene microarray chip. In this study, we revealed that CDCA8 synergized with E2F1 facilitated the proliferation and migration of glioma. In conclusion, our study provides a novel promising therapeutic targets and prognostic biomarkers for malignant glioma treatment.

With high rates of mortality and disability, stroke has caused huge social burden, and 85% of which is ischemic stroke. In recent years, it is a progressive discovery of long non-coding RNA (lncRNA) playing an important regulatory role throughout ischemic stroke. Hypoxia, generated from reduction or interruption of cerebral blood flow, leads to changes in lncRNA expression, which then influence disease progression. Therefore, we reviewed studies on expression of hypoxia-related lncRNAs and relevant molecular mechanism in ischemic stroke. Considering that hypoxia-inducible factor (HIF) is a crucial regulator in hypoxic progress, we mainly focus on the HIF-related lncRNA which regulates the expression of HIF or is regulated by HIF, further reveal their pathogenesis and adaption after brain ischemia and hypoxia, so as to find effective biomarker and therapeutic targets.

Gliomas are common intracranial tumors with high morbidity and mortality in adults. Transmembrane protein 2 (TMEM2) is involved in the malignant behavior of solid tumors. TMEM2 regulates cell adhesion and metastasis as well as intercellular communication by degrading nonprotein components of the extracellular matrix. This study aimed to evaluate the relationship between TMEM2 expression levels and glioma subtypes or patient prognosis. Our findings revealed that TMEM2 expression was abnormally upregulated in high-grade glioma. Moreover, combining TMEM2, the status of isocitrate dehydrogenase (IDH) and 1p19q, we subdivided molecular subtypes with significant differences in survival. Patients in the MT-codel-low subgroup had better prognosis than those in the WT-no-codel-high subgroup, who fared the worst. Additionally, correlation analysis of TMEM2 and immune cell infiltration indicated an altered tumor microenvironment (TME) and cell redistribution in the TMEM2 high-expression subtype. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that focal adhesion and PI3K-Akt signaling pathways were enriched in the TMEM2-expressing group. In conclusion, aberrant TMEM2 expression can be used as an independent prognostic marker for refining glioma molecular subtyping and accurate prognosis. These findings will improve rational decision making to provide individualized therapy for patients with glioma.

Abstract Background The elevation of plasma D‐dimer levels may predict a higher risk of thrombosis and play a role in the pathological process of patients after spontaneous intracerebral hemorrhage (ICH). However, its function in predicting the prognosis of ICH has not been verified on large cases. Patients and Methods Retrospective cohort study of 1,332 consecutive patients with spontaneous ICH at an academic medical center was conducted. Functional outcome at three months after ICH was dichotomized using the modified Rankin Scale (0–2 versus 3–6). D‐dimer level in blood was analyzed within 1 hr of admission. An ICH outcome score combining D‐dimer level for evaluating poor functional outcome and mortality was tested. Results The proportion of patients with poor functional outcome and mortality at three months was significantly higher in patients with elevated D‐dimer level (p < .001). Multivariable analysis demonstrated that elevated D‐dimer level was an independent predictor of poor functional outcome (odds ratio 1.486, 95% confidence interval 1.086–2.060, p = .014) and mortality (odds ratio 2.015, 95% confidence interval 1.186–3.423, p = .01). An increasing ICH outcome score combining D‐dimer level was associated with increased poor functional outcome and mortality. Conclusions Elevated plasma D‐dimer level after spontaneous ICH is associated with poor functional outcome and mortality. The study suggests that elevated D‐dimer level has a predictive value for outcome and mortality in patients with spontaneous ICH.

5-氨基乙酰丙酸(5-aminolevulinic acid,5-ALA)荧光引导下胶质瘤切除术已广泛应用于临床,能显著提升高级别胶质瘤手术切除率并延长病人生存期.然而5-ALA荧光显影在低级别胶质瘤的手术可视性较低,仅约20％病人能检测到可视荧光,导致肿瘤切除程度及预后评估难度远远大于高级别胶质瘤.本文将对5-ALA荧光引导手术在低级别胶质瘤的研究及临床应用展开综述.