3D residual attention hierarchical fusion for real-time detection of the prostate capsule.

BACKGROUND: For prostate electrosurgery, where real-time surveillance screens are relied upon for operations, manual identification of the prostate capsule remains the primary method. With the need for rapid and accurate detection becoming increasingly urgent, we set out to develop a deep learning approach for detecting the prostate capsule using endoscopic optical images. METHODS: Our method involves utilizing the Simple, Parameter-Free Attention Module(SimAM) residual attention fusion module to enhance the extraction of texture and detail information, enabling better feature extraction capabilities. This enhanced detail information is then hierarchically transferred from lower to higher levels to aid in the extraction of semantic information. By employing a forward feature-by-feature hierarchical fusion network based on the 3D residual attention mechanism, we have proposed an improved single-shot multibox detector model. RESULTS: Our proposed model achieves a detection precision of 83.12% and a speed of 0.014 ms on NVIDIA RTX 2060, demonstrating its effectiveness in rapid detection. Furthermore, when compared to various existing methods including Faster Region-based Convolutional Neural Network (Faster R-CNN), Single Shot Multibox Detector (SSD), EfficientDet and others, our method Attention based Feature Fusion Single Shot Multibox Detector (AFFSSD) stands out with the highest mean Average Precision (mAP) and faster speed, ranking only below You Only Look Once version 7 (YOLOv7). CONCLUSIONS: This network excels in extracting regional features from images while retaining the spatial structure, facilitating the rapid detection of medical images.

A Joint Scheduling Scheme for WiFi Access TSN.

In the context of Industry 4.0, industrial production equipment needs to communicate through the industrial internet to improve the intelligence of industrial production. This requires the current communication network to have the ability of large-scale equipment access, multiple communication protocols/heterogeneous systems interoperability, and end-to-end deterministic low-latency transmission. Time-sensitive network (TSN), as a new generation of deterministic Ethernet communication technology, is the main development direction of time-critical communication technology applied in industrial environments, and Wi-Fi technology has become the main way of wireless access for users due to its advantages of high portability and mobility. Therefore, accessing WiFi in the TSN is a major development direction of the current industrial internet. In this paper, we model the scheduling problem of TSN and WiFi converged networks and propose a scheme based on a greedy strategy distributed estimation algorithm (GE) to solve the scheduling problem. Compared with the integer linear programming (ILP) algorithm and the Tabu algorithm, the algorithm implemented in this paper outperforms the other algorithms in being able to adapt to a variety of different scenarios and in scheduling optimization efficiency, especially when the amount of traffic to be deployed is large.

Single-cell RNA sequencing reveals tumor heterogeneity, microenvironment, and drug-resistance mechanisms of recurrent glioblastoma.

Glioblastomas are highly heterogeneous brain tumors. Despite the availability of standard treatment for glioblastoma multiforme (GBM), i.e., Stupp protocol, which involves surgical resection followed by radiotherapy and chemotherapy, glioblastoma remains refractory to treatment and recurrence is inevitable. Moreover, the biology of recurrent glioblastoma remains unclear. Increasing evidence has shown that intratumoral heterogeneity and the tumor microenvironment contribute to therapeutic resistance. However, the interaction between intracellular heterogeneity and drug resistance in recurrent GBMs remains controversial. The aim of this study was to map the transcriptome landscape of cancer cells and the tumor heterogeneity and tumor microenvironment in recurrent and drug-resistant GBMs at a single-cell resolution and further explore the mechanism of drug resistance of GBMs. We analyzed six tumor tissue samples from three patients with primary GBM and three patients with recurrent GBM in which recurrence and drug resistance developed after treatment with the standard Stupp protocol using single-cell RNA sequencing. Using unbiased clustering, nine major cell clusters were identified. Upregulation of the expression of stemness-related and cell-cycle-related genes was observed in recurrent GBM cells. Compared with the initial GBM tissues, recurrent GBM tissues showed a decreased proportion of microglia, consistent with previous reports. Finally, vascular endothelial growth factor A expression and the blood-brain barrier permeability were high, and the O6 -methylguanine DNA methyltransferase-related signaling pathway was activated in recurrent GBM. Our results delineate the single-cell map of recurrent glioblastoma, tumor heterogeneity, tumor microenvironment, and drug-resistance mechanisms, providing new insights into treatment strategies for recurrent glioblastomas.

Clinical significance of histopathological features of paired recurrent gliomas: a cohort study from a single cancer center.

OBJECTIVE: To explore the histopathological characteristics of paired recurrent gliomas and their clinical significance. METHODS: Glioma patients who received both primary surgery and reoperation when recurrence at Sun Yat-sen University Cancer Center from June 2001 to June 2019 were enrolled. Clinical and pathological characteristics were analyzed retrospectively, and histopathology of reoperation specimens was divided into three categories according to tumor cell activity and the degree of necrosis: active group, low-activity group, and necrosis group. RESULTS: A total of 89 patients were included in this study. The 2016 WHO grade of the first operation pathology and IDH1 status were related to survival time after the first operation, but there was no significant association with survival time after reoperation. The time interval between primary and reoperation was shorter for primary high-grade glioma and/or IDH1 wild-type tumor patients than for low-grade glioma and/or IDH1 mutant tumor patients (P < 0.001). Histopathological types of recurrent gliomas were analyzed, and 67 cases (75.3%) were classified into the active group, 14 (15.8%) into the low-activity group, and 8 (8.9%) into the necrosis group. The low-activity or necrosis group was associated with a higher radiotherapy dose and shorter operation interval. Further univariate and multivariate Cox survival analyses showed the histopathological patterns of recurrent gliomas to be related to survival time after reoperation. CONCLUSION: Primary WHO low grade or IDH1 mutant gliomas appeared survival benefit mainly on later recurrence, but was not a prognostic predictor following recurrence. Histopathological feature of recurrent glioma is related to previous treatment, including radiotherapy dosage and chemotherapy treatment, and is also an important independent prognostic factor for patients after reoperation.

Selective Electroreductive Hydroboration of Olefins with B2pin2.

Organoboron showed great potential in the synthesis of various high-value chemical compounds. Direct hydroboration of olefins has been witnessed over time as a mainstream method for the synthesis of organoboron compounds. In this work, an electroreductive anti-Markovnikov hydroboration approach of olefins with readily available B2pin2 to synthesize valuable organoboron compounds with high chemo- and regioselectivities under metal catalyst-free conditions was reported. This protocol exhibited broad substrate scope and good functional-group tolerance on styrenes and heteroaromatic olefins, providing synthetically useful alkylborons with high efficiency and even various deuterium borylation products with good D-incorporation when CD3CN was employed as solvent. Furthermore, gram-scale reactions and extensive functional derivatization further highlighted the potential of this method.

Site-Selective Electrochemical C-H Carboxylation of Arenes with CO2.

Herein, a direct, metal-free, and site-selective electrochemical C-H carboxylation of arenes by reductive activation using CO2 as the economic and abundant carboxylic source was reported. The electrocarboxylation was carried out in an operationally simple manner with high chemo- and regioselectivity, setting the stage for the challenging site-selective C-H carboxylation of unactivated (hetero)arenes. The robust nature of the electrochemical strategy was reflected by a broad scope of substrates with excellent atom economy and unique selectivity. Notably, the direct and selective C-H carboxylation of various challenging arenes worked well in this approach, including electron-deficient naphthalenes, pyridines, simple phenyl derivatives, and substituted quinolines. The method benefits from being externally catalyst-free, metal-free and base-free, which makes it extremely attractive for potential applications.

Driver mutations in ADGRL3 are involved in the evolution of ependymoma.

Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

Survival Benefit from Surgical Resection in Lung Cancer Patients with Brain Metastases: a Single-Center, Propensity-Matched Analysis Cohort Study.

BACKGROUND: Brain metastases (BMs) are the most serious complication of lung cancer, affecting the prognosis of lung cancer patients, and pose distinct clinical challenges. This study was designed to explore the prognostic factors related to lung cancer BM and the value of surgical resection in BMs from lung cancer. METHODS: A retrospective analysis was performed on 714 patients with lung cancer BMs screened between January 2010 and January 2018 at the Sun Yat-sen University Cancer Center. A 1:1 propensity score matching analysis was performed to reduce the potential bias between the surgery and the nonsurgery group. In both the raw and the propensity-score matched dataset, univariate and multivariate Cox proportional hazards regression analyses were used to evaluate risk factors for survival. RESULTS: After matching, 258 patients (129 surgery, 129 no surgery) were analyzed. Multivariate analyses after propensity score matching demonstrated that surgical resection was an independent protective factor for overall survival (OS), and older age, lower Karnofsky Performance Scale (KPS) score, and extracranial metastases were independent risk factors for worse OS. Patients without extracranial metastases, without synchronous BM and with a single BM had a better prognosis. CONCLUSIONS: The findings showed that surgical resection, age, KPS score, and extracranial metastases are independent prognostic factors for predicting the OS of patients with lung cancer BMs, and surgical resection for brain metastatic lesions could significantly improve the OS. However, only certain groups of patients with BMs can benefit from intracranial lesion resection, such as no extracranial metastases and metachronous metastases.

Prognostic value of the modified systemic inflammation score in non-small-cell lung cancer with brain metastasis.

BACKGROUND: Brain metastases (BM) from non-small-cell lung cancer (NSCLC) is the most common brain malignancy. Systemic inflammation biomarkers have recently been evaluated as prognosis indicators in several tumors. The combination of these markers has not been evaluated in NSCLC with BM yet. Here, we explored the predictive value of pretreatment inflammatory biomarkers and established a novel, clinically applicable prognostic index for NSCLC patients with BM. METHODS: A retrospective investigation of 951 NSCLC patients newly diagnosed with BM at Sun Yat-sen University Cancer Center was conducted. We randomly divided patients into a training cohort (n = 674) or validation cohort (n = 277). Receiver operating characteristic (ROC) curve analysis was carried out to obtain the optimal cut-off values of pretreatment systemic inflammatory indexes. The associations between serum biomarkers and overall survival (OS) were analyzed by Kaplan-Meier curves and Cox proportional models. The resulting prediction model has been externally verified through the validation cohort. RESULTS: The optimal cut-off value of the neutrophil-lymphocyte ratio (NLR) in predicting OS was 4.71, while the clinical standard of 40 mg/L was chosen as the optimal cut-off value of albumin. Univariate and multivariate analyses revealed that patients receiving local treatment, chemotherapy, a NLR < 4.71 and albumin ≥ 40 mg/l independently predicted improved survival. We combined the two inflammatory indexes (NLR and albumin level) to establish the modified systemic inflammation score (mSIS) which divides patients into low risk, medium risk or high-risk groups. The 1-year OS rates of three groups were 59.7%, 40.5% and 29.4%, respectively in the training cohort. The same result was verified in the validation cohort with the 1-year OS rates 69.7%, 47.0% and 7.7%, respectively. The mSIS exhibited better discrimination power than the American Joint Committee on Cancer's (AJCC) 7th T + N staging system in the training cohort (Harrell's concordance index (C-index): 0.744 vs 0.502, P < 0.05), and the discrimination was also superior to that of AJCC's 7th T + N staging system in the validation cohort (C-index: 0.724 vs 0.527, P < 0.05). The 1-year and 2-year OS rates of the AUC also exhibited superior survival predictive ability to that of the AJCC's 7th T + N staging system in NSCLC patients with BM. CONCLUSION: The pretreatment mSIS may be an independent prognostic factor for OS in NSCLC patients with BM and warrants further research.

Identify glioma recurrence and treatment effects with triple-tracer PET/CT.

BACKGROUND: Differential diagnosis of tumour recurrence (TuR) from treatment effects (TrE), mostly induced by radiotherapy and chemotherapy, is still difficult by using conventional computed tomography (CT) or magnetic resonance (MR) imaging. We have investigated the diagnostic performance of PET/CT with 3 tracers, 13N-NH3, 18F-FDOPA, and 18F-FDG, to identify TuR and TrE in glioma patients following treatment. METHODS: Forty-three patients with MR-suspected recurrent glioma were included. The maximum and mean standardized uptake values (SUVmax and SUVmean) of the lesion and the lesion-to-normal grey-matter cortex uptake (L/G) ratio were obtained from each tracer PET/CT. TuR or TrE was determined by histopathology or clinical MR follow-up for at least 6 months. RESULTS: In this cohort, 34 patients were confirmed to have TuR, and 9 patients met the diagnostic standard of TrE. The SUVmax and SUVmean of 13N-NH3 and 18F-FDOPA PET/CT at TuR lesions were significantly higher compared with normal brain tissue (13N-NH3 0.696 ± 0.558, 0.625 ± 0.507 vs 0.486 ± 0.413; 18F-FDOPA 0.455 ± 0.518, 0.415 ± 0.477 vs 0.194 ± 0.203; both P < 0.01), but there was no significant difference in 18F-FDG (6.918 ± 3.190, 6.016 ± 2.807 vs 6.356 ± 3.104, P = 0.290 and 0.493). L/G ratios of 13N-NH3 and 18F-FDOPA were significantly higher in TuR than in TrE group (13N-NH3, 1.573 ± 0.099 vs 1.025 ± 0.128, P = 0.008; 18F-FDOPA, 2.729 ± 0.131 vs 1.514 ± 0.141, P < 0.001). The sensitivity, specificity and AUC (area under the curve) by ROC (receiver operating characteristic) analysis were 57.7%, 100% and 0.803, for 13N-NH3; 84.6%, 100% and 0.938, for 18F-FDOPA; and 80.8%, 100%, and 0.952, for the combination, respectively. CONCLUSION: Our results suggest that although multiple tracer PET/CT may improve differential diagnosis efficacy, for glioma TuR from TrE, 18F-FDOPA PET-CT is the most reliable. The combination of 18F-FDOPA and 13N-NH3 does not increase the diagnostic efficiency, while 18F-FDG is not worthy for differential diagnosis of glioma TuR and TrE.

[Research Progress on Application of Sports Beverage to Post-exercise Fluid Restoration].

A good hydration status is important to the exercise performance and cognitive function of exercisers.The effective restoration of fluid balance after exercise is helpful to prevent dehydration,maintain body fluid balance,accelerate fatigue recovery,and enhance exercise performance.As the most effective sports nutrition supplement,sports beverage has different ingredients and formulas,and also has various effects.To provide clues for the development of sports beverage,this article reviews the types,components,effects,and mechanisms of sports beverage currently used in post-exercise fluid restoration.

[Effect of the Seasonal Adaptability on Carbohydrate-electrolyte Beverage Efforts on Post-exercise Rehydration in Healthy Young Men].

Objective To compare the effects of carbohydrate-electrolyte beverage on post-exercise rehydration of healthy young men in different seasons,and to explore the influence of seasonal adaptability on fluid and electrolyte balance.Methods Fifteen healthy men,aged(24.4±0.5)years,completed 2 trails in a random crossover design both in summer and winter.During recovery,they consumed a drink volume equivalent to 100% of their sweat loss with plain boiled water(the water group)or carbohydrate-electrolyte beverage(the beverage group).Recovery was monitored for further 180 minutes by the collection of blood and urine samples.Results The dehydration time in summer was significantly shorter by about 20 minutes than that in winter(t=3.045,P=0.004).In summer,the fluid retention rate of the beverage group was significantly higher than that of the water group at 120 minutes after rehydration [(83.7±2.8)% vs.(73.7±3.7)%,F=5.312,P=0.028],and significantly higher than the water group at 180 minutes [(74.8±3.6)% vs.(66.1±4.3)%,F=4.340,P=0.046].In winter,the fluid retention rate of the beverage group at 180 minutes after rehydration was significantly higher than that of the water group [(74.9±4.7)% vs.(68.0±6.0)%,F=4.128,P=0.048].There was no significantly seasonal difference in the fluid retention effect of carbohydrate-electrolyte beverage at 180 minutes after rehydration.In the beverage group,the changes of blood glucose and serum sodium levels(all P<0.05)in summer were significantly higher than those in winter at 10-180 minutes after rehydration,and the fractional excretion of sodium in summer was significantly higher in summer than in winter at 120 and 180 minutes after rehydration(F120=4.972,P=0.034;F180=8.425,P=0.007);however,there was no significant difference in plasma osmolality(all P> 0.05).For the water group,the plasma osmolality in winter was lower than that in summer,while the degree of dryness and thirst was higher in winter than in summer.Conclusions Seasonal adaptability influenced the hydration status and its regulating factors.People dehydrated faster after exercise in summer than in winter,and the hydration status was relatively stable in winter.However,in summer,the blood glucose and electrolytes responded more rapidly to carbohydrate-electrolyte beverage supply,and the plasma osmolality and subjective perception recovered faster.Therefore,during the 180-minute recovery period,the carbohydrate-electrolyte beverage had a higher rehydration efficiency in a short recovery time in summer although there was no significantly seasonal difference in the fluid retention rate.

Platelet-derived alpha-granules are associated with inflammation in patients with NK/T-cell lymphoma-associated hemophagocytic syndrome.

Due to the variable overlap of multiple symptoms, accurate early diagnosis of NK/T-cell lymphoma-associated hemophagocytic syndrome (NK/T-LAHS) is difficult, making the prognosis extremely poor. Hemophagocytic syndrome (HPS) is now diagnosed primarily based on the hemophagocytic lymphohistiocytosis (HLH)-2004 diagnostic criteria, and platelet count is one of the baseline evaluations. However, in our study, the data showed that decreased platelets were not only a clinical feature of HPS but also the key cells that regulate inflammation by releasing α-granules containing upregulated platelet factor 4 (PF4) and downregulated platelet-derived growth factors (PDGFs). Furthermore, we found that angiopoietin-4 (ANG-4), which has significant differential expression, has been less reported, that may affect hematopoiesis and proinflammatory responses and can be used as diagnostic biomarkers together with PF4 and PDGFs.

Skp2 modulates proliferation, senescence and tumorigenesis of glioma.

BACKGROUND: Gliomas represent the largest class of primary central nervous system neoplasms, many subtypes of which exhibit poor prognoses. Surgery followed by radiotherapy and chemotherapy has been used as a standard strategy but yielded unsatisfactory improvements in patient survival outcomes. The S-phase kinase protein 2 (Skp2), a critical component of the E3-ligase SCF complex, has been documented in tumorigenesis in various cancer types but its role in glioma has yet to be fully clarified. In this study, we investigated the function of Skp2 in the proliferation, stem cell maintenance, and drug sensitivity to temozolomide (TMZ) of glioma. METHODS: To investigate the role of Skp2 in the prognosis of patients with glioma, we first analyzed data in databases TCGA and GTEx. To further clarify the effect of Skp2 on glioma cell proliferation, we suppressed its level in glioblastoma (GBM) cell lines through knockdown and small molecule inhibitors (lovastatin and SZL-P1-41). We then detected cell growth, colony formation, sphere formation, drug sensitivity, and in vivo tumor formation in xenograft mice model. RESULTS: Skp2 mRNA level was higher in both low-grade glioma and GBM than normal brain tissues. The knockdown of Skp2 increased cell sensitivity to TMZ, decreased cell proliferation and tumorigenesis. In addition, Skp2 level was found increased upon stem cells enriching, while the knockdown of Skp2 led to reduced sphere numbers. Downregulation of Skp2 also induced senescence. Repurposing of lovastatin and novel compound SZL-P1-41 suppressed Skp2 effectively, and enhanced glioma cell sensitivity to TMZ in vitro and in vivo. CONCLUSION: Our data demonstrated that Skp2 modulated glioma cell proliferation in vitro and in vivo, stem cell maintenance, and cell sensitivity to TMZ, which indicated that Skp2 could be a potential target for long-term treatment.

Dual-energy spectral CT quantitative parameters for the differentiation of Glioma recurrence from treatment-related changes: a preliminary study.

BACKGROUND: Differentiating glioma recurrence from treatment-related changes can be challenging on conventional imaging. We evaluated the efficacy of quantitative parameters measured by dual-energy spectral computed tomographic (CT) for this differentiation. METHODS: Twenty-eight patients were examined by dual-energy spectral CT. The effective and normalized atomic number (Zeff and Zeff-N, respectively); spectral Hounsfield unit curve (λHU) slope; and iodine and normalized iodine concentration (IC and ICN, respectively) in the post-treatment enhanced areas were calculated. Pathological results or clinicoradiologic follow-up of ≥2 months were used for final diagnosis. Nonparametric and t-tests were used to compare quantitative parameters between glioma recurrence and treatment-related changes. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and accuracy were calculated using receiver operating characteristic (ROC) curves. Predictive probabilities were used to generate ROC curves to determine the diagnostic value. RESULTS: Examination of pre-contrast λHU, Zeff, Zeff-N, IC, ICN, and venous phase ICN showed no significant differences in quantitative parameters (P > 0.05). Venous phase λHU, Zeff, Zeff-N, and IC in glioma recurrence were higher than in treatment-related changes (P < 0.001). The optimal venous phase threshold was 1.03, 7.75, 1.04, and 2.85 mg/cm3, achieving 66.7, 91.7, 83.3, and 91.7% sensitivity; 100.0, 77.8, 88.9, and 77.8% specificity; 100.0, 73.3, 83.3, and 73.3% PPV; 81.8, 93.3, 88.9, and 93.3% NPV; and 86.7, 83.3, 86.7, and 83.3% accuracy, respectively. The respective areas under the curve (AUCs) were 0.912, 0.912, 0.931, and 0.910 in glioma recurrence and treatment-related changes. CONCLUSIONS: Glioma recurrence could be potentially differentiated from treatment-related changes based on quantitative values measured by dual-energy spectral CT imaging.

[Application of Internet-based Interventions in Weight Management].

Overweight and obesity are associated with a range of chronic diseases and have become a major global health concern. With the progress of Internet technology,electronic health care has emerged,providing new tools and Methods for weight management. Internet-based technology has shown certain effectiveness in facilitating interventions on overweight,obesity,and their associated diseases. This article reviews the recent advances in these interventions and evaluates their effectiveness,efficiency,and feasibility.

Low preoperative prognostic nutritional index predicts poor survival in patients with newly diagnosed high-grade gliomas.

Preoperative prognostic nutritional index (PNI) has been widely demonstrated to predict survival of patients with malignant tumors. Its utility in predicting outcomes in patients with high-grade gliomas (HGG) remains undefined. A retrospective study of 188 HGG patients was conducted. An optimal PNI cut-off value was applied to stratify patients into high PNI (≥52.55, n = 78) and low PNI (<52.55, n = 110) groups. Univariate and multivariate analysis was performed to identify prognostic factors associated with overall survival (OS) and progression free survival (PFS). The resulting prognostic models were externally validated using a demographic-matched cohort of 130 HGG patients. In the training set, PNI value was negatively correlated with age (p = 0.027) and tumor grade (p = 0.048). Both PFS (8.27 vs. 20.77 months, p < 0.001) and OS (13.57 vs. 33.23 months, p < 0.001) were significantly worse in the low PNI group. Strikingly, patients in high PNI group had a 52% decrease in the risk of tumor progression and 55% decrease of death relative to low PNI. Multivariate analysis further demonstrated PNI as an independent predictor for PFS (HR = 0.62, 95% CI 0.43-0.87) and OS (HR = 0.56, 95% CI 0.38-0.80). The PNI retained independent prognostic value in the validation set for both PFS (p = 0.013) and OS (p = 0.003). On subgroup analysis by tumor grade and treatment modalities, both PFS and OS were better for the patients with high PNI. The PNI is a potentially valuable preoperative marker for the survival of patients following HGG resection.

Postoperative functional status in patients with supratentorial superficial low-grade glioma.

BACKGROUND: We investigated the functional status of adult supratentorial superficial low-grade glioma (ASS-LGG) after surgery and analyzed its relevant factors to guide the therapeutic strategy and improve the life quality of these patients. METHODS: Clinical materials from January 2008 to December 2010 in 104 adults with ASS-LGG were analyzed retrospectively. The follow-up period ranged from 6 months to 1.5 years. The logistic regression was used to evaluate the preoperative and postoperative variation of functional status in patients to disclose the relevant factors affecting postoperative functional status, such as age, gender, the duration of symptom, size and location of the tumor, hemisphere, resection degree, and tumor pathologic grade and preoperative Karnofsky performance status (Pre-KPS). RESULTS: Four out of nine candidate factors are related to the postoperative functional status. They are age less than 40 years, the size of tumor less than 5 cm in diameter, tumor located in the right hemisphere, and limited resection of tumor in the eloquent area. CONCLUSIONS: It seems more meaningful to evaluate the functional status of the patients with ASS-LGG on the basis of these clinical features, involving age, tumor size, location, and extent of resection.

MiR-181b sensitizes glioma cells to teniposide by targeting MDM2.

BACKGROUND: Although the incidence of glioma is relatively low, it is the most malignant tumor of the central nervous system. The prognosis of high-grade glioma patient is very poor due to the difficulties in complete resection and resistance to radio-/chemotherapy. Therefore, it is worth investigating the molecular mechanisms involved in glioma drug resistance. MicroRNAs have been found to play important roles in tumor progression and drug resistance. Our previous work showed that miR-181b is involved in the regulation of temozolomide resistance. In the current study, we investigated whether miR-181b also plays a role in antagonizing the effect of teniposide. METHODS: MiR-181b expression was measured in 90 glioma patient tissues and its relationship to prognosis of these patients was analyzed. Cell sensitivity to teniposide was tested in 48 primary cultured glioma samples. Then miR-181b stably overexpressed U87 cells were generated. The candidate genes of miR-181b from our previous study were reanalyzed, and the interaction between miR-181b and target gene MDM2 was confirmed by dual luciferase assay. Cell sensitivity to teniposide was detected on miR-181b over expressed and MDM2 down regulated cells. RESULTS: Our data confirmed the low expression levels of miR-181b in high-grade glioma tissues, which is related to teniposide resistance in primary cultured glioma cells. Overexpression of miR-181b increased glioma cell sensitivity to teniposide. Through target gene prediction, we found that MDM2 is a candidate target of miR-181b. MDM2 knockdown mimicked the sensitization effect of miR-181b. Further study revealed that miR-181b binds to the 3'-UTR region of MDM2 leading to the decrease in MDM2 levels and subsequent increase in teniposide sensitivity. Partial restoration of MDM2 attenuated the sensitivity enhancement by miR-181b. CONCLUSIONS: MiR-181b is an important positive regulator on glioma cell sensitivity to teniposide. It confers glioma cell sensitivity to teniposide through binding to the 3'-UTR region of MDM2 leading to its reduced expression. Our findings not only reveal the novel mechanism involved in teniposide resistance, but also shed light on the optimization of glioma treatment in the future.

Enhanced MGMT expression contributes to temozolomide resistance in glioma stem-like cells.

O6-methylguanine DNA methyltransferase (MGMT) can remove DNA alkylation adducts, thereby repairing damaged DNA and contributing to the drug resistance of gliomas to alkylating agents. In addition, glioma stem-like cells (GSCs) have been demonstrated to be involved in the recurrence and treatment resistance of gliomas. In this study, we aimed to investigate MGMT expression and regulatory mechanisms in GSCs and the association of MGMT with temozolomide (TMZ) sensitivity. GSCs were enriched from one MGMT-positive cell line (SF-767) and 7 MGMT-negative cell lines (U251, SKMG-4, SKMG-1, SF295, U87, MGR1, and MGR2) through serum-free clone culture. GSCs from the U251G, SKMG-4G, SF295G, and SKMG-1G cell lines became MGMT-positive, but those from the U87G, MGR1G, and MGR2G cell lines remained MGMT-negative. However, all the GSCs and their parental glioma cell lines were positive for nuclear factor-κB (NF-κB). In addition, GSCs were more resistant to TMZ than their parental glioma cell lines (P < 0.05). However, there was no significant difference in the 50% inhibition concentration (IC50) of TMZ between MGMT-positive and MGMT-negative GSCs (P > 0.05). When we treated the MGMT-positive GSCs with TMZ plus MG-132 (an NF-κB inhibitor), the antitumor activity was significantly enhanced compared to that of GSCs treated with TMZ alone (P <0.05). Furthermore, we found that MGMT expression decreased through the down-regulation of NF-κB expression by MG-132. Our results show that MG-132 may inhibit NF-κB expression and further decrease MGMT expression, resulting in a synergistic effect on MGMT-positive GSCs. These results indicate that enhanced MGMT expression contributes to TMZ resistance in MGMT-positive GSCs.