A potassium-chloride co-transporter with altered genome architecture functions as a suppressor in glioma.

Gliomas, the most lethal tumours in brain, have a poor prognosis despite accepting standard treatment. Limited benefits from current therapies can be attributed to genetic, epigenetic and microenvironmental cues that affect cell programming and drive tumour heterogeneity. Through the analysis of Hi-C data, we identified a potassium-chloride co-transporter SLC12A5 associated with disrupted topologically associating domain which was downregulated in tumour tissues. Multiple independent glioma cohorts were included to analyse the characterization of SLC12A5 and found it was significantly associated with pathological features, prognostic value, genomic alterations, transcriptional landscape and drug response. We constructed two SLC12A5 overexpression cell lines to verify the function of SLC12A5 that suppressed tumour cell proliferation and migration in vitro. In addition, SLC12A5 was also positively associated with GABAA receptor activity and negatively associated with pro-tumour immune signatures and immunotherapy response. Collectively, our study provides a comprehensive characterization of SLC12A5 in glioma and supports SLC12A5 as a potential suppressor of disease progression.

A retrospective longitudinal study of age-related shifts and deformations in the basilar artery bifurcation.

PURPOSE: Previous studies have indicated that cerebral arterial morphology is linked to aging and some cerebrovascular diseases. However, the mechanisms of morphological changes remain unclear. This study evaluated age-related positional changes in the basilar artery (BA) bifurcation based on longitudinal computed tomography angiography (CTA) data. METHODS: This retrospective study evaluated clinical and imaging data from 72 subjects who underwent two CTA scans between July 2011 and August 2019. Three-dimensional (3D) models were reconstructed for each subject based on the two CTA scans with the longest separating interval. Skull landmarks were used to fuse the two models, and the fused model was used to evaluate positional changes in the BA bifurcation. Univariable and multivariable analyses were used to identify variables that were correlated to BA bifurcation shifting. Pearson's correlation test was used to analyze the correlation between the shifting distance and change in the BA bifurcation angle. RESULTS: Significant differences between aneurysm and non-aneurysm cases were observed in terms of sex (p = 0.004), CTA scan interval (p = 0.023), and BA bifurcation shifting distance (p = 0.007). Multivariable linear regression analysis revealed that the BA bifurcation shifting distance was significantly correlated with the CTA scan interval (p = 0.038) and the presence of aneurysms (p < 0.001). Furthermore, the shifting distance was positively correlated with widening of the BA bifurcation angle (p = 0.002). CONCLUSIONS: Aging-related widening of the BA bifurcation angle may be related to distal shifting of the BA bifurcation's position, and larger distal shifting of the BA bifurcation may be associated with the risk of aneurysm formation.

Artesunate inhibits the mevalonate pathway and promotes glioma cell senescence.

Glioma is a common brain malignancy for which new drug development is urgently needed because of radiotherapy and drug resistance. Recent studies have demonstrated that artemisinin (ARS) compounds can display antiglioma activity, but the mechanisms are poorly understood. Using cell lines and mouse models, we investigated the effects of the most soluble ARS analogue artesunate (ART) on glioma cell growth, migration, distant seeding and senescence and elucidated the underlying mechanisms. Artemisinin effectively inhibited glioma cell growth, migration and distant seeding. Further investigation of the mechanisms showed that ART can influence glioma cell metabolism by affecting the nuclear localization of SREBP2 (sterol regulatory element-binding protein 2) and the expression of its target gene HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase), the rate-limiting enzyme of the mevalonate (MVA) pathway. Moreover, ART affected the interaction between SREBP2 and P53 and restored the expression of P21 in cells expressing wild-type P53, thus playing a key role in cell senescence induction. In conclusion, our study demonstrated the new therapeutic potential of ART in glioma cells and showed the novel anticancer mechanisms of ARS compounds of regulating MVA metabolism and cell senescence.

A Reanalysis of Predictors for the Risk of Hemorrhage in Brain Arteriovenous Malformation.

BACKGROUND: Brain arteriovenous malformation (BAVM) is a congenital cerebral vascular disease that characterized with intracranial hemorrhage and epilepsy. It has some risk in current treatments including microsurgery, endovascular, and radiation therapy. Some patients with bAVMs may keep unruptured in their whole life. Whether it should be treated depends on the evaluation of the hemorrhage risk of bAVM. Although previous studies gave many significant predictors, we tried to find some new and more significant predictors in 173 patients with bAVMS by retrospective analysis. METHODS: Except for previous predictors reported such as age, gender, epilepsy, location, aneurysm related with bAVM, volume of nidus, types of venous drainage, and the number of draining veins, we also collected time to peak (TTP) and sum of cross-sectional area of the feeding arteries and sum of cross-sectional area of the draining veins (∑SA/∑SV) data to proceed univariate and multivariate statistical analysis in 173 patients with bAVM. RESULTS: The results of the statistical analysis show that gender, the location of bAVM nidus, and TTP are significant predictors of hemorrhage risk, but age, size, the number of draining veins, and types of venous drainage do not appear so significant. The value of predictors of bleeding risk including TTP was assessed by receiver operating characteristic curve and area under curve to be stronger. CONCLUSIONS: When TTP and ∑SA/∑SV data were added, some previous important indicators such as age, size, the number of draining veins, and types of venous drainage appear less significant in predicting the hemorrhage risk of bAVM in statistics, but TTP, gender, and the location of bAVM nidus are significant; moreover, TTP is a predictor that needs to be emphasized.

Association between polymorphisms in CTR1, CTR2, ATP7A, and ATP7B and platinum resistance in epithelial ovarian cancer.

The copper transporters CTR1, CTR2, ATP7A, and ATP7B regulate intracellular concentration of platinum by mediating its uptake and efflux in cells. We sought to explore the effect of genetic polymorphisms in CTR1, CTR2, ATP7A, and ATP7B on platinum resistance in patients suffering from epithelial ovarian cancer (EOC). A total of 152 Chinese EOC patients were enrolled in this study, all of whom underwent adjuvant chemotherapy using platinum and taxane after maximal debulking surgery. In total, 11 single-nucleotide polymorphisms (SNPs) in CTR1, CTR2, ATP7A, and ATP7B were genotyped in these patients. The CTR1 rs10981694 polymorphism was observed to be associated with carboplatin resistance, while patients with the rs10981694 G allele showed a significantly higher rate of carboplatin resistance (OR = 4.00, 95% CI 1.309 - 12.23, p < 0.01). In addition, we found that ATP7A rs2227291 was associated with cisplatin resistance and that carriers of the C allele were more sensitive to cisplatin (OR = 0.40, 95% CI: 0.17 - 0.94, p = 0.03). Our findings suggest that the CTR1 and ATP7A genetic polymorphisms could affect platinum resistance. The CTR1 and ATP7A genes might be considered a predictive marker for carboplatin and cisplatin resistance, respectively.
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Effect of Siphon Morphology on the Risk of C7 Segment Aneurysm Formation : A Case-control CFD Study.

PURPOSE: Tortuosity of the internal carotid artery (ICA) is associated with intracranial aneurysms (IAs). The siphon is the most curved segment of the ICA, but its morphology has controversial effects on IAs. This study aimed to explore the morphometric features of the siphon and the potential hemodynamic mechanisms that may affect C7 aneurysm formation. METHODS: In this study 32 patients with C7 aneurysms diagnosed at Xiangya Hospital between 2019 and 2021 and 32 control subjects were enrolled after propensity score matching. Computed tomography angiography (CTA) images were acquired to measure morphologic features, and then, by combining clinical data, simplified carotid siphon models were constructed, and computational fluid dynamics (CFD) analysis was performed. RESULTS: The presence of C7 aneurysms was associated with the height of the C4-C6 curved arteries (odds ratio [OR] 0.028, 95% confidence interval [CI] 0.003-0.201; P < 0.001). The heights of the C4-C6 curved arteries in the aneurysm group were significantly shorter than those in the control group. The CFD analysis revealed that shorter C4-C6 bends led to greater blood velocity and pressure in the C7 segment arteries. CONCLUSION: A shorter C4-C6 bend was associated with distal C7 aneurysm formation, and an elaborate hemodynamic mechanism may underlie this association.

USP18 Stabilized FTO Protein to Activate Mitophagy in Ischemic Stroke Through Repressing m6A Modification of SIRT6.

Ischemic stroke (IS) is a dangerous cerebrovascular disorder with a significant incidence and death rate. Ubiquitin-specific peptidase 18 (USP18) has been proven to mitigate ischemic brain damage; however, its potential regulatory mechanisms remain unclear. In vivo and in vitro models of IS were established by middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R). Neurocyte injury was detected by MTT, LDH, ROS level, mitochondrial membrane potential (Δψm), and flow cytometry. Molecular expression was evaluated by qPCR, Western blotting, and immunofluorescence staining. Molecular mechanisms were determined by Co-IP, RIP, and MeRIP. IS injury was determined by neurological behavior score and TTC staining. Mitophagy was observed by TEM. USP18 and fat mass and obesity-associated protein (FTO) expression declined after OGD/R. Dysfunctional mitochondrial and apoptosis in OGD/R-stimulated neurocytes were eliminated by USP18/FTO overexpression via mitophagy activation. USP18-mediated de-ubiquitination was responsible for increasing FTO protein stability. Up-regulation of FTO protein restrained m6A modification of sirtuin6 (SIRT6) in a YTHDF2-dependent manner to enhance SIRT6 expression and subsequent activation of AMPK/PGC-1α/AKT signaling. FTO induced mitophagy to ameliorate nerve cell damage through SIRT6/AMPK/PGC-1α/AKT pathway. Finally, USP18/FTO overexpression relieved IS in rats via triggering SIRT6/AMPK/PGC-1α/AKT axis-mediated mitophagy. USP18 increased FTO protein stability to trigger SIRT6-induced mitophagy, thus mitigating IS. Our data unravel the novel neuroprotective mechanism of USP18 and suggest its potential as a promising treatment target for IS.

Hsa_circ_0092856 Promoted the Proliferation, Migration, and Invasion of NSCLC Cells by Up-Regulating the Expression of eIF3a.

Circular RNA (circRNA) plays a very important regulatory role in a variety of human malignancies such as non-small-cell lung cancer (NSCLC). In the current study, we explored the role of hsa_circ_0092856 in the progression of NSCLC. We screened CircRNA from the eIF3a gene in the Circbase database. The biological functions of hsa_circ_0092856 in NSCLC were analyzed via qRT-PCR, a CCK-8 assay, a plate cloning experiment, scratch testing, a transwell chamber experiment, an RNA nuclear mass separation experiment, an RIP experiment, and a Western blot test. The results showed that hsa_circ_0092856 was highly expressed in NSCLC cells, and the knockdown of hsa_circ_0092856 could inhibit the proliferation, migration, and invasion of NSCLC cells. The overexpression of hsa_circ_0092856 has the opposite effect. The expression of eIF3a also changed with the change in hsa_circ_0092856. These results suggest that hsa_circ_0092856 may play a key role in the progression of NSCLC by regulating the expression of eIF3a.

Association of brain morphology and phenotypic profile in patients with unruptured intracranial aneurysm.

Introduction: Studies have found a varying degree of cognitive, psychosocial, and functional impairments in patients with unruptured intracranial aneurysms (UIAs), whereas the neural correlates underlying these impairments remain unknown. Methods: To examine the brain morphological alterations and white matter lesions in patients with UIA, we performed a range of structural analyses to examine the brain morphological alterations in patients with UIA compared with healthy controls (HCs). Twenty-one patients with UIA and 23 HCs were prospectively enrolled into this study. Study assessment consisted of a brain magnetic resonance imaging (MRI) scan with high-resolution T1-weighted and T2-weighted imaging data, a Montreal Cognitive Assessment (MoCA), and laboratory tests including blood inflammatory markers and serum lipids. Brain MRI data were processed for cortical thickness, local gyrification index (LGI), volume and shape of subcortical nuclei, and white matter lesions. Results: Compared to the HCs, patients with UIA showed no significant differences in cortical thickness but decreased LGI values in the right posterior cingulate cortex, retrosplenial cortex, cuneus, and lingual gyrus. In addition, decreased LGI values correlated with decreased MoCA score (r = 0.498, p = 0.021) and increased white matter lesion scores (r = -0.497, p = 0.022). The LGI values were correlated with laboratory values such as inflammatory markers and serum lipids. Patients with UIA also showed significant regional atrophy in bilateral thalami as compared to the HCs. Moreover, the LGI values were significantly correlated with thalamic volume in the HCs (r = 0.4728, p = 0.0227) but not in the patients with UIA (r = 0.11, p = 0.6350). Discussion: The decreased cortical gyrification, increased white matter lesions, and regional thalamic atrophy in patients with UIA might be potential neural correlates of cognitive changes in UIA.

Development and External Validation of Nomogram for Cerebral Infarction in Moyamoya Diseases.

More than 60% of moyamoya disease (MMD) patients suffers cerebral ischemia and preoperative cerebral infarction (CI) increases the risk of postoperative stroke and unfavorable outcome. We established a nomogram system for risk stratification of CI to help tailoring individualized management. We enrolled 380 patients including 680 hemispheres for the training cohort from our hospital and 183 patients including 348 hemispheres for the validation cohort from multicenter. A nomogram for CI was formulated based on the multivariable logistic regression analysis. The predictive accuracy and discriminative ability of nomogram were determined with concordance index (C-index) and calibration curve. For the training cohort, 246 hemispheres (36.2%) were found with CI. In multivariable logistic regression used generalized estimating equations approach, anterior choroidal artery (AchA) grade (grade 1, OR 0.214, 95%CI 0.124-0.372, P < 0.001; grade 2, OR 0.132, 95%CI 0.066-0.265, P < 0.001), cerebral perfusion (OR 4.796, 95%CI 2.922-7.872; P < 0.001), white matter hyperintensity (OR 3.652, 95%CI 1.933-6.902; P < 0.001), brush sign (OR 3.555, 95%CI 2.282-5.538; P < 0.001), and ivy sign (equivocal, OR 4.752, 95%CI 2.788-8.099, P < 0.001; present, OR 8.940, 95%CI 4.942-16.173, P < 0.001) were significant factors for CI. The C-index of the nomogram for predicting cerebral infarction was 0.890 (95%CI 0.866-0.915) in the training cohort and 0.847 (95%CI 0.805-0.889) in the validation cohort. The nomogram composed of AchA grade, cerebral perfusion, white matter hyperintensity, brush sign, and ivy sign could provide risk stratification of CI before surgery in patients with MMD. Active treatment might be recommended before CI, which could reduce the risk of stroke after surgery.

Computed Tomography-Based Machine Learning Differentiates Adrenal Pheochromocytoma From Lipid-Poor Adenoma.

Objectives: To assess the accuracy of computed tomography (CT)-based machine learning models for differentiating subclinical pheochromocytoma (sPHEO) from lipid-poor adenoma (LPA) in patients with adrenal incidentalomas. Patients and Methods: The study included 188 tumors in the 183 patients with LPA and 92 tumors in 86 patients with sPHEO. Pre-enhanced CT imaging features of the tumors were evaluated. Machine learning prediction models and scoring systems for differentiating sPHEO from LPA were built using logistic regression (LR), support vector machine (SVM) and random forest (RF) approaches. Results: The LR model performed better than other models. The LR model (M1) including three CT features: CTpre value, shape, and necrosis/cystic changes had an area under the receiver operating characteristic curve (AUC) of 0.917 and an accuracy of 0.864. The LR model (M2) including three CT features: CTpre value, shape and homogeneity had an AUC of 0.888 and an accuracy of 0.832. The S2 scoring system (sensitivity: 0.859, specificity: 0.824) had comparable diagnostic value to S1 (sensitivity: 0.815; specificity: 0.910). Conclusions: Our results indicated the potential of using a non-invasive imaging method such as CT-based machine learning models and scoring systems for predicting histology of adrenal incidentalomas. This approach may assist the diagnosis and personalized care of patients with adrenal tumors.

Rs3802278 in 3'-UTR of SULF1 associated with platinum resistance and survival in Chinese epithelial ovarian cancer patients.

Ovarian cancer is the leading cause of death from gynecologic cancers, but platinum resistance remains a major obstacle in the chemotherapy of ovarian cancer. This study aims to examine the role of polymorphisms in sulfatase 1 (SULF1) in platinum resistance and survival in advanced epithelial ovarian cancer (EOC) patients. We genotyped 12 SNPs of SULF1 in 195 EOC patients treated with platinum using MassARRAY method and evaluated the association between the SNPs and platinum response. SULF1 rs3802278 was marginal significantly associated with platinum resistance in recessive model with p value of 0.055. The patients with SULF1 rs3802278 AA were more resistant to platinum-based chemotherapy comparing to those with AG/GG genotype (OR: 2.317, 95%CI: 0.982 ∼ 5.465). In survival analysis, rs3802278 was significantly associated with both of PFS and OS after adjusted by FIGO stage and age. Patients with AA genotypes showed a shorter PFS and OS than with AG/GG genotypes (median PFS: 15 months vs. 21 months, p = 0.010, HR = 1.876, 95%CI: 1.165-3.022; median OS: 42 months vs. 73 months, p = 0.031, HR = 1.928, 95%CI: 1.061-3.504). SULF1 rs3802278 may serve as a potential candidate biomarker for the prediction of platinum resistance and prognosis in Chinese EOC patients.

CT-Based Sarcopenic Nomogram for Predicting Progressive Disease in Advanced Non-Small-Cell Lung Cancer.

BACKGROUND: It is prudent to identify the risk for progressive disease (PD) in patients with non-small-cell lung cancer (NSCLC) who undergo platinum-based chemotherapy. The present study aimed to develop a CT imaging-based sarcopenic nomogram for predicting the risk of PD prior to chemotherapy treatment. METHODS: We retrospectively enrolled patients with NSCLC who underwent platinum-based chemotherapy. Imaging-based body composition parameters such as skeletal muscle index (SMI) for assessment of sarcopenia were obtained from pre-chemotherapy chest CT images at the level of the eleventh thoracic vertebral body (T11). Sarcopenic nomogram was constructed using multivariate logistic regression and performance of the nomogram was evaluated by discrimination, calibration curve, and decision curve. RESULTS: Sixty (14.7%) of the 408 patients in the study cohort developed PD during chemotherapy. The prediction nomogram for developing PD achieved a moderate efficiency with an area under the curve (AUC) of 0.75 (95% CI: 0.69-0.80) for the training cohort, and 0.76 (95%CI: 0.68-0.84) for the validation cohort, as well as a good performance of consistence (bootstrap for training cohort: 0.75 ± 0.02; validation cohort: 0.74 ± 0.06). Favorable clinical application was observed in the decision curve analysis. CONCLUSION: Our CT-based sarcopenic nomogram showed the potential for an individualized prediction of progression for patients with NSCLC receiving platinum-based chemotherapy.

Incorporating SULF1 polymorphisms in a pretreatment CT-based radiomic model for predicting platinum resistance in ovarian cancer treatment.

OBJECTIVE: Early detection of platinum resistance for ovarian cancer treatment remains challenging. This study aims to develop a machine learning model incorporating genomic data such as Single-Nucleotide Polymorphisms (SNPs) of Human Sulfatase 1 (SULF1) with a CT radiomic model based on pre-treatment CT images, to predict platinum resistance for ovarian cancer (OC) treatment. METHODS: A cohort of 102 patients with pathologically confirmed OC was retrospectively enrolled into this study from January 2006 to February 2018. All patients had platinum-based chemotherapy after maximal cyto-reductive surgery. This cohort was separated into two groups according to treatment response, i.e., the group with platinum-resistant disease (PR group) and the group with platinum-sensitive disease (PS group). We genotyped 12 SNPs of SULF1 for all OC patients using Mass Array Method. Radiomic features, SNP data and clinicopathological data of the 102 patients were used to build the differentiation models. The study participants were divided into two cohorts: the training cohort (n = 71) and the validation cohort (n = 31). Feature selection and predictive modeling were performed using least absolute shrinkage and selection operator (LASSO), Random Forest Classifier and Support Vector Machine methods. Model performance for predicting platinum resistance was assessed with respect to its calibration, discrimination, and clinical application. RESULTS: For prediction of platinum resistance, the approach combining the radiomics, clinicopathological data and SNP data demonstrated higher classification efficiency, with an AUC value of 0.993 (95 % CI: 0.83 to 0.98) in the training cohort and 0.967 (95 % CI: 0.83 to 0.98) in validation cohort, than the performance with only the SNPs of SULF1 model (AUC: training, 0.843 [95 %CI: 0.738-0.948]; validation, 0.815 [0.601-1.000]), or with only the radiomic model (AUC: training, 0.874 [95 %CI: 0.789-0.960]; validation, 0.832 [95 %CI: 0.687-0.976]). This integrated approach also showed good calibration and favorable clinical utility. CONCLUSIONS: A predictive model combining pretreatment CT radiomics with genomic data such as SNPs of SULF1 could potentially help to predict platinum resistance in ovarian cancer treatment.

Downregulation of WIF-1 by hypermethylation in astrocytomas.

Wnt inhibitory factor-1 (WIF-1) acts as a Wnt antagonist and tumor suppressor, but hypermethylation of WIF-1 gene promoter and low expression of WIF-1 activate Wnt signaling aberrantly and induce the development of several human tumors. By using RT-PCR, immunohistochemistry and methylation-specific PCR, we analyzed the expression and methylation of WIF-1 in 4 normal brain tissues, 35 freshly resected astrocytoma tissues and 4 glioblastoma-derived cell lines. Significant downregulation of WIF-1 mRNA and protein expression levels was observed in astrocytoma tissues compared with normal brain tissues. Significant association between WIF-1 downregulation and pathological grade of astrocytomas was found. WIF-1 gene aberrant methylation was observed in 19 of 35 (54.29%) tumor samples. The promoter methylation tumors showed low WIF-1 protein and mRNA expression, whereas the promoter unmethylation tumors displayed high protein and mRNA expression levels. Moreover, complete absence of WIF-1 mRNA expression was observed in four cell lines, whereas treatment with demethylating agent, 5-aza-2'-deoxycytidine, restored WIF-1 expression. Our results suggested that the WIF-1 gene is frequently silenced in astrocytoma by aberrant promoter methylation. This may be an important mechanism in astrocytoma carcinogenesis.

The Novel Zinc Finger Protein 587B Gene, ZNF587B, Regulates Cell Proliferation and Metastasis in Ovarian Cancer Cells in vivo and in vitro.

BACKGROUND: The zinc finger protein 587B (ZNF587B) is a novel cisplatin-sensitive gene that was identified in our previous research by using a genome-scale CRISPR-Cas9 knockout library in ovarian cancer (OC) cell lines. ZNF587B belongs to the C2H2-type zinc finger protein (ZFP) family. Many ZFP protein could inhibit tumor development and malignancy. However, the function of ZNF587B remains unknown. METHODS: Quantitative PCR (qPCR) was utilized to compare ZNF587B mRNA expression levels in OC and normal ovarian cell lines. The small interfering RNA (siRNA) and full-length ZNF587B eukaryotic expression plasmid were constructed and transfected into OC cells later. Colony formation, 5-ethynyl-2'-deoxyuridine (EdU) assay, transwell assay, and xenograft experiment were conducted to evaluate the effect of ZNF587B on OC cells. RESULTS: ZNF587B was downregulated by approximately 43% and 17% in the OC cell lines SKOV3 and A2780, respectively, compared with that in the normal ovarian cell line IOSE80. Overexpression of ZNF587B reduced cell proliferation, colony formation, migration, and invasion, which could be reversed by knockdown of ZNF587B via siRNA. Xenograft experiments also confirmed that ZNF587B could suppress tumor growth. Survival data of OC patients in the SurvExpress database showed that with respect to overall survival, low-risk patients grouped by the prognostic index had a higher expression of ZNF587B and a better prognosis than high-risk group (HR = 1.77, 95% CI: 0.55-0.70, p = 0.023). Moreover, overexpression of ZNF587B promoted OC cells apoptosis when pretreated with cisplatin. CONCLUSION: ZNF587B is a novel potential tumor suppressor of OC and may be a therapeutic target for OC.

Computed Tomography Radiomics for Predicting Pathological Grade of Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer and it has the worst prognosis among all renal cancers. However, traditional radiological characteristics on computed tomography (CT) scans of ccRCC have been insufficient to predict the pathological grade of ccRCC before surgery. METHODS: Patients with ccRCC were retrospectively enrolled into this study and were separated into two groups according to the World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading system, i.e., low-grade (Grade I and II) group and high-grade (Grade III and IV) group. Traditional CT radiological characteristics such as tumor size, pre- and post-enhancing CT densities were assessed. In addition, radiomic texture analysis based on the CT imaging of the ccRCC were also performed. A CT-based machine learning method combining the traditional radiological characteristics and radiomic features was used in the predictive modeling for differentiating the low-grade from the high-grade ccRCC. Model performance was evaluated with the receiver operating characteristic curve (ROC) analysis. RESULTS: A total of 264 patients with pathologically confirmed ccRCC were included in this study. In this cohort, 206 patients had the low-grade tumors and 58 had the high-grade tumors. The model built with traditional radiological characteristics achieved an area under the curve (AUC) of 0.9175 (95% CI: 0.8765-0.9585) and 0.8088 (95% CI: 0.7064-0.9113) in differentiating the low-grade from the high-grade ccRCC for the training cohort and the validation cohort respectively. The model built with the radiomic textural features yielded an AUC value of 0.8170 (95% CI: 0.7353-0.8987) and 0.8017 (95% CI: 0.6878-0.9157) for the training cohort and the validation cohort, respectively. The combined model integrating both the traditional radiological characteristics and the radiomic textural features achieved the highest efficacy, with an AUC of 0.9235 (95% CI: 0.8646-0.9824) and an AUC of 0.9099 (95% CI: 0.8324-0.9873) for the training cohort and validation cohort, respectively. CONCLUSION: We developed a machine learning radiomic model achieving a satisfying performance in differentiating the low-grade from the high-grade ccRCC. Our study presented a potentially useful non-invasive imaging-focused method to predict the pathological grade of renal cancers prior to surgery.

Finding the Inferior Petrosal Sinus for Embolizing Cavernous Dural Arteriovenous Fistula Using Preoperative Computed Tomography Angiography.

BACKGROUND: Inferior petrosal sinus (IPS) has been commonly adopted as a route for embolizing cavernous dural arteriovenous fistula (cDAVF). According to previous anatomical studies, >90% of persons have an IPS. Because the exact confluence position of the IPS with an internal jugular vein can be difficult to obtain using preoperative digital subtraction angiography (DSA), catheterizing into the IPS during endovascular treatment can sometimes be very difficult. Because the anatomical information has not been attainable, this route has not been as widely used. Thus, methods remain to be developed to allow the IPS to play its due role in the embolization of cDAVF. METHODS: Seven cases of cDAVF were diagnosed by DSA. The 7 patients also underwent preoperative computed tomography angiography (CTA) and were treated by transvenous embolization. RESULTS: Compared with DSA, the confluence position of the IPS with the internal jugular vein was easier to find using preoperative CTA in 6 cases. Based on this anatomical information, 6 cases were successfully embolized via the IPS route and 1 via the superior ophthalmic vein route. CONCLUSIONS: Detailed anatomical information of the IPS can be obtained from preoperative CTA images. Thus, CTA can help localize the IPS and allow for embolization of cDAVF via the IPS route.

Loss of ZNF587B and SULF1 contributed to cisplatin resistance in ovarian cancer cell lines based on Genome-scale CRISPR/Cas9 screening.

Ovarian cancer is one of the most lethal malignancies of the female reproductive system. Platinum-resistance is the major obstacle in the successful treatment of ovarian cancer. Previous studies largely failed to identify the key genes associated with platinum-resistance by using candidate genes testing, bioinformatic analysis and GWAS method. The aim of the study was to utilize the whole human Genome-scale CRISPR-Cas9 knockout (GeCKO) library to screen for novel genes involved in cisplatin resistance in ovarian cancer cell lines. The GeCKO library targeted 19052 genes with 122417 unique guide sequences. Six candidate genes had been screened out including one previously validated gene SULF1 and five novel genes ZNF587B, TADA1, SEMA4G, POTEC and USP17L20. After validated by CCK-8 and RT-PCR analysis, two genes (ZNF587B and SULF1) were discovered to be involved in cisplatin resistance. ZNF587B may serve as a new biomarker for predicting cisplatin resistance.

[Correlation research between cancer stem cells and the pathological grades of neuroepithelial tumors].

OBJECTIVE: To explore the methods of isolation, culture and identification of brain tumor stem cells (BTSCs) in neuroepithelial tumor tissues in vitro, and to study the correlation between BTSCs and the patholorical grades of neuroepithelial tumors. METHODS: Tumor cells from patients undergoing neuroepithelial tumors excision were acutely dissociated, triturated into single cells, and then seeded into serum-free medium. After the primary brain tumor spheres (BTSs) were generated, they were triturated again and passaged in fresh medium. The expression of Nestin and CD133 of BTSs was detected by immunocytochemistry staining, and the expression of CD133 of tumor specimen sections was detected by immunohistochemistry staining . The expression of CD133 of 46 brain tumors and 5 normal brain tissues were analysed by SABC immunohistochemical staining, and the correlation between the expression and pathological grade of the tumors was analysed. RESULTS: BTSCs from neuroepithelial tumors could be isolated and cultured, and could be generated and passaged in vitro. The expression of Nestin and CD133 could be detected in BTSCs. CD133 could be detected in neuroepithelial tumor tissues, but not in normal brain tissues. There was significant difference between the expression of CD133 and the different grades of tumors (P < 0.01), and there was a positive correlation between the expression of CD133 and the histologic grading of tumors (P < 0.01). CONCLUSION: A small proportion of stem cells have the ability to self-renew in human neuroepithelial tumors, and there is a positive correlation between the expression of CD133 and histologic grading of tumors.