Objective To investigate the values of conventional magnetic resonance imaging (MRI),magnetic resonance angiography (MRA),and high-resolution MRI for diagnosing intracranial arterial dissection (IAD)caused ischemic stroke. Methods From August 2008 to April 2015,59 consecu-tive patients (age 45 ±15years,41males)with IAD caused ischemic stroke admitted to the First Affiliated Hos-pital of Sun Yat-Sen University were enrolled prospectively. All patients underwent conventional cranial MRI/MRA examination,25 of them underwent whole brain DSA examination,and 10 underwent high-resolution MRI. The findings of conventional MRI/ MRA and high-resolution MRI of IAD were analyzed. For patients undergoing DSA,the proportions of detection and compliance of IAD were compared between DSA and conventional MRI / MRA. Results (1)Conventional MRI / MRA revealed typical sign of artery dissection in 42 patients (71. 2%),among them,the intramural hematoma (n = 22,52. 4%)was most common. Other common signs included intimal flap/ double lumen sign (n = 13,31. 0%)and long irregular or thread-like stenosis (n = 9,21. 4%);while dissecting aneurysm (n = 7,16. 7%)and rat tail-shaped occlusion (n = 3, 7. 1%)were relatively rare. In 17 patients (28. 8%)with IAD that conventional MRI/ MRA did not detect the typical dissection sign,the dissections were involved in the middle cerebral artery (11 / 17,64. 7%), they were more common than the 42 patients with IAD (10 / 42,23. 8%)detected the typical dissection sign by conventional MRI/ MRA. There was significant difference (P = 0. 006). (2)Among the 25 patients undergoing DSA,DSA revealed that 15 patients (60%)had the typical dissection sign,and conventional MRI/ MRA only revealed 8 of them (32%)with the typical dissection sign,but there was no significant difference (P = 0. 088). In 15 patients with IAD that DSA detected the typical dissection sign;conventional MRI / MRA detected the typical dissection sign in 8 of them. The diagnostic coincidence rate was 8 / 15. (3)Both conventional MRI/ MRA and DSA revealed non-specific limitation stenosis or cut-off occlusion in 10 patients (16. 9%)with IAD,while the high-resolution MRI revealed intimal flap in 5 of them,intramural hematoma in 4,and intimal flap and intramural hematoma in 1. Conclusion Conventional cranial MRI/MRA is an effective technique for revealing IAD,whereas high-resolution MRI has the unique advantages for diagnosing IAD without typical dissection in other vascular imaging.

OBJECTIVETo discuss the clinicopathologic features of rhabdoid glioblastoma of the brain and its differential diagnoses.

METHODSA 10-year-old and a 45-year-old female both presented with gradually worsening headache, limbs twitch and blurred vision. MRI scan revealed a contrast enhancing tumor in the right temporal lobe and left cerebellum respectively. Both patients underwent tumor resection, followed by postoperative radiotherapy and chemotherapy.

RESULTSMicroscopic examination of both tumors showed rhabdoid tumor cells with an eccentric nuclei and eosinophilic cytoplasms. Both tumors had areas of classic glioblastoma with microvascular proliferation and necrosis. Immunohistochemical staining showed the rhabdoid tumor cells were positive for vimentin diffusely and GFAP, EMA, CK focally. Integrase interactor (INI-1) was expressed in most tumor cells, but IDH1 R132H was not detected in both tumors. Fluorescence in situ hybridization revealed 1p/19q co-deletion in one case. One patient was alive without tumor recurrence after 16 months follow-up, the other patient died of intraspinal tumor dissemination 9 months after surgery.

CONCLUSIONSRhabdoid glioblastoma is a rare glial cell tumor with specific rhabdoid tumor cells, a highly aggressive clinical course and poor prognosis. Combining histological features, a panel of selected immunostains including vimentin, GFAP, CK, EMA, SMA and INI-1 is helpful in making an accurate diagnosis for those diagnostically challenging cases with rhabdoid features in central nervous system.

Biomarkers, Tumor ; metabolism ; Brain Neoplasms ; pathology ; Child ; Diagnosis, Differential ; Female ; Glioblastoma ; pathology ; Humans ; In Situ Hybridization, Fluorescence ; Magnetic Resonance Imaging ; Middle Aged ; Necrosis ; Neoplasm Recurrence, Local ; Rhabdoid Tumor ; pathology ; Temporal Lobe ; pathology

AIM:To explore the influence of ethyl(2,4,6-trimethylbenzoyl)phenylphosphinate(TPOL)on cell apoptosis and its potential mechanism.METHODS:HEK293T cells sensitive to TPOL were treated with different concentrations of TPOL with or without exposure to light radiation,before treatment with various inhibitors,N-acetyl-L-cysteine(NAC),pifithrin-α and Z-DVED-FMK.Cell viability was measured by CCK-8 assay.Annexin V/propidium io-dide staining was used to count the number of apoptotic cells.DCFH-DA staining was used to detect reactive oxygen spe-cies(ROS)levels,and JC-1 staining was used to assess mitochondrial membrane potential by flow cytometry.The expres-sion of apoptosis-related proteins and cell cycle-regulated molecules was measured by Western blot.RESULTS:TPOL enhanced the apoptosis of HEK293T cells in a dose-dependent manner(P<0.05),with a decrease in Bcl-2 and increases in Bax and cytochrome C(Cyto C),followed by up-regulation of activated caspase-9 and caspase-3,and the cleavage of PARP(P<0.05).The TPOL-enhanced cleavage of caspase-3 and PARP was rescued by Z-DVED-FMK(P<0.01).TPOL also led to a rapid increase in ROS,a reduction in mitochondrial membrane potential,and the release of Cyto C(P<0.01),all of which could be reversed by the ROS scavenger NAC.Moreover,the TPOL-caused alterations in p21,p27,Rb,and CDK2 were also recovered by the p53 inhibitor pifithrin-α(P<0.05).The TPOL-induced changes in Bax,Bcl-2,cleaved caspase-9,activated caspase-3,and cleaved PARP were subsequently rescued by pretreatment with pifithrin-α(P<0.05).CONCLUSION:TPOL can induce cellular apoptosis with ROS-mediated mitochondrial membrane damage through the activation of a ROS-dependent p53/p21/p27/Rb/Bax/Cyto C/caspase-mediated signal axis.

Targeted protein degradation(TPD)has rapidly emerged as a therapeutic modality to eliminate previously undruggable proteins by repurposing the cell's endogenous protein degrada-tion machinery.However,the susceptibility of proteins for targeting by TPD approaches,termed"degradability",is largely unknown.Here,we developed a machine learning model,model-free anal-ysis of protein degradability(MAPD),to predict degradability from features intrinsic to protein tar-gets.MAPD shows accurate performance in predicting kinases that are degradable by TPD compounds[with an area under the precision-recall curve(AUPRC)of 0.759 and an area under the receiver operating characteristic curve(AUROC)of 0.775]and is likely generalizable to inde-pendent non-kinase proteins.We found five features with statistical significance to achieve optimal prediction,with ubiquitination potential being the most predictive.By structural modeling,we found that E2-accessible ubiquitination sites,but not lysine residues in general,are particularly associated with kinase degradability.Finally,we extended MAPD predictions to the entire proteome to find 964 disease-causing proteins(including proteins encoded by 278 cancer genes)that may be tractable to TPD drug development.