Gliosarcoma (GS) is a rare variant (2%) of glioblastoma (GBM) that poses clinical genomic challenges because of its poor prognosis and limited genomic information. To gain a comprehensive view of the genomic alterations in GS and to understand the molecular etiology of GS, we applied whole-exome sequencing analyses for 28 GS cases (6 blood-matched fresh-frozen tissues for the discovery set, 22 formalin-fixed paraffin-embedded tissues for the validation set) and copy-number variation microarrays for 5 blood-matched fresh-frozen tissues. TP53 mutations were more prevalent in the GS cases (20/28, 70%) compared to the GBM cases (29/90, 32%), and the GS patients with TP53 mutations showed a significantly shorter survival (multivariate Cox analysis, hazard ratio=23.9, 95% confidence interval, 2.87–199.63, P=0.003). A pathway analysis showed recurrent alterations in MAPK signaling (EGFR, RASGRF2 and TP53), phosphatidylinositol/calcium signaling (CACNA1s, PLCs and ITPRs) and focal adhesion/tight junction (PTEN and PAK3) pathways. Genomic profiling of the matched recurrent GS cases detected the occurrence of TP53 mutations in two recurrent GS cases, which suggests that TP53 mutations play a role in treatment resistance. Functionally, we found that TP53 mutations are associated with the epithelial–mesenchymal transition (EMT) process of sarcomatous components of GS. We provide the first comprehensive genome-wide genetic alternation profiling of GS, which suggests novel prognostic subgroups in GS patients based on their TP53 mutation status and provides new insight in the pathogenesis and targeted treatment of GS.
Glioblastoma ; Gliosarcoma* ; Humans ; Prevalence* ; Prognosis

Objective To investigate the clinical efficacy of low-frequency transcranial magnetic stimulation (rTMS) on post-stroke upper limb spasticity and its mechanism. Methods From September, 2015 to December, 2017, 23 patients with post-stroke upper limb paralysis were randomly divided into control group (n=13) and experimental group (n=10). Both groups received routine rehabilitation, and the experimental group received 1 Hz rTMS at primary motor area (M1) for eight weeks. They were assessed with modified Ashworth Scale (MAS), modified Barthel Index (MBI) and Fugl-Meyer Assessment-Upper Extremities (FMA-UE) before and after treatment, while the activation under fMRI in the task state was observed and the laterality index (LI) was calculated. Results The scores of MAS, FMA-UE and MBI improved after treatment in both groups (Z>2.121, t=6.248, P<0.05), and improved more in the experimental group than in the control group (Z>2.084, t=-2.095, P<0.05). The ipsilateral M1, ipsilateral sensory motor cortex and bilateral supplementary motor area were activated more in the control group than in the experimental group during the movement of affected hand. LI in the M1 increased after treatment in both groups (Z>2.366, P<0.05), and was more in the experimental group than in the control group (Z=-2.430, P<0.05). There was a positive correlation between the change of LI in the M1 and the improvement of the MAS and FMA-UE (r>0.612, P<0.05). Conclusion Low-frequency rTMS may improve the motor function and spasticity of upper limb after stroke by promoting reorganization of the cortex and inducing normalization of cortical function.

The recovery of disorders of consciousness after brain injury is very difficult, music therapy is one of the important ways to promote the awakening. The effects of music therapy are various among individuals, the vegetative state and the minimally conscious state, and the pieces of music. The default mode network is one of the most important networks to maintain awareness, which many other networks participate in. The brain regions affected by music involve in many networks, including hearing, cognition, emotion, and so on.