CIC-DUX4 gene fusion, resulting from either a t(4;19) or t(10;19) translocation, is the most common genetic abnormality detected in EWSR1-negative small blue round cell tumors (SBRCTs). Following their discovery it was debated if these tumors should be classified as variants of Ewing sarcoma (i.e. atypical Ewing sarcoma) or as a stand-alone pathologic entity. As such the WHO classification temporarily grouped the CIC-rearranged tumors under undifferentiated sarcomas with round cell phenotype, until further clinical evidence was available. However, most studies reported so far include small series with limited follow-up information which preclude a more definitive assessment. The present work investigates the clinicopathologic features of a large cohort of sarcomas with CIC gene rearrangement, in order to define their clinical presentation, morphologic spectrum, and outcome. Our study further examines the overall survival of the CIC-positive cohort compared to a control group of EWSR1-rearranged Ewing sarcoma matched for age and stage. The study cohort included 115 patients, with a mean age of 32 years and a slight male predominance. Most tumors occurred in the soft tissue (86%), predominantly deep-seated and equally divided among trunk and extremity, followed by visceral locations (12%) and rarely in the bone (3%). Microscopically, most tumors showed round to ovoid cytomorphology but half of the cases showed also focal areas of spindling and epithelioid/rhabdoid phenotype, with frequent myxoid stromal changes. Variable CD99 reactivity was seen in 84% cases, with a diffuse pattern only in 23% of cases, while nuclear WT1 was seen in 92%. A CIC-DUX4 fusion was detected in 57% of cases, with either DUX4 on 4q35 (35%) or on 10q26 in 25 (22%) cases. No FOXO4 gene rearrangements were present in 39 cases tested. Clinical follow-up was available in 57 patients, with a 5-year survival of 43%, which was significantly lower than the 77% 5-year survival in the control Ewing sarcoma group (p=0.002). Our findings show that CIC-DUX4 sarcomas occur most commonly in young adults within the somatic soft tissues, having a wide spectrum of morphology including round, epithelioid and spindle cells, and associated with an aggressive clinical course, with an inferior overall survival compared to Ewing sarcoma. The results support the classification of CIC-rearranged tumors as an independent molecular and clinical subset of SBRCTs distinct from Ewing sarcoma.

BackgroundThe aim of this study is to assess the prevalence of sarcopenia and investigate the associations between sarcopenia and long‐term mortality and readmission in a population of elderly inpatients in acute care wards.MethodsWe conducted a prospective observational study in the acute care wards of a teaching hospital in western China. The muscle mass was estimated according to a previously validated anthropometric equation. Handgrip strength was measured with a handheld dynamometer, and physical performance was measured via a 4 m walking test. Sarcopenia was defined according to the recommended diagnostic algorithm of the Asia Working Group for Sarcopenia. The survival status and readmission information were obtained via telephone interviews at 12, 24, and 36 months during the 3 year follow‐up period following the baseline investigation.ResultsTwo hundred and eighty‐eight participants (mean age: 81.1 ± 6.6 years) were included. Forty‐nine participants (17.0%) were identified as having sarcopenia. This condition was similar in men and women (16.9% vs. 17.5%, respectively, P = 0.915). During the 3 year follow‐up period, 49 men (22.7%) and 9 women (16.4%) died (P = 0.307). The mortality of sarcopenic participants was significantly increased compared with non‐sarcopenic participants (40.8% vs. 17.1%, respectively, P < 0.001). After adjusting for age, sex and other confounders, sarcopenia was an independent predictor of 3 year mortality (adjusted hazard ratio: 2.49; 95% confidential interval: 1.25–4.95) and readmission (adjusted hazard ratio: 1.81; 95% confidential interval: 1.17–2.80).ConclusionsSarcopenia, which is evaluated by a combination of anthropometric measures, gait speed, and handgrip strength, is valuable to predict hospital readmission and long‐term mortality in elderly patients in acute care wards.

This study was carried out to test the hypothesis that Tongxinluo (TXL) as a Chinese herbal medicine enhances stability of vulnerable plaque dose dependently via lipid-lowering and anti-inflammation effects, similar to a high-dose simvastatin therapy. After abdominal aortic balloon injury, 75 rabbits were fed a 1% cholesterol diet for 10 wk and were then divided into five groups for 8-wk treatment: control group, low-dose TXL group, moderate-dose TXL group, high-dose TXL group, and high-dose simvastatin group. At the end of week 16, an adenovirus containing p53 was injected into the abdominal aortic plaques. Two weeks later, plaque rupture was induced by pharmacological triggering. The incidence of plaque rupture in all treatment groups (14.3%, 7.1%, 7.7%, and 7.1%) was significantly lower than that in control group (73.3%; P>0.01). TXL dose-dependently lowered serum lipid levels and inhibited systemic inflammation. Corrected acoustic intensity and fibrous cap thickness of the aortic plaques were significantly increased, whereas plaque area, plaque burden, vulnerable index, and expression of oxidized low-density lipoprotein (ox-LDL) receptor 1, matrix metalloproteinase 1 (MMP-1), MMP-3, tissue inhibitor of MMP 1, and NF-kappaB in plaques were markedly reduced in all treatment groups when compared with the control group. Similar to high-dose simvastatin group, high-dose TXL group exhibited a low serum level of low-density lipoprotein cholesterol and ox-LDL, a low expression level of systemic and local inflammatory factors and a low plaque vulnerability index, with no differences in the incidence of plaque rupture among all treatment groups. TXL dose-dependently enhances the stability of vulnerable plaques and prevents plaques from rupture. Simvastatin and TXL offer similar protection in terms of lipid-lowering, anti-inflammation, and antioxidation effects.

An increasing number of congenital and infantile sarcomas displaying a primitive, monomorphic spindle cell phenotype have been characterized to harbor recurrent gene fusions, including infantile fibrosarcoma and congenital spindle cell rhabdomyosarcoma. Here we report an unusual spindle cell sarcoma presenting as a large and infiltrative pelvic soft tissue mass in a 4-month-old girl, which revealed a novel TFG-MET gene fusion by whole transcriptome RNA sequencing. The tumor resembled the morphology of an infantile fibrosarcoma with both fascicular and patternless growth, however, it expressed strong S100 protein immunoreactivity, while lacking SOX10 staining and retaining H3K27me3 expression. Although this immunoprofile suggested partial neural/neuroectodermal differentiation, overall features were unusual and did not fit into any known tumor types (cellular schwannoma, MPNST), raising the possibility of a novel pathologic entity. The TFG-MET gene fusion expands the genetic spectrum implicated in the pathogenesis of congenital spindle cell sarcomas, with yet another example of kinase oncogenic activation through chromosomal translocation. The discovery of this new fusion is significant since the resulting MET activation can potentially be inhibited by targeted therapy, as MET inhibitors are presently available in clinical trials.

ObjectiveTo examine the feasibility, acceptability, and preliminary effects of Hatha yoga on oxidative stress, motor function, and non-motor symptoms among individuals with Parkinson’s disease (PD).MethodsThe study has a pilot randomized controlled trial design with two arms: an immediate treatment group and a wait-list control group. The yoga-for-PD program was implemented via twice weekly 60-min group-based classes for 12 weeks. Participants were assessed at baseline, 12 weeks, and 6 months post-intervention. Outcome measures included oxidative stress, motor function, physical activity, cognitive function, sleep quality, and quality of life. Data on program acceptability and yoga adherence were collected during the intervention and at 6 months post-intervention.ResultsParticipants (n = 20) had a mean age of 63 years (SD 8, range 49–75) and disease duration 4.8 years (SD 2.9, range 1–13). All participants had mild-moderate disease severity; 18 (90%) were on dopaminergic medications. Seventeen participants (85%) attended at least 75% of the classes and 4 (20%) attended all classes. Most participants (n = 17) reported they “definitely enjoyed” the intervention program. No adverse events were reported. At 12 weeks, there were no major differences in blood oxidative stress markers between the two groups. Motor function based on the Unified Parkinson’s Disease Rating Scale was better in the treatment group, but their scores on sleep and outlook in Parkinson’s Disease Quality of Life (PDQUALIF) Scale and the physical activity levels based on the Longitudinal Aging Study Amsterdam Physical Activity Questionnaire were worse than those of the control group. In within-group comparisons, motor function, cognitive function, and catalase improved but three PDQUALIF domains (social and role function, sleep, and outlook) and physical activity level worsened by the end of the yoga intervention program compared to baseline. The response rate for the 6-month follow-up survey was 74% (n = 14) with six participants (43%) who signed up for a yoga class and four (29%) who practiced it independently. Health problems were the main barrier to yoga practice.ConclusionYoga is feasible and acceptable and may serve as a complementary method for improving motor function in PD. Further research using a larger sample size is needed to determine its impact on oxidative stress and non-motor symptoms.Trial registrationClinicalTrials.gov Registration Number: NCT02509610031.

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Oral squamous cell carcinoma (OSCC) is affected by the interaction between oral pathogen and holobionts, or the combination of the host and its microbial communities. Studies have indicated the structure and feature of the microbiome in OSCC tissue and saliva, the relationships between microbiota and OSCC sites, stages remain unclear. In the present study, OSCC tissue (T), saliva (S) and mouthwash (W) samples were collected from the same subjects and carried out the microbiome study by 16S sequencing. The results showed the T group was significantly different from the S and W groups with the character of lower richness and diversity. Proteobacteria were most enriched in the T group at the phylum level, while Firmicutes were predominant in groups S and W. At the genus level, the predominant taxa of group T were Acinetobacter and Fusobacterium , and for group S and W, the predominant taxa were Streptococcus and Prevotella . The genera related to late stage tumors were Acinetobacter and Fusobacterium , suggesting microbiota may be implicated in OSCC developing. Both compositional and functional analyses indicated that microbes in tumor tissue were potential indicator for the initiation and development of OSCC.

Introduction: Helicobacter pylori infection consistently leads to chronic and low degree of inflammatory response in gastric mucosa and is closely related with gastrointestinal and extra-gastric diseases. Effects of local microbiome in the stomach have been studied in adults and children with H. pylori infection. It is, however, not known whether the intestinal microbial community differs in children with varying H. pylori infection. The aim of this study is to characterize the altered composition of microbiome induced by H. pylori infection and in gastritis.Materials and Methods: This study involved 154 individuals, including 50 children affected by H. pylori-induced gastritis, 42 children with H. pylori-negative gastritis, and 62 healthy controls. Gut microbiome composition was analyzed using 16S rRNA gene-based pyrosequencing. Fecal bacterial diversity and composition were then compared.Results: On the basis of an analysis of similarities and differences, we found that children with H. pylori-induced gastritis exhibited gut bacteria dysbiosis. The ratio of Firmicutes/Bacteroidetes (F:B) at the phylum level had dramatically decreased in H. pylori-positive gastritis group (HPG) and H. pylori-negative gastritis group (HNG), compared with the healthy control group (HCG). At the family and genus levels, relative abundance of Bacteroidaceae and Enterobacteriaceae was prevalent in HPG and HNG, whereas relative abundance of Lachnospiraceae, Bifidobacteriaceae, and Lactobacillaceae was seen in HCG. Prevalence of different taxa of gut microbiome at the class, order, family, and genus levels was also observed among the three groups.Conclusions: Gastritis can cause changes in composition of fecal microbiome, which is exacerbated by H. pylori infection. These changes in gut microbiome may be related to drug resistance and development of chronic gastrointestinal diseases.