IntroductionThe purpose of this meta-analysis was to explore the value of whole-body computed tomography (WBCT) in major trauma patients (MTPs).MethodsA comprehensive search for articles from Jan 1, 1980 to Dec 31, 2013 was conducted through PubMed, Cochrane Library database, China biology medical literature database, Web of knowledge, ProQuest, EBSCO, OvidSP, and ClinicalTrials.gov. Studies which compared whole-body CT with conventional imaging protocol (X-ray of the pelvis and chest, trans-abdominal sonography, and/or selective CT) in MTPs were eligible. The primary endpoint was all-cause mortality. The second endpoints included: time spent in the emergency department (ED), the duration of mechanical ventilation, ICU and hospital length of stay (LOS), the incidence of Multiple Organ Dysfunction Syndrome (MODS) /Multiple Organ Failure (MOF). Analysis was performed with Review Manager 5.2.10 and Stata 12.0.ResultsEleven trials enrolling 26371 patients were analyzed. In MTPs, the application of WBCT was associated with lower mortality rate (pooled OR: 0.66, 95% CI: 0.52 to 0.85) and a shorter stay in the ED (weighted mean difference (WMD), −27.58 min; 95% CI, −43.04 to −12.12]. There was no effect of WBCT on the length of ICU stay (WMD, 0.95 days; 95% CI: −0.08 to 1.98) and the length of hospital stay (WMD, 0.56 days; 95% CI: −0.03 to 1.15). Patients in the WBCT group had a longer duration of mechanical ventilation (WMD, 0.96 days, 95% CI: 0.32 to 1.61) and higher incidence of MODS/MOF (OR, 1.44, 95% CI: 1.35-1.54; P = 0.00001).ConclusionsThe present meta-analysis suggests that the application of whole-body CT significantly reduces the mortality rate of MTPs and markedly reduces the time spent in the emergency department.

The presence of FMS-like receptor tyrosine kinase-3 internal tandem duplication (FLT3-ITD) mutations in patients with acute myeloid leukemia (AML) is associated with poor clinical outcome. FLT3 tyrosine kinase inhibitors (TKIs), although effective in kinase ablation, do not eliminate primitive FLT3-ITD+ leukemia cells, which are potential sources of relapse. Thus, understanding the mechanisms underlying FLT3-ITD+ AML cell persistence is essential to devise future AML therapies. Here, we show that expression of protein arginine methyltransferase 1 (PRMT1), the primary type I arginine methyltransferase, is increased significantly in AML cells relative to normal hematopoietic cells. Genome-wide analysis, coimmunoprecipitation assay, and PRMT1-knockout mouse studies indicate that PRMT1 preferentially cooperates with FLT3-ITD, contributing to AML maintenance. Genetic or pharmacological inhibition of PRMT1 markedly blocked FLT3-ITD+ AML cell maintenance. Mechanistically, PRMT1 catalyzed FLT3-ITD protein methylation at arginine 972/973, and PRMT1 promoted leukemia cell growth in an FLT3 methylation–dependent manner. Moreover, the effects of FLT3-ITD methylation in AML cells were partially due to cross talk with FLT3-ITD phosphorylation at tyrosine 969. Importantly, FLT3 methylation persisted in FLT3-ITD+ AML cells following kinase inhibition, indicating that methylation occurs independently of kinase activity. Finally, in patient-derived xenograft and murine AML models, combined administration of AC220 with a type I PRMT inhibitor (MS023) enhanced elimination of FLT3-ITD+ AML cells relative to AC220 treatment alone. Our study demonstrates that PRMT1-mediated FLT3 methylation promotes AML maintenance and suggests that combining PRMT1 inhibition with FLT3 TKI treatment could be a promising approach to eliminate FLT3-ITD+ AML cells.

Mesenchymal stem cells derived from Wharton's jelly of the human umbilical cord (hUC-MSCs) possess various advantageous properties, similar to bone marrow-derived mesenchymal stem cells (BM-MSCs), including self-renewal, extended proliferation potential and multilineage differentiation potential. In this study, we hoped to determine whether hUC-MSCs could be induced to differentiate into sweat gland cell-like cells, that would be potential in sweat glands restoration after injury. In this study, the results of flow cytometry analysis revealed that hUC-MSCs showed the typical antigen profile of MSCs and were positive for CD29, CD44, CD90, CD105 and Oct-4; they were negative for the antigens of CD34, CEA and CK14. Remarkably, hUC-MSCs maintained proper proliferation and differentiation ability. After culture in sweat gland cell-conditioned medium (induction group 1) for 3 weeks, hUC-MSCs possessed sweat gland cell-like morphology and expressed markers of sweat gland cells (CEA, CK14 and CK19) more efficiently than those of induction group 2. In reverse-transcription PCR and western blotting analysis, it was further confirmed that induced hUC-MSCs (group 1) also expressed a higher level of sweat gland developmental genes (EDA and EDAR) than group 2. These results together provided evidence that hUC-MSCs could possess a new emerging potential to differentiate into sweat gland cell-like cells with a higher efficacy under our new induction system. Thus, hUC-MSCs could be considered a new strategy for sweat glands restoration after skin injury as well as improvement of cutaneous regeneration.

No abstract

No abstract