Infantile Myofibromatosis: 32 Patients and Review of Literature.

BACKGROUND: Infantile myofibromatiosis (IM) is a rare benign tumor in the infants, but it has a bad prognosis if IM erncroaches on the viscera. Multiple tissues can be invaded by IM, including the subcutaneous tissue, the muscle of the neck, back, and head, but seldom in the bones and the viscera. The histopathologic and immunohistochemical examinations are necessary in daigonosis of IM as it might be misdiagnosed as the malignant tumor. MATERIALS AND METHOD: Thirty-two consecutive patients with IM in our hospital (2003-2013) were enrolled and the clinical date were analyzed to understand IM better, such as the feature of clinical manifestations, pathology, imaging tests, and treatment. RESULTS: All of them underwent excision operations, 4 of them with invasion in the bones, 2 with invasion in the craniums, and the rest in the ulna and the humerus. The immunohistiochemical analysis shown that the tumor cells were positive to vimentin and smooth muscle actin while negative to the S100 protein and desmin. Twenty-five patients were in follow-up, 2 cases recurred. CONCLUSIONS: IM is a benign tumor, but IM with the viscera involvement has a bad prognosis. The strategy of waiting and observation for IM without visceral involvement could be selected.

Mesenchymal Stem Cell-Educated Macrophages Ameliorate LPS-Induced Systemic Response.

Both bone marrow and adipose-derived mesenchymal stem cells (ASCs) have immunomodulatory effects. The goal of this study was to determine whether ASCs-educated macrophages could directly ameliorate LPS-induced systemic response in a mouse model. Mouse peritoneal macrophages were cocultured with ASCs in a Transwell system for 2 days to educate macrophages. Mice were divided into 5 groups: control, LPS, LPS + ASCs, LPS + untreated macrophages, and LPS + educated macrophages. Educated macrophages decreased lung inflammation, weight loss, pulmonary edema, and inflammatory cytokine response. In vitro, ASCs increased expression of M2 macrophages independent of direct cell-to-cell contact when macrophages were treated with LPS or serum from patients with acute respiratory distress syndrome (ARDS). When macrophages were cultured with serum from ARDS patients who were treated with ASCs or placebo in our previous clinical trial, there was no difference in M2 macrophage levels before and after ASCs treatment indicating a suboptimal response to the treatment protocol. ASCs also reduced the levels of LPS-induced proinflammatory cytokines in vitro which were mimicked by IL-10 and blocked by antibodies for IL-10 and IL-10 receptor supporting the notion that educated macrophages exert their anti-inflammatory effects via IL-10-dependent mechanisms.

Differential effects of extracellular vesicles from aging and young mesenchymal stem cells in acute lung injury.

Old age is a known risk factor for mortality in acute respiratory distress syndrome (ARDS)/acute lung injury. Mesenchymal stem cells (MSCs) possess potent immunomodulatory properties, while aging MSCs have reduced capacity. Recent studies have demonstrated that MSC-derived extracellular vesicles (MSC-EVs) are able to mimic MSCs in alleviating acute lung injury. The goals of this study were to determine whether EVs from young and aging MSCs had differential effects on lipopolysaccharide (LPS)-induced lung injury in young mice and unravel the underlying mechanisms. Our results showed that both aging and young MSC-EVs had similar physical and phenotypical properties. As their parental cells, young MSC-EVs alleviated LPS-induced acute lung injury, while aging MSC-EVs did not exhibit the protective effects. In contrast to young MSC-EVs, aging MSC-EVs failed to alter macrophage phenotypes and reduce macrophage recruitment. In addition, the internalization of aging MSC-EVs by macrophages was significantly lower compared with that of young MSC-EVs. Furthermore, aging and young MSC-EVs differed in levels of several miRNAs relating macrophage polarization. In conclusion, aging and young MSC-EVs have differential effects in alleviating acute lung injury and macrophage polarization, which may be associated with internalization of EVs and their miRNA content.

Myeloid-derived suppressor cells in sepsis.

Sepsis is a systemic, deleterious host response to widespread infection. Patients with sepsis will have documented or suspected infection which can progress to a state of septic shock or acute organ dysfunction. Since sepsis is responsible for nearly 3 million cases per year in China and severe sepsis is a common, expensive fatal condition in America, developing new therapies becomes a significant and worthwhile challenge. Clinical research has shown that sepsis-associated immunosuppression plays a central role in patient mortality, and targeted immune-enhancing therapy may be an effective treatment approach in these patients. As part of the inflammatory response during sepsis, there are elevations in the number of myeloid-derived suppressor cells (MDSCs). MDSCs are a heterogeneous population of immature myeloid cells that possess immunosuppressive activities via suppressing T-cell proliferation and activation. The role of MDSCs in sepsis remains uncertain. Some believe activated MDSCs are beneficial to the sepsis host by increasing innate immune responses and antimicrobial activities, while others think expansion of MDSCs leads to adaptive immune suppression and secondary infection. Herein, we discuss the complex role of MDSCs in immune regulation during sepsis, as well as the potential to target these cells for therapeutic benefit.

Intensive insulin therapy for septic patients: a meta-analysis of randomized controlled trials.

Background. Studies on the effect of intensive insulin therapy (IIT) in septic patients with hyperglycemia have given inconsistent results. The primary purpose of this meta-analysis was to evaluate whether it is effective in reducing mortality. Methods. We searched PubMed, Embase, the Cochrane Library, clinicaltrials.gov, and relevant reference lists up to September 2013 and including randomized controlled trials that compared IIT with conventional glucose management in septic patients. Study quality was assessed using the Cochrane Risk of Bias Tool. And our primary outcome measure was pooled in the random effects model. Results. We identified twelve randomized controlled trials involving 4100 patients. Meta-analysis showed that IIT did not reduce any of the outcomes: overall mortality (risk ratio [RR] = 0.98, 95% CI [0.85, 1.15], P = 0.84), 28-day mortality (RR = 0.66, 95% CI [0.40, 1.10], P = 0.11), 90-day mortality (RR = 1.10, 95% CI [0.97, 1.26], P = 0.13), ICU mortality (RR = 0.94, 95% CI [0.77, 1.14], P = 0.52), hospital mortality (RR = 0.98, 95% CI [0.86, 1.11], P = 0.71), severity of illness, and length of ICU stay. Conversely, the incidence of hypoglycemia was markedly higher in the IIT (RR = 2.93, 95% CI [1.69, 5.06], P = 0.0001). Conclusions. For patients with sepsis, IIT and conservative glucose management show similar efficacy, but ITT is associated with a higher incidence of hypoglycemia.