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Although many researches have explored the prognostic factors associated with length of hospital stay (LOS) of adult burn patients, fewer reports concerning pediatric burn patients have been conducted. The present study employed pediatric burn data to identify factors related to LOS and developed a novel model to assess the possibility of requiring surgery. A total of 750 children admitted for burns met the criteria for enrollment. We have analyzed the medical records using multivariable linear regression and logistic regression. The pediatric patients were stratified into medical (nonsurgical) and surgical groups, respectively. The median LOS was 27.11 ± 17.91 days (range: 6–107 days). Following multiple linear regression, surgery (P < .001; 95% confidence interval [CI]: 6.485, 11.918), percent total BSA (%TBSA) (P < .001; 95% CI: 0.271, 0.459), days to surgery (P < .001; 95% CI: 0.349, 0.648), etiology (P < .001; 95% CI: −15.801, −9.422), infection (P < .001; 95% CI: 4.163, 8.329), and erythrocyte loss (P < .001; 95% CI: 1.923, 4.017) were significantly associated with LOS. After logistic regression, the percent full thickness (%FT) (P < .001; odds ratio [OR]: 2.358; 95% CI: 1.680, 3.311), infection (P < .001; OR: 2.935; 95% CI: 2.014, 4.278), and erythrocyte loss (P < .001; OR: 0.572; 95% CI: 0.470, 0.696) within 5 days postadmission were independently related to the probability of requiring surgery. In conclusion, in pediatric patients admitted with burn size of TBSA ≥20%, factors independently influencing LOS were surgery, %TBSA, days to surgery, etiology, erythrocyte loss, and infection. Furthermore, the pivotal predictors of probability requiring surgery were %FT, infection, and erythrocyte loss.

Background. Under septic conditions, LPS induced lung vascular endothelial cell (EC) injury, and the release of inflammatory mediator launches and aggravates acute lung injury (ALI). There are no effective therapeutic options for ALI. Genistein-3′-sodium sulfonate (GSS) is a derivative of native soy isoflavone, which exhibits neuroprotective effects via its antiapoptosis property. However, whether GSS protect against sepsis-induced EC injury and release of inflammatory mediators has not been determined. In this study, we found that GSS not only downregulated the levels of TNF-αand IL-6 in the lung and serum of micein vivobut also inhibited the expression and secretion of TNF-αand IL-6 in ECs. Importantly, we also found that GSS blocked LPS-induced TNF-αand IL-6 expression in ECs via the Myd88/NF-κB signaling pathway. Taken together, our results demonstrated that GSS might be a promising candidate for sepsis-induced ALI via its regulating effects on inflammatory response in lung ECs.

ObjectiveWe aimed to construct a novel prognostic model based on N6-methyladenosine (m6A)-related autophagy genes for predicting the prognosis of lung squamous cell carcinoma (LUSC). MethodsGene expression profiles and clinical information of Patients with LUSC were downloaded from The Cancer Genome Atlas (TCGA) database. In addition, m6A- and autophagy-related gene profiles were obtained from TCGA and Human Autophagy Database, respectively. Pearson correlation analysis was performed to identify the m6A-related autophagy genes, and univariate Cox regression analysis was conducted to screen for genes associated with prognosis. Based on these genes, LASSO Cox regression analysis was used to construct a prognostic model. The corresponding prognostic score (PS) was calculated, and patients with LUSC were assigned to low- and high-risk groups according to the median PS value. An independent dataset (GSE37745) was used to validate the prognostic ability of the model. CIBERSORT was used to calculate the differences in immune cell infiltration between the high- and low-risk groups. ResultsSeven m6A-related autophagy genes were screened to construct a prognostic model: CASP4, CDKN1A, DLC1, ITGB1, PINK1, TP63, and EIF4EBP1. In the training and validation sets, patients in the high-risk group had worse survival times than those in the low-risk group; the areas under the receiver operating characteristic curves were 0.958 and 0.759, respectively. There were differences in m6A levels and immune cell infiltration between the high- and low-risk groups. ConclusionsOur prognostic model of the seven m6A-related autophagy genes had significant predictive value for LUSC; thus, these genes may serve as autophagy-related therapeutic targets in clinical practice.

Under septic conditions, Lipopolysaccharide (LPS)‐induced apoptosis of lung vascular endothelial cells (ECs) triggers and aggravates acute lung injury (ALI), which so far has no effective therapeutic options. Genistein‐3′‐sodium sulphonate (GSS) is a derivative of native soy isoflavone, which has neuro‐protective effects through its anti‐apoptotic property. However, whether GSS protects against sepsis‐induced lung vascular endothelial cell apoptosis and ALI has not been determined. In this study, we found that LPS‐induced Myd88/NF‐κB/BCL‐2 signalling pathway activation and subsequent EC apoptosis were effectively down‐regulated by GSS in vitro. Furthermore, GSS not only reversed the sepsis‐induced BCL‐2 changes in expression in mouse lungs but also blocked sepsis‐associated lung vascular barrier disruption and ALI in vivo. Taken together, our results demonstrated that GSS might be a promising candidate for sepsis‐induced ALI via its regulating effects on Myd88/NF‐κB/BCL‐2 signalling in lung ECs.

Point mutations of TP53 tumour suppressor are very rare in schwannomas. We aim to characterize the frequency of exonic copy-number changes of the gene in the tumour and to examine the association between TP53 alterations, phosphorylation status of p53 protein and clinical phenotypes. The alterations of TP53 were screened by a combination of Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) in a total of 44 vestibular schwannomas. The mutation index (MI) in a tumour was defined as the number of exons mutated/ the number of exons tested. Phosphorylation status of p53 protein was investigated by immunoblotting and immunofluorescence. MLPA analysis showed single and multi-exon deletion mutations of TP53 in 65.7% of the cases. Comparisons of clinical features between mutated and non-mutated patients established an association of TP53 mutations with progressive phenotypes, including an earlier formation and a larger tumour. In addition, there were significant correlations between MI and both patients’ age and tumour size. The Ser 392 phosphorylation level of p53 varied among tumours, and correlation analysis revealed an age-dependent phosphorylation pattern. The majority of tumours with hyperphosphorylated p53 were from mutated and young patients, suggesting an association of Ser392 phosphorylation with the mutational status of TP53 involved in the acceleration of tumour growth in young individuals. Moreover, Ser 392 phosphorylation contributed to a nuclear accumulation of p53 in schwannona cultures with TP53 mutation. An interplay between the mutation status of TP53, phosphorylation patterns and tumour behaviors might be established in the disease.

Quick and effective sterilization of drug-resistant bacteria inevitably became an ever-growing global challenge. In this study, a multifunctional composite (PDA/Cu-CS) hydrogel mainly composed of polydopamine (PDA) and copper-doped calcium silicate ceramic (Cu-CS) was prepared. It was confirmed that PDA/copper (PDA/Cu) complexing in the composite hydrogel played a key role in enhancing the photothermal performance and antibacterial activity. Through a unique "hot ions effect", created by the heating of Cu ions through the photothermal effect of the composite hydrogel, the hydrogel showed high-efficiency, quick, and long-term inhibition of methicillin-resistant Staphylococcus aureus and Escherichia coli. In addition, the hydrogel possessed remarkable bioactivity to stimulate angiogenesis. The in vivo results confirmed that the "hot ions effect" of the composite hydrogel removed existing infection in the wound area efficiently and significantly promoted angiogenesis and collagen deposition during infectious skin wound healing. Our results suggested that the design of multifunctional hydrogels with "hot ions effect" may be an effective therapeutic approach for the treatment of infectious wounds.

Inflammation is characterized by early influx of polymorphonuclear neutrophils (PMNs), followed by a second wave of monocyte recruitment. PMNs mediate monocyte recruitment via their release of heparin binding protein (HBP), which activates CCR2 (CC-chemokine receptor 2) on monocytes. However, the pathways for such signal transmission remain unknown. Accumulating evidences have highlighted the importance of leukocyte-endothelial cell interactions in the initiation of inflammation. In this study, an interesting finding is that HBP enhances the secretion of monocyte chemotactic protein 1(MCP-1), ligand of CCR2, from a third party, the endothelial cells (ECs). HBP-induced increase in MCP-1 production was demonstrated at the protein, mRNA and secretion levels. Exposure of ECs to HBP elicited rapid phosphorylation of FAK/PI3K/AKT and p38 MAPK/NF-κB signaling. MCP-1 levels were attenuated during the response to HBP stimulation by pretreatment with a FAK inhibitor (or siRNA), a PI3K inhibitor, an AKT inhibitor, a p38 inhibitor (or siRNA) and two NF-κB inhibitors. Additionally, pretreatment with inhibitors to FAK, PI3K and AKT led to a decrease in HBP-induced phosphorylation of p38/NF-κB axis. These results showed that HBP induced MCP-1 expression via a sequential activation of the FAK/PI3K/AKT pathway and p38 MAPK/NF-κB axis. Interestingly, the patterns of HBP regulation of the expression of the adhesion molecular VCAM-1 were similar to those seen in MCP-1 after pretreatment with inhibitors (or not). These findings may help to determine key pharmacological points of intervention, thus slowing the progress of inflammatory-mediated responses in certain diseases where inflammation is detrimental to the host.

Acute lung injury (ALI) is characterized by protein-rich pulmonary edema, critical hypoxemia, and influx of pro-inflammatory cytokines and cells. There are currently no effective pharmacon therapies in clinical practice. Syndecan-1 in endothelial cells has potential to protect barrier function of endothelium and suppress inflammation response. Thus, the present study was to identify whether exosomes with encapsulation of syndecan-1 could achieve ideal therapeutic effects in ALI. Exosomes were isolated from the conditional medium of lentivirus-transfected mouse pulmonary microvascular endothelial cells (MPMVECs) and characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and western blotting. ALI mouse models were induced via intratracheal administration of lipopolysaccharide (LPS) and treated with exosomes. Lung edema, inflammation, and glycocalyx thickness were examined. The possible mechanism was verified by immunoblotting in MPMVECs. The purified exosomes included SDC1-high-Exos and SDC1-low-Exos which loaded with up-regulated syndecan-1 and down-regulated syndecan-1 respectively. Compared with SDC1-low-Exos, administration of SDC1-high-Exos could ameliorate lung edema and inflammation, attenuate number of cells and protein levels in bronchoalveolar lavage fluid (BALF), and preserve glycocalyx. Furthermore, SDC1-high-Exos also mitigated the expression of pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6 following LPS challenge. In MPMVECs, SDC1-high-Exos decreased stress fiber formation and ameliorated monolayer hyper-permeability after LPS stimulation. Western blotting analysis demonstrated that FAK/p190RhoGAP/RhoA/ROCK/NF-κB signaling pathway may be involved in LPS-induced ALI. In conclusion, SDC1-high-Exos play a pivotal role in ameliorating LPS-stimulated ALI models and may be served as a potential therapeutic agent for clinical application in the future.

Due to the complexity of the skin tissue structure, the regeneration of the entire skin, including skin appendages such as hair follicles, is a big challenge. In addition, skin trauma is often accompanied by bacterial infections that delay the wound healing. Therefore, developing wound dressings, which promote hair follicle regeneration and inhibit bacterial infection in the wound healing process, is of great clinical significance. In this study, Zn doped hollow mesoporous silica nanospheres (HMZS) were synthesized by a sol-gel method and a novel wound healing dressing was prepared by incorporation of drug ciprofloxacin hydrochloride (CiH)-loaded Zn containing mesoporous silica nanospheres (CiH-HMZS) into polycaprolactone (PCL) electrospun fibers. The CiH-HMZS/P nano-composite electrospun fibers exhibit the ability to promote angiogenesis and skin regeneration by releasing Si ions, and the activity to enhance hair follicle regeneration and inhibit bacterial growth by releasing zinc ions and achieve the synergistic antibacterial effect with both Zn ions and CiH in low concentrations. Thus, the CiH-HMZS/P nano-composite membrane is a promising multi-functional wound healing material for inhibiting bacterial growth in infected wounds and enhancing skin wound healing including hair follicle regeneration.

Thrombocytopenia is a common event in severely burned patients and associated with adverse outcome. The underlying relationship between the dynamic changes of platelet counts and mortality has not been well defined. We performed a 6-year retrospective chart of adult patients with a burn index of 50 or greater admitted to two burn centers and collected data on patient demographics, laboratory results, and patient outcomes. The mean daily increase in the platelet count (∆PC/∆t) from day 3 to day 10 was calculated, and 30-day mortality was determined. For the study, 141 survivors and 65 nonsurvivors were enrolled. The sequential changes in PCs presented a biphasic pattern after admission, with a slump to the nadir during the first 3 days and a subsequent recovery. With respect to 30-day mortality, compared with the AUC of APACHE-Ⅱ score (0.841), no significant difference was noted between ΔPC/ΔT and APACHE-Ⅱ score (p = 0.0648). The ΔPC/ΔT associated with the best discrimination between survivors and nonsurvivors was 20.57 × 10

The bacterial endotoxin or lipopolysaccharide (LPS) leads to the extensive vascular endothelial cells (EC) injury under septic conditions. Guanine nucleotide exchange factor-H1 (GEF-H1)/ROCK signaling not only involved in LPS-induced overexpression of pro-inflammatory mediator in ECs but also implicated in LPS-induced endothelial hyper-permeability. However, the mechanisms behind LPS-induced GEF-H1/ROCK signaling activation in the progress of EC injury remain incompletely understood. GEF-H1 localized on microtubules (MT) and is suppressed in its MT-bound state. MT disassembly promotes GEF-H1 release from MT and stimulates downstream ROCK-specific GEF activity. Since glycogen synthase kinase (GSK-3beta) participates in regulating MT dynamics under pathologic conditions, we examined the pivotal roles for GSK-3beta in modulating LPS-induced activation of GEF-H1/ROCK, increase of vascular endothelial permeability and severity of acute lung injury (ALI). In this study, we found that LPS induced human pulmonary endothelial cell (HPMEC) monolayers disruption accompanied by increase in GSK-3beta activity, activation of GEF-H1/ROCK signaling and decrease in beta-catenin and ZO-1 expression. Inhibition of GSK-3beta reduced HPMEC monolayers hyper-permeability and GEF-H1/ROCK activity in response to LPS. GSK-3beta/GEF-H1/ROCK signaling is implicated in regulating the expression of beta-catenin and ZO-1. In vivo, GSK-3beta inhibition attenuated LPS-induced activation of GEF-H1/ROCK pathway, lung edema and subsequent ALI. These findings present a new mechanism of GSK-3beta-dependent exacerbation of lung micro-vascular hyper-permeability and escalation of ALI via activation of GEF-H1/ROCK signaling and disruption of intracellular junctional proteins under septic condition.

Background Hypertrophic scars are manifestations of an abnormal process of tissue repair. Although photodynamic therapy is a promising treatment, details of the mechanisms underlying its inhibitory effects remain to be elucidated. Methods Fibroblasts were isolated from human hypertrophic scar specimens and subjected to photodynamic therapy; 5-aminolevulinic acid was used as a photosensitizer. The accumulation of 5-aminolevulinic acid-derived protoporphyrin IX was detected under fluorescence microscopy. The potential cytotoxicity of 5-aminolevulinic acid alone and with photodynamic therapy was measured by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide. Hoechst 33258 staining and flow cytometry were conducted to search for clues to apoptosis. Protein and/or mRNA expression levels of apoptosis-related pathways and other hypertrophic scar pathogenesis-associated signaling were investigated by Western blot analysis and/or real-time polymerase chain reaction. Results Protoporphyrin IX accumulation peak was achieved at 1.0 mM 5-aminolevulinic acid. 5-Aminolevulinic acid ranging from 0 to 1.0 mM was demonstrated to be noncytotoxic but reduced cell viabilities in a dose-dependent manner with acid-based photodynamic therapy were demonstrated. Reduction of cell viability was attributed mainly to cell apoptosis and probably to mechanisms such as up-regulation of p53/p21, Bax/Bcl-2 ratio, and cleaved caspase-3. Concurrently, deregulation of transforming growth factor-β1-mediated signaling, serving as another putative mechanism underlying hypertrophic scar formation, was found to be reversely modulated in response to acid-based photodynamic therapy. Conclusion The p53-related apoptosis pathway and transforming growth factor-β1-mediated signaling may be important factors used to predict and evaluate the treatment outcomes of 5-aminolevulinic acid-based photodynamic therapy used in hypertrophic scar patients. Clinical question/level of evidence Therapeutic, V.

We aimed to evaluate the efficacy of combination of propranolol and sclerotherapy in treating parotid hemangiomas. Twenty-six parotid hemangiomas patients were subjected to combined treatment from January 2009 and June 2014. The effects of the therapy modality were evaluated. Nineteen patients were females and 7 were males. The median age of treatment initiation was 4.96 months. Twelve lesions were located on the left side parotid glands, while thirteen lesions affected the right side. One infant had bilateral lesions. One to six (average 2.04) injections were performed and the mean period for propranolol was 8.94 months. All the patients got satisfied aesthetic outcomes. No complications of propranolol or sclerotherapy occurred during the whole medication period. The study demonstrated that combination of propranolol and sclerotherapy was an effective and safe method for infantile parotid hemangiomas. Larger-scale studies should be performed to further investigate the long-term efficacy and results of the present combined method for infantile parotid hemangiomas.