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The incidence of liquefied petroleum gas (LPG)-related accidents in China has increased over the recent years. In addition, infection remains a big challenge in cases of severe burns. Therefore, the present study aimed to provide valuable information for a better control of infections in the event of such disasters. In this study, a total of 16 patients who suffered extremely severe burns after an LPG tanker explosion were included. Thereafter, bacteriological culture results were collected within a week. Of 16 patients, 13 (81.25%) were male and the average age of all patients was 60.63 years. In addition, the mean burned area was 83.03% TBSA. Additionally, a total of 553 organism cultures were conducted out of which 287 isolates (51.90%) showed positive results. Notably, 38.52% were Gram-negative bacteria, 7.59% were Gram-positive bacteria and 5.79% were fungi. Moreover, the most prevalent Gram-negative bacteria were Stenotrophomonas maltophilia (28.97%) followed by Acinetobacter baumannii (28.53%), and Klebsiella pneumoniae (14.02%). On the other hand, the three most predominant Gram-positive bacteria were Enterococcus faecalis (33.33%), Staphylococcus aureus (28.89%) and Staphylococcus sciuri (17.78%). Furthermore, the most common fungi included Candida (38.24%), Fusarium (20.59%) and Aspergillus fumigatus (14.71%). With regard to the bacterial resistance patterns, carbapenem-resistant organisms included Acinetobacter baumannii (97.80%), Pseudomonas aeruginosa (67.57%), and Klebsiella pneumoniae (75.56%). In addition, Staphylococcus sciuri, Staphylococcus epidermidis, and Staphylococcus haemolyticus were identified to be methicillin-resistant. This study revealed that there was a high incidence of infection in victims of severe burns as a result of mass burn accidents, accompanied by early fungal infection.

BACKGROUND: HER2 gene expression is one of the main reference indicators for breast cancer detection and treatment, and it is also an important target for tumor targeted therapy drug selection. Therefore, the correct detection and evaluation of HER2 gene expression has important value for clinical treatment of breast cancer. OBJECTIVE: The study goal is to better classify HER2 images. METHODS: For general convolution neural network, with the increase of network layers, over fitting phenomenon is often very serious, which requires setting the value of random descent ratio, and parameter adjustment is often time-consuming and laborious, so this paper uses residual network, with the increase of network layer, the accuracy will not be reduced. RESULTS: In this paper, a HER2 image classification algorithm based on improved residual network is proposed. Experimental results show that the proposed HER2 network has high accuracy in breast cancer assessment. Conclusion: Taking HER2 images in Stanford University database as experimental data, the accuracy of HER2 image automatic classification is improved through experiments. This method will help to reduce the detection intensity and improve the accuracy of HER2 image classification.

Objectives Early acute kidney injury (AKI) after burn contributes to disastrous prognoses for severely burned patients. Burn-induced renal oxidative stress and secondary proinflammatory mediator release contribute to early AKI development, and Toll-like receptor (TLR) 4 regulates inflammation. Heme oxygenase-1 (HO-1) is a stress-responsive enzyme that plays a vital role in protecting against ischemia-induced organ injury via its antioxidant properties and regulation of inflammation. We investigated the potential effect of HO-1 induction in preventing burn-induced early AKI and its related mechanism. Methods A classic major-burn rat model was established using a 100 °C water bath, and hemin was injected intraperitoneally immediately after the injury to induce HO-1. Histological staining and blood tests were used to assess AKI progression based on structural changes and function. Renal levels of HO-1, oxidative stress, proinflammatory mediators and TLR4-related signals were detected using ELISA, immunostaining, qRT-PCR, and western blotting. The selective TLR4 inhibitor TAK242 and TLR4 inducer LPS were introduced to determine the roles of HO-1 in burn-related renal inflammation and the TLR4 pathway. Results Hemin improved burn-induced renal histological damage and dysfunction, and this beneficial effect was related to reduced renal oxidative stress and the release of proinflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6 and intracellular adhesion molecule-1 (ICAM-1). Hemin downregulated the expression of TLR4 and the subsequent phosphorylation of IKKα/β, IκBα, and NF-κB p65;. TAK242 exerted an effect similar to but weaker than hemin; and LPS reversed the antiinflammatory effect of hemin and the regulation of TLR4 signals. These results suggested that the TLR4 signaling pathway mediated the HO-1-facilitated regulation of renal inflammation after burn. Conclusion The present study demonstrated that HO-1 induction prevented burn-induced early AKI by targeting renal inflammation, which was mediated via regulation of the TLR4/NF-κB signaling pathway.

Treatment of full-thickness skin defects still presents a significant challenge in clinical practice. Three-dimensional (3D) bioprinting technique offers a promising approach for fabricating skin substitutes. However, it is necessary to identify bioinks that have both sufficient mechanical properties and desirable biocompatibilities. In this study, we successfully fabricated acellular dermal matrix (ADM) and gelatin methacrylamide (GelMA) bioinks. The results demonstrated that ADM preserved the main extracellular matrix (ECM) components of the skin and GelMA had tunable mechanical properties. Both bioinks with shear-thinning properties were suitable for 3D bioprinting and GelMA bioink exhibited high printability. Additionally, the results revealed that 20% GelMA with sufficient mechanical properties was suitable to engineer epidermis, 1.5% ADM and 10% GelMA displayed relatively good cytocompatibilities. Here, we proposed a new 3D structure to simulate natural full-thickness skin, which included 20% GelMA with HaCaTs as an epidermal layer, 1.5% ADM with fibroblasts as the dermis, and 10% GelMA mesh with human umbilical vein endothelial cells (HUVECs) as the vascular network and framework. We demonstrated that this 3D bioprinting functional skin model (FSM) could not only promote cell viability and proliferation, but also support epidermis reconstruction in vitro. When transplanted in vivo, the FSM could maintain cell viability for at least 1 week. Furthermore, the FSM promoted wound healing and re-epithelization, stimulated dermal ECM secretion and angiogenesis, and improved wound healing quality. The FSM may provide viable functional skin substitutes for future clinical applications. Statement of significance We propose a new 3D structure to simulate natural full-thickness skin, which included 20% GelMA with HaCaTs as an epidermal layer, 1.5% ADM with fibroblasts as the dermis, and 10% GelMA mesh with HUVECs as the vascular network. It could not only maintain a moist microenvironment and barrier function, but also recreate the natural skin microenvironment to promote cell viability and proliferation. This may provide viable functional skin substitutes for future clinical applications.

BackgroundMachine learning (ML) is a type of artificial intelligence (AI) and has been utilized in clinical research and practice to construct high-performing prediction models. Hidden blood loss (HBL) is prevalent during the perioperative period of spinal treatment and might result in a poor prognosis. The aim of this study was to develop a ML-based model for identifying perioperative HBL-related risk factors in patients with thoracolumbar burst fracture (TBF).MethodsIn this study, single-central TBF patients were chosen. The medical information on patients, including clinical characteristics, laboratory indicators, and surgery-related parameters, was extracted. After comparing various ML model algorithms, we selected the best model with high performance. The model was validated using the internal validation set before performing recursive feature elimination (RFE) to determine the importance of HBL-related risk factors. The area under the receiver operating characteristic (AUC) curve, accuracy (ACC), sensitivity, and specificity were reported as critical model measures for evaluating predictive performance.ResultsIn this study, 62 (38.5%) of the 161 TBF patients were positive for HBL. There was a significant statistical difference in age, body mass index (BMI), diabetes, hypertension, Beta (percentage of vertebral restoration), duration of operation, and other pre-operative laboratory indicators between the HBL-positive and HBL-negative groups. Nine ML-based models were built and validated, with the Random Forest model having the greatest AUC in both the training set (0.905) and internal validation set (0.864). Furthermore, following RFE, age, duration of operation, Beta, pre-operative fibrinogen (Fib), and activated partial thromboplastin time (APTT) were identified as the five main important risk factors in patients with TBF during the perioperative period.ConclusionIn this study, we built and validated ML algorithms for an individualized prediction of HBL-related risk factors in the perioperative period of TBF. The importance of HBL-related risk factors could be determined, which contributes to clinicians' decision-making and improves perioperative management.

BackgroundLarge-scale real-world data to evaluate the impact of chest pain centre (CPC) accreditation on acute coronary syndrome (ACS) emergency care in heavy-burden developing countries like China are rare.MethodsThis study is a retrospective study based on data from the Hospital Quality Monitoring System (HQMS) database. This study included emergency patients admitted with ACS to hospitals that uploaded clinical data continuously to the database from 2013 to 2016. Propensity score matching was used to compare hospitals with and without CPC accreditation during this period. A longitudinal self-contrast comparison design with mixed-effects models was used to compare management of ACS before and after accreditation.ResultsA total of 798 008 patients with ACS from 746 hospitals were included in the analysis. After matching admission date, hospital levels and types and adjusting for possible covariates, patients with ACS admitted to accredited CPCs had lower in-hospital mortality (OR=0.70, 95% CI 0.53 to 0.93), shorter length of stay (LOS; adjusted multiplicative effect=0.89, 95% CI 0.84 to 0.94) and more percutaneous coronary intervention (PCI) procedures (OR=3.53, 95% CI 2.20 to 5.66) than patients admitted in hospitals without applying for CPC accreditation. Furthermore, when compared with the ‘before accreditation’ group only in accredited CPCs, the in-hospital mortality and LOS decreased and the usage of PCI were increased in both ‘accreditation’ (for in-hospital mortality: OR=0.86, 95% CI 0.79 to 0.93; for LOS: 0.94, 95% CI 0.93 to 0.95; for PCI: OR=1.22, 95% CI 1.18 to 1.26) and ‘after accreditation’ groups (for in-hospital mortality: OR=0.90, 95% CI 0.84 to 0.97; for LOS: 0.89, 95% CI 0.89 to 0.90; for PCI: OR=1.36, 95% CI 1.33 to 1.39). The significant benefits of decreased in-hospital mortality, reduced LOS and increased PCI usage were also observed for patients with acute myocardial infarction.ConclusionsCPC accreditation is associated with better management and in-hospital clinical outcomes of patients with ACS. CPC establishment and accreditation should be promoted and implemented in countries with high levels of ACS.

Human umbilical cord mesenchymal stem cell‐derived exosomes (hucMSC‐exosomes) have been implicated as a novel therapeutic approach for tissue injury repair and regeneration, but the effects of hucMSC‐exosomes on coxsackievirus B3 (CVB3)‐induced myocarditis remain unknown. The object of the present study is to investigate whether hucMSC‐exosomes have therapeutic effects on CVB3‐induced myocarditis (VMC). HucMSC‐exosomes were identified using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western blot. The purified hucMSC‐exosomes tagged with PKH26 were tail intravenously injected into VMC model mice in vivo and used to administrate CVB3‐infected human cardiomyocytes (HCMs) in vitro, respectively. The effects of hucMSC‐exosomes on myocardial pathology injury, proinflammatory cytokines and cardiac function were evaluated through haematoxylin and eosin (H&E) staining, quantitative polymerase chain reaction (qPCR) and Doppler echocardiography. The anti‐apoptosis role and potential mechanism of hucMSC‐exosomes were explored using TUNEL staining, flow cytometry, immunohistochemistry, Ad‐mRFP‐GFP‐LC3 transduction and Western blot. In vivo results showed that hucMSC‐exosomes (50 μg iv) significantly alleviated myocardium injury, shrank the production of proinflammatory cytokines and improved cardiac function. Moreover, in vitro data showed that hucMSC‐exosomes (50 μg/mL) inhibited the apoptosis of CVB3‐infected HCM through increasing pAMPK/AMPK ratio and up‐regulating autophagy proteins LC3II/I, BECLIN‐1 and anti‐apoptosis protein BCL‐2 as well as decreasing pmTOR/mTOR ratio, promoting the degradation of autophagy flux protein P62 and down‐regulating apoptosis protein BAX. In conclusion, hucMSC‐exosomes could alleviate CVB3‐induced myocarditis via activating AMPK/mTOR‐mediated autophagy flux pathway to attenuate cardiomyocyte apoptosis, which will be benefit for MSC‐exosome therapy of myocarditis in the future.

Obesity is related to the amplified risk of developing hepatocellular cancer, but its outcome on hepatocellular cancer-related mortality remains uncertain. Hence, the present study aimed to perform a meta-analysis study to evaluate the relationship between weight and hepatocellular cancer-related deaths. Through a systematic literature search up to December 2019, 7 observational studies with 2,349,834 subjects, 4834 hepatocellular cancer-related deaths were identified reporting relationships between body mass index (BMI), and hepatocellular cancer-related mortality. Odd ratio (OR) with 95% confidence intervals (CIs) was calculated comparing obese, BML30kg/m

Melanotic neuro-ectodermal tumor of infancy (MNTI) is an extremely rare tumor. The purpose of this study was to describe the imaging features of maxillary bone MNTIs and introduce the key points for clinical diagnosis of MNTI. We retrospectively reviewed four patients with histology-proven MNTIs arising from the maxillary bone. All patients underwent ultrasonic inspections, CT and/or MR scanning. Combined with previously literature, the imaging features were comprehensively evaluated and analyzed. All MNTIs showed a firm, non-ulcerated rapidly-growing soft-tissue swelling with pigmented (blue-colored or black-colored or gray-colored) mucosa. The onset ages were younger than 6 month-old. CT images showed osteolytic or expansive bone destruction of the involved maxillae, fragmentary cortical bone, “free-floating” tooth germs, with or without spiculated/sunburst periosteal reaction. The tumor appeared lightly hyper-intense on T2-weighted sequences, while isointense or lightly hypo-intense or lightly hyper-intense signal on T1-weighted sequences. Enhanced images all displayed heterogeneous enhancement. No metastasis features of lymph nodes or abdominal organs were demonstrated by cervical and abdominal ultrasonic inspections. As a conclusion, accurate recognition of the imaging features of MNTI combined with history and clinical manifestations (early infancy, painless, firm, pigmented mucosa, non-ulcerating lesion) can provide clues for diagnosis of this rare entity.

The wide use of nano metal oxide particles (NMOPs) brings about their inevitable release into the water environment, affecting the environment and human health. Therefore, the stability, aggregation, and sedimentation process of four typical NMOPs (ZnO NPs, CeO

Infantile hemangiomas are the most common benign childhood tumors and can occur on any part of the human body. Sclerosing agents are used in the early stage of treatment of infantile hemangioma. Sometimes a lip defect remains after sclerosing agent treatment. We developed a simple technique to repair lip defects. The authors performed transposition mucosal flap and autologous fat transplantation surgery on patients who had lip defects caused by sclerosing agents. The flap was transposed 90° from the intraoral labial mucosa to the vermilion defect. Autologous fat was transplanted to the white lip defect. If necessary, a secondary fat transplantation may be performed every half year. All patients were followed up to evaluate the effect of the operation. Patients were asked to rate their satisfaction with the surgery between 1 and 10. Digital three-dimensional evaluation was performed. Sixteen patients underwent the surgery successfully, and the flaps were all viable. No complications occurred after surgery (5 males, 11 females; age range, 5-27 years; 12 upper lip, 3 lower lip, and 1 median lip). The patients were satisfied with the aesthetic outcome of surgery (mean score, 9). Seven patients wanted to undergo a second fat transplantation, whereas 9 patients felt it was unnecessary to transplant fat again. Transposition mucosal flap combined with autologous fat transplantation is reliable and minimally invasive. It is an effective method for repairing moderate lip defects mainly involving vermilion caused by a sclerosing agent.

Tissue-engineered skin (TES), as an analogue of native skin, is promising for wound repair and regeneration. However, a major drawback of TES products is a lack of skin appendages and nerves to enhance skin healing, structural integrity and skin vitality. Skin appendages and nerves are important constituents for fully functional skin. To date, many studies have yielded remarkable results in the field of skin appendages reconstruction and nerve regeneration. However, patients often complain about a loss of skin sensation and even cutaneous chronic pain. Restoration of pain, temperature, and touch perceptions should now be a major challenge to solve in order to improve patients’ quality of life. Current strategies to create skin appendages and sensory nerve regeneration are mainly based on different types of seeding cells, scaffold materials, bioactive factors and involved signaling pathways. This article provides a comprehensive overview of different strategies for, and advances in, skin appendages and sensory nerve regeneration, which is an important issue in the field of tissue engineering and regenerative medicine.

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

Background and AimsPseudopodium-enriched atypical kinase 1 (PEAK1) has reported to be upregulated in human malignancies and related with poor prognosis. Enhanced PEAK1 expression facilitates tumor cell survival, invasion, metastasis and chemoresistance. However, the role of PEAK1 in breast cancer is not clear. Here, we investigated the PEAK1 expression in breast cancer and analyzed its relation with clinicopathological status and chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated the role of PEAK1 on breast cancer cells in vitro and in vivo. MethodsImmunohistochemistry (IHC) was performed in 112 surgical resected breast cancer tissues. The associations between clinicopathological status, multi-drug resistance and PEAK1 expression were determined. Effect of PEAK1 overexpression or down-expression on proliferation, colony formation, invasion, migration, metastasis and Doxorubicin sensitivity in the MCF-7 cells in vitro and in vivo was detected. ResultsPEAK1 was overexpressed in breast cancer tissues and NAC -resistant breast cancer tissues. High PEAK1 expression was related with tumor size, high tumor grade, T stage, LN metastasis, recurrence, Ki-67 expression, Her-2 expression and multi-drug resistance. Targeting PEAK1 inhibited cell growth, invasion, metastasis and reversed chemoresistance to Doxorubicin in breast cancer cells in vitro and in vivo. ConclusionHigh PEAK1 expression was associated with invasion, metastasis and chemoresistance of breast cancers. Furthermore, targeting PEAK1 could inhibit cell growth and metastasis, and reverse chemoresistance in breast cancer cells, which provides an effective treatment strategies for breast cancer.

Multidrug resistance (MDR) is a major cause of disease relapse and mortality in breast cancer. Paired-related homeobox 1 (PRRX1) is associated with the epithelial-mesenchymal transition (EMT), which is involved in tumor development, including cell invasion and MDR. However, the effect of PRRX1 on MDR had not clearly established. The present study investigated the influence of PRRX1 on MDR and the underlying molecular mechanisms in MCF-7 breast cancer cells. MCF-7 cells were divided into PRRX1+ group (cells transfected with a recombinant plasmid carrying the PRRX1 gene), negative control group (cells transfected with a blank vector) and blank group (untreated cells). It was found that the relative protein and mRNA expression levels of PRRX1, N-cadherin, vimentin and P-glycoprotein were significantly higher in PRRX1-overexpressing MCF-7 cells compared with those in control cells. The half-maximal inhibitory concentration of three groups after treatment with docetaxel and cis-platinum complexes were significantly higher in PRRX1-overexpressing MCF-7 cells compared with those in control cells. Furthermore, relative PTEN expression decreased significantly and levels of phosphorylated PI3K and AKT increased substantially in PRRX1-overexpressing MCF-7 cells. These results indicated that PRRX1 overexpression may induce MDR via PTEN/PI3K/AKT signaling in breast cancer. It is highly recommended that PRRX1 gene expression detection should be performed in patients with breast cancer to aid the selection of more appropriate treatments, which will lead to an improved prognosis in clinical practice.

Trauma, disease, surgery, or congentital defects can cause soft tissue losses in patients, leading to disfigurement, functional impairment, and a low quality of life. In the lack of available effective methods to reconstruct these defects, acellular adipose matrices could provide a novel therapeutic solution to such challenge.

Diseases, trauma, and injuries are highly prevalent conditions that lead to many critical tissue defects. Tissue engineering has great potentials to develop functional scaffolds that mimic natural tissue structures to improve or replace biological functions. In many kinds of technologies, electrospinning has received widespread attention for its outstanding functions, which is capable of producing nanofibre structures similar to the natural extracellular matrix. Amongst the available biopolymers for electrospinning, poly (caprolactone) (PCL) has shown favorable outcomes for tissue regeneration applications. According to the characteristics of different tissues, PCL can be modified by altering the functional groups or combining with other materials, such as synthetic polymers, natural polymers, and metal materials, to improve its physicochemical, mechanical, and biological properties, making the electrospun scaffolds meet the requirements of different tissue engineering and regenerative medicine. Moreover, efforts have been made to modify nanofibres with several bioactive substances to provide cells with the necessary chemical cues and a more in vivo like environment. In this review, some recent developments in both the design and utility of electrospun PCL-based scaffolds in the fields of bone, cartilage, skin, tendon, ligament, and nerve are highlighted, along with their potential impact on future research and clinical applications.

Single-nucleotide polymorphisms (SNPs) in protein-coding regions of genes which were previously reported to be associated with nonsyndromic cleft lip, with or without palate involvement (NSCL/P), were investigated. Twelve candidate loci [platelet-derived growth factor C (PDGFC), platelet-derived growth factor subunit A (PDGFA), platelet-derived growth factor receptor alpha (PDGFRA), glycine receptor alpha 2 (GLRA2), glycine receptor beta (GLRB), ATP binding cassette subfamily A member 4 (ABCA4), MAF bZIP transcription factor B (MAFB), interferon regulatory factor 6 (IRF6), CCDC26 long non-coding RNA (CCDC26), paired box 7 (PAX7), ventral anterior homeobox 1 (VAX1), and netrin 1 (NTN1)] covering 1.5 Mbp were sequenced in 136 NSCL/P patients and 54 healthy controls. Twenty-five genomic variants identified were further validated in another 400 NSCL/P and 200 controls. Two SNPs in IRF6 showed a protective effect against the development of NSCL/P (rs12405750, OR = 0.54, 95% CI: 0.41-0.69; and rs2235371, OR = 0.55, 95% CI: 0.43-0.71). The missense variant, rs2235371, alters the conserved amino acid valine to isoleucine at codon 274 (V274I). We observed that SNPs at IRF6 (rs2235371 and rs12405750) and GLRB (rs73856838 and rs72685584) show consistent interaction effects. The association between the missense SNP rs2235371 in gene IRF6 and NSCL/P suggests that this SNP may play an important role as a risk factor for NSCL/P in the Han Chinese populations. The marginal signal near 4q31 detected in previous genome-wide association studies might be caused by an interaction between the IRF6 and GLRB genes. This interaction needs to be further validated by experimentation in follow-up studies.

In human adults, the repair of cutaneous wounds usually leads to scar formation rather than regeneration. Dermal substitutes have been used as a regenerative template for reducing scar formation and improving the extent of dermal regeneration. However, achievement of complete regeneration is still a long way off. Dermal substitutes are characterized by unusual regenerative activity, appearing to function by acting as temporary configurational guides for cell infiltration and synthesis of new stroma. Fibroblasts are important cells with many vital functions in wound-healing processes. They are heterogeneous with distinct characteristics according to their source location, such as subcutaneous tissue, superficial-layer dermis, and deep-layer dermis. Many studies have shown that superficial dermal fibroblasts possess the potential to form dermis-like tissue. Fibroblasts in deep-layer dermis and subcutaneous tissue may play a critical role in the formation of hypertrophic scars. Fibroblast phenotype affects the newly formed dermal architecture and influences the dermal regeneration effect induced by dermal substitutes. It is hypothesized that better regeneration of the dermis can be achieved using dermal substitutes along with dermal fibroblast optimization.

The prevalence of obesity has increased strikingly in recent years. Obesity is associated with increased left ventricular end-diastolic dimension (LVEDD), ventricular wall thickness, left ventricular (LV) mass, left atrial diameter, subtle myocardial systolic as well as diastolic dysfunction and has been identified as an independent predictor of these changes. It's convinced that weight reduction results in cardiac reverse remodelling, while the functional changes after weight reduction are variable. Here, we present a recent case of man with moderate obesity who acquires favourable regression in chamber size, wall thickness and significant improvement in cardiac function. Briefly, after life-style modifications and comprehensive secondary prevention, great amounts of weight loss was achieved simultaneously with decreased LVEDD and increased LV ejection fraction. As dietary intervention and regular physical activity are pivotal for these benefits, this non-invasive approach for weight loss should be advocated in selected patients.

In clinical practice, skin defects occur frequently due to various kinds of acute and chronic diseases. The standard treatment for these wounds is autografting, which usually results in complications such as scar formation and new wounds at donor sites. The advent of dermal substitutes has provided a novel method for wound repair, and rapid angiogenesis of the dermal substitutes is crucial for the graft to take. At present, many strategies have been developed to improve the process of vascularisation, some of which have shown promising potentials, but they could be very far from clinical applications. Most recently, negative-pressure wound therapy (NPWT) has been used extensively in clinical practice for wound care and management. It has been reported that NPWT reduces the time required for vascular ingrowth into the dermal substitute and improves graft take, indicating great potentials for wound repair. This article presents a comprehensive overview of the combined use of NPWT and dermal substitutes for tissue repair and regeneration. Relative concerns and prospects are also discussed.

Purpose To investigate the prognosis of single hormone receptor–positive (HR+) breast cancer (estrogen receptor [ER] positive and progesterone receptor [PR] negative, and ER−PR+) compared to double HR+ (ER+PR+) and double HR− (ER−PR−) tumors. Methods We included 531,605 cases of invasive breast cancer between 1990 and 2012 from the US Surveillance, Epidemiology, and End Results (SEER) database for study and classified cases into 4 phenotypes according to expression of ER and PR: ER+PR+, ER+PR−, ER−PR+, and ER−PR−. Results Overall, 66,091 ER+PR− tumors and 9320 ER−PR+ tumors were identified. The clinical characteristics of the ER+PR− group were similar to those of the double HR+ group, while those of the ER−PR+ and double HR− groups were similar. Overall survival of patients with single HR+ tumors was intermediate between that of double HR+ and double HR− tumors. However, we observed no differences in disease-specific survival between ER−PR+ and ER−PR− patients. In multivariate analysis, outcomes were similar. Relative to the double HR+ patient group, risk of death in the ER+PR− group was higher (hazard ratio, 1.422, 95% confidence interval, 1.394-1.452). However, risk of death was comparable between ER−PR+ and ER−PR− patients (hazard ratio, 1.03; 95% confidence interval, 0.98-1.08). Multivariate Cox proportional analysis showed that survival times of patients in the younger age bracket ( Conclusion Disease-specific survival of single HR+ tumor cases was longer than that of double HR− tumors but poorer than double HR+ tumors. However, differences in disease-specific survival were not significant between the ER−PR+ and ER−PR− groups.

Lower-extremity peripheral arterial disease (PAD) can predict the risk of subsequent cardiovascular disease (CVD) and all-cause mortality. Chronic kidney disease (CKD) as a precursor of CVD has been proven to be independently associated with PAD. However, few data exist regarding the prediction value of kidney function for incident asymptomatic PAD in community-based populations. We aimed to investigate the predicting value of estimated glomerular filtration rate (eGFR) for incident asymptomatic PAD in a Chinese community-based population. A total of 3549 subjects without PAD and eGFR > 30 ml/min/1.73 m2 were included. PAD was defined by an ankle-brachial index (ABI) ≤ 0.9. Multivariate regression models were used to evaluate the associations. Subjects were 56.69 ± 8.56 years old and 35.9% were males. After 2.36 years of follow-up, the incidence of asymptomatic PAD was 3.1%. The risk of incident PAD was graded related to the categories of eGFR. Compared to participants with normal kidney function, the multivariate adjusted OR [95% CI] for new PAD was 1.31 (0.81–2.12) for those with mildly decreased kidney function, 4.13 (1.73–9.89) for those with grades 3 CKD (P for trend: 0.014). Baseline eGFR was significantly and linearly associated with incident PAD (OR [95% CI] for each 5 mL/min/1.73 m2 decrease of eGFR: 1.23 [1.09–1.38]) in participants with baseline eGFR

Hospital-acquired infections are common in burn patients and are the major contributors of morbidity and mortality. Bacterial infections such as Staphylococcus aureus (S. aureus) and Acinetobacter baumannii (A. baumannii) are difficult to treat due to their biofilm formation and rapidly acquiring resistance to antibiotics. This work presents a newly developed hydrogel that has the potential for treating bacterial wound infections. The hydrogel formulation is based on an antimicrobial peptide (AMP), epsilon-poly-l-lysine (EPL) and catechol, which was cross-linked via mussel-inspired chemistry between the amine and phenol groups. In vitro studies showed that EPL-catechol hydrogels possess impressive antimicrobial and antibiofilm properties toward multidrug-resistant A. baumannii (MRAB). In addition, cytotoxicity study with the clonal mouse myoblast cell line (C2C12) revealed the good biocompatibility of this hydrogel. Furthermore, we created a second-degree burn wound on the mice dorsal skin surface followed by contamination with MRAB. Our results showed that the hydrogel significantly reduced the bacterial burden by more than four orders of magnitude in infected burn wounds. Additionally, there was no significant histological alteration with hydrogel application on mice skin. Based on these results, we concluded that EPL-catechol hydrogel is a promising future biomaterial to fight against multidrug-resistant bacterial infections.

Background/Aims: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Our study investigated the functional role of miR-212-5p in TNBC. Methods: Realtime PCR was used to quantify miR-212-5p expression levels in 30 paired TNBC samples and adjacent normal tissues. Wound healing and Transwell assays were used to evaluate the effects of miR-212-5p expression on the invasiveness of TNBC cells. Luciferase reporter and Western blot assays were used to verify whether the mRNA encoding Prrx2 is a major target of miR-212-5p. Results: MiR-212-5p was downregulated in TNBC, and its expression levels were related to tumor size, lymph node status and vascular invasion in breast cancer. We also observed that the miR-212-5p expression level was significantly correlated with a better prognosis in TNBC. Ectopic expression of miR-212-5p induced upregulation of E-cadherin expression and downregulation of vimentin expression. The expression of miR212-5p also suppressed the migration and invasion capacity of mesenchymal-like cancer cells accompanied by a morphological shift towards the epithelial phenotype. Moreover, our study observed that miR-212-5p overexpression significantly suppressed Prrx2 by targeting its 3’-untranslated region (3’-UTR) region, and Prrx2 overexpression partially abrogated miR-212-5p-mediated suppression. Conclusions: Our study demonstrated that miR-212-5p inhibits TNBC from acquiring the EMT phenotype by downregulating Prrx2, thereby inhibiting cell migration and invasion during cancer progression.

para-Chloronitrobenzene ( p-CNB) is one of the important chemicals with high liposolubility and oxidizing properties. Heated p-CNB liquid can cause thermal injury by absorption over skin and wound and even methemoglobinemia by conversion of hemoglobin into methemoglobin. Severe methemoglobinemia is a life-threatening condition that demands immediate treatment. It is very rare for individuals to be injured by heated p-CNB, but they should be carefully attended to because of the peculiarities of this kind of injury. In the past 10 years, we received 5 patients who were injured by heated p-CNB. In addition to the intravenous administration of methylene blue, prompt and thorough wound management played a crucial role in the treatment of these critically ill patients, indicating the potential value of sufficient information for the clinical practitioners. The purpose of this article is to report our experience in the management of patients with thermal burns and p-CNB poisoning.

Purpose This is a single-center, descriptive report of the management and complications of venous catheter use in 19 severely burned passengers from a bus fire that occurred on July 5, 2014, in Hangzhou. Methods We recorded the parameters of the catheters insertion and indwelling. Sampling of each removed catheter was conducted to monitor for catheter-related infections. Bedside ultrasound screening was performed for recording central venous catheter (CVC)-related complications. Results Of the 174 venous accesses placed, 108 were CVCs. 27 (25.0%) catheter tip cultures (CTC) were positive; 12 (11.1%) were catheter-related blood stream infections (CRBSI). Acinetobacter baumannii was the most prominent bacterial infection for both CTC- (55.56%) and CRBSI- (75.00%) positive catheters. CTC- and CRBSI-positive rates were higher during the emergency stage, and both dropped rapidly after reform measures (chi-square test, p = 0.003), and all were negative after the no. 8 catheters. Accumulative regression results indicated that total body surface area burned (TBSA), number of catheters, days of indwelling, and bloodstream infections were independently associated with CTC results, while gender and number of catheters were independently associated with CRBSI results. 1 femur vein thrombosis was detected and cured. Conclusions Bedside ultrasound and professional IV team for CVC management are pivotal for massive burn victims. Their intervention helps control CVC-related infections and other complications. A. baumannii was the most frequent bacterial infection found in both CTC- and CRBSI-positive catheters. Several most important factors associated with catheter-related infections were concluded. This information alerts us to watch for patients with such warning factors.

Trans-sutural distraction osteogenesis (TSDO) promotes midface growth in growing cleft lip and palate (CLP) patients with midfacial hypoplasia. The superficial skeletal changes after therapy revealed rotation advancement of the midfacial skeleton associated with differential displacement in each segment, but reports rarely focus on the changes of internal structures, including circummaxillary sutures, the maxillary tuberosity and the maxillary sinus, which may play a crucial role during this process. This study evaluated the computed tomographic (CT) images of 26 growing CLP patients who received bone-borne TSDO therapy. The results revealed that the most prominent new bone formation occurred in the pterygomaxillary suture and pushed the P-point forward. The maxillary first molar exhibited significantly greater advancement compared with the P-point due to the growth of the maxillary tuberosity. The contribution ratio values of the advancement of the maxillary tuberosity and P-point to the maxillary first molar were 26% and 74%, respectively, in UCLP and 25% and 75%, respectively, in BCLP. Furthermore, the maxillary sinus volume was also significantly increased. In conclusion, midface growth with bone-borne TSDO therapy depends on both secondary displacement promoted by sutural bone formation mainly in the pterygomaxillary suture and primary displacement by growth of the maxillary tuberosity and maxillary sinus volume.

Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO2). Phagocytosis of SiO2 in the lungs initiates an inflammatory cascade that results in fibroblast proliferation and migration followed by fibrosis. According to previous data from our laboratory, monocyte chemotactic protein-1 (MCP-1) plays a critical role in fibroblast proliferation and migration in conventional two-dimensional (2D) monolayer cultures. The present study aimed to explore the downstream cascade of MCP-1 in both 2D and three-dimensional (3D) cell culture models of silicosis. Experiments using primary cultured adult human pulmonary fibroblasts (HPF-a) demonstrated the following: 1) SiO2 treatment induces expression of MCP-1-induced protein (MCPIP1) in a time- and dose-dependent manner in both 2D and 3D cultures; 2) the MAPK and phosphatidylinositol-3-kinase (PI3K)/Akt pathways are involved in SiO2-induced MCPIP1 expression; and 3) MCPIP1 induction mediates the SiO2-induced increase in cell migration in both 2D and 3D cultures. The effect of MCP-1 in silicosis occurs mainly through MCPIP1, which, in turn, mediates the observed SiO2-induced increase in pulmonary fibroblast migration. However, the time frame for MCPIP1 induction differed between 2D and 3D cultures, indicating that, compared with conventional 2D cell culture systems, 3D culture may be useful for analyses of fibroblast physiology under conditions that more closely resemble in vivo environments. Our study determined the link between fibroblast-derived MCPIP1 and SiO2-induced cell migration, and this finding provides novel evidence of the potential of MCPIP1 in the development of novel therapeutic strategies for silicosis.

Chronic or nonhealing wounds is a complex disease influenced by a multitude of factors, such as infection, ischemia, malnutrition, and diabetes and infrequently relates to retroperitoneal carcinoma. We present a case of an adenocarcinoma of ascending colon in a 68-year-old male who had lumbago and waist fistulas with retroperitoneal abscesses preceding other signs or symptoms of colonic malignancy. Supplemental information regarding the diagnosis and treatment of nonhealing wounds and colon carcinoma has also been included in the report. Adenocarcinoma of ascending colon is rarely associated with nonhealing wounds; nevertheless, it should be considered in cases with long-term healing complications. Precise diagnostic deliberation is crucial in the management and treatment of all chronic and long-term nonhealing lesions, and appropriately performed biopsies are essential to determine whether malignancy is the primary cause.

MicroRNAs (miRNAs) have been identified as important post-transcriptional regulators involved in various biological and pathological processes of cells. In the present study, we investigated the roles and mechanisms of miR-200b in human breast cancer (BC). MiR-200b expression was carried out by qRT-PCR in human BC cell lines and clinical samples and the prognostic potential of miR-200b expression was further evaluated. In vitro, effects of miR-200b on BC cell proliferation, apoptosis and cell cycle distribution were tested by CCK-8 kit, flow cytometric analysis respectively. Luciferase assay and Western blot analysis were performed to validate the potential targets of miR-200b after the preliminary screening by employing open access software. We found that miR-200b was significantly down-regulated in both BC tissues and cell lines. The low expression of miR-200b was correlated with late TNM stage, negative oestrogen receptor and positive HER-2 status. Multivariate analysis showed that miR-200b expression was an independent prognostic predictor for BC patients. Integrated analysis identified Sp1 as a direct and functional target of miR-200b. Knockdown of Sp1 inhibited cell proliferation, induce apoptosis and act on cell cycle resembling that of miR-200b high expression. Our data demonstrates that miR-200b has potential to serve as prognostic biomarker and tumour suppressor for BC patients. As a direct and functional target of miR-200b, Sp1 and miR-200b both could be an exciting target for BC treatment strategy.

Drug eluting stents (DES) have been extensively applied nowadays and reduce the incidence of in-stent restenosis (ISR) greatly as compared with bare metal stents (BMS). However, the development of DES is hindered by the risk of late stent thrombosis (LST) due to delayed re-endothelialization, while endothelialization is an important process related to ISR and LST after implantation. 316L is a traditional stent material without bioactivity and have a high risk of ISR. Cu is recognized for angiogenesis stimulation in these years. Hence a copper bearing 316L stainless steel (316L-Cu) was prepared and evaluated about its effect on endothelialization in this paper. Compared with traditional 316L, it was proved that 316L-Cu increased the proliferation of co-cultured human umbilical vein endothelial cells (HUVECs) at first day. Moreover, HUVECs stretched better on the surface of 316L-Cu. It also improved the expression of angiogenesis related genes and tube formation ability in vitro. 316L-Cu-BMS, DES and 316L-BMS were implanted in swine to evaluate the re-endothelialization ability in vivo. And 316L-Cu-BMS showed the best effect on endothelialization with good biosafety. Consequently, 316L-Cu is a kind of promising BMS material for coronary field.

Critical tissue defects frequently result from trauma, burns, chronic wounds and/or surgery. The ideal treatment for such tissue loss is autografting, but donor sites are often limited. Tissue engineering (TE) is an inspiring alternative for tissue repair and regeneration (TRR). One of the current state-of-the-art methods for TRR is gene therapy. Non-viral gene delivery systems (nVGDS) have great potential for TE and have several advantages over viral delivery including lower immunogenicity and toxicity, better cell specificity, better modifiability, and higher productivity. However, there is no ideal nVGDS for TRR, hence, there is widespread research to improve their properties. This review introduces the basic principles and key aspects of commonly-used nVGDSs. We focus on recent advances in their applications, current challenges, and future directions.

Objective We investigated the urinary fluoride level in patients with hydrofluoric acid (HF) burns of different severities and explored the clinical significance of these levels in the diagnosis of acute HF burn. Methods Data from 260 patients with HF burns were collected from the Department of Burns, Zhejiang Quhua Hospital, between July 2006 and June 2016. According to burn severity, patients were divided into non-poisoning, mild poisoning, moderate poisoning, and severe poisoning groups. In addition, 25 healthy controls were recruited from fluorine chemical companies. The urinary fluoride level was measured using a fluoride-selective electrode and values were compared amongst groups. The urinary fluoride level was also measured periodically after exposure to investigate dynamic changes in the moderate and severe poisoning groups. Results Urinary fluoride levels were 0.32–520.0 mg/L (n = 260) on admission to the emergency department, and 182 patients had levels >1.7 mg/L. The levels in controls and the non-poisoning group were lower than in the other two groups, and increased significantly with an increase in severity. Thirty-three patients were admitted 4 h after injury; of these patients, fluoride levels were significantly higher in those with severe poisoning than in those with moderate poisoning. Levels peaked 4 h after injury and then dropped and returned to normal 6 days after injury. Conclusion Urinary fluoride level can be used for the early diagnosis of HF burns and to determine the severity of fluoride poisoning, which is crucial for early treatment.

Hydrofluoric acid (HF), a dangerous inorganic acid, is widely used in various industries and in daily life. Chemical burns caused by HF exposure occur more frequently in some regions worldwide. It has been reported that some cases with HF burns can be lethal due to the hypertoxicity of HF. In this article, we present a case of a 24-year-old worker who suffered HF burns by 53% HF solution to his face, neck, and nasal cavity. This patient quickly developed electrolyte disturbance, that is, hypocalcemia, and hypopotassemia, and myocardial injury after exposure. Multiple measures had been taken to treat this patient, including fluid resuscitation, electrolyte replacement, timely wound treatment with neutralizers, and respiratory tract care. Moreover, continuous renal replacement therapy was also employed to remove fluoride in the circulatory system and rectify the electrolyte disturbance and acid-base imbalance. The patient smoothly pulled though and survived. High fluoride levels in the dialysate solution were confirmed, indicating that continuous renal replacement therapy is an effective and potentially lifesaving treatment for acute HF poisoning.

Treatment of full-thickness skin defects poses significant clinical challenges including risk of infection and severe scaring. Silver nanoparticle (NAg), an effective antimicrobial agent, has provided a promising therapeutic method for burn wounds. However, the detailed mechanism remains unknown. Hence, we constructed a metallic nanosilver particles-collagen/chitosan hybrid scaffold (NAg-CCS) and investigated its potential effects on wound healing. In vitro scratch assay, immunofluorescence staining and antibacterial activity of the scaffold were all studied. In vivo NAg-CCS was applied in full-thickness skin defects in Sprague-Dawley (SD) rats and the therapeutic effects of treatment were evaluated. The results showed that NAg at a concentration of 10 ppm accelerated the migration of fibroblasts with an increase in expression of α-smooth muscle actin (α-SMA). Furthermore, in vivo studies showed increased levels of pro-inflammatory and scar-related factors as well as α-SMA, while markers for macrophage activation were up-regulated. On day 60 post transplantation of ultra-thin skin graft, the regenerated skin by NAg-CCS had a similar structure to normal skin. In summary, we demonstrated that NAg-CCS was bactericidal, anti-inflammatory and promoted wound healing potentially by regulating fibroblast migration and macrophage activation, making it an ideal dermal substitute for wound regeneration.

Background/Aims: Epithelial-mesenchymal transition (EMT) is recognized as a crucial mechanism in breast cancer progression and metastasis. Paired-related homeobox 2 (Prrx2) has been identified as a new EMT inducer in cancer, but the underlying mechanisms are still poorly understood. Methods: The expression of Prrx2 was assessed by immunohistochemistry in breast cancer tissues to evaluate the clinicopathological significance of Prrx2, as well as the correlation between Prrx2 and EMT. Short hairpin RNA knockdown of Prrx2 was used to examine cellular effects of Prrx2, detecte the expression of Wnt/β-catenin signaling and EMT-associated proteins, and observe cell proliferation, invasion and migration abilities in vitro and in vivo . Results: Clinical association studies showed that Prrx2 expression was related to tumor size, lymph node metastasis, tumor node metastasis stages, EMT and poor survival. Results also showed that knockdown of Prrx2 could alter cell morphology, suppressed the abilities of cell proliferation, invasion and migration in breast cancer. Moreover, silencing of Prrx2 induced the mesenchymal-epithelial transition and prevented nuclear translocation of β-catenin, inhibited wnt/β-catenin signaling pathway. Conclusion: Our study indicated that Prrx2 may be an important activator of EMT in human breast cancer and it can serve as a molecular target of therapeutic interventions for breast cancer.

The incidence of liquefied petroleum gas (LPG)-related burns has increased over recent years, and it has become a serious public health issue in developing countries such as India and Turkey. This paper aims to investigate the epidemiological characteristics of LPG-related burns to provide assistance and suggestions for planning prevention strategies.A 5-year retrospective study was conducted in patients with LPG-related burns admitted to the Department of BurnsWound Care Center, Second Affiliated Hospital of Zhejiang University, College of Medicine, between 1st January 2011 and 31st December 2015. Information obtained for each patient included age, gender, education status, occupation, medical insurance, average hospital cost, length of hospital stay, monthly distribution of incidence, place of burns, mechanism of burns, extent of burns, site of burns, accompanying injuries, and treatment outcomes.For the first 4 years (2011-2014), the yearly incidence of LPG-related burns was at approximately 10% of all burns; however, in the fifth year (2015) alone, there was a surge to 26.94%. A total of 1337 burn patients were admitted during this period. Of these, 195 patients were admitted because of 169 LPG-related accidents; there were 11 accidents involving more than one victim. LPG-related burns occurred most frequently in patients aged 21-60 years (73.85%). The majority of injuries occurred from May to August (56.41%), and the most common place was home (83.08%, 162 patients). Gas leak (81.03%) was the main cause of LPG-related burns, followed by inappropriate operation (7.69%) and cooking negligence (2.05%). The mean burn area was 31.32±25.40% of TBSA. The most common sites of burns were the upper extremities (37.47%), followed by the head/face and neck (24.80%) and lower extremities (19.95%). The most common accompanying injuries included inhalation injury (23.59%), shock (8.71%), and external injury (7.18%). The average hospital stay was 22.90±19.47days (range 2-84 days). Only 48 patients (24.62%) had medical insurance, while 124 patients (63.59%) had no medical insurance. The average hospital cost of the no medical insurance group was significantly higher (p0.0001) than that of the medical insurance group. In addition, 72.73% of patients who left against medical advice (LAMA) were uninsured. The number of patients who recovered at our hospital was 165 (84.62%), while 22 patients (11.28%) LAMA. The overall mortality rate was 4.10% (8 patients).Our study shows that the exponential increase in LPG-related burns is alarming. This calls for rigorous precautions. Because gas leak was the main cause of LPG-related burns, any part of LPG stove system that shows signs of weathering should be replaced regularly. In addition, we also found that most of the LAMA patients were uninsured. Thus, comprehensive medical insurance should be involved early in the recovery process to assure a safe and adequate discharge.

Hydrofluoric acid (HF), a dangerous inorganic acid, can cause severe corrosive effects and systemic toxicity. HF enters the human body via where it contacts, such as skin and mucosa, alimentary and respiratory tracts, and ocular surfaces. In the recent years, the incidence of HF burn has tended to increase over time. The injury mechanism of HF is associated primarily with the massive absorption of HF and the release of hydrogen ions. Correct diagnosis and timely treatment are especially important for HF burns. The critical procedure to treat HF burn is to prevent on-going HF absorption, and block the progressive destruction caused by fluoride ions. Due to the distinct characteristics of HF burns, the topical treatment, as well as systemic support, has been emphasised. Whereas, management of patients with HF burns remains a great challenge in some situations. To date, there has been no widely accepted protocol for the rescue of HF burns, partly due to the diversity of HF burns. This paper overviews the current status and problems of treatment strategies for HF burns, for the purpose of promoting the future researches and improvement.

Summary Cell migration is fundamental to the inflammatory response, but uncontrolled cell migration and excess recruitment of neutrophils and other leukocytes can cause damage to the tissue. Here we describe the use of an in vivo model - the Tg(mpx:GFP)i114 zebrafish line in which neutrophils are labelled by green fluorescent protein (GFP) - to screen a natural product library for compounds that can affect neutrophil migratory behaviour. Among 1040 fungal extracts screened, two were found to inhibit neutrophil migration. Subfractionation of these extracts identified sterigmatocystin and antibiotic PF1052 as the active components. Using the EZ-TAXIScan chemotaxis assay, both compounds were also found to have a dosage-dependent inhibitory effect on murine neutrophil migration. Furthermore, neutrophils treated with PF1052 failed to form pseudopods and appeared round in shape, suggesting a defect in PI3-kinase (P13K) signalling. We generated a transgenic neutrophil-specific PtdIns(3,4,5)P3 (PIP3) reporter zebrafish line, which revealed that PF1052 does not affect the activation of PI3K at the plasma membrane. In human neutrophils, PF1052 neither induced apoptosis nor blocked AKT phosphorylation. In conclusion, we have identified an antibiotic from a natural product library with potent anti-inflammatory properties, and have established the utility of the mpx:GFP transgenic zebrafish for high throughput in vivo screens for novel inhibitors of neutrophil migration.

Patients suffering from severe 100% TBSA burns are particularly vulnerable to infection and multiple organ dysfunction syndrome, being on high risks of poor outcomes. Treatment of these patients remains to be a great challenge for burn physicians, and survivors of 100% TBSA burns generally have poor quality of life after burn. Since, to our knowledge, this is the first case report on the long-term follow-up of a 100% TBSA burn survivor, the authors are presenting the initial injury, treatment, and follow-up of this female patient during 27 years. She had received good first aid, successful fluid resuscitation, and effective antibiotic therapy. The wounds healed after 8 sessions of skin grafting by postburn day 108, and she was dismissed after 121 days. To promote her recovery, a structured rehabilitation plan was initiated immediately after the admission and conducted consistently throughout her postburn life. The authors evaluated her quality of life after 27 years' follow-up using adapted Chinese version of the Burn Specific Health Scale-brief version and Chinese translation version of the Short Form-36, the results of which suggest that the patient is satisfied with her life in psychologic perspectives despite lower scores in physical aspects.

The ErbB-2 gene, whose overexpression is observed in many types of tumors including breast cancer, plays an important role in carcinoma formation. Dysregulation of the human transforming acidic coiled-coil 1 (TACC1) and ErbB-2 genes is thought to be important in the development and progression of breast cancer. However, a putative interaction between ErbB-2 and TACC1 remains undetermined in breast cancer. After infecting BT474 cells with lentiviral-mediated ErbB2-specific shRNA, we detected the expression of ErbB-2 and TACC1 by real-time PCR and western blotting. ErbB-2 mRNA expression was decreased in the Lenti-ShERBB2 infected cells, and western blotting indicated a concordant reduction in ErbB-2 protein. TACC1 expression at the mRNA and protein levels was significantly upregulated by ErbB-2 silencing in BT474 cells. CCK-8 assay indicated that the inhibition of ErbB-2 expression increased the sensitivity of BT474 cells to docetaxel treatment. These findings provide proof and the foundation for the molecular and biological relationships of ErbB-2 and TACC1 in breast cancer.

Objective This study analyses the epidemiological characteristics of bus fires in mainland China over the past 10 years to develop prevention strategies and emergency procedures for such incidence and the resulting casualties. Methods We collected reports on bus fires from the media and news websites and looked up on Medline, PubMed, and Chinese National Knowledge Infrastructure databases for relevant publications in English or Chinese from January 1, 2006 to December 31, 2015. Results In the past 10 years, there were 382 bus fires in mainland China. The frequency of fires was markedly higher in 2013 and 2014. The vast majority (89.1%) of the fires were caused by spontaneous combustion, followed by arson (5.0%). There were reports of casualties in 41 (10.7%) of the bus fires, including 144 deaths and 567 injuries. The fires leading to casualties resulted from spontaneous combustion in 22 (53.7%) incidents, arson in 12 (29.3%) incidents, and traffic accidents in 7 (17.1%) incidents. Arson caused the most casualties, including 91 deaths and 323 injuries. Conclusions This epidemiological study presents characteristic findings related to bus fires in China mainland. The general trend of bus fires showed a gradual increase but with a fluctuation in several years. The regional distribution of bus fires revealed some specific characteristics, and most of bus fires happened in those regions locating in the eastern area of China mainland. The largest number of bus fires were caused by spontaneous combustion. Bus fires caused by arson accounting for only 5% of the total bus fires resulted in the most severe casualties. Most of bus arson occurred in the morning and evening rush hours.

Wound healing is an inherent response resulting in the restoration of tissue integrity. It is a complex process involving cell migration, proliferation, differentiation, apoptosis, and the synthesis and remodeling of the extracellular matrix (ECM). The dermal tissue is an important component of skin that acts as a connecting link between the epidermis and hypodermis. The appearance of scars and contractures after autologous split-thickness skin transplantation or single epidermis diaphragm transplantation for full skin defects indicates that the dermal tissue plays an important role in skin regeneration. Theoretically, dermis cannot regenerate like the liver, bone and epidermis after being destroyed by burns or avulsion. Scarring is hard to avoid during the process of natural healing. However, if the dermis could be reconstructed perfectly, this would be a breakthrough in the methods used for wound healing. In this review, we summarize recent research about dermal regeneration and discuss the probability of advances in the field. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1208-1218, 2017.

Background: Silicosis is characterized by the accumulation of fibroblasts and the excessive deposition of extracellular matrix. Fibroblast generation via endothelial-mesenchymal transition (EndMT) is one process responsible for this accumulation of fibroblasts. However, the mechanisms underlying EndMT remain unknown. Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to SiO2 (50 µg/cm2). Specific endothelial and mesenchymal markers were evaluated using immunofluorescence and western blot analysis. Functional changes were evaluated by analyzing cell migration and proliferation. LC3-adenovirus transfections were performed, and changes in autophagy were measured using a marker of autophagy. Results: SiO2 induced decreases in the endothelial cell-specific markers in HUVECs while dramatically increasing mesenchymal cell product levels and mesenchymal functions. Although MCPIP1 expression increased in parallel with the increase in specific mesenchymal cell products, the MCPIP1 expression level was not consistent with the observed decrease in specific endothelial marker expression. Autophagy mediated the effects of MCPIP1, as rapamycin and 3-MA enhanced and attenuated the effect of SiO2 on HUVECs, respectively. MAPKs and the PI3K/Akt pathway were involved in the regulation of MCPIP1 by SiO2, and Pyk2 and MLC-2 mediated cell migration. Conclusion: Our findings reveal a new potential function of MCPIP1, suggesting a possible mechanism of fibrosis in pulmonary silicosis.

Bioabsorbable magnesium alloys are becoming prominent as temporary functional implants, as they avoid the risks generated by permanent metallic implants such as persistent inflammation and late restenosis. Nevertheless, the overfast corrosion of Mg alloys under physiological conditions hinders their wider application as medical implant materials. Here we investigate a simple one-step process to introduce a cross-linked 3-amino-propyltrimethoxysilane (APTES) silane physical barrier layer on the surface of Mg-Zn-Y-Nd alloys prior to electrostatic spraying with rapamycin-eluting poly(lactic-co-glycolic acid) (PLGA) layer. Surface microstructure was characterized by scanning electron microscope and Fourier transform infrared spectroscopy. Nanoscratch test verified the superior adhesion strength of PLGA coating in the group pretreated with APTES. Electrochemical tests combined with long-term immersion results suggested that the preferable in vitro anticorrosion behavior could be achieved by dense APTES barrier. Cell morphology and proliferation data demonstrated that APTES pretreated group resulted in remarkably preferable compatibility for both human umbilical vein endothelial cells and vascular smooth muscle cells. On the basis of excellent in vitro mechenical property, the animal study on the APTES pretreated Mg-Zn-Y-Nd stent implanted into porcine coronary arteries confirmed benign tissue compatibility as well as re-endothelialization without thrombogenesis or in-stent restenosis at six-month followup.

Understanding and predicting whether new drug candidates will be safe in the clinic is a critical hurdle in pharmaceutical development, that relies in part on absorption, distribution, metabolism, excretion and toxicology studies in vivo. Zebrafish is a relatively new model system for drug metabolism and toxicity studies, offering whole organism screening coupled with small size and potential for high-throughput screening. Through toxicity and absorption analyses of a number of drugs, we find that zebrafish is generally predictive of drug toxicity, although assay outcomes are influenced by drug lipophilicity which alters drug uptake. In addition, liver microsome assays reveal specific differences in metabolism of compounds between human and zebrafish livers, likely resulting from the divergence of the cytochrome P450 superfamily between species. To reflect human metabolism more accurately, we generated a transgenic "humanized" zebrafish line that expresses the major human phase I detoxifying enzyme, CYP3A4, in the liver. Here, we show that this humanized line shows an elevated metabolism of CYP3A4-specific substrates compared to wild-type zebrafish. The generation of this first described humanized zebrafish liver suggests such approaches can enhance the accuracy of the zebrafish model for toxicity prediction.

Clusterin/apolipoprotein J (Clu) is a ubiquitously expressed secreted heterodimeric glycoprotein that is implicated in several physiological processes. It has been reported that the elevated level of secreted clusterin (sClu) protein is associated with poor survival in breast cancer patients and can induce metastasis in rodent models. In this study, we investigated the effects of sClu inhibition with small interfering RNAs (siRNAs) on cell motility, invasion, and growth in vitro and in vivo. MDA-MB-231 cells were transfected with pSuper-siRNA/sClu. Cell survival and proliferation were examined by 3-(4,5-dimethyl-thiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and clonogenic survival assay. The results showed that sClu silencing significantly inhibited the proliferation of MDA-MB-231 cells. The invasion and migration ability were also dramatically decreased, which was detected by matrigel assays. TUNEL staining and caspase-3 activity assay demonstrated that sClu silencing also could increase the apoptosis rate of cells, resulting in the inhibition of cell growth. We also determined the effects of sClu silencing on tumor growth and metastatic progression in an orthotopic breast cancer model. The results showed that orthotopic primary tumors derived from MDA-MB-231/pSuper sClu siRNA cells grew significantly slower than tumors derived from parental MDA-MB-231 or MDA-MB-231/pSuper scramble siRNA cells, and metastasize less to the lungs. These data suggest that secretory clusterin plays a significant role in tumor growth and metastatic progression. Knocking-down sClu gene expression may provide a valuable method for breast cancer therapy.

It has been demonstrated that ganoderma acids suppress growth, angiogenesis and invasiveness of highly invasive and metastatic breast cancer cells in vitro and vivo. However, the mechanism of action of ganoderma acids in breast cancer remains unknown. In the present study, we looked into the effect of ganoderic acid Me (GA-Me) on cellular phenotypes and tumor growth in the MDA-MB-231 breast cancer cell line. The results indicated the GA-Me inhibited nuclear factor kappaB (NF-κB) activity at 24 h in MDA-MB-231 cells. When MDAMB- 231 cells were stimulated with tumor necrosis factor-alpha (TNF-α), the inhibitory effects of GA-Me were still maintained. We demonstrated that GA-Me inhibited proliferation and invasion and induced apoptosis in MDA-MB-231 cells via suppressing the NF-κB activity. However, GA-Me did not inhibit the phosphorylation and degradation of IkappaB-α (IkB-α). GA-Me down-regulated the expression of various NF-κB-regulated genes including genes involved in cell proliferation (c-Myc and cyclin D1), anti-apoptosis (Bcl-2), invasion (MMP-9) and angiogenesis (VEGF, interleukin (IL)-6 and -8). I.P. administration of GA-Me inhibited tumor growth of MDA-MB-231 cells in vivo. Our results demonstrated that GA-Me inhibited proliferation, angiogenesis, invasion and induced apoptosis in MDA-MB-231 cells via suppressing NF-κB activity and the expression profile of its downstream genes. These findings provide evidence for a novel role of GA-Me in the prevention and treatment of breast cancer by its ability to modulate the NF-κB signaling pathway.