Evaluation of Platelet Distribution Width as an Early Predictor of Acute Kidney Injury in Extensive Burn Patients.

Background: The extensive burns devastate trauma. The research was designed to analyse the predictive value of early platelet (PLT) indices on the development of acute kidney injury (AKI) after severe burns. Methods and Results: 186 patients with extensive burns (burn area ≥30%) were eventually involved. Multivariate analyses pointed out that platelet distribution width (PDW) in the first 24 h after admission was an independent risk factor for AKI, severe AKI, and RRT requirement in patients with severe burns, and AKI risk showed an increase of 30.9% per increase of 1% in PDW (OR = 1.309, CI, 1.075-1.594, and P = 0.007). It was found that the area under the ROC curve (AUC) of PDW predicting AKI was 0.735 and that the AUC value was 0.81 for AKI after combining PDW and blood urea nitrogen (BUN). Based on the cut-off value PDW = 17.7%, patients were divided into high- (PDW ≥17.7%) and low-risk (PDW <17.7%) groups. In the KM analysis, there was a higher cumulative incidence of AKI if patients were in a high-risk group (in 30 days); and the stages of AKI showed a linear upward trend (chi-square test for linear trend P < 0.001) as there was an increase in the risk level. Conclusion: The PDW level in the early stage serves as an important risk factor for AKI, severe AKI, and RRT requirement in extensive burns. When PDW >17.7%, burn patients are not only at a higher risk for AKI but may also have higher AKI severity. Due to low cost and wide availability, PDW has the potential to be the tool that can predict AKI in extensive burn patients.

Predictive value of lactate dehydrogenase combined with the abbreviated burn severity index for acute kidney injury and mortality in severe burn patients.

BACKGROUND: Extensive burns are devastating trauma. This study aimed to explore the predictive value of early lactate dehydrogenase (LDH) level, the abbreviated burn severity index (ABSI) and their combination on acute kidney injury (AKI) and mortality after severe burns. METHODS AND RESULTS: 194 severe burn patients (TBSA ≥ 30%) were included. After multivariate analyses, early LDH value (first 24 h after admission) was an independent risk factor for early AKI (OR=1.095, CI,1.025-1.169,p = 0.007) and AKI (OR=1.452, CI,1.131-1.864, p = 0.003) in severe burn patients and was still a significant risk factor for mortality (OR=1.059, CI,1.006-1.115，p = 0.03). In ROC analysis, after combining LDH and ABSI, the AUC values were 0.925 for AKI, 0.926 for stage 3 AKI, and 0.904 for mortality. Based on cut-off values, patients were divided into different risk groups. The cumulative incidence of AKI (within 5 days, 30 days) and survival rate (within 60 days) were analyzed by the Kaplan-Meier method. The mortality, AKI incidence, and AKI staging showed a significant upward trend with the increasing risk level (P < 0.001). CONCLUSION: Early LDH level is an independent risk factor for early AKI and AKI. LDH combined with ABSI can better predict mortality and AKI than single indicators.

Chitosan degradation products promote healing of burn wounds of rat skin.

Burns can impair the barrier function of the skin, and small burns can also cause high mortality. The WHO has described that over 180,000 people die of burns worldwide each year. Thus, the treatment of burn wounds is a major clinical challenge. Chitooligosaccharides (COS) are alkaline amino oligosaccharides with small molecular weights obtained by enzyme or chemical degradation of chitosan. With the characteristics of biocompatibility, water solubility and degradability, it has attracted increasing attention in the fields of biomedicine. In the present study, we used COS to treat deep second-degree burn wounds of rat skin and found that COS was able to promote wound healing. We also revealed that COS could promote fibroblast proliferation. Transcriptome sequencing analysis was performed on COS-treated fibroblasts to identify the underlying mechanisms. The results showed that COS was able to promote wound healing through regulation of the mitogen-activated protein kinase (MAPK) pathway and growth factor Hepatocyte Growth Factor (HGF). Our results provide a potential drug for burn wound therapy and the related molecular mechanism.

Effects of nanoparticle-mediated Co-delivery of bFGF and VEGFA genes to deep burn wounds: An in vivo study.

Deep burns are a common form of trauma worldwide, and they are hard to be cured in a short time and enhance psychological pressure of the patients. How to effectively promote the healing of wounds after burns is a continuing challenge currently faced by burn physicians. Various strategies of promoting wound healing of deep burns have been developed, including gene therapy and growth factor therapy. In this study, we developed a combined therapy using PLGA nanoparticles as carriers to deliver bFGF and VEGFA genes to promote healing of burn wounds. We first inserted the bFGF and VEGFA genes into pEGFP-N1 vectors and loaded the mixed generated plasmids into PLGA nanoparticles. Next, we injected the nanoparticle/plasmid complexes into the rats intracutaneously and found that the complexes were successfully transfected in vivo one week later. Finally, we injected the nanoparticle/plasmid complexes containing bFGF and VEGFA around burn wounds. We found that the percentage of wound healing of rats treated with nanoparticles/bFGF+ VEGFA plasmid complexes was higher than that of rats in the scald control group, and the early percentage of wound complete epithelialization was also higher. Therefore, combining gene therapy with nanoparticles may be an effective biological strategy for wound repair.

MicroRNA-205-5p regulates extracellular matrix production in hyperplastic scars by targeting Smad2.

Hypertrophic scar (HS) formation is the result of poor skin-wound healing. At present, the pathogenesis of HS formation is largely unclear. Micro (miR)RNAs have important effects on a variety of biological and pathological processes. The role of miRNA in HS formation remains largely unclear. The present study aimed to investigate the role of miR-205-5p in HS, and explore the underlying molecular mechanism. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of miR-205-5p in HS. Western blot assay and RT-qPCR were performed to assess the expression of associated proteins and genes, respectively. TargetScan was performed to predict the target gene of miR-205-5p, and the luciferase reporter assay was applied to verify the prediction. The function of miR-205-5p on cell proliferation was detected using Cell Counting Kit-8 assay, and cell apoptosis was detected via flow cytometry. miR-205-5p expression was decreased in HS tissues and human hypertrophic scar fibroblasts (hHSFs). Mothers against decapentaplegic homolog (Smad)2 was significantly increased in HS tissues and HSFs, and it was directly targeted by miR-205-5p. Restoration of miR-205-5p suppressed HSF cell proliferation and induced cell apoptosis. It was also demonstrated that RAC-Alpha Serine/Threonine-Protein Kinase (AKT) phosphorylation and the expression of α-smooth muscle actin, collagen I and collagen III were inhibited by miR-205-5p. In addition, Smad2 weakened the effects of miR-205-5p on HSFs. In conclusion, miR-205-5p exhibited an important role in HS by targeting smad2 and suppressing the AKT pathway. These findings provide a clearer understanding of the mechanism for HS that may be used to develop novel treatments for HS.

MicroRNA-26a inhibits hyperplastic scar formation by targeting Smad2.

Hypertrophic scar (HS) is a fibrotic disease in which excessive extracellular matrix forms due to the response of fibroblasts to tissue damage. Novel evidence suggests that microRNAs (miRNAs or miRs) may contribute to hypertrophic scarring; however, the role of miRNAs in HS formation remains unclear. In the present study, miR-26a was significantly downregulated in HS tissues and human HS fibroblasts (hHSFs) was detected by reverse transcription-quantitative analysis. TargetScan was used to predict that mothers against decapentaplegic homolog 2 (Smad2) is a potential target gene of miR-26a and a dual-luciferase reporter assay confirmed that Smad2 was a target gene of miR-26a. The expression of Smad2 was upregulated in HS tissues and hHSFs. Cell Counting Kit-8 and flow cytometry analyses demonstrated that the overexpression of miR-26a significantly suppressed the proliferation ability of hHSFs and the apoptotic rate of hHSFs was significantly upregulated in response to miR-26a mimic transfection. Furthermore, the expression of B-cell lymphoma-2 (Bcl-2)-associated X protein was increased and Bcl-2 expression was decreased following miR-26a mimic transfection. The expression of collagens I and III was significantly inhibited following treatment with miR-26a mimics in hHSF cells. Conversely, miR-26a inhibitors served an opposing role in hHSFs. Furthermore, Smad2 overexpression enhanced the expression of collagens I and c III; however, Smad2 silencing inhibited the expression of collagens I and c III. In conclusion, the results of the present study indicate that miR-26a inhibits HS formation by modulating proliferation and apoptosis ad well as inhibiting the expression of extracellular matrix-associated proteins by targeting Smad2.

Roles of TNF-α, GSK-3ß and RANKL in the occurrence and development of diabetic osteoporosis.

OBJECTIVE: To investigate the roles of TNF-α, GSK-3ß and RANKL in the occurrence and development of diabetic osteoporosis. METHODS: Diabetic rat model was established; tissue section technology was used to observe the situation of osteoporosis in diabetic rats; rat serum levels of OC, RANKL, GSK-3ß, P38mapk, TNF-α and INS were detected by Elisa assay; osteoblasts and osteoclasts were primarily cultured and identified by immunohistochemistry and tartrate-resistant acid phosphatase (TRAP) staining respectively. The effects of GSK-3ß inhibitors, lithium chloride, TNF-α antagonists and RANKL antagonists on the proliferation of osteoblasts and osteoclasts were evaluated; quantitative PCR was used to assess the effects of GSK-3ß inhibitors, lithium chloride, on TNF-α and RANKL gene expression in osteoblasts and osteoclasts, and the effects of TNF-α and RANKL antagonists on GSK-3ß gene expression in osteoblasts and osteoclasts. RESULTS: Diabetic rat model was successfully established; osteoblasts and osteoclasts were successfully isolated and cultured. Elisa experiments showed that in diabetic model group, the levels of RANKL, GSK-3ß, P38mapk and TNF-α were significantly increased, while the levels of osteocalcin (OC) and insulin (INS) were significantly reduced; MTT results showed that osteoclast proliferation in GSK-3ß inhibitor and lithium chloride groups were weaker than the untreated group, while osteoclast proliferation in TNF-α antagonist group and RANKL antagonist Group was very close to the untreated group. Osteoblast proliferation in GSK-3ß inhibitor and lithium chloride groups were weaker than the untreated group, while osteoblast proliferation in TNF-α antagonist group and RANKL antagonist group was higher than the untreated group. In all of the corresponding groups, cell proliferation in the diabetic group was stronger than the untreated group. In GSK-3ß inhibitor and lithium oxide groups, TNF-α and RANKL gene expression levels were elevated, but TNF-α and RANKL gene expression levels in the diabetic group were slightly lower than the control group. GSK-3ß gene expression level in TNF-α antagonist group and RANKL antagonist group was reduced; GSK-3ß gene expression level in diabetic group was lower than the control group. CONCLUSION: In diabetic rats, TNF-α, GSK-3ß and RANKL levels were elevated; GSK-3ß could promote the proliferation of osteoblasts and osteoclasts, and inhibit the expression of TNF-α and RANKL; TNF-α and RANKL can suppress the proliferation of osteoblasts while had little effect on osteoclast proliferation; they also can promote the GSK-3ß gene expression; interactions between the three broke the balance between osteoblasts and osteoclasts, leading to osteoporosis.