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Hemorrhagic shock (HS) is one of the leading causes of death among young adults worldwide. Multiple organ dysfunction in HS is caused by an imbalance between tissue oxygen supply and demand, which is closely related to the poor prognosis of patient. Mitochondrial dysfunction is one of the key mechanisms contributing to multiple organ dysfunction in HS, while mitochondrial quality control regulates mitochondrial function through a series of processes, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, mitochondrial-derived vesicles, and mitochondrial protein homeostasis. Modulating mitochondrial quality control can improve organ dysfunction. This review aims to summarize the effects of mitochondrial dysfunction on organ function in HS and discuss the potential mechanisms of mitochondrial quality control, providing insights into the injury mechanisms underlying HS and guiding clinical management.

Background: Wound infections, especially multidrug-resistant (MDR) bacterial infections, are a major challenge in clinical medicine., Methods: In this study, a new type of antibacterial sponge was prepared from a solution containing a chitosan-polyvinyl alcohol (CTS-PVA) emulsion with added polyhexamethylene guanidine hydrochloride (PHMG) in a homogeneous medium using lyophilization technology. The antibacterial ability of and CTS-PVA/PHMG sponge against Staphylococcus aureus , Pseudomonas aeruginosa , Escherichia coli , Candida albicans , Methicillin-resistant Staphylococcus aureus , multidrug-resistant Pseudomonas aeruginosa , and multidrug-resistant Acinetobacter baumannii in vitro. The structure and physical properties were characterized. The sponge dressing was tested in a Pseudomonas aeruginosa -infected full-thickness mouse skin wound defect model. The effects were evaluated by wound area measurement and histological analysis., Results: The CTS-PVA/PHMG sponge showed broad-spectrum antibacterial ability, including for MDR bacterial stains from clinical sources, while maintaining excellent physicochemical properties, including a high swelling degree and good moisture retention capability. Scanning electron microscopy images displayed the surface morphology of the CTS-PVA/PHMG sponge dressing. The detection of the wound healing rate and histological analysis supported that the new dressing can alleviate the inflammation and accelerate the healing speed of infected wounds and in vivo ., Conclusions: CTS-PVA/PHMG sponge shows broad-spectrum antibacterial activity, which can provide a new pathway for clinical prevention and treatment of superbug-infected wounds., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-21-509). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: Severe burn causes acute lung injury in many victims, but the related mechanisms have been barely investigated. microRNAs (miRNAs) important regulators in numerous physiological and pathophysiological process. However, the roles of miRNAs in burn lung injury are untested., Methods: Six healthy male Sprague-Dawley rats were randomly assigned into burn and sham groups. Lung injury was evaluated by hematoxylin and eosin (HE) staining at 24 h after injury. Differentially expressed miRNAs were determined by array hybridization and verified by real-time quantitative polymerase chain reaction (RT-qPCR). Bioinformatics analysis was undertaken to predict the target genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were employed to identify potentially related biological processes and pathways, respectively. Neutrophil infiltration and apoptosis of the lung were confirmed by immunohistochemical staining of myeloperoxidase (MPO) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)., Results: HE sections showed obvious lung injury, and 21 upregulated and three downregulated miRNAs were detected. Target genes of these miRNAs were most highly enriched in inflammation and apoptosis related GO biological processes and pathways. Inflammation and apoptosis were confirmed by MPO and TUNEL staining., Conclusion: The differentially expressed miRNAs most likely participate in burn-induced lung injury by being involved in inflammation and apoptosis.

Skeletal muscle atrophy, a conventional clinical feature in patients with cancer, chronic obstructive pulmonary disease, sepsis and severe burns, is defined as a reduction in muscle mass. During atrophy, the protein degradation is abnormally activated and the aberrance between protein synthesis and protein degradation results in muscle atrophy. Previous studies have demonstrated that miRNAs, small non-coding RNA molecules, serve an important role in the regulation of muscle atrophy. Further studies have indicated the implications of the ubiquitin-proteasome and PI3K/Akt/FoxO signaling pathways and myogenic regulatory factors in miRNA-mediated muscle atrophy. Therefore, in this review, the effects and molecular mechanisms of miRNAs on muscle atrophy are summarized, leading to the suggestion that miRNAs may serve as potential therapeutic targets in muscle atrophy.

Objective: To explore the phenotypic changes of epidermal stem cells (ESCs) differentiating into sweat glands cells (SGCs) in vitro and its mechanisms., Methods: ESCs and SGCs were isolated and cultured in vitro, which were identified using immunofluorescence staining. ESCs at passage 2 were divided into 4 groups: ESCs and SGCs co-cultured by Transwell plates in group A, ESCs cultured by simply adding sweat supernatant in group B, ESCs and SGCs co-cultured on Transwell plate adding epidermal growth factor (EGF) (60 ng/mL) in group C, and ESCs and SGCs co-cultured on transwell plate adding PD98059 (10 mmol/L) in group D. The inverted microscope was used for observing the morphology of ESCs, flow cytometry for detecting ESCs positive phenotype, and Western blot for exploring mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) pathway., Results: The morphology observation and immunofluorescence staining suggested that cultured cells were ESCs and SGCs. The inverted phase contrast microscope observation showed that cells had similar morphological changes, with flat polygonal shape at 9 days in groups A, C, and D; cells had slow morphological change in group B, and had similar change to that of other groups at 12 days. Significant decreasing of beta1-integrin expression and increasing of carcino-embryonic antigen (CEA) expression of ESCs were observed in group A when compared with group B, which was inhibited by EGF (group C) and enhanced by PD98059 (group D), and there were significant differences among groups A, C, and D (P<0.05). High level of ERK expression was displayed in 4 groups, but it was significantly lower in group B than the other 3 groups (P<0.05). The expression of phosphorylation ERK was the highest in group A and was the lowest in group C, showing significant difference among 4 groups (P<0.05)., Conclusion: ESCs can be induced to differentiate into SGCs with the phenotypic changes under the condition of co-cultured by Transwell plates. The MAPK/ERK pathway plays a key role in the diffrentation of ESCs into GCCs

Quality of life and functional recovery after burn injury is the final goal of burn care, especially as most of burn patients survive the injury due to advanced medical science. However, dysfunction, disfigurement, contractures, psychological problems and other discomforts due to burns and the consequent scars are common, and physical therapy and occupational therapy provide alternative treatments for these problems of burn patients. This guideline, organized by the Chinese Burn Association and Chinese Association of Burn Surgeons aims to emphasize the importance of team work in burn care and provide a brief introduction of the outlines of physical and occupational therapies during burn treatment, which is suitable for the current medical circumstances of China. It can be used as the start of the tools for burn rehabilitation.

Background: In this study, we will establish a stable and optimized rat model that can meet strictly diagnosed criteria and serve as a tool to investigate the potential of novel therapeutics in this preclinical model through comparative analysis of systemic alterations, levels of pro-inflammatory cytokines in serum and infiltrated numbers of inflammatory cells in distant organ between 30% and 50% TBSA with a full-thickness burn., Materials and Methods: The adult male Wistar rats were randomly divided into the following groups: control group, 30% TBSA with a full-thickness burn group, and 50% TBSA with a full-thickness burn group. The blood and serum samples in the 3 groups were collected and detected by blood routine examination and biochemical detection at 6 h, 12 h, 24 h and 48 h post burn. The levels of TNF-α, IL-1β and IL-6 in serum were detected by ELISA. The sections of lung, renal, liver and heart were analyzed by H&E and immunohistochemical staining detection., Results: Our results showed that temperature in 50% TBSA with a full-thickness burn group was always hypothermia, and lower than 36°C at defined timepoints post burn, that was in 30% TBSA with a full-thickness burn group was lower than 36°C only at 48 h post burn. The levels of TNF-α, IL-1β and IL-6 were significantly increased in 30% and 50% groups at 6 h, 12 h, 24 h and 48 h post burn. The apoptosis in distant organs and the biochemical parameters such as ALT, AST, troponin, CK, CK-MB, LDH, urea and creatinine in 30% and 50% groups were also increased at different degrees at defined timepoints after burn, but changes in 50% group were more obvious than that in 30% group., Conclusion: We choose 50% TBSA with a full-thickness burn to establish a stable and optimized rat model that can meet strictly diagnosed criteria and serve as a tool to investigate the potential of novel therapeutics in this preclinical model.

Objective: To explore the efficacies of resuscitation fluid volume after combined burn-blast injury versus a simple burn., Methods: A total of 24 beagle dogs were randomly assigned into 3 groups of normal volume (N), decreased volume (D) and increased volume (I). Fluid volume for group N was calculated with the Parkland formula while groups D and I decreased or increased by 20% respectively. Urinary output (UOP), hemoglobin concentration (HB), cardiac output (CO), intrathoracic blood volume (ITBV), extravascular lung water index (ELWI), oxygen delivery (DO(2)) and oxygen consumption (VO(2)) were determined before and 4, 8, 24, 48 h after injury to evaluate the sufficiency of resuscitation in each group and examine the superiority., Results: UOP were [(0.41 ± 0.13), (0.77 ± 0.17), (0.30 ± 0.13)] ml · kg(-1) · h(-1) at 4 h post-injury in groups N, I and D respectively. Group I was significantly higher than groups N and D (P < 0.001).It were [(0.59 ± 0.05), (0.88 ± 0.05), (0.53 ± 0.06)] ml · kg(-1) · h(-1) at 24 h post-injury in groups N, I and D respectively. Group I was significantly higher than groups N and D (P < 0.001). CO in group I was remarkably higher than those in groups N and D at 4 h and 8 h post-injury [(1.57 ± 0.19) vs (1.25 ± 0.17), (1.05 ± 0.17) L/min; (1.87 ± 0.20) vs (1.57 ± 0.24), (1.20 ± 0.19) L/min respectively] (P < 0.05); ITBV also significantly increased in group I than two other groups at 4 h and 8 h post-injury [(169 ± 16) vs (140 ± 12), (121 ± 12) ml; (161 ± 14) vs (135 ± 22), (112 ± 12) ml] (P < 0.05). VO2 in group I was significantly higher than that in group N at 24 h post-injury [(129 ± 10) vs (106 ± 12) ml · min(-1) · m(-2)] (P < 0.05). No differences were detected among 3 group in ELWI (P > 0.05)., Conclusion: Larger fluid volume may compensate circulatory volume loss sooner, alleviate declining cardiac output better, maintain adequate organ perfusion, promote tissue oxygenation and improve anti-hypervolemia and anti-hypoxia.

In recent years, negative pressure wound therapy (NPWT) technique has been widely used in burn surgery, including wound repair, skin grafting, and cosmetic procedures, showing promising clinical results. Based on the literature and clinical experience, the mechanism of NPWT and its clinical application in burn surgery are briefly iterated herewith.

Burns are common accidental injuries. The main clinical manifestations of severe burn injury are insulin resistance and high metabolism. Insulin resistance results in hyperglycemia, which may lead to skeletal muscle wasting and suspended wound healing. It also elevates the risk of infection and sepsis. Studies have indicated that insulin receptor (IR) and insulin receptor substrate 1 (IRS1) are essential factors involved in the regulation of blood glucose levels. Moreover, the suppression of the IR/IRS1 signaling pathway results in insulin resistance. Recent studies have also indicated that miRNAs, which are small non-coding RNAs consisting of 20-23 nucleotides, target the 3'-untranslated region (3'-UTR) of IRS1 mRNA and attenuate protein translation. miRNAs also play an important role in the development of type II diabetes (T2D) and obesity-induced insulin resistance. In the present review, we discuss the involvement of miRNAs in burn-induced insulin resistance through the targeting of the IR/IRS1 signaling pathway. We also discuss the possibility of miRNAs a novel therapeutic target in insulin resistance in burn patients.

Objective: To comprehensively analyze the recent advancements in the field of mesenchymal stem cells (MSCs) derived exosomes (MSCs-exosomes) in tissue repair., Methods: The literature about MSCs-exosomes in tissue repair was reviewed and analyzed., Results: Exosomes are biologically active microvesicles released from MSCs which are loaded with functional proteins, RNA, and microRNA. Exosomes can inhibit apoptosis, stimulate proliferation, alter cell phenotype in tissue repair of several diseases through cell-to-cell communication., Conclusion: MSCs-exosomes is a novel source for the treatment of tissue repair. Further research of MSCs-exosomes biofunction, paracellular transport, and treatment mechanism will help the transform to clinical application.

Objective: To observe the therapeutic effects of exogenous pulmonary surfactant (PS) on acute lung injury induced by severe burn-blast combined injury in a rat model., Methods: A total of 180 adult male SD rats were randomly divided into 3 groups of sham, treatment and control (n=60 each). Severe burn-blast combined injury was induced by inflicting rats with a moderate blast injury and a full-thickness burn injury of 25% total body surface area. The treatment and control groups received exogenous PS (2 ml/kg) and saline (2 ml/kg) by trachea respectively. At the time points of 0, 6, 24, 48 and 72 h, 12 rats per timepoint in each group underwent PaO2, PaCO2 and pulmonary function tests respectively. And they were then sacrificed for other analyses. Lung tissues were harvested for histological studies. Their arterial blood samples were collected for blood gas analysis. All data were expressed as mean ± standard deviation and analyzed with SPSS 20.0 (SPSS Inc., Chicago, IL, USA). The differences were considered to be statistically significant at P < 0.05., Results: After removing death drain during the experiment, 8 rats were put equally into five phase points of the last three groups, the results were analyzed statistically. PaO2: At each timepoint of 6, 24, 48, 72 h, the control group PaO2 were obviously lower than the sham group ((69.55 ± 5.11), (62.05 ± 6.54), (53.24 ± 7.65), (50.00 ± 7.45) vs (93.75 ± 3.41), (94.25 ± 2.19), (93.63 ± 2.33), (93.25 ± 1.83) mmHg (1 mmHg = 0.133 kPa), all P < 0.01); at 6 h treatment group was close to sham group ((92.63 ± 3.74) vs (93.75 ± 3.41) mmHg, P=0.594); at 6 h control group PaO2 decreased to 70 mmHg and then gradually declined. And at each timepoint the treatment group PaO2 was significantly higher than the control group ((92.63 ± 3.74), (87.50 ± 3.34), (78.75 ± 3.11), (71.38 ± 3.74) vs (69.55 ± 5.11), (62.05 ± 6.54), (53.24 ± 7.65), (50.00 ± 7.45) mmHg, all P < 0.01); PaCO2: treatment group PaCO2 was lower than that of control group at 6, 24, 48 h ((45.50 ± 6.79), (49.38 ± 7.52), (54.13 ± 4.82) vs (53.25 ± 2.76), (59.50 ± 6.61), (63.60 ± 7.33) mmHg, all P < 0.01), both treatment and control groups were significantly higher than those in the sham group ((59.63 ± 6.87), (68.88 ± 6.85) vs (36.38 ± 1.85) mmHg, all P < 0.01). No difference existed between the control and treatment groups (P = 0.051). Deep inspiratory capacity, central airway resistance, lung compliance and tissue elasticity, treatment group was significantly better than control group at 24 h (P < 0.05). And it was close to sham group (P > 0.05). The treatment group alveolar structural damage and pulmonary hemorrhage and edema were better than those in the control group., Conclusion: Exogenous pulmonary surfactant (PS) can improve oxygenation and alleviate pulmonary edema and pulmonary capillary membrane permeability of rats with severe burn blast combined injury.

Objective: To investigate the effect of burn on brown adipose tissue (BAT) in BALB/c mice., Methods: Forty 3-4 months old male BALB/c mice with initial body weight of (20 ± 3) g were randomly divided into control group and burn group (n = 20). BALB/c mice in burn group were subjected to a 30% total body surface area (TBSA) full-thickness thermal injury. BALB/c mice in control group were not treated. The body weight and temperature were observed before and after burn. At 7 days after burn, morphological changes of white adipose tissue (WAT) and BAT were observed, the gene and protein expressions of uncoupling protein 1 (UCP-1) were detected., Results: There was no significant difference in the body weight and body temperature before burn (P > 0.05). At 1, 2, 3, and 4 weeks after burn, the body weight was significantly lower in burn group than in control group (P < 0.05). At 1, 2, 3, and 7 days after burn, the body temperature was significantly higher in burn group than in control group (P < 0.05). At 7 days after burn, the weight of WAT was significantly reduced, and the weight of BAT was significantly increased in burn group (P < 0.05); WAT and BAT cells became smaller, cell number increased, the cytoplasm and mitochondria appeared as compact. The UCP-1 gene and protein expressions of burn group were significantly higher than those of control group (P < 0.05)., Conclusion: BAT plays an important role in burn-induced hypermetabolism.

Hypermetabolism and insulin resistance are prominent features of trauma including burn injury, surgery, and infection. Hypermetabolism results in insufficiency in energy supply, which induces organ function lesion, immune suppression, high infection rate, and wound healing delay, thus exerting a strong impact on patients' quality of life and prognosis. The molecular mechanism in the occurrence and development of hypermetabolism is very complicated, and it has not been fully elucidated. Recently, brown adipose tissue (BAT) was found to be present not only in rodents but also in humans, and its activity was associated with resting metabolic rate. BAT may become the new target of research in prevention and control of metabolic disorder.

Objective: To investigate the effect of burn on the fat metabolism by observing the effect of burn serum on the proliferation and adipose differentiation of 3T3-L1 preadipocytes., Methods: Forty-eight male Sprague Dawley rats were randomly divided into sham burn group and burn at 1, 4, 7, 14, and 21 days groups, 8 rats in each group. The rats in burn groups were made the full-thickness thermal burns comprising 30% total body surface area. At 1, 4, 7, 14, and 21 days after burn, the serum of burn rats was collected. The rats in sham burn group were not treated as normal control. The proliferation activity of 3T3-L1 cells was detected using MTT method after treated by normal and burn serum. The burn serum having the highest proliferation inhibitory effect was chosen for subsequent study. The growth of 3T3-L1 cells in normal serum group (group A), burn serum group (group B), normal serum and adipogenic induction group (group C), burn serum and adipogenic induction group (group D) was observed using inverted microscope. After 7 days of treatment, the adipocytes was stained by oil red O and the absorbance (A) value was measured. The mRNA and protein levels of preoxisome proliferator-activated receptor γ (PPAR-γ) and lipoprotein lipase (LPL) were detected by real-time quantitative PCR and Western blot., Results: The proliferation ability of 3T3-L1 cells was significantly reduced in the group treated by 4- or 7-day burn serum (P < 0.05), especially 7-day burn serum treatment group (P < 0.05). Under inverted microscope, the cell morphology in group A and group B had no obvious change, but a large number of fat cells were observed in group C and a few were observed in group D. The positive or weak positive oil red O staining was observed in group C or group D, respectively. The cell counting and A value were significantly higher in group A than in group B, and in group C than in group D (P < 0.05). The mRNA level of PPAR-γ in group B was significantly reduced when compared with that in group A (P < 0.05). No significant difference was found in LPL mRNA levels and protein levels of PPAR-γ and LPL between group A and group B (P > 0.05). The mRNA and protein levels of PPAR-γ and LPL were significantly attenuated in group D when compared with those in group C (P < 0.05)., Conclusion: The adipose differentiation of 3T3-L1 preadipocytes can be significantly reduced after treated by 7-day burn serum of rat.

Objective: To explore the effect and mechanism of ryanodine receptor antagonist dantrolene on skeletal muscle of rats with severe scald injury., Methods: A total of 56 Wistar rats were divided into control, scald and dantrolene treatment groups according to a random digital table. Rats in scald and dantrolene treatment groups were subject to 50% total body surface area (TBSA) full-thickness scald by a 12-second immersion of back and a 6-second immersion of abdomen in 94 °C water and then received an intraperitoneal injection of Ringer's solution. At the same time, the rats in scald group received 5% mannitol through caudal vein while those in dantrolene treatment group received dantrolene 2 mg/kg (dissolved in 5% mannitol). Rats in control group were sham-injured through an immersion of back and abdomen into 37 °C warm water. Tibialis anterior muscle samples were harvested at Days 1, 4 and 7 post-scalding. Changes of skeletal muscle ultrastructure were observed by transmission electron microscope, subcellular calcium ion (Ca(2+)) contents of skeletal muscle (including cytoplasm, mitochondria & sarcoplasm reticulum) were detected by electron probe X-ray microanalysis (EPMA) and the levels of calpain-1 and calpain-2 protein were determined by Western blot. And the activities of calpain were detected by enzyme-linked immunosorbent assay., Results: In scald group, assorted arrangement appeared immediately at Day 1 post-injury and partial disappearance of Z lines at Day 7 post-injury. There were no significant ultrastructure changes in dantrolene treatment group at Day 1 and 4 post-injury. Curled filament and mild fracture occurred merely in dantrolene treatment group at Day 7 post-injury. The cytoplasmic contents of Ca(2+) were significantly higher in scald group than those in control group at Day 1 and 4 ((0.964 ± 0.060), (0.639 ± 0.067) vs (0.266 ± 0.029) µmol/L respectively, all P < 0.05) while the contents of Ca(2+) within sarcoplasm reticulum were obviously lower in scald group than those in control group at Day 1 and 4 ((0.368 ± 0.060), (0.814 ± 0.089) vs (1.337 ± 0.112) µmol/L respectively, all P < 0.05). However, those subcellular regions in dantrolene treatment group ((0.310 ± 0.069), (0.490 ± 0.039) and (1.241 ± 0.073), (1.161 ± 0.094) µmol/L) had no significant difference with control group (all P > 0.05). Calpain-1 and calpain-2 protein levels in scald group increased significantly at Day 1 and 4 post-injury versus control group (1.371 ± 0.034, 1.214 ± 0.030 vs 0.838 ± 0.017 & 1.464 ± 0.015, 1.390 ± 0.023 vs 0.806 ± 0.026 respectively, all P < 0.05), whereas calpain-1 and calpain-2 protein levels in dantrolene treatment (0.984 ± 0.031, 0.935 ± 0.023 and 0.836 ± 0.014, 0.741 ± 0.020) obviously were lower than those in scald group respectively (all P < 0.05). The activities of calpain in scald and dantrolene treatment groups at Day 1, 4 and 7 post-injury were (8.33 ± 0.21), (9.33 ± 0.21), (10.59 ± 0.18) and (7.76 ± 0.28), (7.86 ± 0.20), (7.91 ± 0.22) µmol/L respectively while the activity of calpain in control group was (7.62 ± 0.19) µmol/L. The activities of calpain in scald group were significantly higher than those in dantrolene treatment and control groups (all P < 0.05) whereas the activities of calpain in dantrolene treatment group had no obvious change versus control group (all P > 0.05)., Conclusions: Dantrolene offers significant protection from skeletal muscle tissue damage and minimizes the ultrastructural change of tibialis anterior muscle induced by severe scald injury. The mechanism is probably through inhibiting an excessive release of Ca(2+) within sarcoplasm reticulum and down-regulated cytoplasmic expression and activity of calpain-1 and calpain-2.

Invasive fungal infection is one of the major complication of severe burns which can induce local or systemic inflammatory response and cause serious substantial damage to the patient. The incidence of fungal infection for burn victims is increasing dramatically during recent years. This guideline, organized by Chinese Society of Burn Surgeons, aims to standardize the diagnosis, prevention and treatment of burn invasive fungal infection. It can be used as one of the tools for treatment of major burn patients.

Objective: To explore the effects of lipopolysaccharide (LPS) pretreatment on endotoxin tolerance of human umbilical cord mesenchymal stem cells (hUCMSCs) and its possible mechanism., Methods: hUCMSCs (1×10(4) cells/well) were exposed to 0, 0.1, 1.0, 10.0, 20.0, 30.0, 40.0, 50.0 µg/ml LPS for 24 h respectively. And the cell viability of hUCMSCs was detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT). 1 µg/ml and 50.0 µg/ml LPS were used as pretreatment and apoptosis induction concentrations respectively. Pyrrolidine dithiocarbamate (PDTC) (20 µmol/L, pretreatment for 20 min) was used as a specific inhibitor of nuclear transcription factor NF-κB. hUCMSCs were randomly divided by Stata software into 7 groups: control (A), LPS induction (B), pretreatment + LPS induction (C), PDTC (D), PDTC+ pretreatment + LPS induction (E), pretreatment (F) and PDTC + pretreatment (G). The apoptosis of hUCMSCs was measured by Hoechst 33258 staining and flow cytometry (FCM). The expressions of NF-κB p65 and cellular FLICE-inhibitory protein (c-FLIP) were measured by Western blot., Results: The cell viability of 0, 0.1, 1.0, 10.0, 20.0, 30.0, 40.0, 50.0 µg/ml LPS groups were 100%, (117.0 ± 8.8)%, (134.7 ± 6.9)%, (105.3 ± 8.3)%, (99.2 ± 8.3)%, (84.2 ± 9.3)%, (66.4 ± 6.6)% and (59.2 ± 8.0)% respectively. In comparison with 0 µg/ml LPS group, the cell viability of 1.0 µg/ml LPS group increased significantly (P = 0.004) while decreased in 40 and 50 µg/ml LPS groups (P = 0.005, 0.002). Hoechst 33258 staining indicated that chromatin of hUCMSCs was distributed evenly in group A; the apoptotic cell in group B dramatically increased; and the apoptotic cell in group C significantly decreased in comparison with that in group B. Apoptotic rates of groups A, B, C, D and E were (2.8 ± 0.8)%, (29.7 ± 3.4)%, (17.8 ± 3.0)%, (2.9 ± 0.4)% and (23.2 ± 2.6)% respectively. Compared with group A, apoptosis rate significantly increased in group B (P < 0.001). The apoptotic rate in group C significantly decreased than that in group B (P < 0.001) while group E was higher than group C (P = 0.015). The levels of NF-κB p65 and c-FLIP in group F (0.851 ± 0.031, 0.534 ± 0.053) was higher than that in group A (0.220 ± 0.021, 0.049 ± 0.009) (both P < 0.001), G (0.418 ± 0.007, 0.299 ± 0.061) (P < 0.001, P = 0.007)., Conclusions: LPS pretreatment can resist LPS-induced hUCMSCs apoptosis and enhance the ability of endotoxin tolerance. And the mechanism may be related with activating the NF-κB signaling pathway and up-regulating the expression of c-FLIP.

Objective: To investigate the effects of different concentrations of lipopolysaccharide (LPS) on proliferation and apoptosis of human umbilical cord mesenchymal stem cells (hUCMSCs) in vitro, and to explore their possible mechanism., Methods: hUCMSCs from umbilical cord tissue of full-term healthy fetus delivered by caesarean section were isolated and cultured in vitro using tissue attachment method. The 3rd passage hUCMSCs were used in the study. Cells were divided into groups A, B, C, D, and E, which were treated with DMEM/F12 medium containing 0, 0.1, 1.0, 10.0, and 100.0 µg/mL of LPS respectively. In groups B, C, D, and E, methyl-thiazole-tetrazolium assay was used to detect proliferative activity of hUCMSCs at post treatment hour (PTH) 12, 24, and 48 (denoted as absorption value), with 5 samples in each group at each time point; apoptosis of hUCMSCs at PBH 24 was identified with acridine orange-ethidium bromide (AO-EB) staining, with 4 samples in each group; apoptotic rate of hUCMSCs was determined by flow cytometer, with 5 samples in each group. Above-mentioned indexes were determined in group A at the same time points. Data were processed with analysis of variance and LSD- t test., Results: (1) There was no statistically significant difference in proliferative activity of hUCMSCs at PTH 12 among groups A, B, C, D, and E (with t values from -1.67 to 1.33, P values above 0.05). Compared with that of group A, proliferative activity of hUCMSCs was increased in groups B, C, and D at PTH 24 and 48 (with t values from -13.42 to 17.34, P < 0.05 or P < 0.01), especially so in group C. Proliferative activity of hUCMSCs was lower in group E at PTH 24 and 48 than in group A (with t values respectively 8.64 and 17.34, P values below 0.01). (2) Obvious apoptosis of hUCMSCs was observed in group E but not in the other 4 groups with AO-EB staining. (3) Apoptosis rates of hUCMSCs in groups A, B, C, D, and E were respectively (3.1 ± 0.6)%, (2.6 ± 0.7)%, (2.9 ± 0.8)%, (3.1 ± 0.4)%, (25.1 ± 2.7)% (F = 272.19, P < 0.01). Apoptotic rate of hUCMSCs in group B, C, or D was respectively close to that in group A (with t values respectively 1.22, 0.57, -0.14, P values above 0.05), but it was higher in group E than in group A (t = -17.63, P < 0.01)., Conclusions: hUCMSCs proliferation may be promoted by low concentration of LPS. hUCMSCs proliferation is inhibited or induced to apoptosis along with the increase in concentration of LPS, and it may be related to activation of different major molecular signaling pathways by different concentrations of LPS.

Wound healing is a dynamic and complicated process, which generally takes three overlapping phases: inflammation, proliferation, and remodeling. If wounds complicated by severe trauma, diabetes, vascular dysfunction disease, or a massive burn injury failed to pass through the three normal phases of healing, they might end up as chronic and refractory wounds. Mesenchymal stem cells (MSCs) play different important roles in the regulation of all the phases of wound healing. MSCs can be recruited into wound and differentiated into wound repair cells, as well as promote wound healing by exerting functions like anti-inflammation, anti-apoptosis, and neovascularization. This review focuses on the role and mechanism of MSCs in each phase of the wound healing process.

Objective: To investigate the effect of the serum from severe burn patients on the biology characteristics of human umbilical cord mesenchymal stem cells (hUCMSCs) in vitro, so as to explore the feasibility of hUCMSCs transplantation for treating severe burn., Methods: The 3rd passage of hUCMSCs were randomly divided into 3 groups: 10% fetal bovine serum group (group A), 10% normal serum group (group B), and 10% burn serum group (group C). At 24 hours, 72 hours, and 6 days after culture, the cell morphology and density were observed by inverted microscope; the cell proliferation was assessed by MTT; after 6 days of culture, the cell cycle by propidium iodide staining and flow cytometry, the apoptosis by acridine orange/ ethidium bromide staining, and the cell senescence by beta-galactosidase staining; the levels of tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), platelet-derived growth factor (PDGF), and insulin-like growth factor 1 (IGF-1) in serum were detected by a double-antibody sandwich ELISA kit., Results: hUCMSCs were long spindle/polygon in 3 groups. The cell fusion of group C was obviously faster than that in group A and group B. The cell proliferation curves showed that the velocity and number of cell proliferation in group C were significantly higher than those in group A and group B at 2-6 days after culture (P < 0.05). The rates of proliferation period (S) of hUCMSCs were 9.21% +/- 1.02%, 11.79% +/- 1.87%, and 20.54% +/- 2.03%, respectively in groups A, B, and C at 6 days, and group C was significantly higher than that of group A and group B (P < 0.05). The hUCMSCs showed normal morphology and structure in 3 groups, and no apoptosis cells was observed. The positive cells percentage of group C (2.6% +/- 0.1%) was significantly lower than that of group A (4.8% +/- 0.2%) and group B (3.8% +/- 0.4%) (P < 0.05). The levels of TNF-alpha, IL-1, PDGF, and IGF-1 in group C were significantly higher than those in group B (P < 0.05)., Conclusion: The higher levels of cytokines in serum from the severe burn patients can significantly stimulate hUCMSCs proliferation, prevent cells apoptosis, and reduce cells senescence. Therefore, it is feasible to use hUCMSCs transplantation for treating severe burn patients.

Objective: To review the research progress of mesenchymal stem cells (MSCs) in burn wound repair., Methods: The recent literature about MSCs involved in burn wound repair and mechanism was extensively reviewed and analyzed., Results: MSCs have the capacity of self-renew, rapid proliferation, differentiation and paracrine, and promote burn wound repair through differentiating into a series of skin wound cells and regulating wound microenvironment., Conclusion: MSCs have great potentials in the burn field. However, the cell survival and outcome are also facing challenges from poor microenvironment of the burn wound.

Objective: To establish a simple and efficient method to isolate and culture the umbilical vein vascular endothelial cells in canine., Methods: Twelve umbilical cords [(13.0 +/- 1.5) cm in length] were taken from 12 newborn pups of Beagles. And then the vascular endothelial cells were isolated from these umbilical cords digested by 1% collagenase type I for 5, 7, and 10 minutes respectively (4 umbilical cords in each group). After cultured, the vascular endothelial cells were identified by morphology, immunofluorescence, and flow cytometry. And the growth curvature of umbilical vein vascular endothelial cells was detected by MTT assay., Results: Few vascular endothelial cells were collected at 5 and 10 minutes after digestion; many vascular endothelial cells were seen at 7 minutes, and became cobblestone with culture time, with a large nucleus; after passage, cell morphology had no obvious change. Fluorescence microscope results showed that positive von Willebrand factor (vWF) and CD31 cells were observed in most of cells. The flow cytometry test displayed that the positive cell rates of vWF and CD31 were 99.0% +/- 0.7% and 98.0% +/- 1.2%, respectively. The above results indicated that cultured cells were vascular endothelial cells. MTT assay showed that vascular endothelial cells proliferation increased significantly with culture time., Conclusion: Enzyme digestion is a convenient method to isolate vascular endothelial cells from canine umbilical vein, and a large number of cells and high purity of cells can be obtained by the method.

Objective: To investigate the effectiveness of repairing severe cicatricial contracture deformity in the web-space by kite-like incision combined with full-thickness skin grafting., Methods: Between June 2008 and September 2011, 31 patients (87 web-spaces) with severe cicatricial contracture deformities in the web-spaces were treated. There were 24 males and 7 females, aged 5-43 years (median, 22 years). The causes of injuries were flame burn (26 cases), scald (3 cases), electric arc burn (1 case), and chemical burn (1 case). The degree of burn was deep second degree (14 cases) and third degree (17 cases). The interval time from injury to operation was 10 months to 17 years (median, 2.2 years). The kite-like incision was marked on the scar in the web-space. The rhombic scar between the adjacent metacarpophalangeal joints was excised, and cicatricial contracture was released completely. The secondary wound in the web-space was repaired with full-thickness autogeneic skin grafting. The secondary wound at donor site was directly sutured., Results: All full-thickness skin grafts survived well. The incisions at donor sites healed primarily. Of 31 patients, 29 (82 web-spaces) were followed up 6-18 months (mean, 13 months). The sizes and depths of reconstructed web-spaces were similar to those of normal ones. No secondary cicatricial contracture was observed, and the function of fingers recovered well., Conclusion: The short-term effectiveness is satisfactory by kite-like incision combined with full-thickness skin grafting for repairing severe cicatricial contracture deformities in the web-space, while the long-term effectiveness needs further observation.

Objective: To investigate the feasibility of repairing secondary wounds after scar excision in patients with scar contracture in whole dorsum of the hands by expanded full-thickness skin grafts., Methods: Between February 2008 and February 2011, 15 patients (19 hands) with scar contracture in whole dorsum of the hands were treated. There were 12 males (14 hands) and 3 females (5 hands), aged 18-43 years (mean, 28.6 years). The disease duration was 6-22 months (mean, 13.2 months). All cases complicated by different degrees of metacarpophalangeal joint extension deformity and interphalangeal joint flexion deformity. In one-stage operation, soft tissue expanders were implanted at donor sites, and the time of water injection was 4-5 months; in two-stage operation, scar was excised and secondary wound (14 cm x 9 cm-25 cm x 16 cm in size) was repaired with the expanded full-thickness skin grafts., Results: After one-stage operation, the others had good blood supply except 1 case of skin necrosis in the center of expanded skin flap. After two-stage operation, the full-thickness skin grafts survived well in 18 hands; subepidermal effusion occurred in 1 hand, which was cured after changing dressing. The incisions at donor sites healed well in all cases. All patients were followed up 6-18 months (mean, 13.7 months). The grafts were excellent in color, texture, and elasticity, and no hypertrophic scar was observed at the edge and joint of the grafts. The hand function recovered well; the flexion and extension of wrist joint, metacarpophalangeal joint and interphalangeal joint were normal., Conclusion: The expanded full-thickness skin graft is a suitable solution to repair effectively scar contracture in whole dorsum of the hands because it has good results in the cosmetic appearance and function recovery of the hands.

Objective: Endoplasmic reticulum stress (ERS) mediated apoptosis is one of the eukaryotic cellular apoptotic pathways, to investigate the potential role of ERS during myocardium apoptosis in rats with severe burn injury., Methods: Sixty-four 7-week-old male Wistar rats, weighing 200-220 g, were randomly divided into 2 groups. Thirty percentage of total body surface area full-thickness thermal injury was produced in 32 rats of burn group, while sham burn was produced in 32 rats of control group. The heart tissues were harvested from 8 rats in each group at 1, 4, 7, and 14 days after burn to observe the changes of myocardium ultrastructure with transmission electron microscope (TEM). Myocardium apoptosis was detected with TUNEL assay. The expressions of glucose regulated protein 78 (GRP 78), C/EBP-homologous protein (CHOP), and cleaved Caspase 12 in different pathways of ERS were analysed with Western blot., Results: All rats survived during the experiment. Apoptotic changes of cardiomyocytes were observed in burn group, and the apoptosis index in burn group was significantly higher than that in control group at each time point (P < 0.05), and it reached peak at 7 days after burn injury (P < 0.05). The expressions of myocardial GRP 78, CHOP, and cleaved Caspase 12 showed persistent elevation in burn group. The expressions of GRP 78 and cleaved Caspase 12 in burn group were significantly higher than those in control group at each time point (P < 0.05), while the expression of CHOP was higher than that in control group at the other time points (P < 0.05) except 1st day after burn injury., Conclusion: ERS and CHOP, Caspase 12 mediated apoptotic pathway are activated in myocardium after severe burn injury, and this may be one pathway of myocardium apoptosis.

Objective: To summarize the research progress of biological characteristics and advantages of Wharton's jelly-mesenchymal stem cells (WJ-MSCs)., Methods: The related literature on the biological characteristics of WJ-MSCs, umbilical cord blood MSCs (UBMSCs) and bone marrow MSCs (BMSCs) was extensively reviewed and analyzed., Results: A large number of MSCs which are able to self-replicate, self-renew and have high proliferation and multipotent differentiation can be isolated from the Wharton's jelly of umbilical cord. WJ-MSCs have many advantages in isolation time, isolation efficiency, expansion time, passage capacity, expansion capacity when compared with UBMSCs and BMSCs., Conclusion: WJ-MSCs have numerous advantages of convenient and abundant sources, relatively pure, non-ethical issues, and so on, which can be used for cell transplant therapy, gene therapy, and the ideal seed cells of building tissue engineered organ, so they provide new ideas for tissue regeneration repair and reconstruction.

Objective: To review the latest research progress of full-thickness tissue engineered skin (FTTES), to thoroughly understand its current state of research and application so as to lay a solid foundation for developing new type FTTES and improving the quality of skin substitutes., Methods: Domestica and international literature concerning FTTES in recent years was extensively reviewed and comprehensively analyzed., Results: Some progress of FTTES had made in seed cells, scaffold materials and construction, and some therapeutic efficacy had also been achieved in clinical application. But FTTES grafting successful rate was lower, and it had no complete skin structure and had not reached the requirements of clinical application., Conclusion: FTTES is an ideal skin substitute and has great development prospects. However, in seed cells, scaffold materials, construction and applications of FTTES, further studied is still needed.

Objective: To prepare and study the biocompatibility of selectively decellular xenoskin which has the character of the lower antigen, continuous epidermis, and the dermal matrix without any cellular components., Methods: The porcine skin was treated with glutaraldehyde solution, trypsin, and detergent solution TritonX-100 to prepare the selectively decellular xenoskin. The cytotoxicity was tested according to GB/T16886.5-2003 biological evaluation of medical devices for in vitro cytotoxicity, and the levels of cytotoxicity were evaluated with the United States Pharmacopeia. Subdermal implantation was tested according to GB/T16886.6-1997 biological evaluation of medical devices for local effects after implantation. Seventy-two mature Wistar rats were randomly assigned to groups A, B, and C (n = 24). Three kinds of materials were implanted into subcutaneous of rats back. Selectively decellular xenoskin was transplanted into group A, fresh porcine skin was transplanted into group B, and allogeneic skin was transplanted into group C. The samples were collected to make the observation of gross and histology after 1, 2, 4, 8, 12, and 16 weeks., Results: The cytotoxicity was proved to be first grade by biocompatibility test. The gross and histological observation of subdermal implantation: after implantation, the most severe inflammatory reactions were seen in group B which dispersion was very slow. Inflammatory reactions in groups A and C alleviated gradually. In groups A and C, there was an increased collagen fiber density and angiogenesis at late stage; the transplanted skin was gradually degraded and absorbed. In group B, no obvious degradation and absorption were observed., Conclusion: Selectively decellular xenoskin, prepared with glutaraldehyde solution, trypsin, and detergent solution, possesses characteristics of integral skin structure and excellent biocompatibility, so it can be used as a new type substitute to repair the burn wound.

Objective: To investigate the method to repair immedicable ulcer in skull cap in senile patient and the clinical effect of expanded bipedical axial flap in skull cap., Methods: From September 2002 to June 2006, 5 patients with immedicable and chronic ulcer in skull cap were treated. All patients were males, aging 55-76 years. Among them, the causes of disease were trauma in 1 case, infection in 1 case, squamous cell carcinoma in 2 cases, and basal cell carcinoma in 1 case. The disease course was 6-25 months. All patients had been treated by 1-4 operations. The area of ulcer ranged from 5 cm x 3 cm to 10 cm x 9 cm. At first stage, soft tissue expander was implanted under the frontal branch of superficial temporal artery and the musculus frontalis according to preoperative design. Then periodic saline injection was carried out after operation. At second stage, the soft tissue expander was taken out. The immedicable ulcer in skull cap was removed, then expanded bipedical axial flap in forehead was designed and transferred to the wound according to the size of the wound. And the donor site was covered with odd expanded flap or split-thickness skin graft. The defect size was 6.0 cm x 3.5 cm to 12.0 cm x 10.5 cm. The size of the flap was from 26 cm x 10 cm to 34 cm x 17 cm., Results: All the expanded bipedical axial flap survived after operation. The wound had a primary healing. The donor sites healed well. No complications occurred at donor site. All patients were followed up from 3 to 24 months (mean 10 months). No ulcer recurrence and no incompetence in papebral fissure was found. The patients were satisfied with the operation results., Conclusion: The satisfactory clinical results are obtained in repairing immedical ulcer in skull cap in old patients by using expanded bipedical axial flap in skull cap. This operation design can be used as a new method to repair immedical ulcer in skull cap in senile patients.

Objective: To investigate the influence of lipopolysaccharide (LPS) on the proliferation and collagen synthesis of normal human skin fibroblasts so as to elucidate its relation with skin wound healing., Methods: Fibroblasts were isolated and cultured in vitro, and then exposed to different doses of LPS(0.005, 0.010, 0.050, 0.100, 0.500, and 1.000 microg/ml) from E. coli055:B5 respectively. Then the absorbance (A) value of fibroblasts was determined with the colorirneteric thiazolyl blue (MTT) assay, and the cell number was counted under inverted phase contrast microscope from the 1st day to the 9th day after LPS administration, and collagen synthesis of fibroblasts in culture medium was measured with the method of pepsin digestion after incorporation of 3H-proline into stable, single-layered, confluent fibroblasts at 7 days after LPS administration., Results: Compared with control group, A value increased with the increasing concentration of LPS (0.005 microg/ml-0.500 microg/ml) and LPS of 0.100 microg/ml group had the strongest effect. The difference was remarkable from the 5th day to the 9th day(P<0.05). A value decreased when challenged with the LPS of 1.000 microg/ml and the difference was remarkable from the 3rd day to the 9th day(P<0.05). Cell number increased with the administration of LPS of different concentrations (0.005 microg/ml-0.500 microg/ml) and LPS of 0.100 microg/ml group had the strongest effect. The difference was remarkable from the 1st day to the 6th day(P<0.05). Cell number decreased remarkably when challenged with LPS of 1.000 microg/ml and the difference was remarkable from the 2nd day to the 9th day (P < 0.05). Collagen synthesis increased when challenged with LPS of different concentrations (0.005 microg/ml-0.500 microg/ml) and the 0.100 microg/ml group had the strongest effect. However, when the dose of LPS reached 1.000 microg/ml, it inhibited collagen synthesis., Conclusion: LPS could promote the proliferation and collagen synthesis of fibroblasts within a certain range of low doses, but over-high dose of LPS might inhibit the proliferation and collagen synthesis of fibroblasts, suggesting that LPS of certain concentrations might contribute to wound healing, while excessive LPS has negative effect on wound healing.

Objective: To evaluate the effect of a combined cervical expanded skin flap in repairing cervical scar contracture deformity after burn injury., Methods: From April 2001 to May 2003, 16 cases (10 males and 6 females) of scar contracture deformity in the cervix were treated with expanded clavipectoral axis skin flap combined with reverse axis skin flap. The tissue expanders were embedded under the part containing cutaneous branches of transverse cervical artery in cervical segments and the second and/or the third perforating branch of internal thoracic artery for the first operation. Normal saline was injected regularly. The expanded clavipectoral skin flap and reverse axis skin flap with perforating branch of internal thoracic artery were designed, the scar in the cervix was loosed or dissected according to the size of the skin flaps, the skin flaps were transferred to cover the wound, and the contracture deformity in the cervix was corrected. The size of the flaps were 9 cm x 5 cm-15 cm x 7 cm., Results: All skin flap survived. The function and appearance of the cervix was improved significantly after 6-30 months follow-up. However, venous return dysfunction in reverse perforating branch of internal thoracic artery occurred in 1 case, and blood circulation was improved after treatment., Conclusion: Expanded clavipectoral axis skin flap combined with reverse axis skin flap can be used to repair scar contracture deformity in cervix, which lessen scar and abate the chance to contract again.

Objective: To develop a new kind of skin substitute, selective acellular porcine skin, to cover excised wounds in treatment of extensive deep burns on the basis of controlled de-cell technique., Methods: Partial thickness porcine skin was treated with 0.25% trypsin for 2 hours at 37 degrees C after crosslinked with glutaraldehyde, and then it was glued to a container with the edge embedded with glue. The skin was shaken in 0.5% SDS for 24 hours, and then washed before use. The selective acellular skin was used with micro-autografts on the dermal side to cover 2 surgically excised burn wounds in a patient. The recoveries of function and appearance were observed., Results: Morphological observation showed that the treated porcine skin had an intact epithelial layer and an acellular dermis. After being used to cover burn wounds, its acellular dermis could serve as host dermal matrix, and its devitalized epithelial layer could prevent the dermis from drying. The devitalized epithelium was finally replaced by host epithelial cells, and the healed wounds could achieve good cosmetic and functional results., Conclusion: Selective acellular porcine skin can be used as promising skin substitute to cover excised wounds.

Objective: To investigate the influence of escharectomy and skin-grafting during early burn stage on the production of acute-phase reactants by the liver in severely burned rats., Methods: Ninety-six Wistar rats were randomly divided into three groups: normal control group (C), escharectomy on postburn day (PBD) 1 group (0) and escharectomy on PBD4 group (F). 30% III degrees (total body surface area full-thickness) burn injury was caused by immersing the back in boiling water for 10 seconds. Escharectomy and skin grafting with cryopreserved allogeneic skin were performed one day or 4 days after the burn injury. ON days 1, 2, 4, 5 and 7 after burn injury blood was withdrawn from the abdominal aorta of 8 rats for each experimental group. The serum contents al-antitrypsin (AT), al-acid glycoprotein (AGP), C-reactive protein (CRP), albumin (Alb), and transferrin (Trf) were measured by turbidimetry., Results: Significant increase in concentrations of positive acute-phase reactant, CRP, AGP, and AT, was observed in group O and group F as compared with normal control, (P < 0.05), while the concentrations of negative acute-phase reactants, Alb and Trf, decreased markedly (P < 0.05). The serum concentrations of AT and AGP in group O began to decrease significantly on PBD 5 and PBD7 respectively in comparison with that of the group F (P < 0.05), however, they still maintained a rather higher levels on PBD7. The concentration of CRP in group O began to decrease on PBD4, and the values on PBD4, 5, and 7 were significantly lower than those of the group F (P < 0.05). The concentration of CRP in PBD1 group reached the normal level on PBD7, however, the concentration of CRP in group F kept increasing till PBD5, and remained significantly higher than that in group C (P < 0.05). The concentration of Alb in group O was significantly higher on PBD7 than that in group F (P < 0.05). The concentration of Trf in group O on PBD5 and PBD7 was significantly higher than those in group F (P < 0.05)., Conclusion: Escharectomy and skin grafting during early burn stage attenuates acute-phase response after burn injury and are beneficial to the organism.

Objective: To study the effects of glucocorticoid on skeletal muscle protein metabolism in burn sepsis and its possible mechanism., Methods: The rats were randomly divided into four groups with 15 rats in each group. Group B, 30% TBSA full-thickness burn was produced on the back and endotoxin (6 mg/kg bw) was given intraperitoneally after the injury to simulate burn sepsis. Groups C and D, glucocorticoid receptor antagonist RU38486 (10 mg/kg bw) was given by gavage 2 hours before or 2 hours after burn with endotoxin, respectively. Group A, the rats received only normal saline in same volume as endotoxin. Plasma levels of cortisol were determined with standard procedure. Extensor digitorium longus muscles (EDL) were procured from both legs 12 hours after the injury. After weighing, the proteolytic rate was determined in vitro in an incubation system with oxygen rich environment by high performance liquid chromatography. The gene expressions of ubiquitin, E(2)-14kDa and C2 in the muscles were determined by Northern blot analysis., Results: The weight of EDL was significantly lower in group B than in group A (t = 9.03, P < 0.01). Although the weight of EDL muscles was also lower in groups C and D than in group A, it was significantly higher than in group B (t = 2.26, 6.42, P < 0.05 or P < 0.01). The concentrations of plasma cortisol were markedly higher in groups B, C and D than in group A (t = 9.03 - 22.94, P < 0.01). A 58.8% (210/357) of the total and 335.5% (4.16/1.24) of myofibrillar proteolytic rate in group B was higher than in group A (t = 36.99 and t = 46.19, P < 0.01), respectively. The total and myofibrillar proteolytic rate in group D was 28.3% (161/567) and 49.6% (2.68/5.40) and in group C 18.9% (108/567) and 23.2% (1.25/5.40), which were lower than those in group B (t = 5.34 approximately 34.68, P < 0.01), respectively. Although the expressions of ubiquitin mRNA (2.4 kb), E(2)-14 kDa mRNA (1.2 kb) and C2 mRNA in groups C and D were significantly higher than in group A, all the values were lower than those in group B (t = 3.22, 11.32, P < 0.01), especially in group C., Conclusions: The proteolytic rate of skeletal muscle, especially the myofibrillar proteolytic rate, was enhanced during burn with sepsis. Hypersecretion of glucocorticoid could upgrade the gene expression of ubiquitin system, resulting in hyperdegradation of skeletal muscle protein during burn with sepsis. Glucocorticoid receptor antagonist RU38486 could decrease the hyperdegradation of skeletal muscle during burn with sepsis.

Objective: To explore the effects of recombinant human growth hormone (rhGH) when applied postoperatively on the metabolism of branch chain amino acid in severely burned patients., Methods: Fifty burn patients, aged 12 - 50 years and inflicted by more than 30% TBSA with 10% or more of III degree burn and admitted from the January of 1999 to the January of 2001 were enrolled in the study. The patients were randomly divided into rhGH treating (rhGH group) and control groups. Escharectomy was performed within 3 postburn day (PBDs). rhGH (0.3 IU/kg) was injected percutaneously every evening for ten days since the 1st postoperative day (POD). The changes of the plasma levels of GH and branch chain amino acid and the urine level of 3-methyl histidine (3-MH) were observed in the morning in the patients from the two groups., Results: The plasma GH level before operation decreased obviously in two groups of patients when comparing with normal value (P < 0.05). The plasma GH level in rhGH group was evidently higher than that in control group since the 3rd POD (P < 0.05). There was significant increase of the output amount of urine 3-MH in all patients, but which was obviously higher in control group than that in rhGH group (P < 0.05). The plasma levels of branch chain amino acid in burn patients before and one day after operation were lower than normal levels. The plasma levels of valine, isoleucine and leucine increased to peak values at POD 3 in rhGH group and at POD 7 in control group and decreased thereafter. The plasma branch chain amino acid level in rhGH group was evidently lower than that in control group since POD 7 (P < 0.05). The plasma GH level in rhGH group was negatively and significantly correlated with the urine output amount of 3-MH (P < 0.01)., Conclusion: Postoperative application of rhGH in major burn patients might be beneficial to the protein synthesis from amino acids by skeletal muscles and to the decrease of muscle protein degrading rate.

Objectives: To observe the changes in proteolytic rate and the influence of escharectomy and skin-grafting during shock stage on the proteolytic rate of skeletal muscle in severely scalded rats, and to investigate necessity of escharectomy during shock stage., Methods: Wistar rats afflicted with 30%TBSA (total body surface area) full-thickness burn on the back were randomly divided into 3 groups: burn injury group (group B), escharectomy during shock stage group (group S), and escharectomy after shock stage group (group N). Escharectomy and skin-grafting was performed on the postburn day 1 (PBD1) and PBD4 in group S and N. The extensor digitorium longus (EDL) muscle was collected using a technique without injury to the muscle, and the proteolytic rate of the EDL was determined by the in-vitro muscle incubation system with sufficient oxygen supply and amino acid automatic analyzer., Results: The total proteolytic rate (TPR) in rat EDL muscles increased significantly (t > 2.988, P < 0.01) on PBD1, but no prominent changes were observed at other time points. There were no statistically significant changes in TPR between group S and group N, but the myofibrillar proteolytic rate (MPR) in rat EDL muscles increased markedly at each time point after scald (t > 2.988, P < 0.01). The MPR in group S decreased significantly as compared with that in group N on PBD2, 4, 5 (t = 2.311, P < 0.05; t = 3.054, 3.319, P < 0.01), and the mean values were 3.17, 2.33, 1.75 nmol/wet weight in g/3 h, respectively. No significant changes were observed between group N and S., Conclusion: The high protein catabolism of skeletal muscle can be alleviated by escharectomy and skin-grafting during shock stage, and it is beneficial to organics.

Objective: To investigate the relationship between the use of antibiotics in a burn unit and the change in the drug - resistance of Staphylococcus aureus (S. aureus)., Methods: By calculating the defined daily doses (DDD) of accumulated consumption of antibiotics per unit time and expense consumption, the use of different kinds of antibiotics in a burn unit in recent five years was analyzed, and correlation analysis between the change of antibiotics consumption amount and the change in drug - resistance level of S. aureus were carried out., Results: Amikacin, gentamycin and cephazolin were the commonest antibiotics used in our burn unit. They were relatively cheaper than some other antibiotics. The consumption amount of compound antibiotics application was negatively correlated with the penicillin resistance level of S. aureus. Seven correlation coefficients between the consumption of first generation cephalosporins and seven coefficiences of resistance rate of S. aureus were negative. The consumption amount of the 3rd generation of cephalosporin application was positively related to the resistance of S. aureus to erythromycin and oxacillin., Conclusion: Accumulated DDD might be one of the ideal indices of reflecting antibiotic use. The changes in the consumption amount of the 1st and 3rd generation of cephalosporins containing beta-lactamase-inhibitor might affect the drug-resistance levels of S. aureus to some degree.

Objectives: To observe the effect of recombinant human growth hormone on metabolism in severely burned patients., Methods: From January 1999 to January 2001, 50 patients, aged 12 to 50 years, with over 30% total body surface area (TBSA) and 10% full-thickness burns, were randomized in a double-blind study. In the control group normal saline was used as a placebo (control group), while 0.3 IU/kg(-1) /d(-1) recombinant human growth hormone was given from postoperative day 1 to day 10 in the rhGH group. The excised burn wounds were closed with microautograft and allograft skin. Blood samples were collected at 6:00 am for assaying of growth hormone, blood glucose, blood insulin, anti-insulin antibody, glucagon, cortisol, serum amino acid profile, transferring, proalbumin, total protein, dielectric, and resting energy expenditure (REE) was also measured., Results: The concentration of blood GH in both groups was lower (t = 2.806, P < 0.05) than that of physiological values before surgery. However, the concentration of GH on POD 3 in the rhGH group was significantly higher than that of normal values, but a higher level was observed on POD 7 in the rhGH group than that of the control group (t = 3.142, P < 0.05). Although the concentration of anti-insulin antibody was slightly increased, there was no significant difference between the two groups. The concentration of glucagons tended to decrease with an increase in the concentration of blood glucose, and it was marked in the rhGH group. There was no significant difference between the two groups. The concentration of cortisol was higher than normal values, but no significant difference was observed between the two groups. With the administration of rhGH, the plasma concentration of amino acids was lower than that of the control group (t = 2.714, P < 0.05), and the urinary output of 3-MH in the rhGH group was lower than that of the control group (t = 2.207, P < 0.05)., Conclusions: Administration of rhGH in patients with major burn after surgery could improve their metabolic status, namely, increased lipolysis energy, accelerated protein synthesis, accelerated gluconeogenesis, reduced muscle proteolytic rate, and reduced REE expenditure. There is no effect on stress hormone. rhGH exerts a beneficial effect on metabolism in severely burned patients, but hyperglycemia is apt to occur, and water, Na(+), Cl(-) retention are suggested.