Multicenter effect analysis of one-step acellular dermis combined with autologous ultra-thin split thickness skin composite transplantation in treating burn and traumatic wounds.

To evaluate the efficacy of one-step acellular dermis combined with autologous split thickness skin grafting in the treatment of burn or trauma wounds by a multicenter controlled study. In patients with extensive burns, it is even difficult to repair the wounds due to the shortage of autologous skin. The traditional skin grafting method has the disadvantages of large damage to the donor site, insufficient skin source and unsatisfactory appearance, wear resistance and elasticity of the wound tissue after skin grafting. One-step acellular dermis combined with autologous ultra-thin split thickness skin graft can achieve better healing effect in the treatment of burn and trauma wounds. A total of 1208 patients who underwent single-layer skin grafting and one-step composite skin grafting in the First Affiliated Hospital of Wannan Medical College, Wuhan Third People's Hospital and Lu 'an People's Hospital from 2019 to 2022 were retrospectively analysed. The total hospitalization cost, total operation cost, hospitalization days after surgery, wound healing rate after 1 week of skin grafting and scar follow-up at 6 months after discharge were compared and studied. The total cost of hospitalization and operation in the composite skin grafting group was significantly higher than those in the single-layer autologous skin grafting group. The wound healing rate after 1 week of skin grafting and the VSS score of scar in the follow-up of 6 months after discharge were better than those in the single-layer skin grafting group. One-step acellular dermis combined with autologous ultra-thin split thickness skin graft has high wound healing rate, less scar, smooth appearance and good elasticity in repairing burn and trauma wounds, which can provide an ideal repair method for wounds.

Safety and efficacy of waterjet debridement vs. conventional debridement in the treatment of extremely severe burns: A retrospective analysis.

INTRODUCTION: Patients with extremely severe burns often require rapid wound closure with a tangential excision or escharectomy combined with a skin graft to reduce life-threatening complications such as infection. Traditional tangential excision surgery using the Watson or Humby knife does not allow accurate excision of necrotic tissue and often removes too much active tissue, which is detrimental to the rapid healing of the wound. Importantly, the Versajet hydrosurgical system, with its smaller handle, allows for more precise excision of necrotic burn tissue and preserves more active dermal tissue, positively affecting wound healing and scarring. This study compared the safety and efficacy of hydrosurgical combined with autologous skin grafting to conventional excision combined with autologous skin grafting in patients with extremely severe burn. METHODS: Information of sixty burn patients with total body surface area (TBSA) > 50 % treated at the first affiliated hospital of Anhui Medical University from January 2019 to August 2022 were analyzed. The patients were divided into a conventional debridement group (n = 37) and a hydrosurgical debridement group (n = 23) according to the approach used. The hydrosurgical debridement group and the conventional debridement group were compared from the difference between the duration of the first debridement surgery, wound healing time, the changes of red blood cells and hemoglobin concentration postoperative, total blood transfusion, hospitalization cost, skin grafting frequency, procalcitonin, wound bacterial culture, albumin and prealbumin. RESULTS: Information on age, gender, weight, inhalation injury, hypovolemic shock, preoperative procalcitonin, preoperative albumin, preoperative prealbumin, the operation frequency (n ≥ 3), preoperative trauma culture and postoperative trauma culture were compared between both groups (P > 0.05). Operative time and wound healing time were significantly shorter in patients with hydrosurgical debridement combined with autologous skin grafting than those in the control group (P < 0.05), while hospitalization costs were not significantly different between the two groups (P > 0.05). The changes of red blood cells and hemoglobin concentration during the postoperative period in the hydrosurgical debridement group were less significantly than those in the conventional debridement group (P < 0.05). The total amount of red blood cells transfused during hospitalization was significantly lower in the hydrosurgical debridement group than that in the conventional debridement group (P < 0.05), but the total amount of fresh frozen plasma transfused during hospitalization was not statistically significant between the two groups (P > 0.05). Albumin on the third day after surgery and prealbumin on the first, third and fifth day after surgery improved more significantly than those in the control group(P < 0.05), however, there were no significant differences between the two groups in albumin on the first and fifth postoperative days (P > 0.05). The PCT level in the conventional debridement group was significantly higher than that in the hydrosurgical debridement group on the first, third and fifth days after surgery(P < 0.05). CONCLUSION: The hydrosurgical debridement group presented with shorter operative time, less blood loss during surgery, faster postoperative nutritional recovery, less postoperative inflammatory response and faster wounds healing, and did not increase the hospitalization cost, postoperative bacterial culture of the wounds and the number of skin grafting surgeries. In patients with extremely severe burn, hydrosurgical debridement combined with autologous skin grafting group is safer and more effective than those in the conventional debridement combined with autologous skin grafting group.

Diagnostic value of procalcitonin and red blood cell distribution width at admission on the prognosis of patients with severe burns: A retrospective analysis.

The plasma procalcitonin (PCT) concentration and red blood cell distribution (RDW) value after severe burns can be used as prognostic indicators, but at present, it is difficult to give consideration to sensitivity and specificity in diagnosing the prognosis of severe burns with a single indicator. This study analysed the diagnostic value of plasma PCT concentration and RDW value at admission on the prognosis of severe burn patients to improve its sensitivity and specificity. A total of 205 patients with severe burns who were treated in the First Affiliated Hospital of Anhui Medical University from November 2017 to November 2022 were retrospectively analysed. The optimal cut-off values of plasma PCT concentration and RDW were analysed and counted through the subject curve (ROC curve). According to the cut-off value, patients were divided into high PCT group and low PCT group, high RDW group and low RDW group. The independent risk factors of severe burns were analysed by single-factor and multiple-factor COX regression. Kaplan-Meier survival was used to analyse the mortality of high PCT group and low PCT group, high RDW group and low RDW group. The area under the curve of plasma PCT concentration and RDW value at admission was 0.761 (95% CI, 0.662-0.860, P < .001), 0.687 (95% CI, 0.554-0.820, P = .003) respectively, and the optimal cut-off values of serum PCT concentration and RDW were 2.775 ng/mL and 14.55% respectively. Cox regression analysis found that age, TBSA, and RDW were independent risk factors for mortality within 90 days after severe burns. Kaplan-Meier survival analysis showed that there was a significant difference in the 90-day mortality rate of severe burns between the PCT ≥ 2.775 ng/mL group and the PCT < 2.775 ng/mL group (log-rank: 24.162; P < .001), with the mortality rate of 36.84% versus 5.49%, respectively. The 90-day mortality rate of severe burns was significantly different between the RDW ≥ 14.55% group and the RDW < 14.55% group (log-rank: 14.404; P < .001), with the mortality rate of 44% versus 12.2% respectively. The plasma PCT concentration and RDW value at admission are both of diagnostic value for the 90-day mortality of severe burns, but the plasma PCT concentration has higher sensitivity and the RDW value has higher specificity. Age, TBSA, and RDW were independent risk factors for severe burns, and then plasma PCT concentration was not independent risk factors.

Efficacy of hydrosurgical excision combined with skin grafting in the treatment of deep partial-thickness and full-thickness burns: A two-year retrospective study.

INTRODUCTION: Deep partial-thickness and full-thickness burn wounds often undergo tangential excision or escharectomy to expose healthy tissue, combined with skin grafting to promote wound healing. However, conventional tangential excision with the humby knife leads to inevitable damage to the dermis while excising burn tissue due to the lack of precision. Indeed, the preservation of dermal tissue is a key factor in determining wound healing and scar quality. The precision and tissue selectivity of the Versajet Hydrosurgical System has been established for excising burn tissue while preserving dermal tissue. In this study, we retrospectively compared the efficacy of "Hydrosurgical excision combined with skin grafting" and "Conventional tangential excision combined with skin grafting" in treating deep partial-thickness and full-thickness burn wounds to demonstrate that hydrosurgery improved the treatment of deep partial-thickness and full-thickness burns. METHODS: A total of 86 patients with deep partial-thickness and/or full-thickness burns with a total burn surface area (TBSA) ≤ 25% from July 2018 to July 2020 were included in this study and were divided into experimental (hydrosurgical excision combined with skin grafting, n = 43) and control (conventional tangential excision combined with skin grafting, n = 43) groups. Parameters were analyzed, including the intraoperative blood loss volume per unit area of grafted skin, surgery duration, wound healing time, skin graft survival, and the treatment costs per unit of burned area. Scar assessment was performed at 1 year with the modified Vancouver Scar Scale linked with TBSA (mVSS-TBSA). RESULT: No significant difference was found in male to female ratio, age, weight, TBSA, burn depth, skin grafting area (SKA), skin grafting methods, cases treated with carbon dioxide fractional laser or incidence of inhalation injury, and the incidence of hypovolemic shock between two groups(p > 0.05). Compared with the control group, patients treated with hydrosurgical excision combined with skin grafting experienced less intraoperative blood loss volume per unit area of grafted skin (p < 0.05). The mVSS-TBSA of patients that underwent hydrosurgical excision combined with skin grafting was significantly improved in comparison to the control group (p < 0.01). No significant difference was found in surgery duration, wound healing time, skin graft survival and treatment costs per unit of burned area between the two groups (p > 0.05). CONCLUSION: Hydrosurgical excision combined with skin grafting reduced intraoperative blood loss volume per unit area of grafted skin, improved scarring 1-year after injury, and did not increase the treatment costs per unit of burned area. This technique provides a novel alternative for managing deep partial-thickness and full-thickness burn wounds.

Exosomal miR-451 from human umbilical cord mesenchymal stem cells attenuates burn-induced acute lung injury.

BACKGROUND: The aim of this study was to investigate the molecular mechanism of human umbilical cord mesenchymal stem cells (MSCs)-derived exosomes (hUCMSC-Exos) in regulating burn-induced acute lung injury (ALI). METHODS: In this study, we initially isolated exosomes from hUCMSCs and identified them by transmission electron microscopy. The expression of the protein markers CD9 and CD63 in the exosomes was determined by western blot analysis. The expression of miR-451 in the hUCMSC-Exos was determined by qRT-PCR. The levels of TNF-α, IL-1ß, and IL-6 in lung tissues and serum as well as the levels of malondialdehyde, myeloperoxidase, superoxide dismutase in lung tissues were detected by ELISA. Hematoxylin-eosin stain was used to observe the morphological changes of lung tissues after burn. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assays were performed to detect apoptosis in lung tissues after burn. The expression of proteins related to the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway in lung tissues after burn was analyzed by western blotting. RESULTS: Our results showed that hUCMSC-Exos successfully decreased TNF-α, IL-1ß, and IL-6 levels in rats after burn, and this reduction was reversed when the miR-451 expression in the hUCMSC-Exo group was inhibited. HUCMSC-Exo-derived miR-451 improves ALI via the TLR4/NF-κB pathway. CONCLUSION: We demonstrated that exosomes derived from hUCMSCs mediate miR-451 to attenuate burn-induced ALI.

The Modulation of Regulatory T Cells via HMGB1/PTEN/ß-Catenin Axis in LPS Induced Acute Lung Injury.

Sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) remains the leading complication for mortality caused by bacterial infection. The regulatory T (Treg) cells appear to be an important modulator in resolving lung injury. Despite the extensive studies, little is known about the role of macrophage HMGB1/PTEN/ß-catenin signaling in Treg development during ALI. Objectives: This study was designed to determine the roles and molecular mechanisms of HMGB1/PTEN/ß-catenin signaling in mediating CD4+CD25+Foxp3+ Treg development in sepsis-induced lung injury in mice. Setting: University laboratory research of First Affiliated Hospital of Anhui Medical University. Subjects: PTEN/ß-catenin Loxp and myeloid-specific knockout mice. Interventions: Groups of PTENloxp/ß-cateninloxp and myeloid-specific PTEN/ß-catenin knockout (PTENM-KO/ß-cateninM-KO) mice were treated with LPS or recombinant HMGB1 (rHMGB1) to induce ALI. The effects of HMGB1-PTEN axis were further analyzed by in vitro co-cultures. Measures and Main Results: In a mouse model of ALI, blocking HMGB1 or myeloid-specific PTEN knockout (PTENM-KO) increased animal survival/body weight, reduced lung damage, increased TGF-ß production, inhibited the expression of RORγt and IL-17, while promoting ß-catenin signaling and increasing CD4+CD25+Foxp3+ Tregs in LPS- or rHMGB-induced lung injury. Notably, myeloid-specific ß-catenin ablation (ß-cateninM-KO) resulted in reduced animal survival and increased lung injury, accompanied by reduced CD4+CD25+Foxp3+ Tregs in rHMGB-induced ALI. Furthermore, disruption of macrophage HMGB1/PTEN or activation of ß-catenin significantly increased CD4+CD25+Foxp3+ Tregs in vitro. Conclusions: HMGB1/PTEN/ß-catenin signaling is a novel pathway that regulates Treg development and provides a potential therapeutic target in sepsis-induced lung injury.

Hypertonic saline resuscitation protects against kidney injury induced by severe burns in rats.

BACKGROUND: Proper fluid resuscitation can relieve visceral damage and improve survival in severely burned patients. This study compared the effectiveness of resuscitation with 400mEq/L hypertonic saline (HS) and sodium lactate Ringer's solution (LR) in rats with kidney injury caused by burn trauma. METHODS: Rats (Sprague-Dawley) underwent burn injury and were randomized into sham, LR, and HS groups. Samples from the kidney were assayed for water content ratio, histopathology, and oxidative stress (superoxide dismutase (SOD) and malondialdehyde (MDA)). Serum sodium, renal function (creatinine and cystatin (Cys)-C), and inflammatory response (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and high mobility group protein box (HMGB)-1) were also examined as serum markers. RESULTS: Hypertonic saline resuscitation reduced the renal water content ratio and improved renal histopathology caused by severe burns. This effect was accompanied by reductions in serum creatinine and Cys-C as well as TNF-α, IL-1ß, and HMGB1. Serum sodium concentration and SOD activity were increased, whereas MDA content was decreased in the kidney tissue of the HS group. CONCLUSIONS: The data indicate that 400mEq/L HS solution reduces hyponatremia and renal edema, inhibits the release of inflammatory mediators, and alleviates oxidative stress injury, thus protecting against kidney injury induced by severe burns.

Nocardia rubra cell wall skeleton accelerates cutaneous wound healing by enhancing macrophage activation and angiogenesis.

Objective This study was performed to investigate the effect of Nocardia rubra cell wall skeleton (N-CWS) on wound healing of full-thickness skin defects. Methods Two 2- × 2-cm full-thickness wounds, one on each side of the midline, were made on the back of 12 rats. One wound was covered with Vaseline gauze soaked in normal saline, whereas the other was covered with Vaseline gauze and N-CWS. Wound dressings were changed every other day from day 0 (wound creation) to day 11. Four of the 12 rats were killed on day 7, and biopsy samples were obtained for biochemical and histopathological analyses. The expression levels of CD31, CD68, and F4/80 in the tissues were examined immunohistologically. The expression of transforming growth factor (TGF)-ß1 in the wound was determined by western blot. Results N-CWS increased the wound healing rate, reduced the complete wound healing time, and increased the expression levels of CD31, CD68, and F4/80 on day 7. The TGF-ß1 expression level in the wound was significantly higher in the N-CWS group than in the control group on day 7. Conclusions N-CWS can activate macrophages, increase TGF-ß1 expression, and enhance angiogenesis and thus accelerate cutaneous wound healing.

200mM hypertonic saline resuscitation attenuates intestinal injury and inhibits p38 signaling in rats after severe burn trauma.

BACKGROUND: An overabundant discharge of inflammatory mediators plays a significant role in intestinal injury throughout the early stages of critical burns. The present study aims to explore the outcome of 200mM hypertonic saline (HS) resuscitation on the intestinal injury of critically burned rats. MATERIALS AND METHODS: Fifty-six Sprague-Dawley rats were randomized into three groups: sham group (group A), burn plus lactated Ringer's group (group B), and burn plus 200mM HS group (group C). Samples from the intestine were isolated and assayed for wet-weight-to-dry-weight (W/D) ratio, histopathology analyses, and p38 mitogen-activated protein kinase (MAPK) activity. Serum interleukin 1ß (IL-1ß) and high mobility group protein box 1 (HMGB1) concentrations were also examined. RESULTS: Initial resuscitation with 200mM Na+ HS significantly decreased the intestinal W/D ratio and improved intestinal histopathology caused by severe burn. HS resuscitation also inhibited the increase of serum IL-1ß and HMGB1 concentrations, and p38 MAPK activity in the intestine of critically burned rats. CONCLUSIONS: The overall findings of this study suggest that preliminary resuscitation with 200mM HS after severe thermal injury reduces intestinal edema, inhibits systemic inflammatory response, and attenuates intestinal p38 MAPK activation, thus reduces burns-induced intestinal injury.

[Effects of adipose-derived stem cells and non-methylated CpG-oligodeoxynucleotides on peripheral blood CD4+CD25+ regulatory T cells in young mice with food allergy].

OBJECTIVE: To investigate the effects of adipose-derived stem cells (ADSC) and non-methylated CpG-oligodeoxynucleotides (CpG-ODN) on the expression of peripheral blood CD4+CD25+ regulatory T (Treg) cells in young mice with food allergy, as well as their immune intervention effects. METHODS: A total of 40 female BALB/c mice were randomly divided into control group, allergic group, ADSC treatment group, and CpG-ODN treatment group, with 10 mice in each group. A mouse model of food allergy was established by intraperitoneal injection and intragastric administration of ovalbumin (OVA) for sensitization and challenge. The mice in the control group were treated with normal saline at the same dose; the mice in the ADSC treatment group were given intraperitoneal injection of ADSC (1×106 cells for each mouse) before and after OVA challenge, and those in the CpG-ODN treatment group were given intraperitoneal injection of non-methylated CpG-ODN solution (40 µg for each mouse) at 1 hour before challenge by gavage. The allergic symptom scores were determined for each group after model establishment. ELISA was used to measure the serum level of OVA-IgE. Flow cytometry was used to measure the percentage of peripheral blood CD4+CD25+ Treg cells. Hematoxylin and eosin staining was used for the pathological analysis of the jejunum. RESULTS: The allergic group had significantly higher allergic symptom scores and serum level of OVA-IgE than the control group (P<0.05). There were no significant differences in the allergic symptom score and the serum level of OVA-IgE between the ADSC treatment group and the CpG-ODN treatment group (P>0.05), but these two groups had significantly lower allergic symptom scores and serum level of OVA-IgE than the allergic group and significantly higher allergic symptom scores and serum level of OVA-IgE than the control group (P<0.01). The allergic group had a significantly lower percentage of peripheral blood CD4+CD25+ Treg cells than the control group (P<0.05). The ADSC treatment group and the CpG-ODN treatment group had a significantly higher percentage of peripheral blood CD4+CD25+ Treg cells than the allergic group (P<0.05); there were no significant differences between these two groups or between them and the control group (P>0.05). Pathological results showed structural damage and edema in the jejunal villi, a large number of eosinophils, and lymphocyte infiltration in the allergic group, while the ADSC treatment group and the CpG-ODN treatment group had less structural damage and edema in the jejunal villi, a lower number of eosinophils, and less lymphocyte infiltration. CONCLUSIONS: ADSC and non-methylated CpG-ODN have a certain effect in the treatment of food allergy and can increase the percentage of peripheral blood CD4+CD25+ Treg cells and reduce the level of OVA-IgE. They may be associated with the induction of immune tolerance and these two treatment have comparable effects. Detailed mechanisms of action still need further investigation.

Inhibitor of Tec kinase, LFM-A13, decreases pro-inflammatory mediators production in LPS-stimulated RAW264.7 macrophages via NF-κB pathway.

Tec kinase, a prototypical member of the Tec tyrosine kinases family, was shown to mainly govern lymphocyte proliferation. In the present study, we investigated the role of Tec kinase in acute inflammatory response in lipopolysaccharide (LPS) challenge. First, we demonstrate that Tec kinase activity was observed in RAW264.7 macrophages exposed to LPS. Tec and phosphorylated Tec expression were upregulated in a dose- and time-dependent manner after LPS stimulation. LPS increased monocyte chemotactic protein (MCP)-1 secretion and intercellular adhesion molecule (ICAM)-1 expression, and increasing mRNA expression was consistently observed. LPS also induced IκBα phoshporylaytion and its degradation, increased NF-κB p65 phoshporylaytion and translocation to nuclei in RAW264.7 cells. Pretreatment with LFM-A13 decreased LPS-induced cytokines and chemokines production and mRNA levels, blocked NF-κB transactivation. These effects of LPS were also prevented by Tec-siRNA. Additionally, LFM-A13 or Tec-siRNA obviously inhibited LPS-induced TGFß-activated kinase 1(TAK1) phosphorylation. Taken together, our results suggest that Tec kinase involves in acute inflammation process in LPS-stimulated RAW264.7 cells, at least mediated by activating TAK1/ NF-κB signal pathway.

Modified reversed superficial peroneal artery flap in the reconstruction of ankle and foot defects following severe burns or trauma.

OBJECTIVE: Challenges persist in the reconstruction of the ankle and the foot with exposed tendons, joints, and bones as a result of severe burns and trauma. In flap elevation involving the sensitive superficial nerve, the local nerve was always sacrificed to obtain an anesthetic donor site; however, such a procedure introduced the possibility of painful neuromas. In this study, we present a desired clinical application of a modified reversed superficial peroneal artery flap, in which the superficial peroneal nerve is preserved. METHODS: From 2008 to 2015, 12 patients with ankle or foot defects were treated with the modified reversed superficial peroneal artery flap. The defects of the patients were caused by hot liquid scald (one patient), electrical injury (five patients), and trauma (six patients). The flap was utilized for covering defects on the ankle (seven patients) and the foot (five patients). The size of the flaps ranged from 4.0cm×6.0cm to 18.0cm×10.0cm. The superficial peroneal artery was involved in the flap, whereas the superficial peroneal nerve was spared by dedicate dissection. The reverse-flow flap was nourished by the superficial peroneal artery through the terminal peroneal artery perforator. RESULTS: The obtained outcomes were satisfactory functionally and aesthetically. The flaps in 11 patients survived completely without complications, whereas partial necrosis occurred in a 78-year-old patient when the flap survived a week later during follow up. CT angiography revealed the stenosis of the popliteal artery. The wound healed after interventional treatment involving placing a stent and changing the dressings. Basic functions and configurations were salvaged in all cases. All patients were completely satisfied with the proposed flap and suffered no paresthesia in their lower leg. CONCLUSION: Exhibiting beneficial characteristics such as reliable blood supply, favorable thickness, wide rotating arc, and retention of major vessels and the superficial peroneal nerve, the modified reversed superficial peroneal artery flap is useful in the reconstruction of ankle and foot defects that would not cause any hypoesthesia of the foot.

Pediatric deep burns caused by hot incense ashes during 2014 Spring Festival in Fuyang city, China.

BACKGROUND: The Chinese people in Fuyang city, a northwest city of Anhui Province, are accustomed to burning incense at home for blessing during the Spring Festival. Their children, especially toddlers, like playing around the burning incense and are at risk of burning by hot incense ashes. The purpose of this study was to describe the unique cause and clinical characteristics of pediatric deep burns caused by hot incense ashes during 2014 Spring Festival. METHODS: Twelve consecutive children admitted to our Burn Center and Fuyang People's Hospital during 2014 Spring Festival, with burn injuries caused by hot incense ashes which were epidemiologically studied retrospectively. Data on age, gender, size, depth and site of burn, incidence by day, number of operation, hospital stay, and causes of burns were collected. RESULTS: All patients came from Fuyang city. Of the 12 patients, the average age was 2.17 years, with a range of 1-6. The boy-to-girl ratio was 2: 1. The mean total burn surface area (TBSA) was 5.83%, and 91.67% of the children sustained full-thickness burn. Hands were the most common parts of the body to be injured. Dry necrosis developed in 14 fingers of 3 patients. January 31, 2014, the first day of the Chinese New Year, was the time of highest incidence. Six patients (50%) required surgical intervention while the number of operations including escharectomy, excision, skin grafting, or amputation of necrotic fingers, per patient was 2. A total of 14 fingers were amputated of the necrotic parts. All children survived and mean length of hospital stay of the patients was 20 days. CONCLUSION: Hot incense ashes cause serious injuries to children in Fuyang city during the Spring Festival. Preventive programs should be directed towards high risk groups to reduce the incidence of this burn.

Bioactive glycosides from the roots of Ilex asprella.

Context The roots of Ilex asprella (Hook. et Arn.) Champ. ex Benth. (Aquifoliaceae) are widely used in Chinese medicine to treat influenza, amygdalitis, pertussis, etc. Their mechanism of action is still unknown, which raises the need to identify new bioactive compounds in this plant. Objective In this study, we isolated a novel saponin containing sulphonic groups, namely, asprellcoside A (1) and a known phenolic glycoside compound (2) from the roots of Ilex asprella and evaluated their bioactivities. Materials and methods Molecular structures were elucidated by analysing their spectral and chemical properties. The viability of A549 cells was tested using a MTT assay. Ability of the compounds to inhibit viruses was determined using the neuraminidase activity assay. Their anti-inflammatory effects were tested using the IP-10 activity assay using various concentrations (compound 1: 0.6, 0.2, 0.6, 1.70, 5.00 and 15.00 µM; compound 2: 0.4, 1.2, 3.6, 11.0, 33.0 and 100 µM). Their inhibitory effect on platelet aggregation induced by adenosine diphosphate (ADP) in rabbit plasma was determined at 60 and 80 µM. Results Both compounds inhibit influenza virus strain A/PuertoRico/8/1934 (H1N1) strongly with EC50 values of 4.1 and 1.7 µM, respectively. Both compounds inhibit the secretion of IP-10 with EC50 values of 6.6 and 2.5 µM, respectively. Compound 1 alone inhibited platelet aggregation significantly, with the rate of suppression being 47 ± 8 and 38 ± 3%, at 60 and 80 µM, respectively. Conclusions The results suggest that both compounds may be valid therapeutics against influenza virus infection and that compound 1 may be a novel agent for treating thrombosis.

Puerarin attenuates severe burn-induced acute myocardial injury in rats.

BACKGROUND: Puerarin, the main isoflavone glycoside extracted from the root of Pueraria lobata, is widely prescribed for patients with cardiovascular disorders in China. This study investigates the effect of puerarin on severe burn-induced acute myocardial injury in rats and its underlying mechanisms. MATERIALS AND METHODS: Healthy adult Wistar rats were divided into three groups: (1) sham group, sham burn treatment; (2) burn group, third-degree burns over 30% of the total body surface area (TBSA) with lactated Ringer's solution for resuscitation; and (3) burn plus puerarin group, third-degree burns over 30% of TBSA with lactated Ringer's solution containing puerarin for resuscitation. The burned animals were sacrificed at 1, 3, 6, 12, and 24 h after burn injury. Myocardial injury was evaluated by analyzing serum creatine kinase MB fraction (CK-MB) activity and cardiac troponin T (cTNT) level. Changes in cardiomyocyte ultrastructure were also determined using a transmission electron microscope. Tumor necrosis factor (TNF)-α concentration in serum was measured by radioimmunoassay. Cardiac myeloperoxidase (MPO) activity and malondialdehyde (MDA) concentration were measured to determine neutrophil infiltration and oxidative stress in the heart, respectively. The expression of p38 mitogen-activated protein (MAP) kinase in the heart was determined by Western blot analysis. RESULTS: After the 30% TBSA full-thickness burn injury, serum CK-MB activities and cTnT levels increased markedly, both of which were significantly decreased by the puerarin treatment. The level of serum TNF-α concentration in burn group at each time-point was obviously higher than those in sham group (1.09±0.09 ng/ml), and it reached the peak value at 12 h post burn. Burn trauma also resulted in worsen ultrastructural condition, elevated MPO activity and MDA content in heart tissue, and a significant activation of cardiac p38 MAP kinase. Administration of puerarin improved the ultrastructural changes in cardiomyocytes, decreased TNF-α concentration in serum as well as suppressed cardiac MPO activity and reduced MDA content, and abolished the activation of p38 MAP kinase in heart tissue after severe burn. CONCLUSIONS: These results suggest that puerarin attenuates inflammatory responses, reduces neutrophil infiltration and oxidative stress in the heart, and protects against acute myocardial injury induced by severe burn.

Superthin Abdominal Wall Glove-Like Flap Combined With Vacuum-Assisted Closure Therapy for Soft Tissue Reconstruction in Severely Burned Hands or With Infection.

Severe burn and infection to hands always involves the deep structures, such as tendons, joints, and bones. These wounds cannot be closed immediately and therefore creates a high risk for complication. We presented 9 cases with deep dermal burns to the dorsal of the hand (6 electrical burns and 3 thermal crush injuries) with wound infections in 2 cases. The vacuum-assisted closure system was used continuously until the flap reconstruction was performed. A random pattern and superthin abdominal wall skin flap-like glove was designed. The flap was transferred to the defected portion of the dorsum of the hand and resected from the abdominal wall about 3 weeks later. The flaps in 8 of the patients treated by this technique survived completely and partial necrosis of the distal flap occurred in 1 patient. The defect resolved after operative treatment and the function of the hands and fingers were successfully salvaged. All patients resulted in having a satisfactory aesthetic outcome with no or minor discomfort at the abdominal donor area. Integration of the vacuum-assisted closure system and the superthin abdominal wall glove-like flap reconstruction appeared to be successful and should be considered in patients with severely burned hands.

Current understanding of tyrosine kinase BMX in inflammation and its inhibitors.

Tec family kinases, which include tyrosine kinase expressed in hepatocellular carcinoma (TEC), Bruton's tyrosine kinase (BTK), interleukin (IL)-2-inducible T-cell kinase (ITK), tyrosine-protein kinase (TXK), and bone marrow tyrosine kinase on chromosome X (BMX), are the second largest group of non-receptor tyrosine kinases and have a highly conserved carboxyl-terminal kinase domain. BMX was identified in human bone marrow cells, and was demonstrated to have been expressed in myeloid hematopoietic lineages cells, endothelial cells, and several types of cancers. Significant progress in this area during the last decade revealed an important role for BMX in inflammation and oncologic disorders. This review focuses on BMX biology, its role in inflammation and possible signaling pathways, and the potential of selective BMX inhibitors.

[Effect of high mobility group box protein 1 on the Kupffer cells of rats with severe burn and the role of receptor for advanced glycation end products in the process].

OBJECTIVE: To investigate the effect of high mobility group box protein 1 (HMGB1) on the production of pro-inflammatory cytokines by Kupffer cell (KC) of rats with severe burn and the role of receptor for advanced glycation end products (RAGE) in the process. METHODS: Model of 30% TBSA full-thickness burn was reproduced in 32 SD rats through immersing the back in 98°C water for 12 s. KC (32 samples) was isolated from rat liver 24 h after injury and inoculated in 24-well plate in the concentration of 1×10(6) cell per well. (1) Cells were divided into control group (cultured with 1 mL PBS) and HMGB1 group (stimulated with 100 ng/mL HMGB1 in the volume of 1 mL) according to the random number table, with 8 samples in each group. At post culture hour (PCH) 48, the expression of RAGE (denoted as grey value ratio) was detected with Western blotting. (2) Another portion of cells were divided into control group (cultured with 1 mL PBS), HMGB1 group (treated with 100 ng/mL HMGB1 in the volume of 1 mL), HMGB1 + anti-RAGE antibody group (treated with 100 ng/mL HMGB1 in the volume of 1 mL after being pre-incubated with 20 µg/mL anti-RAGE monoclonal antibody in the volume of 1 mL for 2 hours), HMGB1 + recombinant rat RAGE/Fc chimera (rrRAGE/Fc) group (treated with the mixture of 100 ng/mL HMGB1 in the volume of 0.5 mL and 5 µg/mL rrRAGE/Fc in the volume of 0.5 mL which were pre-incubated for 2 hours) according to the random number table, with 8 samples in each group. At PCH 48, the protein levels of TNF-α and IL-1ß in supernatant were determined with enzyme-linked immunosorbent assay, while the mRNA expression of TNF-α and IL-1ß (denoted as grey value ratio) were determined with Northern blotting. Data were processed with one-way analysis of variance, t test, and LSD test. RESULTS: (1) The expression of RAGE in HMGB1 group (1.036 ± 0.101) was significantly higher than that of control group at PCH 48 (0.191 ± 0.024, t = -23.158, P = 0.000). (2) In HMGB1 group, HMGB1 + anti-RAGE antibody group, and HMGB1 + rrRAGE/Fc group, the contents of TNF-α in supernatant were respectively (10.59 ± 1.39), (9.91 ± 1.68), (11.51 ± 2.27) ng/mL; the contents of IL-1ß in supernatant were respectively (2.49 ± 0.33), (2.08 ± 0.32), (2.42 ± 0.42) ng/mL; the mRNA levels of TNF-α in cells were respectively 0.311 ± 0.009, 0.301 ± 0.047, 0.326 ± 0.016; the mRNA levels of IL-1ß in cells were respectively 0.237 ± 0.021, 0.244 ± 0.041, 0.245 ± 0.013. There were no statistically significant differences in the above indexes among these three groups (with P values all above 0.05). Their levels were all significantly higher than those of control group [with contents of TNF-α and IL-1ß in supernatant respectively (2.69 ± 0.14), (0.43 ± 0.05) ng/mL, and mRNA levels of TNF-α and IL-1ß in cells respectively 0.140 ± 0.022, 0.077 ± 0.005, P values all below 0.01]. CONCLUSIONS: HMGB1 can induce the production of pro-inflammatory cytokines TNF-α and IL-1ß from the KC in rats with severe burn. However, RAGE does not play a predominant role in this process.

Effect of 200 mEq/L Na+ hypertonic saline resuscitation on systemic inflammatory response and oxidative stress in severely burned rats.

BACKGROUND: Excessive release of inflammatory mediators and oxidative stress play important roles in the increased vascular permeability and systemic edema during the early stage of severe burn. This study investigates the effect of 200 mEq/L Na(+) hypertonic saline (HS) on systemic inflammatory response and oxidative stress in severely burned rats. MATERIALS AND METHODS: Sprague-Dawley rats were divided into three groups: sham group, burn plus lactated Ringer's group, and burn plus HS group. Lung edema was assessed in terms of wet-weight-to-dry-weight ratio. Tumor necrosis factor α and interleukin 6 concentrations in serum were examined by enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells were isolated and the expression of p38 mitogen-activated protein kinase was determined by Western blot analysis. The lung and intestinal concentrations of malondialdehyde, an indicator of oxidative stress, were also measured. RESULTS: Resuscitation with 200 mEq/L Na(+) HS significantly decreased the lung wet-weight-to-dry-weight ratio and abolished hyponatremia induced by burn injury. HS treatment also prevented the increases of myeloperoxidase activity and malondialdehyde content in the lung and intestine of severely burned rats. However, there were no significant differences, either in serum tumor necrosis factor α and interleukin 6 concentrations or with respect to the p38 mitogen-activated protein kinase expression in peripheral blood mononuclear cells, between the burn plus lactated Ringer's group and burn plus HS group (P > 0.05). CONCLUSIONS: Initial resuscitation with 200 mEq/L Na(+) HS after severe burn injury decreases pulmonary edema, prevents hyponatremia, and attenuates oxidative stress, but is not capable of inhibiting the systemic inflammatory response.

Sodium butyrate protects against severe burn-induced remote acute lung injury in rats.

High-mobility group box 1 protein (HMGB1), a ubiquitous nuclear protein, drives proinflammatory responses when released extracellularly. It plays a key role as a distal mediator in the development of acute lung injury (ALI). Sodium butyrate, an inhibitor of histone deacetylase, has been demonstrated to inhibit HMGB1 expression. This study investigates the effect of sodium butyrate on burn-induced lung injury. Sprague-Dawley rats were divided into three groups: 1) sham group, sham burn treatment; 2) burn group, third-degree burns over 30% total body surface area (TBSA) with lactated Ringer's solution for resuscitation; 3) burn plus sodium butyrate group, third-degree burns over 30% TBSA with lactated Ringer's solution containing sodium butyrate for resuscitation. The burned animals were sacrificed at 12, 24, and 48 h after burn injury. Lung injury was assessed in terms of histologic changes and wet weight to dry weight (W/D) ratio. Tumor necrosis factor (TNF)-α and interleukin (IL)-8 protein concentrations in bronchoalveolar lavage fluid (BALF) and serum were measured by enzyme-linked immunosorbent assay, and HMGB1 expression in the lung was determined by Western blot analysis. Pulmonary myeloperoxidase (MPO) activity and malondialdehyde (MDA) concentration were measured to reflect neutrophil infiltration and oxidative stress in the lung, respectively. As a result, sodium butyrate significantly inhibited the HMGB1 expressions in the lungs, reduced the lung W/D ratio, and improved the pulmonary histologic changes induced by burn trauma. Furthermore, sodium butyrate administration decreased the TNF-α and IL-8 concentrations in BALF and serum, suppressed MPO activity, and reduced the MDA content in the lungs after severe burn. These results suggest that sodium butyrate attenuates inflammatory responses, neutrophil infiltration, and oxidative stress in the lungs, and protects against remote ALI induced by severe burn, which is associated with inhibiting HMGB1 expression.