Search

Recently, Far-infrared Light Emitting Diodes have attracted considerable interest in the research field worldwide. Emerging light therapy requires effective red/far-infrared light resources in clinical and plant photomorphogenesis to target or promote the interaction of light with living organisms. Here, Gd3Al4GaO12:Cr3+ (hereinafter referred to as: GAGG:Cr3+) phosphor was synthesized by high-temperature solid-phase method, and the crystal structure, morphology, and luminescence properties of this series of phosphor samples were studied. Through X-ray powder diffraction to obtain pure phase GAGG:Cr3+ series phosphor. Under the excitation of 420nm blue light, a broad band emission from 640 to 850nm is obtained, which is the result of the transition of Cr3+ 4T2→4A2 level. A sharp emission peak at 693nm is the R line belonging to Cr3+ in Gd3Al4GaO12 garnet. R line is assigned to the spin-forbidden 2E→4A2 transitions of Cr3+ ions that occupy the ideal octahedral sites. As the Cr3+ doping concentration increases, the luminous intensity of the sample increases first and then decreases. When the doping concentration of Cr3+ is 0.1mol phosphor,the luminous intensity is strongest at one single broad peak at about 712nm. At 440k, the R sharp line (693nm) and broad band (712nm) emission intensity maintained 78.6% and 71.8% , compared to room temperature intensity, respectively. The change of fluorescence lifetime at different temperatures gives the mechanism of fluorescence change with temperature. The current exploration will pave a promising way to engineer GAGG:Cr3+ activated optoelectronic devices for all kinds of photobiological applications.

Background. To determine if the use of the Proton Pump Inhibitors (PPI) impacts the clinical efficacy of Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC), a meta-analysis was conducted. Method. Eleven studies from PubMed, EMBASE, Cochrane Library, Web of Science, and other databases up to May 2022, were selected. The pertinent clinical outcomes were assessed by applying the Progression-free survival (PFS), Overall Survival (OS), Hazard Ratio (HR), and 95% Confidence Interval (CI). Result. This study included eleven articles containing 7,893 NSCLC patients. The result indicated that PPI use was dramatically related to poor OS (HR: 1.30 [1.10–1.54]), and poor PFS (HR: 1.25 [1.09–1.42]) in case of patients treated with ICIs. With regard to the subgroup analysis, PPI use was dramatically associated with poor OS (Europe: HR = 1.48 [1.26, 1.74], Worldwide: HR = 1.54 [1.24, 1.91]), and poor PFS (Europe: HR = 1.36 [1.18, 1.57], Worldwide: HR = 1.34 [1.16, 1.55]) in patients from Europe and multi-center studies across the world, poor OS in patients with age less than or equal to 65 (HR = 1.56 [1.14, 2.15]), poor PFS in patients aged more than 65 (HR = 1.36 [1.18, 1.57]), poor OS for patients receiving with PD-1 (HR = 1.37 [1.04, 1.79]), poor PFS for patients receiving with PD-L1 (HR = 1.33 [1.19, 1.49]), and poor OS (−30: HR = 1.89 [1.29, 2.78], ±30: HR = 1.44 [1.27, 1.64]) and poor PFS (−30: HR = 1.51 [1.11, 2.05], ±30: HR = 1.32 [1.20, 1.45]) for patients who received PPI at 30 days before and/or after starting the ICIs treatment. Conclusion. Our meta-analysis indicated that PPI combined with ICIs in the treatment of NSCLC patients could result in poor OS and PFS. PPI use should be extremely cautious in clinical practices to avoid the impact on the efficacy of the ICIs.

In this article, we consider the varying coefficient multiplicative regression model, which is very useful to model the positive response. The criterion of least product relative error (LPRE) is extended to the varying coefficient multiplicative regression model by kernel smoothing techniques. Consistency and asymptotic normality of the proposed estimator are established. Some numerical simulations are carried out to assess the performance of the proposed estimator. As an illustration, the ethanol data is analyzed.

Keloid, a skin benign tumor, is characterized by overgrowth of fibroblasts and the excessive deposition of extracellular matrix in wounded skin. Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist was recently evaluated to inhibit fibrosis. This study explored the underlying mechanisms. Fibroblasts isolated from 25 keloid patients (KFs) and fibroblasts isolated from healthy controls (NSFBs) were also subjected to treatment with PPAR-γ agonist troglitazone and antagonist GW9662 or for transfection with miR-92 mimics or inhibitor, Axl siRNA, and miR-92b or Axl promoter constructs, as well as being subjected to qRT-PCR, ELISA, Western blot, protein array, luciferase, and ChIP assays. The data demonstrated that TGF-β1 and Axl proteins were significantly elevated in samples from keloid patients, while troglitazone treatment significantly reduced levels of TGF-β1 and Axl mRNA and proteins in KFs. Moreover, knockdown of Axl expression reduced expression of TGF-β1 and its pathway genes (such as α-SMA and Snail). PPAR-γ regulation of Axl expression was through transcriptional activation of miR-92b. miR-92b expression downregulated Axl expression at both mRNA and protein levels, whereas GW9662 completely reversed the inhibitory effects of miR-92b mimics on Axl expression. Gene ontology analysis of miR-92b targeting genes showed that TGF-β and Axl were both potential targets of miR-92b, as confirmed by luciferase assay. These findings demonstrated that PPAR-γ-induced miR-92b expression inhibited Axl expression and in turn reduced expression of TGF-β1 and the downstream genes in KFs, suggesting that targeting of this novel gene pathway may be useful for therapeutic control of fibrosis or keloid.

Nuclear receptor peroxisome proliferator-activated receptor-γ (PPAR-γ) activity has been identified as an important endogenous anti-fibrotic defense mechanism. Troglitazone, a PPAR-γ agonist, has been used to suppress the formation of keloids and growth of hypertrophic scar fibroblasts. Indeed, the PPAR-γ agonist was able to inhibit collagen I expression in hypertrophic scar fibroblasts, which clearly demonstrates its therapeutic potential, and clarification of the underlying molecular mechanisms could further indicate the usefulness of the PPAR-γ agonists in the treatment of keloids. Moreover, increasing evidence has suggested that aberrant expression of miRNAs leads to the development and progression of fibrosis diseases. Thus, fully understanding the biological functions and molecular mechanisms of miRNAs in the regulation of fibrosis could provide insight for advancements in the diagnosis and treatment of fibrosis. This commentary briefly summarizes the current evidence for the ability of PPAR-γ agonist troglitazone to suppress collagen synthesis and regulate miRNA expression and downstream targets in cells.

The catalytic reforming of toluene was performed to investigate the possibility for directly converting tar components from hot coke oven gas (COG) with lower steam/carbon (S/C) molar ratio to light fuel gases. The Ni0.25Me0.25/Mg2.5(Al)O (Me=Fe, Cu, Zn, Mn) bimetallic catalysts derived from hydrotalcite showed excellent catalytic activity. The effects of various reaction conditions on the catalytic performance were investigated in detail. Toluene could be completely converted into small gas molecules of CH4, CO and CO2 over the catalyst at S/C=0.7 and 650-750 oC under atmospheric pressure. Lower reaction temperature and higher H2 content in feed gas both could promote the formation of CH4, while higher S/C molar ratio benefited the CO yield.

The performance of Ni/SiO2 Catalysts modified by La2O3, ZrO2 and CeO2 were tested in a BaCo0.7Fe0.2Nb0.1O3-δ (BCFNO) membrane reactor by catalytic partial oxidation of coke oven gas (COG) under atmospheric pressure. The results show that the oxygen permeation flux increased dramatically with Ni/RxOy/SiO2 (R = La, Zr or Ce) catalysts by adding the element of rare earth especially the La during the reforming reaction. At optimized reaction conditions, the dense oxygen permeable membrane had an oxygen permeation flux around 16.4 ml/cm2•min and a CH4 conversion of 99.2% have been achieved at 900 oC.

The BaCo0.7Fe0.2Nb0.1O3-δ (BCFNO) membranes combined with Ce0.8Re0.2O2-δ (Re=La, Y) layer on the permeation side were used for hydrogen production by partial oxidation reforming of coke oven gas (COG). The Ce0.8Re0.2O2-δ improved the oxygen permeation flux of the membrane by 11–28% at 750 oC. The high oxygen permeation flux achieved using the Ce0.8Re0.2O2-δ surface-coating layer in this work are quite encouraging with a maximum value reaching 19.7 ml/cm2•min at 900 oC, which will be promising surface modification materials in the catalytic partial oxidation reforming of COG.

Sirtuin1 (SIRT1), the founding member of mammalian class III histone deacetylases, is reported to be a drug target involved in fibrotic diseases. However, whether it is an effective drug target in hypertrophic scar treatment is still not known.In the present study, we observed that SIRT1 localized to both the epidermis and the dermis of skin tissues by immunohistochemistry. After knock-down of SIRT1 by shRNA or up-regulating SIRT1 by resveratrol, the expression of α-SMA, Col1 and Col3 in fibroblasts were detected by western blots. A mouse excision wound healing model was used to observe the changes in collagen fibre associated with the different expression levels of SIRT1.SIRT1 expression was inhibited in hypertrophic scar tissue. The down-regulation of SIRT1 resulted in an increased expression of α-SMA, Col1 and Col3 in hypertrophic scar-derived fibroblasts. In contrast, the up-regulation of SIRT1 not only inhibited the expression of α-SMA, Col1 and Col3 in hypertrophic scar-derived fibroblasts but also blocked the activation of TGFβ1-induced normal skin-derived fibroblasts. In the mouse model of wound healing, the deletion of SIRT1 resulted in denser collagen fibres and a more disordered structure, whereas resveratrol treatment led to a more organized and thinner collagen fibre, which was similar to that observed during normal wound healing.The results revealed that SIRT1 negatively regulates TGFβ1-induced fibroblast activation and inhibits excessive scar formation and is, therefore, a promising drug target for hypertrophic scar formation.

Background Previous studies have investigated the relationship between human bone morphogenetic protein 4 gene (BMP4) rs17563 polymorphism and nonsyndromic cleft lip with or without cleft palate (NSCL/P). However, the results remained inconsistent. Therefore, we conducted a meta-analysis to assess the effect of BMP4 rs17563 polymorphism on NSCL/P. Methods Electronic searches in 5 databases were conducted to select all eligible studies up to March 2017. Odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated to estimate the association. Sensitivity analysis was performed to evaluate the results stability by excluding each study in turn. Publication bias was assessed by Begg funnel plots and Egger test. Results A total of 11 case-control studies were included in the meta-analysis. The pooled frequency of the minor allele C for BMP4 rs17563 was lower in Asians (pooled frequency = 0.33, 95% CI: 0.29-0.37) than in Brazilian population (pooled frequency = 0.47, 95% CI: 0.40-0.54). The overall results showed no significant association of BMP4 rs17563 polymorphism with NSCL/P risk. However, the results turned out to be different when stratified by ethnicity. BMP4 rs17563 polymorphism was associated with a higher risk of NSCL/P among Asian ethnicity (C vs T: OR = 1.33, 95% CI: 1.02-1.73; CC vs TT: OR = 2.10, 95% CI: 1.28-3.43; CC vs TT + TC: OR = 2.16, 95% CI: 1.34-3.47) and among Caucasian population (TC vs TT: OR = 3.36, 95% CI: 2.03-5.54; TC + CC vs TT: OR = 3.71, 95% CI: 2.43-5.69). Among Brazilian population, BMP4 rs17563 polymorphism exerted a significantly protective effect on NSCL/P (C vs T: OR = 0.70, 95% CI: 0.58-0.84; CC vs TT: OR = 0.54, 95% CI: 0.33-0.88; TC vs TT: OR = 0.55, 95% CI: 0.44-0.69; TC + CC vs TT: OR = 0.56, 95% CI: 0.45-0.69). Conclusion The results suggest that the C allele of BMP4 rs17563 may be a risk factor for NSCL/P among Asians and Caucasians, and may be a protective factor for NSCL/P in Brazilian population. Future large-sample studies with appropriate designs among specific populations are warranted to evaluate the association.

Deep sternal wound infection is a severe complication after open heart surgery. According to the different severity and dimensions of the deep sternal wound infection, the treatment method is different. In this study, we aimed to describe our experience with the rectus abdominis myocutaneous flap for large sternal wound management, especially when 1 or 2 internal mammary arteries were absent. Between October 2010 and January 2016, a retrospective review of 9 patients who suffered from the extensive thoracic defects after deep sternal wound infection was conducted. All of these sternal defects encompassed almost the full length of the sternum after debridement. Defect reconstruction was achieved by covering with a rectus abdominis myocutaneous flap. When the ipsilateral or bilateral internal mammary artery had been harvested previously, we took advantage of the inferior epigastric artery to provide additional blood supply to the rectus abdominis myocutaneous flap. Thus, this flap had a double blood supply. There was no recurrent infection in all 9 patients. Three patients received the rectus abdominis myocutaneous flap with a double blood supply. Flap complications occurred in 2 patients (22%). One patient who did not have the double blood supply flap suffered from necrosis on the distal part of the flap, which was then debrided and reconstructed with a split-skin graft. The other patient had a seroma at the abdomen donor site and was managed conservatively. None of the patients died during the hospital stay. This study suggests that the rectus abdominis myocutaneous flap may be a good choice to repair the entire length of sternal wound. When 1 or 2 internal mammary arteries have been harvested, the inferior epigastric artery can be anastomosed to the second intercostal artery or the internal mammary artery perforator to provide the rectus abdominis myocutaneous flap with a double blood supply.

To investigate the clinical application of free superficial iliac circumflex artery skin flaps, as well as the management of donor site defects.17 free superficial iliac circumflex artery skin flaps were applied for the traumatic defects or deformities on face, neck, foot, hand, ankle and lower leg, respectively. The donor site defects were closed directly or covered by paraumbilical island flaps.The 17 flap size ranged from 5 cm x 3 cm to 19 cm x 14 cm. 16 flaps survived completely except 1 flap with partial necrosis, which was closed by free skin graft. The donor site defects were closed directly in 10 cases, and covered by paraumbilical island flaps in 7 flaps without no flap necrosis. The abdomen had a good appearance.Good appearance can be achieved with free superficial iliac circumflex artery skin flaps for the defects on face, neck, foot, hand, ankle and lower leg. Paraumbilical island flap can be used for the donor site defects.

Joints involved in deep burn often result in joint contracture, limb dysfunction, psychological disorder, or even loss of living and working abilities. The management of post-burn joint contracture will directly orientate the functional recovery of the patients. Comprehensive intervention may prevent the contracture process of the affected joints. Orthoses application is an important measure and should be maintained throughout the whole process of burn care, from positioning the joints at the early stage to maintaining the range of joint motion at the late stage. Orthoses should be used on the premise of protecting the joint functions. In order to maintain the tissue tension while enhancing the joint mobility and muscle strength, the static orthoses and the dynamic orthoses are often alternately used. It is showed in clinical practice that orthoses are designed and applied on the basis that biomechanics will lead to a better outcome.

To observe the influence of negative pressure wound therapy on the angiogenesis of wounds in diabetic rats.Diabetes model was reproduced by intraperitoneal injection of 20 g/L streptozotocin in the dosage of 65 mg/kg in 40 SD rats. Two weeks later, rats were divided into control group (C) and negative pressure group (NP) according to the random number table, with 20 rats in each group. A piece of full-thickness skin in the center of the back of each rat in the size of 2 cm×2 cm was excised to produce a wound. Immediately after injury, wounds in group C were given conventional dressing change; wounds in group NP were treated with continuous negative pressure (-16.0 kPa) therapy for four hours a day, which lasted for seven days. (1) Blood glucose and body weight of rats in two groups were respectively measured by glucose meter and electronic scale before treatment, and 1 and 2 week (s) after. (2) Wound blood flow was detected by laser Doppler perfusion imager before treatment and on post treatment day (PTD) 1, 3, 7, with 5 rats at each time point. (3) On PTD 3 and 7, respectively, five rats from each group were sacrificed. The wound tissue was excised and divided into two parts. The angiogenesis in the left part tissue was observed with immunohistochemical staining. The microvessel density was calculated. (4) The full-thickness skin excised before treatment and the right part tissue freeze on PTD 3 and 7 were collected. On PTD 1 and 14, wound tissue was excised in the above-mentioned method. The mRNA levels of the vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 1 (Fit-1), angiopoietin 1 (Ang-1), Ang-2, and tyrosine kinase receptor 2 (Tie-2) were determined with real-time fluorescence quantification PCR. Data were processed with two-way analysis of variance or LSD-t test.(1) No significant difference was observed between two groups in blood glucose level and body weight as a whole or at each time point (with F values respectively 0.667, 0.176, t values from 0.311 to 0.707, P values all above 0.05). (2) The difference in the overall wound blood flow of rats between two groups was significant (F = 24.66, P0.05). On PTD 1, 3, 7, values of wound blood flow of rats in group NP were (179 ± 24), (219 ± 12), (192 ± 30) perfusion unit, significantly higher than those of rats in group C[(127 ± 16), (179 ± 8), (144 ± 17) perfusion unit, with t values respectively 3.71, 5.57, 2.77, P0.05 or P0.01]. (3) The difference in the overall microvessel density in the wound of rats between two groups was significant (F = 33.25, P0.05). On PTD 3, the microvessel density in the wound of rats in group NP was (80 ± 12) per 100-time visual field, which was significantly higher than that of group C[(38 ± 4) per 100-time visual field, t = 9.257, P0.05]. On PTD 7, the microvessel density in the wound of rats in two groups were close (t = 1.159, P0.05), but the vessels in group NP were regularly arranged with spacious lumen, while the vessels in group C were disorderly arranged with narrow lumen. (4) On PTD 1, 3, mRNA expression levels of VEGF, Fit-1, and Ang-1 in group NP were obviously higher than those in group C (with t values from 1.28 to 11.60, P values all below 0.01). On PTD 7, the mRNA expression level of Ang-1 (27.59 ± 3.55) in group NP was obviously higher than that in group C (19.87 ± 1.86, t = 7.23, P0.001), while the mRNA level of its antagonist Ang-2 (5.79 ± 0.61) in group NP was obviously lower than that in group C (17.62 ± 0.85, t = 19.88, P0.001). On PTD 3, 7, 14, mRNA levels of Tie-2 in group NP were obviously lower than those in group C (with t values from 8.92 to 15.60, P values all below 0.01).Negative pressure wound therapy may promote wound angiogenesis by enhancing the expression of Ang-1 and lowering the expression of Ang-2 in diabetic rats.

To reproduce a stable mouse model of deep partial-thickness scald and to determine the hypoxia status in the wound.(1) A homemade scald-producing apparatus with constant steam (92 °C) emission was used to reproduce scald injury on the back (2 cm in diameter) in 80 male BALB/c mice for different duration (2, 4, 6, and 8 s), with 20 mice for each scald duration. The nozzle was aligned perpendicularly to the back of mice, 2 cm above the skin surface. The gross condition of wound was observed with naked eyes immediately after injury. Skin samples of 5 mice with different burn duration were harvested 0, 12, 24, and 48 h after scald for histopathological observation with hematoxylin and eosin staining, to screen the scalding time and time for biopsy of scalded skin to determine proper scalding time for the experiment. (2) Model of deep partial-thickness scald was reproduced with the desired scalding time as shown in the preliminary experiment in another 5 BALB/c mice. The hypoxia status in subcutaneous tissue was observed with immunohistochemical staining 72 h after scald. Another 20 BALB/c mice were divided into normal control group (n = 5, without scald) and deep partial-thickness scald group (n = 15, scalded for a suitable duration as determined in the preliminary experiment) according to the random number table. The subcutaneous oxygen content in wound center, the margin of the wound, and the normal skin adjacent to the wound was detected with laser Doppler transcutaneous oxygen tension 72 h after scald, with 5 mice in each region. Data were processed with one-way analysis of variance.(1) The wound of mice with different scald durations was pale, clean, and no exudate was observed right after injury. (2) The burn depth developed gradually along with the scalding time and sample harvesting time, and it became stable 24 h after scalding. A deep partial-thickness injury was observed in the dermis of mice scalded for 4 s and harvested 24 h after scald, and it was shown that the external hair sheath was still present, and it was determined to be a deep partial-thickness scald. (3) Dense staining of pimonidazole (hypoxia) was found in deep partial-thickness scald wound 72 h after scald, especially in the marginal zones of the wounds. The partial oxygen pressure in the wound center, wound margin, and normal skin around the wound was respectively (36.2 ± 3.2), (37.0 ± 1.4), (37.4 ± 2.7) mm Hg (1 mm Hg = 0.133 kPa), showing no statistically significant difference among them (F = 74.705, P0.05), but they were significantly lower than that of the control group [(53.1 ± 2.4) mm Hg, with F values respectively 82.377, 91.375, 100.531, P values all below 0.05].Deep partial-thickness scald model can be reproduced in (20.0 ± 1.0) g male BALB/c mice by scalding with 92 °C hot steam for 4 s, and the depth of wound becomes stable 24 h after scalding. Hypoxia can be found in the scalded wounds, especially in the marginal zones of the wounds.

To investigate the effect of adipose-derived stem cells (ADSC) on renal injury in mice with burn injury and sepsis and its underlying mechanism.(1) Adipose tissue was collected from both inguinal regions of 5 C57BL/6J mice to isolate, culture and purify ADSC through enzyme digestion, density gradient centrifugation, and adherence method. Cells of the third passage were used in the experiment. The morphologic change in cells was observed and the growth curve of cells was determined. The expression of cell surface antigen phenotype was analyzed by flow cytometry, and the cells were identified by adipogenic and osteogenic differentiation. (2) Another 37 C57BL/6J mice were divided into normal control group (n = 5), saline group (n = 16), and group ADSC (n = 16) according to the random number table. The mice in saline group and group ADSC were injected with Pseudomonas aeruginosa after being subjected to 15% TBSA full-thickness burn on the back to reproduce septic burn model. Then the mice were injected with saline and ADSC through tail vein respectively. At post burn hour (PBH) 12, 24, 48, and 72, the pathological change in kidney tissue was observed, the levels of blood urea nitrogen and serum creatinine were determined, and the levels of TNF-α, IL-12, IL-10, and cyclooxygenase-2 (COX2) mRNA were determined with real-time fluorescence quantitative PCR in both groups. Above-mentioned indexes were also examined in the normal control group (without burn). Data were processed with multifactor analysis of variance and LSD- t test.(1) Cells in the third passage were orderly arranged with the shape similar to fibroblasts. The percentages of CD90(+), CD105(+), CD34(-), and CD45(-) cells were all above 90%. The cells could differentiate into osteoblasts and adipocytes. The cells were identified to be ADSC. (2) From PBH 12 to PBH 72, the neutrophil infiltration gradually increased, and the structure of kidney tubules and glomeruli were deranged in saline group. The pathological change in kidney tissue in group ADSC was less serious than that of normal control group at each time point. From PBH 12 to PBH 72, the levels of blood urea nitrogen and serum creatinine in saline group were significantly higher than those of normal control group and group ADSC (P values all below 0.01). Compared with those of the normal control group, the levels of TNF-α and IL-12 mRNA were higher in group ADSC and saline group at PBH 24 (P values all below 0.05). At PBH 24, the level of TNF-α mRNA in group ADSC (1.58 ± 0.19) was lower than that of saline group (3.36 ± 0.30, P0.05). At PBH 24, the levels of IL-10 and COX2 mRNA in group ADSC (2.89 ± 0.47, 4.90 ± 0.59) were higher than those in normal control group (1.00 ± 0.15, 1.00 ± 0.27) and saline group (1.32 ± 0.38, 1.57 ± 0.38, P values all below 0.05).ADSC can decrease the levels of blood urea nitrogen and serum creatinine, promote the production of anti-inflammatory cytokines IL-10 and COX2, and reduce the release of the pro-inflammatory cytokines TNF-α and IL-12 to offer protective effects against renal injury in burn mice with sepsis.

Translational medicine is an emerging arena in the 21st century, and it bridges research results of basic sciences to clinical applications. The importance of translational research attracted considerable concern of scientists worldwide, including clinicians and researchers in the field of burn surgery in China. This review highlights some key points on translational medicine practised in the basic and clinical research of burn surgery, and they are summarized here as: the motive of the research project should be focused on how to solve problems of patients; much attention should be drawn to the difference between the cell biology and biochemical reaction in vitro and that in vivo; an animal model which simulates human pathology as much as possible should be reproduced; collaboration and sharing of resources among different disciplines should be strengthened; national and standardized criteria should be established for evaluation of the experimental result and guiding for clinical application. The aforementioned suggestions would be helpful for the application of new medicine and therapeutic approach in treating severe burn.

To explore the methods of systemic treatment of defects of skin and soft tissue on the knees after severe trauma or burn.Twenty patients with defects of skin and soft tissue on the knees after severe trauma or burn hospitalized in our center from January 2009 to December 2011. The injury areas on the knees ranged from 5 cm×4 cm to 30 cm×20 cm. The wounds were treated with radical debridement, vacuum sealing drainage, and douche through dripping to control infection in early stage. Then they were covered with transplantation of skin grafts plus flap or only with flap. Totally 8 local flaps (including 6 local rotation or transposition flaps and 2 saphenous artery flaps) and 12 free flaps (including 8 anterolateral thigh flaps and 4 latissimus dorsi musculocutaneous flaps) were used. The flap size ranged from 6 cm×5 cm to 32 cm×22 cm. The rehabilitation training of the knee joints was carried out in the early stage after wound healing.All free skin grafts and flaps used in 15 patients survived. Thirteen of them were primarily healed, while some small parts of skin grafts of the other two patients were in poor condition because of infection, and they healed after another session of skin transplantation. Infection occurred under the free flap in one of the 5 patients transplanted with flaps only, which was healed after continuous douche through dripping and another surgical debridement following wet dressing. The knee joints were in good function during the follow-up period of 1 - 3 years.The systemic therapy of radical debridement, vacuum sealing drainage technique, douche through dripping, transplantation of large autologous grafts and flaps, and the early rehabilitation training are effective and reliable in repairing defects of skin and soft tissue at the knee region after severe injuries.

Intensive insulin therapy during critical illness protects the endothelium and thereby prevents organ failure. This study tested the hypothesis that insulin directly affects the attenuation of burn injury-induced damage to pulmonary endothelial tight junction and investigated the underlying mechanisms. Sprague Dawley rats with severe burn injury were randomized to treatment with insulin dissolved in normal saline (maintenance of blood glucose at a level between 5.0 and 7.0 mmol/L) or normal saline alone (in vivo treatment). Pulmonary damage was evaluated. Rat pulmonary microvascular endothelial cells were treated with 20% burn serum or 20% burn serum + insulin (in vitro treatment). Selected cultures were pretreated with phosphatidylinositol 3-kinase/protein kinase B (AKT) inhibitor (LY294002). Permeability was assessed by migration of bovine serum albumin across cell monolayers. Cells were stained with rhodamine phalloidin and were examined. Cell extracts were obtained to assess zonula occludens-1, occludin, and phosphorylated AKT levels by immunoblotting. Treatment with insulin attenuated the pulmonary edema, hemorrhage, and inflammatory cell infiltration of rats with severe burn injury. Burn serum significantly enhanced monolayer permeability to albumin, whereas treatment with insulin (10(-7 ) mol/L) limited this effect. Meanwhile, insulin (10(-7 ) mol/L) reduced burn serum-induced F-actin stress fiber formation and decreased zonula occludens-1 expression. LY294002 decreased cytoplasmic AKT phosphorylation and inhibited the protection effects of insulin. Through the phosphatidylinositol 3-kinase/AKT pathway, insulin independent of glucose toxicity can attenuate increased pulmonary endothelial permeability induced by burn injury. The effect is attributed to the attenuation of the architectural disruption of protein components of the endothelial tight junction. This result is useful in inhibiting multiple organ failure after burn injury.

To explore the means for the reconstruction of extensive deep burn wounds with exposure of bone and joint in late stage.Among all the patients with extensive deep burn hospitalized between January 2009 and May 2011, 5 patients presented wounds with exposure of bone and joint in the late stage of treatment that could not be covered by free skin grafts or flaps. Two of the five patients had more than 2 and the other 3 patients had only one such wound(s). The wound size ranged from 8 cm×5 cm to 21 cm×8 cm. Wounds were repaired by transplantation of 7 free muscle flaps (including 4 free rectus abdominis flaps and 3 latissimus dorsi flaps) combined with split-thickness skin grafts harvested from scalp.All the muscle flaps and skin grafts survived. Wounds with bone and joint exposure healed well. At one-year follow-up of some patients, good appearance of repaired areas and normal function of joints were observed with no signs of ulceration, arthritis, or osteomyelitis.Transplantation of free muscle flaps combined with split-thickness skin grafts harvested from the scalp provides satisfactory reconstruction for wounds with deep tissue exposure in patients with a shortage of skin donor site.

Skin is the largest organ in human body. It guards the underlying muscles, bones, ligaments, and internal organs. The skin faces the environment, and it is the first line to defend against the assaults of external physical, chemical, and micro-organic factors. The other functions of skin include systemic metabolism, temperature regulation, sensation, and production of vitamin D and folate. Skin injury usually leads to barrier function damage. Extensive skin injury would induce a series of problems such as water-electrolyte disorder, hypoproteinemia, and severe infection. Thus it is important to choose a suitable wound dressing when the skin is severely injured. The characteristics of wound dressings have undergone repeated and noticeable changes over the last several years. Compared with that of the traditional dressing, the ability of new dressings is improved obviously in the properties of wound protection, infection prevention, and wound healing promotion. This article deals with an overview on the characteristics of different wound dressings.

To study the role of Wnt/beta-catenin signaling in the phenotype change of normal skin fibroblasts (NFb) into myofibroblasts and the underlying mechanism.NFb were isolated by collagenase digestion and cultured. (1) Experiment one. NFb were divided into four groups according to the random number table. Cells in control group were cultured with serum-free DMEM nutrient solution (briefly called nutrient solution). Cells in TGF-beta1 group were cultured with nutrient solution containing 10 ng/mL recombinant human TGF-beta1 (the same concentration for following experiments). Cells in Wnt3a group were cultured with nutrient solution containing 150 ng/mL Wnt3a (the same concentration for following experiments). Cells in TGF-beta1 + Wnt3a group were cultured with nutrient solution containing TGF-beta1 and Wnt3a. The mRNA and protein expression levels of beta-catenin and alpha-smooth muscle actin (alpha-SMA) were determined by real-time fluorescent quantitative PCR and Western blotting at post culture hour (PCH) 48. (2) Experiment two. NFb were divided into four groups according to the random number table. Cells in control group and TGF-beta1 group were treated as those in the corresponding groups in experiment one. Cells in SB415286 (glycogen synthase kinase-3beta inhibitor) group were cultured with nutrient solution containing 10 micromol/L SB415286 (the same concentration for following experiments). Cells in TGF-beta1 + SB415286 group were cultured with nutrient solution containing TGF-beta1 and SB415286. The mRNA and protein expression levels of alpha-SMA were determined by real-time fluorescent quantitative PCR and Western blotting, and the alpha-SMA-positive myofibroblasts were detected by immunofluorescence cytochemical staining at PCH 48. The experiments were all repeated for three times. Data were processed with analysis of variance and LSD- t test.(1) Experiment one. There was no statistically significant difference among four groups in beta-catenin mRNA level (F = 0.302, P = 0.823). There were statistically significant differences among four groups in beta-catenin protein level (F = 16.713, P = 0.001). The protein level of beta-catenin was higher in TGF-beta1 group (0.73 +/- 0.12) and Wnt3a group (0.82 +/- 0.17) than in control group (0.34 +/- 0.11, with t values respectively 3.028, 3.727, P0.05 or P0.01). The protein level of beta-catenin in TGF-beta1 + Wnt3a group (1.23 +/- 0.21) was higher than that of the other three groups (with t values respectively 6.911, 3.883, 3.184, P values all below 0.01). There were statistically significant differences among four groups in alpha-SMA mRNA level (F = 31.830, P = 0.001). Compared with that of control group, the expression level of alpha-SMA mRNA was up-regulated in TGF-beta1 group and down-regulated in Wnt3a group (with t values respectively 6.759, 2.535, P0.05 or P0.01). The expression level of alpha-SMA mRNA in TGF-beta1 + Wnt3a group was lower than that of TGF-beta1 group (t = 4.532, P0.01). The protein levels of alpha-SMA in control, TGF-beta1, Wnt3a, and TGF-beta1 + Wnt3a groups were respectively 0.83 +/- 0.17, 1.43 +/- 0.20, 0.53 +/- 0.12, and 0.89 +/- 0.14 (F = 16.597, P = 0.001). Compared with that of control group, the protein level of alpha-SMA was up-regulated in TGF-beta1 group and down-regulated in Wnt3a group (with t values respectively 4.582, 2.291, P0.05 or P0.01). The protein level of alpha-SMA in TGF-beta1 + Wnt3a group was lower than that of TGF-beta1 group (t = 4.123, P0.01). (2) Experiment two. There were statistically significant differences among four groups in alpha-SMA mRNA level (F = 34.101, P = 0.001). The alpha-SMA mRNA level in SB415286 group was lower than that of control group (t = 2.511, P0.05). The alpha-SMA mRNA level in TGF-beta1 + SB415286 group was lower than that of TGF-beta1 group (t = 3.587, P0.01). There were statistically significant differences among four groups in alpha-SMA protein level (F = 11.381, P = 0.003). The alpha-SMA protein level was lower in SB415286 group than in control group (t = 2.364, P0.05). The alpha-SMA protein level was down-regulated in SB415286 +TGF-beta1 group as compared with that of TGF-beta1 group (t = 2.556, P0.05). There were few alpha-SMA-positive fibroblasts in control group. Compared with that of control group, the expression of alpha-SMA was significantly increased in TGF-beta1 group (t =11.198, P0.01), and the expression of alpha-SMA was down-regulated in SB415286 group. Meanwhile, the expression of alpha-SMA in TGF-beta1 + SB415286 group were significantly lower than that of TGF-beta1 group (t = 5.902, P0.01).The Wnt/beta-catenin signaling might be involved in the fibroblasts-myofibroblasts transition, and it negatively regulate the TGF-beta1 -mediated profibrotic effects.

The generation of induced neuronal cells from human bone marrow stromal stem cells (hBMSCs) provides new avenues for basic research and potential transplantation therapies for nerve injury and neurological disorders. However, clinical application must seriously consider the risk of tumor formation by hBMSCs, neural differentiation efficiency and biofunctions resembling neurons. Here, we co-cultured hBMSCs exposed to retinoic acid (RA) with human olfactory ensheathing cells (hOECs) to stimulate its differentiation into neural cells, and found that hBMSCs following 1 and 2 weeks of stimulation promptly lost their immunophenotypical profiles, and gradually acquired neural cell characteristics, as shown by a remarkable up-regulation of expression of neural-specific markers (Tuj-1, GFAP and Galc) and down-regulation of typical hBMSCs markers (CD44 and CD90), as well as a rapid morphological change. Concomitantly, in addition to a drastic decrease in the number of BrdU incorporated cells, there was a more elevated synapse formation (a hallmark for functional neurons) in the differentiated hBMSCs. Compared with OECs alone, this specific combination of RA and hOECs was significantly potentiated neuronal differentiation of hBMSCs. The results suggest that RA can enhance and orchestrate hOECs to neural differentiation of hBMSCs. Therefore, these findings may provide an alternative strategy for the repair of traumatic nerve injury and neurological diseases with application of the optimal combination of RA and OECs for neuronal differentiation of hBMSCs.

To observe the effects of myrrh extract on biological characteristics of human dermal fibroblasts (Fb), and to explore its possible mechanisms in promoting wound healing.Normal Fb was isolated from human foreskin tissue and cultured in vitro. The third to fifth passages of Fb were used in the experiment. (1) Fb were planted onto 96-well plate and divided into control group, and 1 × 10(-4), 1 × 10(-3), 1 × 10(-2), 1 × 10(-1), 1, 10, 1 × 10(2) g/L myrrh water extract groups and myrrh ethanol extract groups according to the random number table. Fb in control group were cultured with DMEM medium containing 0.25% calf serum (briefly called low-concentration serum medium), and those in various concentrations of myrrh water extract and myrrh ethanol extract groups respectively with low-concentration serum medium containing corresponding concentration of 2 kinds of myrrh extract. After being cultured for 48 h, cell morphology was observed with inverted-phase contrast microscope, and Fb proliferation activity (denoted as absorbance value) was determined with MTT method. (2) Fb were respectively planted into flasks and dishes and divided into two groups according to the random number table. Fb in control group were cultured with low-concentration serum medium, and that in 1 g/L myrrh water extract group with low-concentration serum medium containing 1 g/L myrrh water extract. After being cultured for 72 h, Fb cell cycle and the type I and III collagen mRNA expression were respectively determined by flow cytometry and real-time fluorescent quantitative PCR. Data were processed with LSD-t test.(1) Fb in all groups grew in long-spindle shape, but the cell fusion was much obvious in 1 g/L myrrh water extract group than in control group. Fb absorbance value in 1 × 10(-3), 1 × 10(-2), 1 × 10(-1), 1, 10 g/L myrrh water extract groups was respectively 0.378 ± 0.032, 0.402 ± 0.007, 0.390 ± 0.038, 0.453 ± 0.036, 0.390 ± 0.037, all higher than that in control group (0.332 ± 0.044, with t value respectively 2.24, 2.93, 2.69, 5.73, 2.71, P values all below 0.05). Compared with that in control group, Fb absorbance value in 1 × 10(-4) g/L myrrh water extract group was not statistically different (0.312 ± 0.048, t = 2.84, P0.05), while that in 1 × 10(2) g/L myrrh water extract group was significantly lower (0.154 ± 0.009, t = 7.17, P0.05). Fb absorbance values in 1 × 10(-3), 1 × 10(-1), 1, 10, 1 × 10(2) g/L myrrh ethanol extract groups were significantly lower than that in control group (with t values from 2.30 to 24.79, P values all below 0.05). (2) Compared with those in control group [(82.2 ± 7.9)% and (13.3 ± 2.3)%, (4.5 ± 0.8)%], the percentage of cells in G0/G1 phase in 1 g/L myrrh water extract group was obviously decreased [(74.3 ± 6.3)%, t = 6.77, P0.05], while those in S and G2/M phases increased [(16.6 ± 3.4)%, (9.1 ± 1.6)%, with t value respectively 7.53, 6.34, P values below 0.05]. Compared with those in control group (1.00 ± 0.05, 1.00 ± 0.06), the mRNA level of collagen III in 1 g/L myrrh water extract group was significantly up-regulated (1.38 ± 0.12, t = 3.81, P0.01), while that of collagen I was not statistically different (0.89 ± 0.08, t = 1.17, P0.05).Myrrh water extract can notably promote the proliferation of Fb, accelerate the cell cycle of Fb, and up-regulate the mRNA expression of type III collagen in Fb, which may be related to its mechanisms in promoting wound healing.

To investigate the protective effects of insulin on burn serum-challenged cardiocyte apoptosis and its mechanism.Burn-serum challenged cardiocytes were pretreated with insulin and inhibitors to pathway SB203580 and LY294002. The expression of cardiac myofilament proteins cleaved-caspase-3, Bax and phosphorylation nuclear factor-ΚB inhibitive factor α (p-IΚBα) were examined by Western blotting. The mRNA expression of tumor necrosis factor-α (TNF-α) was determined by real-time reverse transcription-polymerase chain reaction (RT-PCR). Apoptosis of cardiocyte was observed after Hoechst 33258 staining. Further blocking experiments were used to investigate the cytoprotective pathway of insulin.Insulin could significantly decrease the expression of cleaved-caspase-3 (2.22 ± 0.30 vs. 4.84 ± 0.74, P0.01), Bax (1.33 ± 0.35 vs. 3.74 ± 0.65, P0.01), p-IΚBα (1.43 ± 0.62 vs. 3.62 ± 0.74, P0.01), TNF-α (0.72 ± 0.27 vs. 2.02 ± 0.63, P0.01) and the cardiocyte apoptosis rate [(9.4 ± 3.4)% vs. (19.1 ± 5.6)%, P0.01] in cardiocytes challenged by burn serum. Further blocking experiments showed that LY294002, phosphatidylinositol-3-kinase (PI3K)/Akt activation inhibitor, could mitigate the protective effects of insulin. Meanwhile, SB203580, an inhibitor of p38 mitogen-activated protein kinase (p38MAPK) pathway, was able to inhibit cardiocyte injury challenged by burn serum, and it was as effective as insulin.For cardiocytes challenged by burn serum, insulin may decrease inflammatory cytokine expression and apoptosis via regulating PI3K/Akt and p38MAPK pathway.

Scar, either hypertrophic scar or keloid, is one of the most common complications due to proliferative disorder of fibrosis in the process of wound healing after burn injuries, trauma, and surgical operations. To repair the cosmetic and functional impairments caused by scars poses a great challenge to all the burn surgery workers. With the advances in both basic research and clinical treatment, the understanding of scar formation and the therapeutic strategies of scar have been improved significantly. However, the remaining problems are still outstanding. In this discussion, the advances and problems in the scientific research in this field, including genetic predisposition, candidate gene, dysfunction of fibroblasts, interaction between fibroblasts and keratinocytes, as well as animal models for hypertrophic scar and keloid were summarized. In addition, the progresses in the clinical therapies are also discussed, including pressure treatment, silicone gel sheeting, corticosteroids, laser, and other emerging treatment strategies. The understanding and treatment of scar will improve in the future with further deepening basic research and clinical trials with stricter standard of assessment.

Recent studies have investigated the most efficacious dose of intravenous tissue plasminogen activator (IV-tPA) for acute ischemic stroke (AIS) patients. There remains no definitive consensus concerning the superior efficacious IV-tPA dose (standard- vs. low-dose), prompting us to perform a meta-analysis comparing the efficacy and safety profile of standard- versus low-dose IV-tPA.We identified relevant studies pertaining to the specific aim of our meta-analysis by searching PubMed and EMBASE (January 1990-September 2015) Either a fixed- or random-effects model was employed (dependent upon data heterogeneity) to analyze the efficacy and safety outcome.Ten cohort studies involving 4389 sum patients were included in the meta-analysis. By using the random-effects model, the meta-analysis indicated no statistically significant difference in favorable functional outcome (modified Rankin scale 0-1) at 3 months (heterogeneity: χ = 17.45, P = 0.04, I = 48%; OR: 0.88 [95% CI: 0.71-1.11]; P = 0.28) and incidence of symptomatic intracranial hemorrhage (SICH) (heterogeneity: χ = 14.41, P = 0.11, I = 38%; OR: 1.19 [95% CI: 0.76 to 1.87]; P = 0.45) between the standard- and low-dose groups. The fixed-effects model demonstrated no significant difference in mortality within 3 months (heterogeneity: χ = 6.73, P = 0.57, I = 0%; OR: 0.91 [95% CI: 0.73-1.12]; P = 0.37) between the standard- and low-dose groups.Low-dose IV-tPA is comparable to standard-dose IV-tPA in both efficacy (favorable functional outcome) and safety (SICH and mortality). Confirmation of these findings through randomized trials is warranted.

Chronic wounds are a major healthcare problem costing billions of dollars a year over the world. However, it is regrettable that a large number of chronic wounds are still treated simply by conventional dressing change in local clinics, lacking of definite diagnosis and personalized care. This situation results in a low wound healing rate, unsatisfied life quality of the patients, and higher medical cost for the prolonged promiscuous care. We should not only emphasize the importance of wound care in clinical practice, but also emphasize the importance of establishing wound care centers. With the experience of our practice in wound care center, the construction of wound care technology platform is strongly suggested. This platform could act as an education base to train more professional wound care doctors, nurses, and care workers, as well as resolve many technical difficulties involved in the treatment of many complicated chronic wounds.

To compare the difference of protein expression in the supernatant of heat injured keratinocytes (KC) and normal KC.A model of heat injured KC was produced in vitro. The supernatant of normal KC and heat injured KC was collected after culture for 12 hours, and was ultrafiltered and lyophilized to get the protein. The protein sample was separated by immobilized pH gradient based two dimensional gel electrophoresis (2-DE). The gel was stained and the different expression of protein was analyzed using ImageMaster 2D analysis software.(1) Average protein spots were 1,898 +/- 113, 1,877 +/- 97 in the supernatant of normal and heat injured KC and 1,118 protein spots could be used for statistical analysis. (2) Statistical result showed that 26 protein spots were significantly different between the two groups. 16 protein spots were higher in the supernatant of normal KC and then 10 protein spots were lower in the normal group. (3) 16 protein spots, which included 10 kinds of proteins, were identified successfully as different spots. Lower expression proteins were alpha-enolase, actin cytoplasmic 2, peroxiredoxin-4, phosphoglycerate mutase 1, G protein-regulated inducer of neurite outgrowth l in the supernatant of heat injured KC. Higher expression proteins in heat KC were purine nucleoside phosphorylase, tumor necrosis factor ligand superfamily member 10, proteasome subunit alpha type-7, UDP-glucose 6-dehydrogenase in the supernatant of heat injured KC.The result indicated that there are some significant different expression proteins in the supernatant of normal KC and heat injured KC. These findings provide new data for screening major molecules of tissue repair and finding the mechanism of wound repair.

To observe the effect of vacuum sealing drainage (VSD) on the proliferation of Pseudomonas aeruginosa (PA) in infected wound, and to explore its possible mechanism.Full-thickness skin wounds each with area of 1 cm x 1 cm were produced on the back of 40 C57 BL/6 mice, and then they were contaminated with wild type PA strains PAO1 marked with target gene of bacterial luciferase luxCDABE (PAO1-lux), they were dressed for 24 hours to reproduce PA infection model. Then mice were divided into experiment [E, with treatment of VSD (pressure value at -16.625 kPa)] and control (C, with treatment of conventional dressing change) groups according to the random number table, with 20 mice in each group. The fluorescence intensity of PAO1-lux and blood flow in wound was respectively measured by in vivo optical imaging system and laser Doppler perfusion imager before treatment and at post treatment hour (PTH) 24. The expression levels of IL-1beta and vascular endothelial growth factor (VEGF) mRNA in wound edge were determined by real-time fluorescence quantitative RT-PCR before treatment and at PTH 24. The specimens of wound edge tissue were collected for observation of pathological change at PTH 24. Data were processed with t test.There were no obvious difference in fluorescence intensity of PAO1-lux and blood flow in wound between E and C groups before treatment (with t value respectively 0.03, 0.50, P values all above 0.05). The fluorescence intensity of PAOl-lux and blood flow in wound in E group at PTH 24 [(2.69 +/- 0.75) photons x s(-1) x cm(-2) x sr(-1) and (96 +/- 9) PU] was respectively lower and higher than that inC group [(5.18 +/- 0.96) photons x s(-1) cm x (-2) x sr(-1) and (70 +/- 11) PU, with t value respectively 3.54, 3.13, P values all below 0.05]. The expression levels of IL-1beta and VEGF mRNA in both groups before treatment were similar (with t value respectively 0.19, 0.07, P values all above 0.05). The expression levels of IL-1beta and VEGF mRNA in E group at PTH 24 was respectively 4.72 +/- 0.37, 2.68 +/- 0.39, all markedly higher than those in C group (2.24 +/- 0.50, 1.22 +/- 0.13, with t value respectively 6.90, 6.12, P values all equal to 0.00). The number of inflammatory cell infiltrating the wound edge in E group at PTH 24 was increased by nearly 77% as compared with that in C group.Compared with conventional dressing change, VSD can reduce the amount of Pseudomonas aeruginosa in full-thickness skin defect wound at the early stage, it may be related with an increase in blood flow and number of inflammatory cells in wound tissue, promoting expression of IL-1beta and VEGF mRNA.

To study the mechanism underlying the inhibitory effects of peroxisome proliferator-activated receptor γ (PPARγ) agonists on transforming growth factor β1 (TGF-β(1))-induced scarring of skin.Fibroblasts isolated from healthy adult skin were cultured in vitro and divided into blank control group (serum-free DMEM culture), TGF-β(1) group (with stimulation of 10 ng/mL TGF-β(1) for 48 hours), troglitazone group (with the same treatment as in TGF-β(1) group after stimulation of 10 µmol/L troglitazone for 2 hours), and 15-dioxygen prostaglandin J2 (15d-PGJ2) group (with the same treatment as in TGF-β(1) group after stimulation of 10 µmol/L 15d-PGJ2 for 2 hours) according to the stimulation added into DMEM. The expression of connective tissue growth factor (CTGF) was determined with Western blot. The mRNA levels of CTGF, matrix metalloproteinase-1 (MMP-1) and platelet-derived growth factor (PDGF) were determined with real-time fluorescence RT-PCR. Data were processed with one-way analysis of variance.The expression of CTGF at mRNA and protein levels in skin fibroblasts were significantly increased in TGF-β(1) group as compared with control group; while expression of CTGF at mRNA and protein levels in 15d-PGJ2 and troglitazone groups were significantly decreased as compared with that in TGF-β(1) group. The mRNA level of MMP-1 in TGF-β(1) group (0.193 ± 0.051) was obviously lower than that in blank control group (1.281 ± 0.195, F = 12.811, P0.01), while the mRNA levels of MMP-1 in troglitazone group (0.417 ± 0.043) and 15d-PGJ2 group (0.485 ± 0.027) were significantly increased as compared with that in TGF-β(1) group (F = 12.811, P values all below 0.01). The mRNA level of PDGF in TGF-β(1) group (1.044 ± 0.237) was obviously higher than that in control group (0.349 ± 0.057, F = 16.848, P0.01), while the levels in troglitazone group (0.677 ± 0.055) and 15d-PGJ2 group (0.511 ± 0.017) were significantly decreased as compared with that in TGF-β(1) group (F = 16.848, P values all below 0.01).The inhibitory effect of activated PPARγ on the expression of CTGF induced by TGF-β(1) may be the main mechanism of its inhibitory effect on TGF-β(1)-induced scarring on skin, and its influence on MMP-1 and PDGF may also be one of the underlying mechanisms.

To study the microsurgical method of repairing skin and soft tissue defects on head, face, and neck.Thirty-one patients with skin and soft tissue defects on the head, face, or neck were hospitalized from July 2007 to May 2010, including 10 cases of scalp defects, 4 cases of skin and soft tissue defects on face, and 17 cases of skin and soft tissue defects on neck. Among them, the cause in 20 cases was trauma, and in 11 cases they were secondary to release of cicatricial contraction. Free flaps were transplanted to repair the wounds, including 13 latissimus dorsi flaps, 3 lateral thoracic flaps, 5 scapular flaps, and 10 anterolateral thigh flaps. The area of flaps ranged from 8 cm × 5 cm to 25 cm × 18 cm.All flaps survived, and all the wounds healed by first intention. The average length of hospital stay was 16.7 days. Twenty-eight patients were followed up for 2 months, and in all of them satisfactory function and appearance were restored.Free flap graft based on microsurgery can repair wound of skin and soft tissue defects on head, face and neck by a single operation, which eases suffering of patients, and shortens the length of hospital stay.

To study the safety and effects of free composite tissue flaps in repairing devastating wounds in early stage.One hundred and twenty-three patients with 128 devastating wounds hospitalized in our burns center from 2005 to 2009 were repaired with free flaps or composite tissue flaps. Flap types used included 58 latissimus dorsi muscular flaps, 32 anterolateral thigh flaps, 21 circumflex scapular flaps, 6 dorsalis pedis composite flaps, 3 big toe nail skin flaps, 3 forearm flaps, and 1 lateral thoracic flap. One wound was repaired with lateral lower leg flap with fibula, and 3 wounds with free latissimus dorsi muscular flap plus skin graft.Vascular crisis was observed in 10 transplanted flaps 1 to 5 days after operation; 6 flaps with this complication were saved after emergency surgical exploration. Total survival rate of transplanted flaps and composite tissue flaps was 95.3% (122/128). All patients were followed up for 3 months to 4 years; satisfactory appearance and restoration of partial function were found in all of them.Free composite tissue transplantation reduces amputation rate, achieves primary reconstruction of function with good appearance, shortens length of hospital stay, and reduces surgical operation time, complications, and treatment cost. It is a good approach in the repair of massive devastating soft tissue injury.

The restoration of destroyed skin tissue in extensive deep burn injury has been perplexing burn surgeons for a long time due to impossibility of de novo formation of true skin in the process of burn wound healing with the current treatment methods. Stem cells possess the capacity to repair the damaged tissue through regeneration of the original structure and function, and it is considered as the expected ideal outcome of burn wound healing and also the final goal of multidisciplinary wound managements. In the skin tissue, the resident stem cells do exist, and they retain an autonomous self-renewal potential, and they respond to guiding signals to differentiate in repairing burn wound. Besides, the remote mesenchymal stem cells and the adjacent adipose-derived stem cells have been shown to be involved in burn wound healing. The basic studies demonstrated that the microenvironmental feature or extracellular regulators, the selective activation of intracellular signaling pathways, and the expression of specific genes have a significant influence on the proliferation, differentiation or function of stem cells in wound repair. Therefore, further investigation and manipulation of the molecular mechanisms by which stem cells could participate well in regenerating skin tissue would be a valuable and promising way in burn wound treatment. The recent discovery of reprogramming a mature body cell into a pluripotent stem cell, which can then be converted to any type of human body cell sheds a new light to regenerative medicine. Stem cell-based regeneration is offering the next coming frontier of medical therapy by yielding new treatment through delivery of pluripotent stem cells to achieve structural and functional repair in the damaged tissues or organs due to trauma or chronic diseases. Therefore, it is a pressing task for us to expedite the study on the role and utility of stem cells in burn wound treatment, especially aiming to explore the possibility in regenerating skin appendages or even the entire structure of the normal skin, and avoiding the formation of hypertrophic scar or chronic wound after burn.

To study the inhibitory effects of insulin on nuclear factor-kappa B (NF-kappaB) nuclear translocation of vascular endothelial cells induced by burn serum and its correlative mechanism.Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and divided into 5 groups: blank control group (BC, ordinary culture without any stimulation), normal serum control group (NS, cultured with nutrient solution containing 20% healthy human serum), burn serum stimulation group (BS, cultured with nutrient solution containing 20% burn human serum), burn serum+insulin treatment group (BI, cultured with nutrient solution containing 20% burn human serum and 1x10(-7) mol/L insulin), inhibitor pretreatment group [IP, pretreated with 50 micromol/L protein kinase B (Akt) specific inhibitor LY-294002, then cultured with the same medium as used in BI group 30 minutes later] according to the random number table. Six hours later, the injury and apoptosis of HUVECs was respectively observed by the scanning electron microscope and determined by the flow cytometry. Meanwhile, the phosphorylation of inhibitor kappa B-alpha (p-IkappaB-alpha) and Akt (p-Akt) in cytoplasm, and the content of NF-kappaB-p65 in nucleus were determined with Western blot.(1) Compared with those in BC group, HUVECs in BS group shrank obviously with irregular nuclear structure, and intercellular links jagged or vanished. Slight change was observed in HUVECs structure in NS and BI groups, with the cell ductility and nuclear structure much better than those in BS group. (2) The apoptosis rates of HUVECs in BS group [(28.5+/-2.3)%], BI group [(22.3+/-1.8)%], and IP group [(29.7+/-2.4)%] were all obviously higher than that in BC group [(15.7+/-2.2)%, F=14.288, P0.05 or P0.01]. There was no significant statistical difference between NS group [(17.0+/-2.5)%] and BC group in apoptosis rate (F=14.288, P0.05). The apoptosis rate of HUVECs in BI group was obviously lower than that in BS group (F=14.288, P0.05). (3) Compared with those in BC group, the protein expressions of p-IkappaB-alpha in cytoplasm and NF-kappaB-p65 in nucleus were up-regulated, and the protein expression of p-Akt in cytoplasm was down-regulated in BS and IP groups. The expression levels of the three proteins in NS and BI groups were close to those in BC group.Insulin could inhibit the IkappaB phosphorylation, and then restrict NF-kappaB nuclear translocation and improve the vascular endothelial cells function accordingly through regulating phosphatidylinositol 3 kinase/Akt pathway.

To observe the effect of the supernatant of heat injured keratinocytes (KC) on biological behavior of the dermal fibroblasts (Fb).Human dermal Fb were isolated and cultured. A model of heat injured KC (HaCaT) was reproduced in vitro. Supernatant of normal KC and the supernatant of KC culture 12 hours after heat injury were collected and diluted with non-serum DMEM in 1:1 volume ratio to make normal KC conditioned medium (NKCM) and heat injury KC conditioned medium (HKCM) respectively. Fb was respectively treated with non-serum DMEM and 2 kinds of conditioned medium. (1) The proliferation of Fb was detected with MTT method at post culture hour (PCH) 12, 24, 36, 48. (2) The apoptosis of Fb was determined by flow cytometry at PCH 12 (Fb were heat injured in advance; Fb without heat treatment was used as control). (3) At PCH 24, expression of a-SMA in Fb cytoplasm was determined with immunofluorescence method; expression of a-SMA mRNA in Fb was determined with real-time quantified PCR. Data were processed with one-way analysis of variance, and pairwise comparison among groups with LSD-t test.(1) The proliferation of Fb: the absorbance value of Fb cultured with HKCM at PCH 12, 24, 36, 48 was respectively higher than that of Fb cultured with non-serum DMEM (with t value respectively 1.89, 2.35, 2.02, 1.94, and P values all below 0.01). There were significant statistical differences between the absorbance values of Fb cultured with HKCM and those of Fb cultured with NKCM at PCH 12, 24, and 48 (at PCH 12, t = 1.83, P0.01; at PCH 24, t = 2.91, P0.05; at PCH 48, t = 1.83, P0.05). (2) Apoptosis of Fb cultured with HKCM was diminished as compared with that of Fb cultured with NKCM and of Fb without treatment (t = 3.31, P0.05; t = 1.47, P0.01). (3) The expression of alpha-SMA (red fluorescence) in Fb cultured with non-serum DMEM or NKCM was less as seen under fluorescence scope, and it was obviously increased in Fb cultured with HKCM. (4) The relative expression amount of alpha-SMA mRNA in Fb cultured with HKCM was 1.32 +/- 0.06, which was higher than that both in Fb cultured with NKCM (1.14 +/- 0.07, t = 2.51, P0.05) and in Fb cultured with non-serum DMEM (1.00 +/- 0.09, t = 1.77, P0.05).The supernatant of KC 12 hours after heat injury can obviously promote the proliferation of Fb, inhibit its apoptosis and accelerate transdifferentiation of Fb to myofibroblasts.

With the advances in resuscitation, infection control, and metabolic management, the treatment strategies for burn patients have improved remarkably in the last half century. As a result, more patients with deep burn wound survived, and how to optimize the burn wound care aiming at recovery of the normal appearance and physiologic function of patients has been investigated and discussed widely through both the whole treatment strategy making and the new techniques performing. In the present discussion, early tissue reconstruction as well as early wound covering and repair are emphasized by summarizing the improved aesthetic and functional effects obtained by applying the principles of plastic surgery in early burn wound repair, the use of composite skin grafting, the grafting with split-thickness autografts on the preserved denatured dermis or on the preserved healthy fat tissue, etc. Besides these, more attention should be given to the repair and reconstruction in specialized functional parts of the body, such as head and face, neck, hand, female breast, perineum, and joint areas, after a deep burn. The role of rehabilitation during and after the burn wound treatment process is elucidated by demonstrating its potential biophysical mechanism and preventing scar deformity. Adequate treatment of deep burn wound demands a number of important measures including the timing of surgery, adoption of essential techniques, suitable types of wound covering materials, motivated rehabilitation, and necessary psychological therapy. The optimal recovery of damaged part of body after burn should depend on the similarity of rebuild tissue structure to simulate the nature of the original tissue in the cellular, histological, anatomic characteristics, which is the aim of all burn wound care and the basis of the appearance and function repair or reconstruction.

To elucidate the effects of interferon-gamma (IFN-gamma) on the transforming growth factor beta (TGF-beta)/Smad pathway in keloid-derived fibroblasts (KFb), and to investigate the underlying mechanism in the treatment of pathologic scar with IFN-gamma.Keloid tissue of 3 patients were obtained, and then KFb were separated and cultured in vitro. KFb from passages 3 to 5 were used for the study. (1) KFb were divided into control group (incubated with serum-free DMEM), TGF-beta(1) group (treated with 10 ng/mL TGF-beta(1)), IFN-gamma group (treated with 100 ng/mL IFN-gamma), and TGF-beta(1)+IFN-gamma group (incubated with 10 ng/mL TGF-beta(1) combined with 100 ng/mL IFN-gamma). The expression level of mRNA and protein of connective tissue growth factor (CTGF), alpha smooth muscle actin (alpha-SMA) protein and expression of alpha-SMA positive KFb were detected by real-time fluorescent quantitation RT-PCR (FQ-RT-PCR), Western blot and immunofluorescence cytochemical staining. (2) Another sample of KFb was obtained and treated with 10 ng/mL IFN-gamma. The expression level of Smad 3 and Smad 7 protein was detected by Western blot before and 1, 2, 4, 6, 8 h post stimulation (PSH). The expression level of Smad 3 and Smad 7 mRNA was assessed by FQ-RT-PCR before stimulation and 30 mins post stimulation and at PSH, 1, 2, 4, 6, 8. (3) Another sample of KFb was obtained and divided into 1, 10 and 100 ng/mL IFN-gamma groups based on the concentration of IFN-gamma, treated for 4 hours; KFb without IFN-gamma treatment was set up as control group. The expression levels of the protein and mRNA of Smad 3 and Smad 7 were measured by FQ-RT-PCR and Western blot.(1) The level of mRNA and protein of CTGF in IFN-gamma group (0.017 +/- 0.009 and 1.198 +/- 0.004) was respectively lower than that in control group (0.024 +/- 0.013 and 1.229 +/- 0.011, P0.05). The level of mRNA and protein of CTGF in TGF-beta(1)+IFN-gamma group (0.634 +/- 0.138 and 1.204 +/- 0.010) was respectively lower than that in TGF-beta(1) group (1.331 +/- 0.298 and 1.727 +/- 0.004, P0.01). The fluorescence intensity of alpha-SMA positive KFb (0.922 +/- 0.059) and the expression level of alpha-SMA protein (0.3051 +/- 0.0031) in IFN-gamma group decreased significantly than those in control group (1.055 +/- 0.005 and 0.4513 +/- 0.0094, P0.01). The fluorescence intensity of alpha-SMA positive KFb (1.129 +/- 0.004) and the expression level of alpha-SMA protein (0.6734 +/- 0.0098) in TGF-beta(1)+IFN-gamma group decreased significantly than those in TGF-beta(1) group (1.270 +/- 0.005 and 1.3842 +/- 0.0024, P0.01). (2) The expression level of Smad 3 mRNA and protein at the first time point after IFN-gamma treatment increased temporarily then decreased gradually, and mRNA expression level reached the nadir at PSH 4, it rose gradually later, though it was still lower at PSH 8 than that before treatment (P0.01); protein expression level at PSH 8 was significantly lower than that before treatment (P0.01). The expression level of Smad 7 mRNA and protein increased gradually to the maximum at PSH 2 and 4 respectively, then decreased but was still higher at PSH 8 than that before treatment (P0.05). (3) Compared with those in control group, the expression levels of Smad 3 mRNA and protein in 1, 10 and 100 ng/mL IFN-gamma group were significantly lower, the expression levels of Smad 7 mRNA and protein were significantly higher (P0.05 or P0.01). The higher concentration of IFN-gamma, the more significant differences were observed.IFN-gamma can down-regulate the expression of Smad 3 while up-regulate the expression of Smad 7 in a time- and dose-dependent manner, and reduce the expression level of CTGF and alpha-SMA in the basic state or induced by TGF-beta(1), which shows a significant inhibitory effect on the TGF-beta/Smad signal pathway. This may be an important mechanism in the treatment of pathologic scar by IFN-gamma.

To observe the effect of comprehensive rehabilitation treatment on hand burn, and to make a cost-effectiveness analysis.Sixty-two patients with ninety-eight affected hands were divided into rehabilitation group (32 cases, 48 hands) and control group (30 cases, 50 hands). Patients in rehabilitation group received comprehensive rehabilitation treatment at early stage after burn; patients in control group were given instructions for function training at the same time. The functions of the hands to be restored including grasp, hold, pinch, nip, forearm pronation and supination, fetching, laying, and writing abilities of patients in both groups were quantitatively evaluated with Carroll's upper extremity function test before treatment and 5 months after. Direct medical costs of patients in both groups within 5 months were respectively added up to make a cost-effectiveness analysis.In rehabilitation group, function of digital opposition, palmar opposition, holding, and pinching of 37 hands recovered well, with which patients could pick food, put on clothes, go to toilet, and self-care etc. independently. Function of digital opposition, palmar opposition, holding, pinching half recovered in 7 hands, accompanied with well recovered of metacarpophalangeal function, but recovery of function of interphalangeal joint was less satisfactory. Although patients could grasp and hold, they were still poor in fine and harmonized activities. Joint ranges of motion of 4 hands were poor with limited function, and this was resulted from not strictly following treatment for remaining granulation wound. In control group, 23 hands received reconstructive surgery, 14 of them recovered with good function, but were poor in most of fine and harmonized activities. Severe claw hands were found in 13 hands. The ratio between total mean cost value and total function increment value in rehabilitation group (181 +/- 11) was obviously lower than that in control group (298 +/- 30, P0.01).Comprehensive rehabilitation treatment at early stage after hand burn has a good effect on prevention and treatment of hand deformity, promoting recovery of hand function and improving hand appearance. It is also less costly.

Destructive burns and traumas which create composite tissue damages, as well as intractable wounds, usually cause the difficulties or inefficacy in the repair and management through ordinary skin grafting or tissue transplantation owing to the complex defects, unhealthy healing condition, or high requirements for the function and appearance reconstruction of the injured local tissues. The advantages of free tissue transplantation with microsurgical techniques in the tissue repair and reconstruction have been demonstrated as meeting the composite tissues restoration, improving blood supply, avoiding further damage to the wound surrounding tissues, and simplifying the distant tissue transplantation procedure, and therefore significantly decreasing the deformities with good functional and morphological outcomes, and dramatically reducing the hospitalization duration with less complications and faster restitution. In the present discussion, basing on the general literature review and the summary of our long-time clinical application of microsurgical techniques in dealing with serious injuries, we put forward the view that the microsurgical techniques should be considered as the first option for the treatment of destructive burns and traumas, and intractable wounds. And in some cases, only microsurgical techniques can be used, otherwise amputation would be unavoidable, or the optimal treatment would be abandoned or delayed. Meanwhile, it should be emphasized that the risk and the failure rate of performing microsurgical operation can be overcome through strictly hard training.

To investigate the feasibility of debridement at early stage by combining lavation and drainage under continuous negative pressure in the limb salvage surgery of patients suffering from diabetic foot complicated by plantar abscess.Ten patients suffering from diabetic foot (10 feet affected) combined with plantar abscess were involved. After being debrided, wounds of patients were lavaged and drained for 7 - 14 ds under continuous negative pressure through a detained stomach tube. Suction under negative pressure continued for 3 - 5 ds after lavation, and then drainage tube was removed. Stitches on wound were removed about 3 weeks after surgery. The condition of the wounds was observed.After above-mentioned treatment, local inflammatory response of patients was obviously ameliorated, and the wounds healed with satisfactory preservation of function and shape of the feet.Debridement combined with local lavation and drainage under continuous negative pressure is satisfactory for the treatment of diabetic foot complicated by plantar abscess, and it can preserve the length of the affected limb.