Principles of extramural health care for chronic wounds in China.

Development of extramural health care for chronic wounds is still in its infancy in China, and thus it is urgent and vital to establish a correct concept and practicable principles. The authors reviewed recent domestic and international literature and summarized the following treatment procedures and principles for extramural health care of chronic wounds. (1) The patient needs to do self-assessment of the wound by using available simple methods; (2) The patient consults with professional physicians or nurses on wound care to define the severity and etiology of the non-healing wound; (3) Professionals evaluate the existing treatment strategies; (4) Etiological treatments are given by professionals; (5) Patients buy needed dressings via the more convenient ways from pharmacies, e-commerce platform or others; (6) Professionals provide a standardized and reasonable therapeutic plan based on the patient's wound conditions; (7) Both professionals and the patient pay attention to complications to prevent adverse outcomes; (8) Professionals strengthen the public education on wound care and integrated rehabilitation. This review expected to provide new perspectives on the therapeutic strategies for chronic wounds in an extramural setting.

Effects of hydrogen-rich saline on early acute kidney injury in severely burned rats by suppressing oxidative stress induced apoptosis and inflammation.

BACKGROUND: Early acute kidney injury (AKI) in severely burned patients predicts a high mortality that is multi-factorial. Hydrogen has been reported to alleviate organ injury via selective quenching of reactive oxygen species. This study investigated the potential protective effects of hydrogen against severe burn-induced early AKI in rats. METHODS: Severe burn were induced via immersing the shaved back of rats into a 100°C bath for 15 s. Fifty-six Sprague-Dawley rats were randomly divided into Sham, Burn + saline, and Burn + hydrogen-rich saline (HS) groups, and renal function and the apoptotic index were measured. Kidney histopathology and immunofluorescence staining, quantitative real-time PCR, ELISA and western blotting were performed on the sera or renal tissues of burned rats to explore the underlying effects and mechanisms at varying time points post burn. RESULTS: Renal function and tubular apoptosis were improved by HS treatment. In addition, the oxidation-reduction potential and malondialdehyde levels were markedly reduced with HS treatment, whereas endogenous antioxidant enzyme activities were significantly increased. HS also decreased the myeloperoxidase levels and influenced the release of inflammatory mediators in the sera and renal tissues of the burned rats. The regulatory effects of HS included the inhibition of p38, JNK, ERK and NF-κB activation, and an increase in Akt phosphorylation. CONCLUSION: Hydrogen can attenuate severe burn-induced early AKI; the mechanisms of protection include the inhibition of oxidative stress induced apoptosis and inflammation, which may be mediated by regulation of the MAPKs, Akt and NF-κB signalling pathways.

Astaxanthin attenuates early acute kidney injury following severe burns in rats by ameliorating oxidative stress and mitochondrial-related apoptosis.

Early acute kidney injury (AKI) is a devastating complication in critical burn patients, and it is associated with severe morbidity and mortality. The mechanism of AKI is multifactorial. Astaxanthin (ATX) is a natural compound that is widely distributed in marine organisms; it is a strong antioxidant and exhibits other biological effects that have been well studied in various traumatic injuries and diseases. Hence, we attempted to explore the potential protection of ATX against early post burn AKI and its possible mechanisms of action. The classic severe burn rat model was utilized for the histological and biochemical assessments of the therapeutic value and mechanisms of action of ATX. Upon ATX treatment, renal tubular injury and the levels of serum creatinine and neutrophil gelatinase-associated lipocalin were improved. Furthermore, relief of oxidative stress and tubular apoptosis in rat kidneys post burn was also observed. Additionally, ATX administration increased Akt and Bad phosphorylation and further down-regulated the expression of other downstream pro-apoptotic proteins (cytochrome c and caspase-3/9); these effects were reversed by the PI3K inhibitor LY294002. Moreover, the protective effect of ATX presents a dose-dependent enhancement. The data above suggested that ATX protects against early AKI following severe burns in rats, which was attributed to its ability to ameliorate oxidative stress and inhibit apoptosis by modulating the mitochondrial-apoptotic pathway, regarded as the Akt/Bad/Caspases signalling cascade.

Levels of brain natriuretic peptide are associated with peripheral arterial disease in subjects with type-2 diabetes mellitus.

BACKGROUND: The effects of brain natriuretic peptide (BNP) on the risk of cardiovascular disease and atherosclerosis have been studied. However, little information is available regarding peripheral arterial disease (PAD), particularly among subjects with type-2 diabetes mellitus (T2DM). The aim of our study was to assess the potential relationship between BNP levels and PAD among T2DM patients. METHODS: The study cohort was 507 T2DM outpatients in which BNP levels were measured. Cross-sectional associations between BNP levels (in tertiles) and PAD were examined. RESULTS: Compared withT2DM patients without PAD, BNP levels were markedly higher in patients with PAD (p = 0.001). Correlation analyses showed that the BNP level was negatively correlated with the ankle-brachial index (r = -0.453, p = 0.033). At a cutoff value of 78.2 pg/ml, the BNP level showed a sensitivity of 71.9%, a specificity of 68.1%, and a positive predictive value of 84.3% for a diagnosis of PAD. The area under the receiver-operating characteristic curve increased significantly if BNP levels were incorporated into a predictive model of the potential risk factors for PAD (0.85 vs 0.81, p = 0.029). CONCLUSIONS: BNP is a potential and promising biomarker for PAD screening in T2DM patients.

Association between RUNX3 promoter methylation and gastric cancer: a meta-analysis.

BACKGROUND: Runt-related transcription factor 3 (RUNX3) is a member of the runt-domain family of transcription factors and has been reported to be a candidate tumor suppressor in gastric cancer. However, the association between RUNX3 promoter methylation and gastric cancer remains unclear. METHODS: We systematically reviewed studies of RUNX3 promoter methylation and gastric cancer published in English or Chinese from January 2000 to January 2011, and quantified the association between RUNX3 promoter methylation and gastric cancer using meta-analysis methods. RESULTS: A total of 1740 samples in 974 participants from seventeen studies were included in the meta-analysis. A significant association was observed between RUNX3 promoter methylation and gastric cancer, with an aggregated odds ratio (OR) of 5.63 (95%CI 3.15, 10.07). There was obvious heterogeneity among studies. Subgroup analyses (including by tissue origin, country and age), meta-regression were performed to determine the source of the heterogeneity. Meta-regression showed that the trend in ORs was inversely correlated with age. No publication bias was detected. The ORs for RUNX3 methylation in well-differentiated vs undifferentiated gastric cancers, and in intestinal-type vs diffuse-type carcinomas were 0.59 (95%CI: 0.30, 1.16) and 2.62 (95%CI: 1.33, 5.14), respectively. There were no significant differences in RUNX3 methylation in cancer tissues in relation to age, gender, TNM stage, invasion of tumors into blood vessel or lymphatic ducts, or tumor stage. CONCLUSIONS: This meta-analysis identified a strong association between methylation of the RUNX3 promoter and gastric cancer, confirming the role of RUNX3 as a tumor suppressor gene.

Clinical guideline on topical growth factors for skin wounds.

An increased number of patients with skin wounds have been witnessed in the past decades. Among the various kinds of treatments for skin wounds, topical exogenous growth factors are indispensable and have been used in many countries. However, whether they have reliable effects remains controversial, and their application for skin wound treatment needs to be further standardized and optimized in terms of socio-economic considerations. Thus, the Chinese Burn Association developed this guideline indicating efficacy, application details, adverse reactions and precautions of five clinically common topical growth factors using the Grading of Recommendations Assessment Development and Evaluation method to promote the rational application of topical exogenous growth factors in skin wounds and to benefit more patients.

Randomized controlled trial of the absorbency of four dressings and their effects on the evaporation of burn wounds.

BACKGROUND: Wound dressings are divided into traditional and new types. The new dressings are thought to accelerate wound healing. The purpose of this study was to supplement the scanty data on the absorbency of the new dressings and their effects on evaporation from the burn surface. METHODS: The water absorption rate of four dressings (carbon fiber dressing, hydrogel dressing, silver nanoparticle dressing, and vaseline gauze) were measured by the immersion-weight gain method. A total of 120 inpatients with 10% superficial partial-thickness burn wounds were randomly assigned to four groups, each with 30 participants. Carbon fiber dressing, hydrogel dressing, and silver nanoparticle dressing were used in groups A, B, and C as the primary dressing, and traditional vaseline gauze was used in group D as the control. Multi-spot evaporation from normal skin and naked wound, and from wounds covered with each of the four dressings was measured post-burn on days 1, 3, 5, and 7 by an EP-I evaporimeter under conditions of 21 degrees C - 22 degrees C ambient temperature and 74% - 78% humidity. RESULTS: The absorption rates of the four dressings were 988% with carbon fiber dressing, 96% with silver nanoparticle, 41% with vaseline gauze, and 6% with hydrogel. Evaporation from the naked burn wounds was about 1/3 higher than from normal skin (P < 0.01). Compared with wounds without applied dressing, evaporation from dressed wounds decreased and was time-dependent (P < 0.01). The evaporation of wounds with carbon fiber dressing was the lowest ((13.40 +/- 2.82) mlxh(-1)xm(-2), P < 0.01) on day 1 post-burn, compared with the other groups. CONCLUSION: All four dressings have water retention capacity while carbon fiber dressing has the highest absorption rate and shows the best containment and evaporation from the burn wound.

[Effect of silver nanoparticle dressing on second degree burn wound].

OBJECTIVE: To explore the influence of silver nanoparticle dressing on prevention of infection and healing of the second degree burn wound. METHODS: One hundred and ninety-one burn patients with second degree including superficial and deep burn wound were randomly divided into three groups. Group A including 65 cases was treated by silver nanoparticle dressing on wounds, and group B (63 cases) and group C (63 cases) were treated by 1% silver sulfadiazine cream and vaseline gauze on their wounds, respectively. Dressing was changed daily, and wound swab bacterial cultures were performed before and after dressing change, and also wound healing times were recorded in each patient. RESULTS: Group A and B were similar in their bacterium colonizations on wound after treatment with the silver nanoparticle dressing and 1% silver sulfadiazine cream, and they had a similar effect on reducing bacterium colonization on wound after treatment, while in vaseline gauze group bacterium colonization on wound increased after treatment. In group A the wound healing time of superficial second degree was significantly shorter than those in group B and group C (P < 0.01). In deep second degree wounds the healing time in group A was much shorter than that in group C (P < 0.01), but had no significant difference when compared with group B (P > 0.05). CONCLUSION: Silver nanoparticle dressing can be used on second degree burn wound and can decrease the risk of wound infection and accelerate wound healing.

Optimizing Technology Use for Chronic Lower-Extremity Wound Healing: A Consensus Document.

Innovations in technology are used in managing chronic wounds. Despite the wide range of technologies available, healing of chronic wounds remains variable. In this paper, the authors offer an evidence based approach to the use of technology for diagnosis and management based on the concept of standardised care.

Beneficial effects of hydrogen-rich saline on early burn-wound progression in rats.

INTRODUCTION: Deep burn wounds undergo a dynamic process known as wound progression that results in a deepening and extension of the initial burn area. The zone of stasis is more likely to develop more severe during wound progression in the presence of hypoperfusion. Hydrogen has been reported to alleviate injury triggered by ischaemia/reperfusion and burns in various organs by selectively quenching oxygen free radicals. The aim of this study was to investigate the possible protective effects of hydrogen against early burn-wound progression. METHODS: Deep-burn models were established through contact with a boiled, rectangular, brass comb for 20 s. Fifty-six Sprague-Dawley rats were randomly divided into sham, burn plus saline, and burn plus hydrogen-rich saline (HS) groups with sacrifice and analysis at various time windows (6 h, 24 h, 48 h) post burn. Indexes of oxidative stress, apoptosis and autophagy were measured in each group. The zone of stasis was evaluated using immunofluorescence staining, ELISA, and Western blot to explore the underlying effects and mechanisms post burn. RESULTS: The burn-induced increase in malondialdehyde was markedly reduced with HS, while the activities of endogenous antioxidant enzymes were significantly increased. Moreover, HS treatment attenuated increases in apoptosis and autophagy postburn in wounds, according to the TUNEL staining results and the expression analysis of Bax, Bcl-2, caspase-3, Beclin-1 and Atg-5 proteins. Additionally, HS lowered the level of myeloperoxidase and expression of TNF-α, IL-1ß, and IL-6 in the zone of stasis while augmenting IL-10. The elevated levels of Akt phosphorylation and NF-κB p65 expression post burn were also downregulated by HS management. CONCLUSION: Hydrogen can attenuate early wound progression following deep burn injury. The beneficial effect of hydrogen was mediated by attenuating oxidative stress, which inhibited apoptosis and inflammation, and the Akt/NF-κB signalling pathway may be involved in regulating the release of inflammatory cytokines.

[Isolation, culturation and adipogenisis committed differentiation of adult human mesenchymal stem cell].

OBJECTIVE: To isolate MSCs from adult human bone marrow cells and to induce them into adipocytes. METHODS: MSCs were isolated from adult human bone marrow aspirated by Percoll and expanded in L-DMEM. The surface antigen of MSCs, CD14, CD34, CD45, CD44, VLA-1, HLA-DR and cell cycle were analysed on a FACScan flow cytometer. MSCs were cultured in adipogenisis inducing medium including insulin, 1-methyl-3-isobutylxanthine, indomethine and dexamethasone for 7 days and stained with Oil Red O. RESULTS: MSCs grew as adherent cells and expanded more than 10 passages. They were positive for CD44 and negative for CD14, CD34, CD45, HLA-DR. The expression of VLA-1 was weak. After 7 days of adipocyte inducing, about 85%of the cells displayed accumulation of lipid vacuoles, as detected by Red Oil O. CONCLUSION: MSCs isolated and cultured from adult human bone marrow can be induced to adipogenisis committed differentiation.

[A study of the abnormalities of human epiderm in keloids and hypertrophic scars].

OBJECTIVE: To investigate the abnormalities of human epiderm in keloids and hypertrophic scars. METHODS: Biopsies from ten untreated keloids (duration of disease 3 - 30 years) and ten hypertrophic scars (duration of disease 6 - 10 months) and five normal adult skin specimens. Total RNA was isolated from normal adult skin. A cDNA fragment (base 5941 - 6481 bp) of the full-length human Tenascin-C cDNA was synthesized by polymerase chain reaction and subcloned in pGEM-T-easy. Dioxigen-labeled anti-sense and sense probes were synthesized by using a Sp6/T7 in vitro RNA synthesis kit in the present of Dig-UTP. In situ hybridization was performed on 4% paraformaldehyde-fixed and wax-embedded sections of keloids and hypertrophic scars. NBT-NCIP was used in color detection. Immunohistochemical procedure. The sections were incubated with antibodies (anti-Tenascin-C, anti-CK-16 and anti-Ki-67). Ultrasensitive Streptavidin Peroxidase staining was performed following established procedures. RESULTS: The study show that the proliferation of epidermal keratinocytes in keloids and hypertrophic scars is very clear. The expressions of Tenascin-C mRNA in keloids epidermal keratinocytes markedly increased in contrast with epidermal keratinocytes of hypertrophic scars and adult skin. The CK-16 and Ki-67 stainings significantly enhanced in the epidermal keratinocytes of keloids and hypertrophic scars. CONCLUSIONS: The different expressions of Tenascin-C, CK-16 and Ki-67 among normal adult skin, keloids and hypertrophic scars show the abnormalities of epidermal keratinocytes proliferation and differentiation in keloids and hypertrophic scars.

[Postoperative electron beam irradiation therapy for keloid:a follow-up study of 48 patients].

OBJECTIVE: To explore the effectiveness of postoperative electron beam irradiation therapy for keloid. METHODS: Forty-eight patients with 65 keloid sites were treated by surgical removal and postoperative 25 Gy electron beam irradiation from 1994 to 2002 and followed for over eighteen months. Statistical analysis was performed and therapeutic outcome was evaluated. RESULTS: The overall recurrence rate was 26%. Higher post-treatment recurrence rates were noted with keloid forming at infected sites and in patients with family history (47.8% and 53.3%) (P < 0.05). Meanwhile, patient age, sex, keloid size and location had no increased likehood of recurrence rate. CONCLUSION: The study shows that postoperative electron beam irradiation therapy is a kind of safe and effective method in inhibiting recurrence of keloid formation and eradicating it.

Effect of heparin on prevention of flap loss in microsurgical free flap transfer: a meta-analysis.

The effectiveness of heparin for thromboprophylaxis during microvascular free flap transfer is uncertain. The purpose of this meta-analysis was to determine the effect of heparin on the prevention of flap loss in microsurgical free flap transfer.A search of PubMed, Cochrane databases, and Google Scholar using combinations of the search terms heparin, free flap, flap loss, free tissue transfer was conducted on March 15, 2013. Inclusion criteria were: 1) Prospective randomized trials. 2) Retrospective, non-randomized studies. 3) Patients received free tissue transfer. Flap loss rate was used to evaluate treatment efficacy. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated and compared between therapies. Four studies meet the criteria for analysis and were included. Two studiescompared aspirin and heparin, and the ORs of the 2 studies were 1.688 and 2.087. The combined OR of 2.003 (95% CI 0.976-4.109, p = 0.058) did not indicate any significant difference between heparin and aspirin therapies. Two studiescompared high and low doses of dalteparin/heparin therapies, and the ORs of the 2 studies were 4.691 and 11.00. The combined OR of 7.810 (95% CI 1.859-32.808, p = 0.005) revealed a significant difference indicating that high dose dalteparin or heparin therapy is associated with a greater flap loss rate than low dose therapy. Heparin and aspirin prophylaxis are associated with similar flap loss rates after free flap transfer, and high dose dalteparin or heparin therapy is associated with a greater flap loss rate than low dose therapy.

[Tissue engineered skin and regenerative wound repair].

Various skin defects resulting from mechanical injury, burns, chronic ulcers, and resection of tumor etc. are very common in clinic. The traditional treatment measure, such as grafting of autologous split-thickness skin remains the gold standard. However, its limitations are obvious, such as shortage of donor sites, creation of new injury, and scar formation. To realize regenerative or scarless repair of tissue defects has always been the dream of human being. The advent of tissue engineered skin (TES) provides an ideal access to tissue regeneration. After decades of development, several kinds of TES products have been developed and used in clinic, with promising effects. However, a large number of basic scientific problems regarding TES, as well as difficulties in translation of basic research to bedside should be taken into serious consideration. This article presents a comprehensive overview of strategies of construction of TES, the role of TES in regenerative wound repair, and its opportunities and challenges.

[Advances in the research of treatment of hydrofluoric acid burn].

Hydrofluoric acid (HF) is one of the most common inorganic acids used widely in industrial circle. HF not only causes cutaneous burn, but also induces systemic toxicity by its unique injury mechanism. Accurate and timely diagnosis and treatment are critical after HF burns. To date, the strategies for treating HF burns have been developed, mainly including topical treatments and systematic support. However, there is no standard treatment strategy with wide acceptance in the world. This paper presents a comprehensive overview of the advances in the research of strategies for the treatment of HF burns.

Endostatin inhibits hypertrophic scarring in a rabbit ear model.

OBJECTIVE: The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation. METHODS: Eight male New Zealand white rabbits were randomly assigned to two groups. Scar model was established by making six full skin defect wounds in each ear. For the intervention group, intraperitoneal injection of endostatin was performed each day after the wound healed (about 15 d post wounding). For the control group, equal volume of saline was injected. Thickness of scars in each group was measured by sliding caliper and the scar microcirculatory perfusion was assessed by laser Doppler flowmetry on Days 15, 21, 28, and 35 post wounding. Rabbits were euthanatized and their scars were harvested for histological and proteomic analyses on Day 35 post wounding. RESULTS: Macroscopically, scars of the control group were thicker than those of the intervention group. Significant differences between the two groups were observed on Days 21 and 35 (p<0.05). Scar thickness, measured by scar elevation index (SEI) at Day 35 post wounding, was significantly reduced in the intervention group (1.09±0.19) compared with the controls (1.36±0.28). Microvessel density (MVD) observed in the intervention group (1.73±0.94) was significantly lower than that of the control group (5.63±1.78) on Day 35. The distribution of collagen fibers in scars treated with endostatin was relatively regular, while collagen fibers in untreated controls were thicker and showed disordered alignment. Western blot analysis showed that the expressions of type I collagen and Bcl-2 were depressed by injection of endostatin. CONCLUSIONS: Our results from the rabbit ear hypertrophic scar model indicate that systemic application of endostatin could inhibit local hypertrophic scar formation, possibly through reducing scar vascularization and angiogenesis. Our results indicated that endostatin may promote the apoptosis of endothelial cells and block their release of platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF), thereby controlling collagen production by fibroblasts. Blood vessel-targeted treatment may be a promising strategy for scar therapy.

[Facing wound healing-let our mind soar].

When I started my career as a burn doctor, I looked over all those chapters dealing with wound healing wishing desperately to help me understand the healing process and mechanism of wound. Whereas is that the whole picture of wound healing? Decades have passed; we are still following these protocols. Do we really have nothing better to do with wound healing? When I was asked to write this comment, I was thinking that we should think high and wide in facing wound healing.

[Advances in research of the strategies for promoting angiogenesis in tissue engineering].

Rapid angiogenesis is one of the major issues in the field of tissue engineering, and it is an urgent problem to be solved. The process and related mechanism of angiogenesis have been deeply researched. Meanwhile, various methods or strategies for promoting angiogenesis, involving the application of stem cells and growth factors, and construction and modification of biomaterial scaffolds, have also been reported. On one hand, many remarkable advances in the field of promoting angiogenesis have been achieved; on the other hand, the complexity of mechanism and regulation of angiogenesis have gradually been recognized and emphasized. This paper presents a comprehensive overview of advances in research of the strategies for promoting angiogenesis in the field of tissue engineering.

Elevated skin autofluorescence is strongly associated with foot ulcers in patients with diabetes: a cross-sectional, observational study of Chinese subjects.

OBJECTIVE: This study was designed to evaluate the association between skin autofluorescence (AF), an indicator of advanced glycation end-products (AGEs), and foot ulcers in subjects with diabetes. METHODS: In this study, 195 Chinese diabetic subjects were examined. Their feet were examined regardless of whether an ulcer was present or not. Skin AF was measured with an AGE reader. Demographic characteristics and blood data were recorded. RESULTS: The mean values of skin AF were 2.29 ± 0.47 for subjects without foot ulcers, and 2.80 ± 0.69 for those with foot ulcers, a significant difference (P<0.05). Skin AF was strongly correlated with age and duration of diabetes. After adjusting for these factors, multivariate logistic regression showed that skin AF was independently associated with foot ulcerations. CONCLUSIONS: Skin AF is independently associated with diabetic foot ulcerations. It might be a useful screening method for foot ulceration risk of diabetic patients.