Prevalence and prognosis of hard-to-heal wounds with comorbidities in China.

OBJECTIVE: Regular retrospective analysis is necessary for potential improvement in clinical practice for the treatment of hard-to-heal wounds. Comorbidities and outcomes have demonstrated spatial and temporal diversity, emphasising the importance of updates in epidemiology. The complexity of healing hard-to-heal wounds has long been known, and so we sought evidence-based improvement on the current principles of treatment. METHOD: Demographic and clinical information of patients from the WoundCareLog database was collected. Patients who met the inclusion criteria and completed follow-up after treatment were included. Comorbidities were diagnosed and classified into eight categories based on ICD-10. We compared the demographic and aetiological characteristics between patients with and without comorbidities by t-test and Chi-squared test. The impact of comorbidities on wound healing were evaluated with a multivariate Cox model. RESULTS: A total of 2163 patients met the inclusion criteria and were enrolled, of whom 37.0% were aged 61-80 years, 36.0% were aged 41-60 years and 60.8% were male. The lower extremities and buttocks were the most commonly affected areas with hard-to-heal wounds. Non-traumatic wounds accounted for 66.6% of cases, and infection, pressure and diabetes were the most common causes. Paralysis and diabetes were the most important factors which led to a prolonged healing process and inferior clinical outcomes. CONCLUSION: Comorbidities of hard-to-heal wounds were treated as separate contributors and their weighted effect on outcome was calculated through correlation analysis. Paralysis and diabetes were the most unfavourable comorbidities affecting the treatment of non-traumatic hard-to-heal wounds. Our study highlighted the priority of comorbidity treatment through data-driven approaches. It provides potential value in developing better public health strategies and preventive medicine.

Different therapeutic effects between diabetic and non-diabetic adipose stem cells in diabetic wound healing.

OBJECTIVE: This study aimed to investigate how adipose tissue-derived stem cells (ASCs) from diabetic and from non-diabetic rats affect wound healing in different microenvironments. METHOD: The two types of ASC-rich cells were distinguished by characteristic surface antigen detection. The ASC-rich cells were transplanted into the wounds of diabetic and non-diabetic rats. Wound healing rates were compared and the healing process in the wound margin sections was used to determine how ASC-rich cells affect wound healing in different microenvironments. RESULTS: ASC density was decreased in diabetic rats. The generation time of ASC-rich cells from diabetic rats (d-ASC-rich cells) was longer than that of ASC-rich cells from non-diabetic rats. The number of pre-apoptotic cells in the third generation (passage 3) of d-ASC-rich cells was higher than that among the ASC-rich cells from non-diabetic rats. CD31 and CD34 expression was higher in d-ASC-rich cells than in ASC-rich cells from non-diabetic rats, whereas CD44 and CD105 expression was lower than that in ASC-rich cells from non-diabetic rats. Transplantation of ASC-rich cells from non-diabetic rats promoted wound healing in both non-diabetic and diabetic rats. In contrast, d-ASC-rich cells and enriched nuclear cells only promoted wound healing in non-diabetic rats. ASC-rich cell transplantation promoted greater tissue regeneration than d-ASC-rich cell transplantation. CONCLUSION: ASC-rich cells promoted wound healing in diabetic and non-diabetic rats. ASC density was lower in the adipose tissue of diabetic rats compared with non-diabetic rats. d-ASC-rich cells did not promote wound healing in diabetic rats, suggesting that caution is warranted regarding the clinical use of diabetic adipose stem cell transplantation for the treatment of diabetic wounds.

WoundCareLog APP - A new application to record wound diagnosis and healing.

The incidence of chronic wounds has been increasing over the past 20 years. However, the standardized diagnosis and treatment practice of chronic refractory wounds have not been established. In addition, the properties of the wound are characterized by morphology and thus correct description of the wound in medical history collection plays a vital role, which directly affects the definitive diagnosis. To develop more accurate format of clinical history record which can correctly reflect a patient's course and treatment progress, and to standardize the medical history record of chronic refractory wounds, at the national or regional level, we designed the WoundCareLog APP. It acts as a recording and communication tool for wound healing specialists at all levels of medical institutions in China. The WoundCareLog APP is fully compatible to meet the criteria and requirements of conventional medical records by embedding 9 modules. In addition, the demands for morphological description of wounds in wound healing diagnosis and treatment have been fulfilled by enroll of digital imaging technology to overcome the inadequacies of traditional medical history records.

Histomorphological observation of surgical debridement combined with negative pressure therapy in treatment of diabetic foot.

PURPOSE: To further study the mechanism of epithelization on the fascia side of the flap after surgical incision and the treatment of the negative pressure therapy. METHODS: With the patients' informed consent, parts of tissue samples were obtained from a 51-year-old diabetic patient who was suffering lower extremity ulcers. The samples were processed with hematoxylin and eosin (HE) staining and Masson trichrome staining. The keratin 19, keratin 15 and carcino-embryonic antigen (CEA) were immunohistochemically detected. RESULTS: The results of HE staining showed that the specimen was divided into two regions, newborn area and original epithelial area. There were more inflammatory cells infiltrating in the dermis in the newborn epithelial area, compared with the original epithelial area. Cells in newborn epithelial area were more active and many dinuclear and polynuclear cells were observed in newborn epithelial area. But there were more cuticular layers and obvious rete pegs in original epithelial area. In addition, the cells with keratin 19 and CEA positive were found around hair follicle, while keratin 15 was negative. Masson trichrome staining showed that there was a lot of de novo collagen in newborn epithelial area. CONCLUSION: Epidermal cells on the fascia side of the flap could be derived from the stem cells. Negative pressure wound therapy would attract not only cells but also other elements such as growth factors, cytokines, some nutrients and extracellular matrix. With the formation of the appropriate microenvironment after debridement, the migrated cells can grow, differentiate and spread, eventually leading to the epithelization on the fascia side of the flap in diabetic foot.

Dynamic hypoxia in scar tissue during human hypertrophic scar progression.

BACKGROUND: The skin color of human hypertrophic scar changes dynamically during scar progression. OBJECTIVE: To investigate whether hypoxia is dynamic during scar progression. METHODS: Thirty-five patients with early, proliferative, regressive, and mature scars were involved in this study. Tissue oxygen tension was measured before scar surgery. After surgery, the scar stage was further defined using hematoxylin and eosin staining, and microvessel density and hypoxia inducible factor-1 (HIF-1) expression were detected using immunohistochemistry to determine a correlation with oxygen level. RESULTS: Mild hypoxia is present in early scars, moderate hypoxia in proliferative scars, and severe hypoxia in regressive scars. Oxygen levels then return to normal in mature scars, which was consistent with the dynamic change in microvessel density. Meanwhile, HIF-1 expression also changed dynamically along with alteration in oxygen levels. CONCLUSION: Hypoxia is dynamic in scar tissue and is possibly correlated with scar formation and regression.

Mechanistic study of endogenous skin lesions in diabetic rats.

Pathological and physiological changes in dermal tissue in a rat model of diabetes mellitus (DM) were investigated. Sixteen male 8-week-old Sprague-Dawley rats were randomized into two groups of eight, the DM group (Group DM) and the normal control group (Group (NC) normal control). Group DM rats were injected with streptozotocin (STZ) intraperitoneally at a dose of 65 mg/kg body weight. Group NC rats were injected with the same volume of citric acid buffer. All rats were sacrificed 12 weeks later. The impact of exposure to (AGE) advanced glycation end products-modified human serum albumin (AGE-HSA) on epidermal cells and ECV304 cells was evaluated in cell culture experiments. The diabetic rats exhibited changes in skin tissue, including a decrease in thickness, disappearance of the multilayer epithelium structure, degeneration of collagen fibres and an increase in the infiltration of inflammatory cells, in addition to a significant increase in skin glucose and AGEs. Moreover, diabetic rats had increased plasma glycosylated protein (GSP) and malondialdehyde (MDA) and decreased plasma glutathione (GSH). The percentage of epidermal cells in S phase was similar between the two group rats; however, there was a marked decrease in the G2/M phase in Group DM. Additionally, exposure of ECV304 cells to AGE-HSA led to a time-dependent and dose-dependent increase in apoptosis. Therefore, the high glucose in the skin tissue, coupled with the accumulation of toxic substances such as AGEs, promote the dysfunction of dermal cells and/or the matrix. This may be a significant mechanism of diabetes-induced early-stage endogenous skin damage.

A review of the effectiveness of antimitotic drug injections for hypertrophic scars and keloids.

Hypertrophic scars and keloids are common problems after injury and cause functional and cosmetic deformities. A wide variety of treatments have been advocated for hypertrophic scars and keloids regression. Unfortunately, the reported efficacy has been variable. This article explores antimitotic drugs described in the literature such as steroid injection, 5-FU, mitomycin C, and bleomycin, which mainly target the fibroblasts in scar tissue, have been proposed as the effective modalities for scar treatment and scar prevention after surgery, but restricted due to possible side effects. The current accepted treatment for hypertrophic scar and keloid are combination therapy and the early treatment which could achieve better efficacy and less adverse effect.

Antimitotic drug injections and radiotherapy: a review of the effectiveness of treatment for hypertrophic scars and keloids.

Scars are a common complication of surgery or burn wound management. Scars occur over the body, affecting people of both sexes and all ages. Scar therapy is a constant clinical challenge; antimitotic drugs and radiotherapy are used with varying degrees of success. This article examines the success of both these types of treatment modalities.

[Impact of advanced glycosylation end products-modified human serum albumin on migration of epidermal keratinocytes: an in vitro experiment].

OBJECTIVE: To explore the impact of advanced glycosylation end products (AGE)-modified human serum albumin (AGE-HSA) on keratinocyte migration and the mechanism thereof. METHODS: AGE-HSA was prepared in vitro. Epidermal keratinocytes from Sprague-Dawley rats' back were cultured and treated with AGE-HSA of the terminal concentrations of 0, 30, 60, 90, 120, and 150 microg/ml for 1, 3, 5, and 7 days respectively. MTT method was used to detect the keratinocyte adhesion rate, expressed by absorbance. Keratinocyte migration ability was assessed by scratch wound healing assay and Transwell assay. Expression of integrin alpha3 was determined by flow cytometry. Scanning electron and inverted microscopes were used to observe the pseudopodium and microfilament of the keratinocytes. Immunofluorescence staining was used to detect the form of F-actin in the cells. RESULTS: The adhesion rates of the keratinocyte cultured with AGE-HSA for 12 and 24 hours were (0.112 +/- 0.022) and (0.173 +/- 0.012) respectively, both significantly lower than those of the control group [(0.122 +/- 0.004) and (0.267 +/- 0.024) respectively, both P < 0.05)]. Scratch wound healing assay showed that the amount of migrating cells in the AGE-HSA group was (7 +/- 4)/HP, significantly less than that of the control group [(61 +/- 11)/HP, P < 0.05)], and Transwell assay showed that the amount of migrating cells in the AGE-HSA group was (72 +/- 18)/HP, significantly less than that of the control group [(288 +/- 52)/HP, P < 0.05]. The expression rate of keratinocyte integrin alpha3 in the AGE-HSA group was (3.2 +/- 1.2)%, significantly lower than that in the control group [(36.6 +/- 11.2)%, P < 0.05]. The spreading of cell body, and the formation of pseudopodium and microfilament of the AGE-HSA group were all depressed in comparison with the control group. CONCLUSION: Keratinocyte migration is inhibited by AGE accumulation in high glucose condition. The mechanism may be the abnormality in the integrin inside-out signaling pathway and AGE-RAGE signaling pathway.

[Study on the biological function of dermal fibroblasts in the wounds of diabetic and non-diabetic rats with deep burns].

OBJECTIVE: To explore the changes of the biological function of dermal fibroblasts (FBs) in the wounds of diabetic and non-diabetic burned rats and the pathogenesis of impaired wound healing in diabetes. METHODS: 80 Sprague-Dawley (SD) rats weighing 220 g were randomly divided into control and STZ-induced diabetic groups, and then deep partial thickness scald involving 10% TBSA was reproduced in the two groups. The diabetic groups were randomized into pre-scalding, post-scalding day (PSD 3), PSD 7, PSD 14 and PSD 21 groups, with 6 rats in each group. Controls were also randomized into 5 groups. Skin specimens from the wound were harvested at each time point. Cell cycles of FBs were analyzed with flow cytometry. The amount of hydroxyproline in the skin tissue was assessed on 0, 3, 7, 14, and PSD 21. The type I and III collagens were determined by ELISA. The expression of alpha-SMA in the dermal fibroblasts of each group was assessed by immunohistochemistry method. Transmission electron microscopy was used to observe the ultrastructure changes of FBs. RESULTS: Compared with that in the normal rats, the percentage of the cells in G(0)/G(1) phase in the DM group was evidently lower on PSD 0 (65.79 +/- 5.24 vs 82.43 +/- 9.68, P < 0.01). After the scalding, the percentage of the cells in G(0)/G(1) phase in DM group was significantly higher (70.00 +/- 4.27 vs 42.04 +/- 12.96, on PSD 3, P < 0.01), meanwhile the percentage of S phase was remarkably lower than those in C group on 3, 7, 14, 21PSD (P < 0.05, P < 0.01). The amount of hydroxyproline in the diabetic skin tissue was obviously lower than those of the responding control groups before (0.72 +/- 0.06 vs 1.42 +/- 0.28, P < 0.01) and after burn injury (P < 0.01). Furthermore, the rate of I/III collagen on 7, 14 and PSD 21 was much higher in DM group than that in C group (P < 0.01). The expression of alpha-SMA in DM groups on PSDS 3, 7, 14 and PSD 21 was evidently lower than those of the controls (levels 10.28 +/- 3.99, C group 28.42 +/- 2.73, on PSD 14, P < 0.01), although that inclined to be heightened after burn injury. Ultrastructure changes of FBs in the wounds of diabetic rats could be observed, such as the outstretched endoplasmic reticulum, un development of Golgi's body, lackness of microtubule and microfilament, a sharp increase of cytolysosomes, and so on. CONCLUSION: The FB proliferation in the diabetic skin is abnormal, the synthetical ability of collagen is weakened, the expression of alpha-SMA is insufficient, the microtubule and microfilament is lack, and the number of cytolysosomes increases. The pathogenesis of impaired-wound healing in diabetics might be related with the above mentioned factors.

The Influence of AGEs Environment on Proliferation, Apoptosis, Homeostasis, and Endothelial Cell Differentiation of Human Adipose Stem Cells.

The aim of this study was to evaluate the changes of proliferation, apoptosis, homeostasis, and differentiation of human adipose-derived stem cells (hASCs) in the simulated diabetic microenvironment and discuss the potential of the mesenchymal stem cell in the treatment of chronic diabetic wound. We simulated diabetic microenvironment with glycation end products (AGEs) in vitro and studied the changes of hASCs in proliferation and apoptosis. We found that AGEs inhibited the proliferation and lead to hASCs apoptosis, and the endothelial cell directed differentiation was also inhibited. AGEs upregulated growth-related oncogene and monocyte chemoattractant protein-1 and downregulated urokinase-type plasminogen activator receptor, which may inhibit the proliferation and transference of endothelial cells. The simulated diabetic microenvironment affects the proliferation, apoptosis, and homeostasis of hASCs, the endothelial cell migration, and the synthesis of collagen protein, leading to delayed wound healing.

Regenerative medicine in China: main progress in different fields.

Regenerative medicine (RM) is an emerging interdisciplinary field of research and China has developed the research quickly and impressed the world with numerous research findings in stem cells, tissue engineering, active molecules and gene therapy. Important directions are induced differentiation of induced pluripotent stem and embryo stem cells as well as somatic stem cell differentiation potential and their application in trauma, burns, diseases of aging and nerve regeneration. The products ActivSkin and bone repair scaffolds have been approved and are applied in the clinic, and similar products are being studied. About 10 engineered growth-factor drugs for repair and regeneration have been approved and are used in the clinic. Gene therapy, therapeutic cloning and xenotransplantation are some of the strategies being studied. However, China needs to develop standards, regulations and management practices suitable for the healthy development of RM. Aspects that should be strengthened include sound administrative systems, laws, and technical specifications and guidelines; conservation of stem cell resources; emphasis on training and retention of talented stem cell researchers; and reasonable allocation of resources, diversification of investment and breakthroughs in key areas. Finally, broad and deep international cooperation is necessary.

[Effects of the cutaneous and blood contents of glucose on wound healing in diabetic rats with superficial partial thickness scalding].

OBJECTIVE: To study the effect of the cutaneous and blood contents of glucose on wound healing in diabetic rats with superficial partial thickness scalding. METHODS: 96 Sprague-Dawley rats were randomized into control group and STZ-induced diabetic group, inflicted with superficial partial thickness scalding of 10% TBSA on the back. The glucose content in the blood and wound tissue were evaluated before injury and at day 1, day 3, day 5, day 7, day 10 and day 14 after injury. Wound healing process in the rats was dynamically observed by naked eyes and histologically examined. The cell cycles of keratinocytes from wound site were determined before injury and at day 3, day 7 and day 10 after injury. RESULTS: The concentrations of blood glucose in diabetic wound was significant increased than normal group (27.28 mmol/L +/- 0.80 mmol/L vs. 4.65 mmol/L +/- 0.14 mmol/L, P < 0.01). The content of local glucose in wound tissue were significantly correlated with that in the blood (r = 0.881, P < 0.05). When compared with the control group, wound healing of the diabetic rats were delayed with the characteristics of impaired epithelialization and decreased. percentages of S stage and G(2)/M stages of keratinocytes. CONCLUSION: Local glucose content in diabetic wound was varied with blood glucose concentration. The increased glucose concentration in diabetic wound was attributed to the impaired wound healing in diabetes. High glucose concentration could inhibit the epithelialization and decrease the keratinocyte proliferation.

[Amelioration of latent skin lesions in streptozotocin-induced diabetic rats by insulin].

OBJECTIVE: To explore the latent skin lesions in streptozotocin-induced diabetic rats and the mechanism of insulin prevention. METHODS: 81 male Sprague-Dawley (SD) rats were randomized into control (C, n = 27) and STZ-induced diabetic groups (n = 54), and then the diabetic rats were randomized into 2 groups: Group A group (n = 27) that was treated with insulin enough to control the high concentration of blood glucose strictly, and Group B group (n = 27) in which insulin was given too nut not sufficient to control the high blood glucose. Twenty-seven normal rats were used as controls. Four, eight, and twelve weeks after STZ-induction, skin specimens from the back were collected to undergo hematoxylin-eosin staining and histological examination. The skin glucose content was measured by Beckman's autoanalyzer. The skin advanced glycation end products (AGEs) concentration was assessed by fluorescence spectrophotometry and immunohistochemistry. The ultrastructure changes of skin microvessel were observed by electron microscopy. RESULTS: Twelve weeks after the establishment of the DM model the skin thickness of Group B was decreased, the features of multilayer epithelium structure disappeared in epidermis, and part of the collagen fibers in dermis became atrophic, swollen and degenerated, infiltration of inflammatory cells to different degrees was found, and subcutaneous fat showed progressive atrophy or disappeared. However, such changes were not detected in Group A. The skin glucose contents of Group B at different time points were all higher than those of Group A and Group (all P < 0.01) without a significant difference between Groups A and C. The fluorescence values of skin collagen extracts of Groups A and B were significantly higher than that of normal rats. The 8-week fluorescence value of skin collagen extracts of Groups B was 34 U/mg +/- 4 U/mg, significantly higher than that of Group A (29 U/mg +/- 3 U/mg, P < 0.05). The 12-week fluorescence value of skin collagen extracts of Groups B was 41 U/mg +/- 4 U/mg, significantly higher than that of Group A (32 U/mg +/- 4 U/mg, P < 0.05). The 8-week AGEs positive expression rate of Group B was 32% +/- 4%, significantly higher than that of Group A (25% +/- 5%, P < 0.05), and the 12-week AGEs positive expression rate of Group B was 39% +/- 5%, significantly higher than that of Group A (27% +/- 4%, P < 0.05). Degeneration of endothelial cells and thickening of basement membrane were more markedly in Group B than in Group A. CONCLUSION: Accumulation of AGEs in skin and high concentration of glucose are important causes of diabetic skin complications. Insulin application at the early stage postpones the course of diabetic skin lesions with the possible mechanisms of lowering the high glucose, inhibiting AGEs synthesis, and blocking the action of AGEs.

[Proliferation-inhibiting effect of advanced glycation end products modified human serum albumin to vascular endothelial cell ECV304].

OBJECTIVE: To study the proliferation-inhibiting and apoptosis-inducing effects of advanced glycation end products (AGE) modified human serum albumin (AGE-HSA) on human vein endothelial cells. METHODS: Human umbilical vein endothelial cells ECV304 were cultured in vitro with AGE-HSA of the concentrations of 12.5, 25, 50, 100, and 200 micro g/ml for 6, 12, 24, or 48 hour, then 20 micro l of 5 mg/ml MTT were added and the optical density (OD) at each time point was determined. Another ECV304 cells were cultured with AGE-HAS for 2, 4, or 8 days and then were stained with trypan blue to calculate the number of dead cells so as to calculate the proliferation-inhibiting rate. Another ECV304 cells were cultured with AGE-HAS for 6, 12, 24, or 48 hours and then stained with annexin V Fitc and propidium iodide (PI). Flow cytometry was used to calculate the annexin V Fitc positive cells (early and middle stage apoptotic cells) and Annexin V Fitc/PL positive cells (late apoptotic cells). Inverted microscope, transmission electron microscope, and fluorescence microscope were used to observe the histological changes of apoptotic cells. FCV304 cells incubated with HSA of the above-mentioned and without addition of the other agents concentrations were used as controls. RESULTS: The OD values of ECV304 cells cultured for 48 h with low concentrations (12.5, 25, and 50 micro g/ml) of AGE-HSA were not significantly different from those of the control (1.104 +/- 0.080, 1.098 +/- 0.097 and 1.059 +/- 0.122 VS. 1.159 +/- 0.088, all P > 0.05). The OD values of ECV304 cells cultured with low concentrations of AGE-HSA for 4 days and 6 days were significantly lower than those in the control group. The OD values of ECV304 cells cultured with high concentrations (100 and 200 micro g/ml) of AGE-HSA for 6 - 48 hours decreased to 0.117 +/- 0.033 and 0.081 +/- 0.020 in comparison with that of the control group (P < 0.01). Flow cytometry and fluorescence microscopy showed higher proportions of apoptotic cells among the ECV304 cells cultured with high concentrations of AGE-HAS than among the control cells at each time point (P < 0.01). The numbers of cells in the control group exponentially increased after culture for 2, 4, and 6 days. The number of cells cultured with low concentrations of AGE-HAS for 2 days was not significantly different from that of the control group (P > 0.05), however, the numbers of cells cultured with low concentrations of AGE-HAS for 4 and 6 days were significantly lower than those of the control group (both P < 0.01). The numbers of cells cultured with 100 or 200 micro g/ml AGE-HAS for 2 days were significantly lower than those of the control group (both P < 0.01) with a proliferation-inhibiting rate of 39.56% +/- 2.82% and 60.32% +/- 4.51% respectively. The apoptotic rates in cells cultured with low concentrations of AGE-HAS for 48 hours were not significantly different from those in the control group. The apoptotic rates in cells cultured with 100 or 200 micro g/ml AGE-HAS for 6, 12, 24, or 48 hours were significantly higher than those in the control group (all P < 0.01). The apoptotic rates in 200 micro g/ml group at different time points were significantly higher than those in the 100 micro g/ml group (P < 0.05 or 0.01). The apoptotic rate and number of apoptotic cells increased along with the increase of culture time and concentration of AGE-HAS. Microscopy showed morphological changes among the cells cultured with 100 micro g/ml AGE-HAS for 6, 12, 24, and 48 hours and the numbers of apoptotic cells, mainly late apoptotic cells, and dead cells increased remarkably since the cells were cultured for 48 hours. CONCLUSION: AGE-HSA inhibits the proliferation of vascular endothelial cells and induces apoptosis in dose and time dependent manner. AGE modification-induced pathobiological cascade may be involved in the pathogenesis of impaired wound healing in diabetes by the mechanism of angiogenesis retardation.

The change of break modulus drives human fibroblast differentiation in 3D collagen gels.

Extracellular matrix is one of the key environmental factors influencing cell survival and provides signals for cell morphological change, migration, proliferation and differentiation. However, the mechanism through which denatured collagen modulates the biological properties of fibroblasts, is unclear. We investigated the regulation of human fibroblast differentiation in vitro grown in collagen gels with different properties. The break modulus of collagen with denatured collagen and half-load normal collagen was reduced compared with that of normal collagen gel. Fibroblasts cultured in denatured collagen gels showed increased expression of matrix metalloproteinase9 ( MMP-9), tissue inhibitor of metalloproteinase 2 (TIMP2), α-smooth muscle actin (α-SMA), osteoblast cadherin, phosphorylated Myosin phosphatase target subunit1 (p-MYPT1), connective tissue growth factor, type I collagen, type III collagen, α-smooth muscle actin messenger RNA, RhoA, rho-associated protein kinase, and transforming growth factor ß receptors 1 and 2 compared with that in cells cultured in normal collagen gel. But there was no significant difference regarding expression level between denatured collagen gel and half-load normal collagen gel .These findings suggest that the change in break modulus caused by decreasing normal collagen concentration may be the key factor inducing fibroblast differentiation.

[Mechanism of scar formation and strategy of treatment].

So far, studies on the mechanism of scar formation have mainly focused on cells, cytokines and extracellular matrix. Some studies have shown that fibroblast is one of the most important element in the process of scar formation, while epidermal and endothelial cells exert synergistic effects as well. Genetic factor can not be ignored in scar formation, either. Recently, studies have shown decisively the loss or damage of the three-dimensional structure of dermal tissue is the initiator of scar formation. Thus, the defect of epidermis template is proposed as a theory in order to explain the mechanism of scar formation. There are various techniques for scar treatment. The commonly accepted methods are physical therapy, pressure therapy, pharmaceutical therapy, radiotherapy, etc.

[Enhance the connotation of establishment of wound healing department].

Following the development of social economy, the acceleration of aging problem, and the changes in disease spectrum, the incidence of various chronic wound diseases increased significantly, and it has become one of the most frequently encountered diseases that affect the people's health. The contradiction between the increase of medical need of wound diseases and the insufficiency of the medical service in our country is becoming increasingly conspicuous. Wound healing department, as a new cross subject that has emerged as the times require, needs to be perfected in its diagnostic and treatment strategies and methods. At present time, how to explore the new theory and pathologic mechanism of various chronic wounds, in order to establish the clinical guidelines in diagnosis and treatment that conform to national conditions of our country, and to establish efficient clinical pathway and medical-seeking model have become serious challenges to the establishment of wound healing department in our country. Thus, it is imperative for us to enhance the connotation of establishment of wound healing department. For this purpose, this article mainly elaborates on three aspects, including "enriching traditional diagnostic system with new theory and new technology", "improving treatment effect by ameliorating traditional methods and absorbing new technology from relating subspecialty", "establishing a new medical-seeking model by applying digital technology and vertically integrating medical resources".

[Enhance the establishment of wound healing centers and promote the specialized treatment of chronic skin wounds].

It is important to establish some comprehensive wound healing centers in order to treat those complicated chronic skin wounds. In this paper, I would like to summarize our practices in some hospitals dealing with the construction of wound healing centers and give my suggestions for their future development.