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.

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.

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.

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.

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.

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.

A severely infected diabetic foot treated successfully without using systemic antibiotics.

About 50% to 70% of all lower extremity amputations are related to diabetes infection. And antibiotic therapy is routinely used for all infected wounds to reduce the mortality of diabetic foot. Here, we report a case of diabetic foot with acute and deep severe infection. During hospital therapy, we used negative pressure therapy and extensive debridement without systemic antibiotic application, and we successfully rescued a foot from amputation. Negative pressure therapy and extensive debridement are very important and effective methods to control infection and promote wound healing in diabetes foot.

[Wound information management system: a standardized scheme for acquisition, storage and management of wound information].

OBJECTIVE: To form a wound information management scheme with objectivity, standardization, and convenience by means of wound information management system. METHODS: A wound information management system was set up with the acquisition terminal, the defined wound description, the data bank, and related softwares. The efficacy of this system was evaluated in clinical practice. RESULTS: The acquisition terminal was composed of the third generation mobile phone and the software. It was feasible to get access to the wound information, including description, image, and therapeutic plan from the data bank by mobile phone. During 4 months, a collection of a total of 232 wound treatment information was entered, and accordingly standardized data of 38 patients were formed automatically. CONCLUSIONS: This system can provide standardized wound information management by standardized techniques of acquisition, transmission, and storage of wound information. It can be used widely in hospitals, especially primary medical institutions. Data resource of the system makes it possible for epidemiological study with large sample size in future.

[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".

[Exploring the three-dimensional structure of dermal tissues of normal skin and scar in rat with synchrotron radiation X-ray imaging technology].

OBJECTIVE: To compare the morphological difference between dermal tissue of normal skin and that of scar in rat, and to explore its structural pattern. METHODS: The full-thickness skin and the scar tissue formed 3 weeks after wound healing from SD rats were harvested as samples, which were prepared appropriately afterwards. Samples were scanned and imaged with synchrotron radiation technology, micro-CT, and phase-contrast imaging technology. The images were rebuilt with three-dimensional software. RESULTS: The micro-CT was materialized by using X-ray generated by synchrotron radiation light source. The structure of dermal tissues was clearly shown with the assistance of phase-contrast imaging technology in the process. It was demonstrated that the dermal tissues of normal skin of rat were mainly composed of collagenous fibers, which twined together to form an olive-like structure. These olive-like structures as basic units were arranged randomly in a certain way. The collagenous fibers in dermal tissue of the scar were arranged in a parallel manner, while some fibers were crooked and arranged in a disorderly manner. CONCLUSIONS: Dermal tissue of normal skin in rat has stable three-dimensional structure, and its basic structure and manner of composition are obviously different from those of scar dermal tissue.

[Effects of advanced glycation end products and its receptor on oxidative stress in diabetic wounds].

OBJECTIVE: To investigate the accumulation of advanced glycation end products (AGE) and the inflammatory response of skin and wound in diabetic patients, and to analyze their relationship in vitro. METHODS: Histological staining and immunohistochemical staining was respectively performed on skin and wound tissue specimens collected from 10 patients with Type II diabetes mellitus (diabetes group) and 12 non-diabetic patients with skin injury (control group) to observe the arrangement of collagen and the distribution of inflammatory cells, and to determine the expression levels of AGE and its receptor (RAGE). Malondialdehyde (MDA) levels in skin and wound tissue homogenates were assayed by enzyme-linked immunosorbent assay. In vitro, human neutrophils were isolated and treated with RPMI-1640 culture medium or that containing AGE-human serum albumin in the concentration of 0.315, 0.625, 1.250 mg/mL, and they were identified as normal control (NC) group, low concentration (L) group, moderate concentration (M) group, and high concentration (H) group. Cell viability in each group was determined by MTT colorimetric assay, and the reactive oxygen species (ROS) in cell was measured with 2', 7'-dichlorofluorescein-diacetate. Data were processed with t test. RESULTS: Compared with those of skin in control group, collagens of skin tissues in diabetes group atrophied and disorderly arranged. Inflammatory cells in wounds in diabetes group were dispersed, in which collagens arranged loosely and irregularly, as compared with those of wounds in control group. Expression levels of AGE and RAGE of skin in diabetes group were higher than those in control group. In diabetes and control groups, especially in diabetes group, the numbers of RAGE-positive cells in wound tissue were more than those in skin tissue. Large amount of inflammatory cells with positive expression of RAGE were observed in diabetes group. MDA level of skin and wound tissue in diabetes group was respectively (6.3 ± 1.0), (7.1 ± 2.4) nmol per milligram protein, which were obviously higher than those in control group [(2.9 ± 1.0), (3.6 ± 1.4) nmol per milligram protein, with t value respectively 8.017, 4.349, P < 0.05 or P < 0.01]. Cell viability and ROS levels in neutrophils were increased in L, M, and H groups [(59 ± 8)%, (77 ± 5)%, (67 ± 6)% and 1.67 ± 0.14, 2.13 ± 0.17, 3.48 ± 0.48] as compared with those in NC group [(34 ± 5)% and 0.58 ± 0.06, with t value respectively 7.195, 14.890, 11.130 and 20.195, 24.905, 16.864, P < 0.05 or P < 0.01]. CONCLUSIONS: Abnormal oxidative stress in diabetic skin leads to an atypical origin of wound repair. AGE-RAGE effect is a critical mediator for oxidative stress in diabetic wound tissue during wound healing.

[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.

Abnormal regulation of neo-vascularisation in deep partial thickness scalds in rats with diabetes mellitus.

OBJECTIVE: This study observed the degree of neo-vascularisation and differential expression of angiogenesis growth factors and their receptor in deep partial-thickness scald wound with diabetes mellitus. METHODS: Sixty Sprague-Dawley rats were randomised into a control group and an STZ-induced diabetic group, inflicted with partial-thickness scalding of 20% total body surface area (20% TBSA) on the back. Wound specimens were harvested immediately after scald and on 1, 3, 7, 10, 14 and 21 post-scald days (PSDs) to observe histological changes, and wound healing rates were calculated. The degree of neo-vascularisation in wound (labelled with blue microsphere) and the quantity of vascular endothelial cells (labelled with red CD31) were also measured by double-labelling immunofluorescence. Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), Tie-2, vascular endothelial growth factor (VEGF) and Flt-1 messenger RNA (mRNA) were analysed by real-time RT-PCR. Ang-1, Ang-2 and VEGF protein expressions were measured by Western blotting. RESULTS: Wound healing was markedly impaired in diabetic rats. The diabetic rats show inhibited vascularity in the wound edge at every time point (the quantitation of vascularity was 60.0±3.0 in the control group and 12.0±1.4 in the diabetic group, p<0.01 on day 7). Although neo-vascularisation in the number of endothelial cells was not significantly different compared with the normal group, part of new vascular endothelial cells did not form the vascular function. After injury, expression of Ang-2 mRNA and protein were increased in both groups, and the normal group showed decreases on day 7, 14 and 21, whereas the diabetic group showed significant increases. Although the expression VEGF and its receptors before injury was higher than the normal group, the level at 1, 3 and 7 days after injury was significantly lower than that 14 days, and that at 21 days after injury was significantly higher than the normal group. CONCLUSION: Vascular endothelial cells can proliferate actively in the diabetic wound with deep partial-thickness burns, but it is still poor in blood supply due to lack of functional capillaries. The mechanism may be related to sustained abnormal high expression of Ang-2 and down-regulated VEGF.

[Relationship between cutaneous glycometabolic disorders and cutaneous neuropathy in diabetic rats].

OBJECTIVE: To analyze the relationship between cutaneous glycometabolic disorders and cutaneous neuropathy in diabetic rats, and to look for the mechanism of neuropathy and impaired wound healing. METHODS: Eighty male SD rats were randomly divided into the normal control group (NC, n = 20), diabetic group (D, n = 20), aminoguanidine-interfered group (AI, n = 20), and insulin-interfered group (II, n = 20) by drawing lots. Diabetes was reproduced in rats of D, AI, and II groups with intraperitoneal injection of streptozotocin (STZ). Then, rats in AI group were fed with 100 mg×kg(-1)×d(-1) aminoguanidine, while rats in II group were subcutaneously injected with insulin for satisfactory control of blood glucose. Changes in mechanical and heat pain thresholds of pad of hind limb were measured at post injection week (PIW) 2, 4, 8. Skin specimens were collected during PIW 2-8 from pads for determination of contents of glucose, advanced glycation end product (AGE), substance P (SP), calcitonin gene-related peptide (CGRP), and observation of distribution and ultrastructure of skin nerve fibers. Data were processed with t test. RESULTS: The mechanical and heat pain thresholds in D group at PIW 2 [(6.3 ± 1.5) g, (6.0 ± 0.9) s, respectively ] were obviously lower than those in NC group [(13.0 ± 3.2) g, (10.3 ± 1.2) s, with t value respectively 2.71, 3.42, P values all below 0.05]. Contents of glucose and AGE in skin tissue in D group were significantly increased when compared with those in NC group, especially at PIW 8 [(2.85 ± 0.33) mg/g, (31.7 ± 3.2) U/mg of hydroxyproline vs. (0.82 ± 0.22) mg/g, (22.2 ± 1.9) U/mg of hydroxyproline, with t value respectively 1.65, 6.47, P values all below 0.01]. The myelinated nerve fibers were edematous and degenerated, with axons compressed, while the unmyelinated nerve fibers were vacuolated, with microfilament and microtubule disorderly arranged. Content of SP in skin tissue in D group was lower as compared with that in NC group, especially at PIW 2 [(16.8 ± 3.4) pg/g vs. (28.5 ± 5.0) pg/g, t = 2.42, P < 0.01]. There was no obvious difference in content of CGRP between NC and D groups, and also in content of glucose in skin between D and AI groups. Compared with those in D group, content of AGE in AI group at PIW 8 was decreased markedly [(27.2 ± 1.4) U/mg of hydroxyproline, t = 3.38, P < 0.05]; contents of glucose and AGE in II group at PIW 8 were significantly decreased [(1.42 ± 0.38) mg/g, (23.6 ± 1.3) U/mg of hydroxyproline, with t value respectively 1.74, 8.17, P < 0.05 or P < 0.01]. Compared with that in D group, contents of SP in AI and II groups were increased, with a delay in time of trough value. Content of CGRP showed no obvious difference among D, AI, and II groups. CONCLUSIONS: High glucose and accumulation of AGE are key mediators of cutaneous neuropathy and impaired wound healing in diabetes mellitus, which confirms that diabetic wound takes an atypical footing during wound repairing. Aminoguanidine and insulin can reduce contents of glucose and AGE in diabetic skin tissue, and ameliorate diabetic cutaneous neuropathy.

[Effect of topical application of aminoguanidine cream on skin tissue of rats with diabetes].

OBJECTIVE: To investigate the effects of aminoguanidine cream on the proliferation of keratinocytes (KC), content of advanced glycosylation end products (AGE) and oxidative stress in skin tissue of rats with diabetes. METHODS: Stearic acid, liquid paraffin, vaseline, lanolin, isopropyl myristate fat, glycerol, 50 g/L alcohol paraben, aminoguanidine hydrochloride etc. were mixed in certain proportion to make aminoguanidine cream, and cream without aminoguanidine was used as matrix. The dorsal skin of normal rats were harvested and treated by aminoguanidine cream with dose of 5, 10 g/L, or 5 g/L together with 10 g/L azone. The transdermal effect was respectively measured at post treatment hour 2, 4, 7, 10, 12, 24. Thirty SD rats were divided into normal control (NC, n = 6), diabetes (D, n = 8), aminoguanidine cream-interfered (AI, n = 8), matrix cream-interfered groups (MI, n = 8) according to the random number table. Diabetes was reproduced by intraperitoneal injection of STZ (65 mg/kg) in rats of D, AI, and MI groups, and rats in NC group were injected with 0.05 mmol/L citrate buffer as control. One week later, dorsal skin of rats in AI and MI groups were respectively treated with 10 g/L aminoguanidine cream and matrix cream by external use for 4 weeks. AGE content was determined with fluorescence detection from skin collagen extract. KC cell cycle was detected by flow cytometry. Skin tissue specimens were obtained for determination of levels of superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO), and total antioxidant capacity. Data were processed with t test. RESULTS: Transdermal effect of aminoguanidine cream with dose of 10 g/L was better than that with 5 g/L or 5 g/L + 10 g/L azone cream. One rat was not induced successfully in MI group. Four weeks after model reproduction, 4 rats died in D group and 1 rat died in AI group. The AGE content in D group was obviously higher than that in NC group [(36.8 +/- 2.6), (24.6 +/- 2.7) U per milligram hydroxyproline, respectively, t = 7.2, P < 0.01], and that in AI group [(28.6 +/- 3.7) U per milligram hydroxyproline] was also lower as compared with that in D group (t = -3.9, P < 0.05). There was no significant difference in AGE content between MI [(32.2 +/- 5.2) U per milligram hydroxyproline] and D groups (t = 1.6, P > 0.05). The percentage of KC in S phase was obviously lower in D group than in NC group [(5.3 +/- 0.6)%, (7.6 +/- 0.9)%, respectively, t = 4.50, P < 0.01], while that in MI group [(9.2 +/- 1.5)%] was higher as compared with that in D group ( t = 4.90, P < 0.01). It was more higher in AI group than in D group on KC percentage in S and G2/M phase (with t value respectively 6.80, 3.17, P values all below 0.01). The oxidative stress indexes of skin tissue in D group were all higher than those in NC group, in which levels of MPO and SOD showed statistical difference (with t value respectively 4.4, 3.7, P values all below 0.05). The oxidative stress indexes were all lower in AI group than in D group, especially in SOD level (t = -1.4, P < 0.05). Levels of MAD, MPO in MI group were significantly lower than those in D group (with t value respectively 2.6, 2.9, P values all below 0.05). CONCLUSIONS: Aminoguanidine cream can promote KC proliferation and appropriately reduce oxidative stress through inhibiting AGE formation to a certain extent in skin tissue of rats with diabetes. Signal use of matrix cream can also reduce oxidative stress in skin tissue of rats with diabetes.

[Exploration on the linkage mechanism between wound healing department and community health system].

Discipline of wound healing, has been emerged with the demand of patients suffering from various wounds. A unique way different from traditional medical system, in accordance with the incidence of wound diseases, medical demand, and current medical system of China, should be operated for the specialty, so as to benefit medical service for patients, rational allocation of medical resources. An overall layout with characteristic of "small ward, big clinic" is likely to meet the discipline demand associated with wound diseases, which present the linkage mechanism between wound healing department and community health system. By means of jointing wound healing clinic in community, two-way referral pathway for patients, training for general practitioner in community, guarantee and incentive system, an new operation pattern of wound healing discipline would be formed, described as linkage mechanism of wound healing department and community health system.