The bone mesenchymal stem cell-derived exosomal miR-146a-5p promotes diabetic wound healing in mice via macrophage M1/M2 polarization.

A diabetic wound is a refractory disease that afflicts patients globally. MicroRNA-146a-5p (miR-146a-5p) is reported to represent a potential therapeutic target for diabetic wounds. However, microRNA easily degrades in the wound microenvironment. This study extracted bone marrow mesenchymal stem cell (BMSC)-derived exosomes (EXO). Electroporation technology was used to load miR-146a-5p into EXO (labeled as EXO-miR-146a). The endothelial cells (human umbilical vein endothelial cells [HUVECs]) and macrophages were cocultured in transwell chambers in the presence of high glucose. Cell proliferation, migration, and angiogenesis were measured with cell counting kit 8, scratch, and tube forming assays, respectively. Flow cytometry was introduced to validate the biomarker of macrophages and BMSCs. The expression level of macrophage polarization-related proteins and tumor necrosis factor receptor-associated factor 6 (TRAF6) was assessed with western blotting analysis. The full-thickness skin wound model was developed to verify the in vitro results. EXO-miR-146a promoted the proliferation, migration, and angiogenesis of HUVECs in the hyperglycemic state by suppressing the TRAF6 expression in vitro. Additionally, EXO-miR-146a treatment facilitated M2 but inhibited M1 macrophage polarization. Furthermore, EXO-miR-146a enhances reepithelialization, angiogenesis, and M2 macrophage polarization, thereby accelerating diabetic wound healing in vivo. The EXO-miR-146a facilitated M2 macrophage polarization, proliferation, migration, and angiogenesis of HUVECs through TRAF6, thereby ameliorating intractable diabetic wound healing. These results established the basis for using EXO to deliver drugs and revealed mediators for diabetic wound treatment.

The role of Gel-Ppy-modified nerve conduit on the repair of sciatic nerve defect in rat model.

The serious clinical challenge of peripheral nerve injury (PNI) is nerve regeneration. Nerve conduit represents a promising strategy to contribute to nerve regeneration by bridging injured nerve gaps. However, due to a unique microenvironment of nerve tissue, autologous nerves have not been substituted by nerve conduit. Nerve regeneration after nerve conduit implantation depends on many factors, such as conductivity and biocompatibility. Therefore, Gelatin (Gel) with biocompatibility and polypyrrole (Ppy) with conductivity is highly concerned. In this paper, Gel-Ppy modified nerve conduit was fabricated with great biocompatibility and conductivity to evaluate its properties of enhancing nerve regeneration in vivo and in vitro. The proliferation of Schwann cells on Gel-Ppy modified nerve conduit was remarkably increased. Consistent with in vitro results, the Gel-Ppy nerve conduit could contribute to the regeneration of Schwann cell in vivo. The axon diameters and myelin sheath thickness were also enhanced, resulting in the amelioration of muscle atrophy, nerve conduction, and motor function recovery. To explain this interesting phenomenon, western blot results indicated that the Gel-Ppy conduit facilitated nerve regeneration via upregulating the Rap1 pathway to induce neurite outgrowth. Therefore, the above results demonstrated that Gel-Ppy modified nerve conduit could provide an acceptable microenvironment for nerve regeneration and be popularized as a novel therapeutic strategy of PNI.

Fibroblast Growth Factor 9 Inhibited Apoptosis in Random Flap via the ERK1/2-Nrf2 Pathway to Improve Tissue Survival.

BACKGROUND: The application of random pattern skin flaps is limited in plastic surgery reconstruction due to necrosis. Fibroblast growth factor 9 (FGF9) was reported to exert a protective effect against myocardial damage and cerebral ischemia injury, but the impact of FGF9 in random flap survival is still unclear. In this study, we used a mouse model of random flaps to verify that FGF9 can directly increase flap survival area and blood flow intensity by promoting angiogenesis. MATERIALS AND METHODS: In total, 84 male C57BL/6 mice weighing between 22 and 25 g were randomly divided into three groups (n = 28 each group). After skin flap operation, one group served as a control, a treatment group received FGF9, and a treatment group received FGF9+U0126. All flap samples were incised on postoperative day 7. RESULTS: Our results showed that flap survival was significantly increased in the FGF9 group compared with that in the control group. This protective function was restrained by U0126. The results of histopathology, laser Doppler, and fluorescent staining all showed significant increases in capillary count, collagen deposition, and angiogenesis. FGF9 also significantly increased the expression of antioxidant stress proteins SOD1, eNOS, HO-1, vascular marker proteins CD31, VE cadherin, and pericyte marker protein PDGFRß. Western blot showed that the phosphorylation degree of ERK1/2 increased after FGF9 treatment, and the expression of Nrf2, a downstream factor, was u-regulated. Western blot and immunofluorescence results of apoptosis-related proteins cleaved caspase-3, BAX, and Bcl2 showed that FGF9 inhibited apoptosis. ERK inhibitor U01926 reduced the beneficial effects of FGF9 on skin flap survival, including promoting angiogenesis, and showing antiapoptosis and antioxidative stress activities. CONCLUSIONS: Exogenous FGF9 stimulates angiogenesis of random flap and survival of tissue. the impact of FGF9 is closely linked to the prevention of oxidative stress mediated by ERK1/2-Nrf2. In the function of FGF9 in promoting effective angiogenesis, there may be a close interaction in the FGF9-FGFR-PDGFR-ERK-VE cadherin pathway. In particular, PDGFR and VE cadherin may interact.

Exploring the Correlation Between the Regulation of Macrophages by Regulatory T Cells and Peripheral Neuropathic Pain.

OBJECTIVE: Intractable pain after peripheral nerve injury has become a major concern in the field of pain. Current evidence shows that routine medications or surgical treatment is associated with inconsistent results and different curative effects. Stable and effective treatment methods in clinical practice are also lacking. To date, there is no consensus on the pathophysiological mechanisms of pain. The present study investigates the potential regulatory role of regulatory T cells in the differentiation of macrophages on dorsal root ganglion (DRG) and explores the mechanism of nociceptive signals in the signal transfer station. The findings are expected to guide the prevention of various types of peripheral neuropathic pain. METHODS: Thirty-six male Sprague Dawley (SD) rats and 18 male Nude rats, of equal weight (250-300g), were used in this study. The rats were divided into 3 groups: SD rat sciatic nerve transection group (SNT group, n = 18), SD rat nerve transection experimental group (SNT/RAPA group, n = 18) and Nude rat nerve transection experimental group (SNT/NUDE group, n = 18). The behavior related to neuropathic pain of animals were comprehensively evaluated in all groups. Furthermore, we analyzed the degree of neuroma development, histology, gene, and protein expression, and compared their correlation with the ultrastructural changes of M1/M2 type differentiation of macrophages in DRG. RESULTS: Sciatic nerve transection (SNT), induced the aggregation of several types of macrophages in lumbar DRG of SD rats leading to a higher ratio of M1/M2. Following the inhibition of the M1 type polarization of macrophages, axon outgrowth increased significantly. A significantly lower average autotomy score was reported in the SNT/NUDE group (*p < 0.05) and the SNT/RAPA group (@ p < 0.05) as compared to that of the SNT group. The SNT/NUDE group showed no noticeable neuroma formation 30 days after the nerve transection. However, bulbous neuromas were observed in the nerve stumps of both the SNT control and SNT/RAPA groups. Immunofluorescence staining revealed a significant decrease in the proportion of M1/M2 macrophages in lumbar DRG of the SNT/NUDE group (** p < 0.001) and the SNT/RAPA group (@ p < 0.05) compared to the SNT group. The expression of pain-related proteins was also decreased (@ p < 0.05, *p < 0.05,** p < 0.001). Also, the expression of alpha-smooth muscle actin (α-SMA), neurofilament 200 (NF-200), and nerve growth factor low-affinity receptor p75 were significantly down-regulated in the nerve tissue (@ p < 0.05, @@ p < 0.001, ** p < 0.001). CONCLUSION: M1/M2 type differentiation of macrophages on DRG plays a significant role in the formation of traumatic painful neuroma after neurotomy. In combination with our previous study, the results of this study suggest that regulatory T cells reduce the ratio of M1/M2 macrophages and alleviate the pain of neuroma by regulating the polarization direction of macrophages on neuroma. These findings provide key insights into developing new strategies to manage painful neuroma.

Augmenting Peripheral Nerve Regeneration with Adipose-Derived Stem Cells.

Peripheral nerve injuries (PNIs) are common and debilitating, cause significant health care costs for society, and rely predominately on autografts, which necessitate grafting a nerve section non-locally to repair the nerve injury. One possible approach to improving treatment is bolstering endogenous regenerative mechanisms or bioengineering new nervous tissue in the peripheral nervous system. In this review, we discuss critical-sized nerve gaps and nerve regeneration in rats, and summarize the roles of adipose-derived stem cells (ADSCs) in the treatment of PNIs. Several regenerative treatment modalities for PNI are described: ADSCs differentiating into Schwann cells (SCs), ADSCs secreting growth factors to promote peripheral nerve growth, ADSCs promoting myelination growth, and ADSCs treatments with scaffolds. ADSCs' roles in regenerative treatment and features are compared to mesenchymal stem cells, and the administration routes, cell dosages, and cell fates are discussed. ADSCs secrete neurotrophic factors and exosomes and can differentiate into Schwann cell-like cells (SCLCs) that share features with naturally occurring SCs, including the ability to promote nerve regeneration in the PNS. Future clinical applications are also discussed.

Microvascular Replantation of Totally Avulsed Scalps: Failures and Successes.

Total scalp avulsion is a rare but devastating injury currently without proven reconstructive techniques. While microsurgical anastomosis procedures have advanced and allowed for the replantation of digits and limbs, special anatomical considerations and risk of fatal blood loss add to the difficulty of replanting totally avulsed scalps. The authors present their replantation experience of 4 totally avulsed scalps between 2008 and 2017. Despite meticulous reconstructive techniques with proven success in limb and digit replantation, the first 3 cases failed due to various factors (i.e., thrombosis, venous congestion, reavulsion), and with experience, the fourth case was successful. Since total scalp avulsions are rare injuries, case reports are scarce, with only few publications commenting on failures which hold crucial information for surgeons to avoid pitfalls and optimize techniques. In this article, we highlight our experience with both successful and failed replantation of totally avulsed scalps, and offer recommendations and insight for optimization of this rare procedure.

Therapeutic potential of pravastatin for random skin flaps necrosis: involvement of promoting angiogenesis and inhibiting apoptosis and oxidative stress.

Background: Random skin flap is frequently used in plastic and reconstructive surgery, but its distal part often occurs ischemia and necrosis. Pravastatin (Prava) with bioactivities of pro-angiogenesis, anti-apoptosis and anti-oxidative stress, may be beneficial for flap survival. Materials and methods: A modified McFarlane flap model was performed in Sprague-Dawley rats. The animals were divided into the Control and Prava groups and treated as follows: the Prava group was injected intraperitoneally with 2 mg/kg Prava for consecutive 7 days, and the Control group received an equal volume of vehicle daily. On day 7, the necrosis skin flaps were observed, while visualization of blood flow below the tissue surface was performed by Laser Doppler blood flow imaging (LDBFI). Then animals were euthanized, and levels of angiogenesis, apoptosis and oxidative stress were analyzed. Results: Prava decreased necrosis and edema of skin flaps compared with the Control group, with more blood flow in the flap under LDBFI. Prava treatment increased the mean vessels density, elevated the expression levels of angiogenic proteins (matrix metallopeptidase 9, vascular endothelial growth factor, Cadherin5) and antioxidant proteins (superoxide dismutase 1 (SOD1), endothelial nitric oxide synthase, heme oxygenase), and decreased the expression of apoptotic factors (BAX, CYC, Caspase3). In addition, malondialdehyde content was reduced, and glutathione level and SOD activity were increased in the skin flaps after treatment with Prava. Conclusion: Prava promotes survival of random skin flap through induction of angiogenesis, and inhibition of apoptosis and oxidative stress.

Valproic acid enhances the viability of random pattern skin flaps: involvement of enhancing angiogenesis and inhibiting oxidative stress and apoptosis.

BACKGROUND: Random skin flaps are commonly applied during plastic surgery, but distal flap necrosis limits their clinical applications. Valproic acid (VPA), a histone deacetylase inhibitor and a traditional antiepileptic agent, may promote flap survival. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into VPA-treated and control groups. All rats received VPA or saline by intraperitoneal injections once daily for 7 days after the modified McFarlane flap model was established. On postoperative day 7, flap survival, laser Doppler blood flow, and water content were examined for flap viability, hematoxylin and eosin staining (H&E), immunohistochemistry (IHC), and Western blot analysis, and the status of angiogenesis, apoptosis, and oxidative stress were detected in the ischemic flaps. RESULTS: VPA increased the survival area, blood flow, and number of microvessels in skin flaps on postoperative day 7 and reduced edema. VPA promoted angiogenesis by enhancing vascular endothelial growth factor (VEGF) mRNA transcription and upregulating VEGF and cadherin 5 expression, inhibited apoptosis via reduction of caspase 3 cleavage, and relieved oxidative stress by increasing superoxide dismutase (SOD) and glutathione (GSH) levels and reducing the malondialdehyde (MDA) level. CONCLUSION: VPA promoted random skin flap survival by enhancing angiogenesis and inhibiting oxidative stress and apoptosis.

Stem Cell Transplantation for Peripheral Nerve Regeneration: Current Options and Opportunities.

Peripheral nerve regeneration is a complicated process highlighted by Wallerian degeneration, axonal sprouting, and remyelination. Schwann cells play an integral role in multiple facets of nerve regeneration but obtaining Schwann cells for cell-based therapy is limited by the invasive nature of harvesting and donor site morbidity. Stem cell transplantation for peripheral nerve regeneration offers an alternative cell-based therapy with several regenerative benefits. Stem cells have the potential to differentiate into Schwann-like cells that recruit macrophages for removal of cellular debris. They also can secrete neurotrophic factors to promote axonal growth, and remyelination. Currently, various types of stem cell sources are being investigated for their application to peripheral nerve regeneration. This review highlights studies involving the stem cell types, the mechanisms of their action, methods of delivery to the injury site, and relevant pre-clinical or clinical data. The purpose of this article is to review the current point of view on the application of stem cell based strategy for peripheral nerve regeneration.

Adenotonsillectomy outcomes regarding bone age and osteocalcin in treatment of obstructive sleep apnea syndrome in children.

BACKGROUND: To investigate the effect of adenotonsillectomy (AT) on bone development, quality of life and polysomnography evaluation in children with obstructive sleep apnea syndrome (OSA). METHODS: Preoperative and postoperative (6 months) physical examination, PSG, bone age (BA) and osteocalcin (OC) evaluation were performed on the selected OSA children (n=92) and the healthy children (n=87). The OSA children were also scored based on the OSA 18-item questionnaire. A two-year follow-up was conducted to evaluate BA and OC changes. RESULTS: After AT, 81 (88.04%) OSA children recovered completely, eight (8.70%) achieved remarkable improvements, and three (3.26%) achieved moderate improvements. In the OSA children, postoperative OSA 18-item score and the scores of the five domains were significantly higher than preoperative ones. Compared with the preoperative, body mass index (BMI), weight for age Z-sores, height for age Z-sores, weight for height Z-sores and BMI Z-score in the OSA group 6 months after the operation were significantly increased, but no significant difference was detected between the OSA and the control group. The changes of BA and chronological age in the OSA group were significantly different from those in the control group. Two years after AT, BA between the two groups was no longer significantly different. Preoperative serum OC in the OSA group was lower than that in the control group, but increased to normal levels 6 months after AT. Correlation analysis showed serum OC levels were negatively correlated with apnea hyponea index, obstructive apnea index, arousal index, and lowest oxygen saturation. CONCLUSIONS: After AT, bone growth and development in children with OSA recovered gradually, and the serum OC levels decreased to the normal level. Therefore, preventive measures and positive treatments should be applied to minimize the negative effects of OSA in children.

Nerve defect repair by differentiated adipose-derived stem cells and chondroitinase ABC-treated acellular nerves.

OBJECTIVE: To evaluate the effects of differentiated adipose-derived stem cells (dADSC) and chondroitinase ABC (ChABC)-treated acellular nerves (ACN) in building artificial nerves and repairing nerve defects. METHODS: ADSC were isolated from the adipose tissue of Wistar rats, induced to differentiate into Schwann-like cells, and implanted into ChABC-treated ACN to repair a 15-mm sciatic nerve defect in Sprague-Dawley rats (the experimental group, group D). The control groups were an autologous nerve transplantation group (group E); ACN (group A), ChABC-treated ACN graft group (group B), and dADSC + ACN (group C). Twelve weeks after surgery, electromyography recordings, tricep surae muscle wet weight recovery rate, and axon counts were measured to evaluate the repair of peripheral nerve defects. RESULTS: The nerve conduction velocity, compound muscle action potentials, tricep surae muscle wet weight recovery rate, and myelinated axon counts in the ChABC-ACN/dADSC group were significantly higher than in the other groups (P < 0.05), which were all lower than the autologous group (P < 0.05). CONCLUSIONS: The combination of ChABC-treated ACN and dADSC exhibited a synergistic effect in promoting nerve regeneration, and could be an alternative for effective tissue-engineered nerves.

The Effect of Hypoxic Preconditioning on Induced Schwann Cells under Hypoxic Conditions.

OBJECT: Our objective was to explore the protective effects of hypoxic preconditioning on induced Schwann cells exposed to an environment with low concentrations of oxygen. It has been observed that hypoxic preconditioning of induced Schwann cells can promote axonal regeneration under low oxygen conditions. METHOD: Rat bone marrow mesenchymal stem cells (MSCs) were differentiated into Schwann cells and divided into a normal oxygen control group, a hypoxia-preconditioning group and a hypoxia group. The ultrastructure of each of these groups of cells was observed by electron microscopy. In addition, flow cytometry was used to measure changes in mitochondrial membrane potential. Annexin V-FITC/PI staining was used to detect apoptosis, and Western blots were used to detect the expression of Bcl-2/Bax. Fluorescence microscopic observations of axonal growth in NG-108 cells under hypoxic conditions were also performed. RESULTS: The hypoxia-preconditioning group maintained mitochondrial cell membrane and crista integrity, and these cells exhibited less edema than the hypoxia group. In addition, the cells in the hypoxia-preconditioning group were found to be in early stages of apoptosis, whereas cells from the hypoxia group were in the later stages of apoptosis. The hypoxia-preconditioning group also had higher levels of Bcl-2/Bax expression and longer NG-108 cell axons than were observed in the hypoxia group. CONCLUSION: Hypoxic preconditioning can improve the physiological state of Schwann cells in a severe hypoxia environment and improve the ability to promote neurite outgrowth.

T Lymphocyte Subsets and Cytokines in Rats Transplanted with Adipose-Derived Mesenchymal Stem Cells and Acellular Nerve for Repairing the Nerve Defects.

OBJECTIVE: The aim of this study was to explore the immunity in rats transplanted with adipose-derived mesenchymal stem cells (ADSCs) and acellular nerve (ACN) for repairing sciatic nerve defects. METHODS: ADSCs were isolated from the adipose tissues of Wistar rats. Sprague-Dawley rats were used to establish a sciatic nerve defect model and then divided into four groups, according to the following methods : Group A, allogenic nerve graft; Group B, allograft with ACN; Group C, allograft ADSCs+ACN, and Group D, nerve autograft. RESULTS: At the day before transplantation and 3, 7, 14, and 28 days after transplantation, orbital venous blood of the Sprague-Dawley rats in each group was collected to detect the proportion of CD3(+), CD4(+), and CD8(+) subsets using flow cytometry and to determine the serum concentration of interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) using enzyme-linked immunosorbent assay (ELISA). At each postoperative time point, the proportion of CD3(+), CD4(+), and CD8(+) subsets and the serum concentration of IL-2, TNF-α, and IFN-γ in group C were all near to those in group B and group D, in which no statistically significant difference was observed. As compared with group A, the proportion of CD3(+), CD4(+), and CD8(+) subsets and the serum concentration of IL-2, TNF-α, and IFN-γ were significantly reduced in group C (p<0.05). CONCLUSION: The artificial nerve established with ADSCs and ACN has no obvious allograft rejection for repairing rat nerve defects.

[Characteristics and replantation of degloving injury of distal finger].

OBJECTIVE: To explore clinical characteristics and replantation methods of degloving injury of distal finger. METHODS: From 2004 to 2009,18 cases of 19 distal finger degloving were admitted, and included 14 males and 4 femals with an average age of 31 years old ranging from 18 to 51 years old. The distal finger degloving injury was divided into 3 types according to the different levels of degloveing digital artery and skin involving 6 fingers of type I, 10 fingers of type II, 3 fingers of type III. Among them, 3 cases of 4 fingers were failed to be replantaed due to severed injured digital artery, and 15 cases of 15 distal finger degloving injury were replanted with microsurgical technique. RESULTS: Among 15 patients (15 fingers) conpleted the reimplant operation, 13 fingers were survived, 2 fingers were necrosis after operation. Thirteen survived fingers were followed up from 6 to 24 months (averaged 14 months). The appearance of injured fingers and nails obtained satisfactory results. According to Chinese Hand Surgery Society Criteria for function assessment replantation, the results were excellent in 9 cases, good in 3 cases and poor in 1. CONCLUSION: Replantation of distal degloving injury is effective and it should strive for replantation.

Dorsal pentagonal local flap: a new technique of web reconstruction for syndactyly without skin graft.

BACKGROUND: Many techniques for web space reconstruction have been described over the years. However, few techniques are completely satisfactory in terms of cosmetic requirement and functional recovery due to scar contracture, web creep, or conspicuous scarring resulting from skin grafting or additional incisions on the dorsal palm. Based on the anatomy of the dorsal metacarpal artery, the authors describe a local pentagonal advancement flap including perforators of the dorsal metacarpal artery to optimize web reconstruction and facilitate direct closure in the syndactyly treatment. METHODS: A local dorsal pentagonal advancement flap was used to reconstruct 17 web spaces in ten patients. The skin of the syndactylized fingers was brought to the web space from the dorsum of the two adjacent syndactylized fingers to cover the web area, facilitating a skin graft-free procedure for web reconstruction. RESULTS: All 17 web releases were successfully reconstructed. During the follow-up period of 23-35 months, the appearance of all the reconstructed webs was similar to that of the adjacent normal webs, and all the patients had full functional recovery. No case of web creep was reported during this period, and none of the patients required a secondary operation. CONCLUSION: The dorsal pentagonal advancement flap is a dependable flap based on known perforators from the dorsal metacarpal arteries. The reported technique is a simple and effective technique for the correction of simple syndactyly and is especially suitable for reconstruction of two webs in multiple syndactyly simultaneously, avoiding the need for skin grafts and leaving acceptable scars on the dorsum of the hand for web reconstruction.

The free dorsoradial forearm perforator flap: anatomical study and clinical application in finger reconstruction.

The perforator flaps are characterized by their thinness and the adjustable length of their vascular pedicle. The purpose of this investigation is to refine the anatomy of the perforators in the middorsoradial forearm and present our clinical experience using this free perforator flap in the reconstruction of finger defects. Anatomic study was conducted on 46 cadaver forearms. It was noted that a perforator was consistently observed in the midforearm exhibiting 4 patterns, in which a dorsoradial perforator was present with 37 cases (80.4%) originating from the interosseous artery system (patterns 1-3) and 9 cases (19.6%) from the descending branch of the radial recurrent artery (pattern 4). This perforator consistently emerged in the intermuscular septum between the extensor carpi radialis longus and extensor digitorum communis. Twenty free flaps based on this middorsoradial cutaneous perforator were elevated for the coverage of soft tissue defects of fingers (range: 3 cm × 2.0 cm to 5 cm × 2.5 cm) in 17 patients. All the flaps survived with satisfactory outcomes. Clinical findings on this perforator in terms of its origins and courses coincided with the anatomic results (χ2 = 0.287, P = 0.962). The free flap based on this perforator is a reliable perforator flap in spite of varied origins.

[Clinical significance of MESS scoring system in the treatment of fractures of lower limb combined with vascular injuries].

OBJECTIVE: To study the clinical significance of MESS scoring system in the treatment of fractures of lower limb combined with vascular injuries, and to evaluate its reliance. METHODS: From March 2006 to March 2008, 28 patients with fractures of lower limb combined with vascular injuries were graded by MESS scoring system. There were 17 patients were male and 11 patients were female, ranging in age from 23 to 53 years, averaged 38 years. Seventeen patients had fractures at the superior segment of tibia and fibia, 7 patients had fractures at the inferior segment of femur, and other 4 patients had dislocation of knee joint. Among the patients, 18 patients had MESS scores more than 7.0 point, in which 13 patients were treated with one-stage amputation, 5 patients were treated with two-stage amputation; the other 10 patients had the MESS scores less than 7.0 point, and were treated with open reduction and internal fixation, in which 8 patients were treated with transplantation of great saphenous vein to repair blood vessles, and 2 patients were treated with vascular end to end anastomosis. RESULTS: Among the patients, including 18 patients whose MESS scores more than 7.0 point were treated with one-stage or two-stage amputation, and 10 patients whose MESS scores less than 7.0 point were treated with limb salvage operations, all the limbs survived. During the follow-up period (ranged from 0.5 to 1 year, the movement and sensory function of the limbs recovered well. CONCLUSION: MESS is a simple and reliable tool to determine the proper strategy for the patients suffering from vascular injuries with fractures.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist inhibits transforming growth factor-beta1 and matrix production in human dermal fibroblasts.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists are increasingly used in patients with diabetes, and some studies have suggested a beneficial effect on organ fibrosis, but their effects on dermal cell growth and extracellular matrix (ECM) turnover are unknown. To investigate the effect of the PPAR-gamma agonist troglitazone on cell growth and matrix production in human dermal fibroblasts (HDF), HDF were cultured and grown in a different concentration of troglitazone. PPAR-gamma expression and matrix production were measured in HDF in the presence of troglitazone. The mRNA expressions of TGF-beta1, collagen I (Col I) and fibronectin (FN) were determined by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). The protein of transforming growth factor-beta1 (TGF-beta1) was determined by enzyme-linked immunosorbent assay (ELISA) and proteins of Col I and FN were determined by Western blotting. The mRNA expression of TGF-beta1, Col I and FN were significantly decreased in HDF in 15-30 micromol l(-1) troglitazone compared to the control group with Dulbecco's modified Eagle's medium (P<0.01). An obvious decrease of TGF-beta1 protein was found in troglitazone-treated groups as compared to the control group (P<0.05). Exposure of HDF to troglitazone reduced col I secretion (P<0.05), and fibronectin secretion (P<0.05). This study suggests that PPAR-gamma agonist will provide a novel approach with therapeutic potential in dermal fibrosis, such as hypertrophic scar, keloid and so on.

Vein grafting in fingertip replantations.

In this retrospective study, the survival rates of fingertip replantation with and without vein grafting were evaluated along with their postoperative functional and cosmetic results. One hundred twenty-one-fingertip amputations were performed in 103 patients between September 2002 and July 2007. Thirty-four amputated fingertips were replanted without vein grafting, while 87 amputated fingertips were replanted with vein grafting for arterial and/or venous repairs. The overall survival rates of the replantations with and without vein grafting were 90% (78/87) and 85% (29/34), respectively. The survival rates were 88% (36/41) with venous repair, 93% (25/27) with arterial repair, and 89% (17/19) with both. Nineteen patients without vein grafting and 48 patients with vein grafting had a follow-up period of more than one year. Good cosmetic and functional outcomes were observed in both groups of patients. The results show that vein grafting is a reliable technique in fingertip replantations, showing no significant difference (P > 0.05) in survival between those with and without vein grafting. Furthermore, no significant difference (P > 0.05) in survival was found between cases with vein grafts for arterial and/or venous repairs. In fingertip replantations with vein grafting, favorable functional and esthetic results can be achieved without sacrificing replantation survival.