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Aim: The effects of MALAT1 from human adipose-derived stem cell (ADSC) exosomes in skin wound healing were investigated. Material & methods: The viability, apoptosis and migration ability of human skin fibroblasts (HSFs) were evaluated by Cell Counting Kit-8 assay, flow cytometry and scratch assay, respectively. A mouse model was established to evaluate the role of exosomal MALAT1 in skin wound healing in vivo. Results: Human ADSC exosomes promoted the proliferation and migration of HSFs and increased MALAT1 expression. MALAT1 silencing in human ADSCs inhibited HSF viability and migration, promoted HSF apoptosis and inhibited angiogenesis by upregulating miR-378a. Overexpression of miR-378a inhibited the migration and proliferation of HSFs by downregulating FGF2 expression. ADSC exosomes promoted skin wound healing by mediating MALAT1 in vivo. Conclusion: Exosomal MALAT1 accelerated skin wound healing by regulating the miR-378a/FGF2 axis, suggesting that MALAT1 might be used as a potential target for cutaneous wound treatment.

Skin wound healing is a process of synergistic action of multiple factors. Adipose-derived stem cells (ADSCs), a group of stem cells, are recruited into damaged tissues and secret several cytokines, which promote nascent tissue formation. ADSC-derived exosomes play crucial roles in wound healing as a paracrine vehicle for delivering chemokines, growth factors and RNAs to host cells. LncRNAs are involved in multiple physiological processes, including tissue repair. Furthermore, lncRNA MALAT1 is associated with endothelial cell migration and angiogenesis in different types of diseases. This study demonstrated that hADSC exosomes promoted the proliferation and migration of human skin fibroblasts and increased MALAT1 expression. MALAT1 silencing in human ADSCs inhibited human skin fibroblast viability and migration, promoted apoptosis and suppressed angiogenesis by upregulating miR-378a. miR-378a overexpression inhibited the phenotypic characteristics of human skin fibroblasts by downregulating FGF2. Exosomal MALAT1 appeared to accelerate skin wound healing by mediating the miR-378a/FGF2 axis.

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Angiogenesis plays a key in the process of tissue repair and wound healing. Human adipose-derived mesenchymal stem cells (HADSCs) have been found to act a promotion role during angiogenesis. Moreover, miR-125a-3p in HADSCs could promote the angiogenesis of HUVECs, but their specific mechanism in wound healing needs further study. Western blotting and qRT-PCR were used for detecting the protein and mRNA level, respectively. Exosomes were isolated successfully, and transmission electron microscope was used to identify exosomes. Angiogenesis, cell migration, and proliferation were detected with tube formation, wound healing, and MTT assays. The interactions of miR-125a-3p and PTEN were validated using dual-luciferase reporter assay. Animal model was used to evaluate the effect of miR-125a-3p on wound healing. HADSCs-exosome remarkably promoted the viability, migration, and angiogenesis of HUVECs. Knockdown of miR-125a-3p in HADSCs could inhibit the effect of HADSCs-exosome, while overexpression of miR-125a-3p could further promote the effect of HADSCs-exosome on HUVECs. MiR-125a-3p from HADSCs-exosome inhibited the expression of PTEN in HUVECs. Knockdown of PTEN promoted the viability, migration, and angiogenesis of HUVECs and reversed the effect of miR-125a-3p knockdown on HUVECs. Finally, miR-125a-3p from HADSCs-exosome could promote wound healing and angiogenesis in mice by inhibiting PTEN in mice wound granulation tissues. MiR-125a-3p from the HADSCs-exosome promoted the wound healing and angiogenesis, and these effects were achieved through regulating PTEN. This study may provide a new thought for the treatment and prevention of tissue repair.

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It has been reported that adipose mesenchymal stem cells (ADSCs) accelerate wound healing. Moreover, exosomes, which serve as paracrine factors, play a vital role in wound healing. However, the mechanism remains unclear. This research aimed to determine the roles of exosomes derived from ADSCs (ADSC-Exos) in wound skin tissue repair. Flow cytometry and electron microscopy were carried out to identify ADSCs and ADSC-Exos, respectively; RT-qPCR was performed to assess the lncRNA H19 (H19), microRNA19b (miR-19b) and SRY-related high-mobility-group box 9 (SOX9) levels; Western blotting was carried out to evaluate collagen and ß-catenin expression; CCK-8, scratch and transwell assays were conducted to evaluate human skin fibroblast (HSF) cell proliferation, migration and invasion, respectively; the potential binding sites between H19 and miR-19b, miR-19b and SOX9 were detected by dual-luciferase reporter gene assay and RIP assay; and H&E staining was conducted to observe skin wound tissues. ADSC-Exos accelerated the proliferation, migration and invasion of HSF cells via H19. H19 acts as a molecular sponge towards miR-19b, which targets SOX9. ADSC-Exos inhibited miR-19b expression via H19, resulting in accelerated HSF proliferation, migration and invasion. ADSC-Exos upregulated SOX9 to activate the Wnt/ß-catenin pathway, resulting in accelerated HSF cell proliferation, migration and invasion, and ADSC-Exos promoted skin wound healing via H19 in mice.The high expression of H19 in ADSC-Exos may upregulate SOX9 expression via miR-19b to accelerate wound healing of skin tissues. Our study may provide novel perspectives for therapy to accelerate skin wound healing.

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OBJECTIVE: To explore the operative technique and clinical results of using peroneal perforator-based sural neurofasciocutaneous flaps to repair skin and soft tissue defects in lower extremities. METHODS: From January 2009 to March 2012, 26 patients with skin and soft tissue defects at distal region of leg and foot were hospitalized. Among them, 9 patients suffered from tendon or bone exposure at the distal region of leg after injury due to traffic accident; 4 patients suffered from skin defects in the ankle as a result of electric injury; 8 patients suffered from chronic ulcer at the distal part of leg and foot; 5 patients suffered from plantar pressure ulcer. After debridement, soft tissue defect sizes ranged from 11 cm×5 cm to 18 cm×13 cm. According to the position and size of the defects, peroneal perforator-based sural neurofasciocutaneous flaps were designed and procured to repair the skin and soft tissue defects. The size of flaps ranged from 12 cm×6 cm to 20 cm×15 cm. Flap donor sites were closed by direct suture or skin grafting. RESULTS: Twenty-five flaps survived completely. Only one flap suffered partial margin necrosis in the size of 2 cm×1 cm, which was healed after dressing change. Patients were followed up for 6 to 12 months. The appearance and sensation of flaps were satisfactory; no ulcer occurred; the movement of lower extremities was normal. CONCLUSIONS: It is suitable to repair the skin and soft tissue defects at distal region of leg and foot with the peroneal perforator-based sural neurofasciocutaneous flap, as it possesses reliable blood supply, long and non-bulky pedicle, and sufficient available size. The operation is also easy to perform.

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BACKGROUND: Thoracodorsal artery perforator (TAP) flaps without latissimus dorsi muscle - have been used for reconstruction of the extremities, head and neck as free style flaps, and as pedicled flaps for reconstruction of the chest wall and axillary wounds. This retrospective study aimed to analyse the clinical applications and relevant anatomic findings of TAP flaps. METHODS: From April 2007 to August 2011, 67 free or pedicled TAP flaps were transferred in 67 patients for reconstruction of wounds of the extremities, chest wall and axilla. Eight were used as free flaps for reconstruction of extremities, and 59 used as pedicled flaps for reconstruction of axillary or chest wounds. Patient ages ranged from 7 to 55 years (26.04±12.83). Perforator arteries were detected and identified with a hand-held Doppler. The size of flaps ranged from 6 by 9 to 14 by 18 cm ((8.66±2.05) by (12.62±2.03)). Flaps were designed with the perforator artery included, with all flaps based on one or two perforator arteries. RESULTS: All of the flaps survived. There were no problems with vascular spasm or occlusion. Significant venous congestion was not observed in any of the cases. Two cases developed minor wound dehiscence but healed with conservative therapy. None of the donor sites developed seromas. CONCLUSIONS: The thoracodorsal artery flap without associated latissimus dorsi muscle can provide a thin, large and reliable flap with robust blood supply. The TAP flap can significantly reduce donor site morbidity.

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BACKGROUND: Deep inferior epigastric artery perforator (DIEP) flap has proved to be an effective method in perineal reconstruction. However, a few literatures have reported thinned DIEP flap which yields a better functional and cosmetic result. There are also no clear guidelines on the degree to which a DIEP flap may be debulked of excess tissue before flap viability becomes compromised. In this preliminary report, a series of patients are presented whereby perineal reconstruction was achieved using the pedicled, thinned DIEP flap, based on debulking parameters from our clinical findings. METHODS: Between September 2007 and August 2010, 12 pedicled, thinned DIEP island flaps for perineal reconstruction were performed on three patients with vulval or vaginal tumour, five patients with congenital vaginal agenesis and four patients with perineal Paget's disease. The flap was thinned in the plane inferior to the superficial inferior epigastric vein based on the subcutaneous vasculature of the abdominal wall, as depicted by preoperative computed tomography (CT) angiography (CTA) examination. RESULTS: Preoperative abdominal CTA can perfectly display the anatomy of DIEP flap. With a sensitivity of 100% and a specificity of 100% (Φ>0.5 mm), it helped in reducing the harvesting time for the flap and in guiding flap thinning. Partial necrosis of the distal flap occurred in a relatively large transverse flap measuring 24 cm×8.5 cm. One patient experienced dehiscence and a subsequent suture was successfully made. The other ten flaps were transplanted successfully without any complications. CONCLUSION: This series demonstrates that DIEP flap can be reliably debulked in the plane inferior to the superficial inferior epigastric vein with relatively no risk of necrosis and can be used safely in perineal reconstruction. The abdominal CTA can be employed as an assisting tool to plan the DIEP flap as well as guide flap thinning.

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OBJECTIVE: To investigate the clinical application of superior or inferior gluteal artery perforator flaps for the gluteal sores. METHODS: Before operation, the perforator artery was detected by Doppler flowmeter and labeled. The perforator flap was designed, including the perforator artery, but not the gluteal maximum muscle. RESULTS: From Aug. 2006 to May 2009, 15 cases were treated. The flap size ranged from 6 cm x 8 cm to 7 cm x 15 cm. All the flaps survived completely without hematoma, seroma or other complication. CONCLUSIONS: The gluteal maximum muscle-reserved gluteal artery perforator flap is a good choice for gluteal sore with reliable blood supply and less morbidity in donor site.

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OBJECTIVE: To explore the application of computed tomography angiography (CTA) in preoperative design of deep inferior epigastric artery perforator (DIEAP) flap. METHODS: From Jan, 2007 to Mar, 2008, preoperative CTA of deep inferior epigastric artery was performed in 13 patients, including 5 patients with congenital absence of the vagina, 4 patients with penile and scrotal Paget's disease and 4 patients after mastectomy. The images were analyzed, including multiple planar reformation (MPR), maximum intensity projection (MIP) and volume rendering (VR). Then the distributions, branches and locations of perforators of deep inferior epigastric artery were measured. The images from CTA were compared with intraoperative observation. RESULTS: The images demonstrated the distributions of deep inferior epigastric artery and locations of its perforators, which were proved to be true by intraoperative observation. CONCLUSIONS: The preoperative CTA of deep inferior epigastric artery is very useful for preoperative design of DIEAP flaps.

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OBJECTIVE: To explore a new surgical procedure for vaginal reconstruction with pedicled deep inferior epigastric perforator (DIEP) flap. METHODS: Since June 2007, 6 cases underwent vaginal reconstruction, including five congenital vaginal absence and one immediately after total vaginal resection due to carcinoma. Intensive CT scans were performed preoperatively for perforator selection. The DIEP flaps were designed vertically on the anterior abdominal wall and transferred for vaginal reconstruction. RESULTS: All the patients recovered uneventfully with no flap loss and other complication. The patients were followed up for 1 to 8 months (mean, 4 months) with satisfactory results. CONCLUSION: Vaginal reconstruction with vertical DIEP flaps is a safe and reliable method.

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OBJECTIVE: To evaluate the efficacy of free transplantation of denervated muscles and vessels in the treatment of long-standing facial paralysis. METHODS: A total of 26 patients with facial paralysis (10 males and 16 females, aged 16-65 years, mean: 47 years) were enrolled in this study to receive transplantation of denervated extensor digitorum brevis (EDB) and extensor hallusis brevis (EHB). The muscle tendon was slung to the ala nasi, the middle point of the nasolabial sulcus, the angulus oris and the chin to correct the nasal and oral deformity. The muscle belly was buried around the nerves that innervated the masseter muscle. Microsurgery was applied to anastomosing the tarsus lateral vessels to the superficial temporalis vessels. RESULTS: After operation, all the patients immediately obtained satisfied static appearance. The movement of the paralyzed corner of the mouth could be obtained one month later and the smile of the paralyzed side could be restored after 3 months of training. And 88% patients achieved perfect results, 8% obtained satisfactory results, and 4% got improvement 6 months after operation according to Stennert's paresis scoring system. CONCLUSIONS: Free transplantation of denervated muscles and vessels for the treatment of long-standing facial paralysis, which seldom causes atrophy or liquefaction of the transferred muscles, can maintain muscle viability and induce reliable nerve regeneration. Therefore, it is a safe and efficient treatment method for the patients suffering from facial paralysis.

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