Periostin, a secreted extracellular matrix protein, is involved in the wound healing and pathological process of various human cancers. Keloid scars are fibroproliferative tumor-like lesions and develop under local hypoxia. Using suppression subtractive hybridization, in a previous study, we found that periostin is overexpressed in keloids compared with hypertrophic scars. However, little is known about the regulation and function of periostin in keloids. In this study, we examined the effects of periostin on the bioactivity of keloid fibroblasts (KFs) in order to determine whether periostin is involved in hypoxia-stimulated keloid pathogenesis by measuring the expression levels of periostin in KFs cultured under hypoxic conditions. We also investigated the association between periostin and hypoxia-inducible factor-1α (HIF-1α). The mRNA, intracellular protein and secreted protein level of periostin was examined by RT-PCR (and quantitative PCR), western blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. We also used shRNA targeting periostin to knockdown its expression in the KFs. We report that hypoxia (2% O(2)) upregulates both HIF-1α and periostin expression in KFs. In addition, hypoxia-upregulated periostin expression was regulated by HIF-1α. The inhibition of periostin by short hairpin RNA decreased the hypoxia-stimulated proliferation, collagen synthesis, migration and invasion of KFs and altered the cell cycle, but did not affect apoptosis; treatment with recombinant human periostin protein reversed these effects. Periostin also activated the αvβ3 integrin-PI3K/Akt pathway in the KFs. These findings suggest that hypoxia initiates hyperplasia of KFs and increases periostin expression under hypoxic conditions; periostin is involved in the pathogenesis of keloids, which indicates that periostin may be a novel therapeutic target for keloids and other fibroproliferative disorders.

Periostin, a secreted extracellular matrix protein, is highly expressed in wound healing and in various types of human cancer and is involved in angiogenesis. Keloids, considered dermal benign tumors, are granulomatous lesions characterized by capillary proliferation. However, the underlying regulatory mechanism of angiogenesis in keloids remains to be elucidated. The present study aimed to examine the effect of periostin on angiogenesis in keloids. The expression of periostin was upregulated and the vessel density was higher in human keloids compared with normal tissue, observed following staining with CD31 and CD105. Periostin demonstrated a markedly positive correlation with blood vessel density, which was assessed using CD31 staining (r=0.711; P<0.01) and a weak correlation was observed using CD105 staining (r=0.251; P<0.01). Conditioned medium from keloid fibroblasts (KFs) promoted the migration and tube formation of human umbilical vein endothelial cells (HUVECs) compared with normal fibroblasts and this effect may have been abrogated by the short hairpin RNA knockdown of periostin. Treatment with recombinant human periostin promoted the migration and tube formation of HUVECs by activating the extracellular signal-regulated kinase 1/2 and focal adhesion kinase signaling pathway. In addition, periostin increased the secretion of vascular endothelial growth factor and angiopoietin-1 in the KFs. In conclusion, these data suggested that upregulation in the level of periostin may promote angiogenesis directly and indirectly in keloids and may be a key factor in keloid development. Periostin may, therefore, be a promising therapeutic target in the treatment of keloids and other angioproliferative diseases.

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Flap necrosis is a common complication after mastectomy, and nitroglycerin (NTG) ointment has been used successfully to treat it. However, it is not clear whether topical NTG can completely prevent the occurrence of flap necrosis after breast cancer surgery, and it is also unclear whether this treatment may cause side effects. Three randomized controlled trials (RCTs) and two retrospective cohort studies (RCSs) were included in our investigation. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We found that NTG significantly reduced the rates of mastectomy flap necrosis, full-thickness flap necrosis, and debridement as well as the rate of early complications other than flap necrosis. However, there was no significant difference in drug-related adverse reactions, explantation, superficial flap necrosis, infection, hematoma or seroma between the NTG and placebo groups. Flap-related complications are extremely common after breast surgery, among them, flap necrosis is the most serious and leads to a poor prognosis. In the literature, the reported rates of mastectomy flap necrosis (MFN) range from 5% to 30% 1-9. The rate may continue to rise as nipple-sparing mastectomy and immediate breast reconstruction (IBR) become more prevalent in young breast cancer patients, although there is some evidence that the risks of flap necrosis and implant failure are higher in IBR than in mastectomy alone 10. Nitroglycerin (NTG) effectively increases local blood flow by dilating arteries and veins without altering the ratio of precapillary to postcapillary resistance. Many studies have shown that NTG treatment may improve the survival of random-pattern skin flaps by increasing local blood flow 11-13. Nonetheless, not all studies confirm the utility of NTG in skin flap preservation. Several scholars have found that daily application of NTG slow-release pads offer no greater flap survival than a control treatment 14-17. Furthermore, some of the side effects of NTG may limit its use. However, Ricci has argued that NTG is safe and effective and does not increase the occurrence of side effects 18. Given the lack of consensus on the use of NTG to prevent MFN, the purpose of this meta-analysis is to determine the efficacy and safety of NTG for the prevention of MFN. Debridement is an important solution to skin flap necrosis, but it causes psychological and physical trauma to patients. Further attention should be paid to the debridement rate after mastectomy, especially after IBR, in which circumstances it may cause the tissue expander/implant to be lost. Unfortunately, some studies have suggested that NTG cannot reduce the rate of debridement after IBR 19-21. Hence, another purpose of this article is to determine whether NTG can reduce the flap debridement rate after mastectomy.

Background Implant-based breast reconstruction is easy to be performed but has flaws that an unnatural appearance might be presented when no sufficient coverage existing. While autologous tissue reconstruction also has disadvantages like donor site scar and skin patch effect. There is a demand for a new method to obtain natural and aesthetic appearance while surmounting drawbacks of conventional breast reconstruction surgery. Methods A retrospective review of thirty-one patients undergoing tissue expander (TE)/implant two-stage breast reconstruction with latissimus dorsi muscle flap (LDMF) transfer through endoscopic approach in Peking University Third Hospital from April 2016 to August 2020 was performed. The LDMF harvest time, drain time, and complications were reviewed. The 3D volume was obtained to assess the volume symmetry of bilateral breasts. The BREAST-Q reconstruction module was used to evaluate the satisfaction. Results The mean endoscopic LDMF harvest time was 90.4 min. In the mean follow-up of 11.2 months, there were no severe capsular contracture happened. The reconstructed side achieved good volume symmetry to the contralateral side (P = 0.256). Based on the evaluation of the BREAST-Q scores, the outcome of Satisfaction with Breasts was excellent or good in 87.1% of the cases. Conclusions The novel type of two-stage breast reconstruction protocol, which includes tissue expansion followed by implant insertion with endoscopy-assisted LDMF transfer, could effectively reduce visible scars, avoid the patch effect, while require short time for LDMF harvest and present low incidence of complications. It is a promising method for breast reconstruction because it achieves good outcomes in the mastectomy patients.