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A special kind of scar, keloid, sometimes grows huge, disturbing patients in different ways. We discussed the pathogenesis of keloids and found researches about fibroblasts and collagen disorders, with little emphasis on immunity. Coupled with few effective treatments in keloid at present, we have focused on the immunological mechanisms of keloids with an aim to unravel some new therapeutic approaches in the future. In this review, the immunological processes are separately illustrated by the classification of different immune cells. In addition, we also discuss possible reasons for the repeated recurrence of keloids, the phenomenon of cell talks, and inflammation-related signal pathways involved in the pathogenesis of keloids.

A cavernous hemangioma, well-known as vascular malformation, is present at birth, grows proportionately with the child, and does not undergo regression. Although a cavernous hemangioma has well-defined histopathological characteristics, its origin and formation remain unknown. In the present study, we characterized the cellular heterogeneity of cavernous hemangioma using single-cell RNA sequencing (scRNA-seq). The main contribution of this study is the discovery of mesenchymal stem cells (MSCs) that cause tumour formation in cavernous hemangioma and we propose that these MSCs may be abnormally differentiated or incompletely differentiated from epiblast stem cells.Other new findings include the responsive ACKR1 positive endothelial cell (ACKR1+EC) and BTNL9 positive endothelial cell (BTNL9+EC) and the BTNL9-caused checkpoint blockade enhanced by the CXCL12-CXCR4 signalling. The activated CD8+T and NK cells may highly express CCL5 for their infiltration in cavernous hemangiomas, independent on the tumor cell-derived CCL5-IFNG-CXCL9 pathway. The highly co-expression of CXCR4 and GZMB suggested that plasmacytoid dendritic cells (pDCs) function for anti-tumour as CD8+T cells in cavernous hemangiomas. The oxidised low-density lipoprotein (oxLDL) in the TME of cavernous hemangiomas may play an important role as a signalling molecular in the immune responses. Notably, we propose that oxLDL induces the oxLDL-OLR1-NLRP3 pathway by over-expression of OLR1 in M1-like macrophages, whereas oxLDL induces the oxLDL-SRs-C1q (SRs are genes encoding scavenger receptors of oxLDL except OLR1) pathway by over-expression of other scavenger receptors in M2-like macrophages.The present study revealed the origin of cavernous hemangiomas and discovered marker genes, cell types and molecular mechanisms associated with the origin, formation, progression, diagnosis or therapy of cavernous hemangiomas. The information from the present study makes important contributions to the understanding of cavernous hemangioma formation and progression and facilitates the development of gold standard for molecular diagnosis and effective drugs for treatment.

Background Minimally invasive McKeown esophagectomy (MIE McKeown) with cervical anastomosis is a widely used approach for the treatment of esophageal cancer (EC). Anastomotic leak is one of the most serious complications following esophagectomy. This study aimed to summarize the anastomosis procedure and assess the clinical outcomes of our modified layered hand-sewn cervical end-to-side anastomosis for cervical anastomosis during MIE McKeown. Methods We retrospectively reviewed clinical data of 508 consecutive EC patients who underwent MIE McKeown using the modified layered hand-sewn cervical end-to-side anastomosis between June 2016 and June 2020. Results The incidence of anastomotic leakage in our cohort was 2.0%. The postoperative stricture rate was 6.9% and the incidence of other postoperative complications was less than 9.3%. The mean time for setting up MIE McKeown was approximately 211.0 min and the average duration of postoperative hospital stay was 9.1 days. Conclusion This modified layered hand-sewn cervical end-to-side anastomosis is a safe and effective method for MIE McKeown with a low incidence of anastomotic leakage, anastomotic stricture, or other postoperative complications.

To review the various mechanical forces that affect fibroblasts, keratinocytes, endothelial cells, and adipocytes at the cellular and molecular level as well as scar-reducing mechanical devices currently in clinical use.This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.After participating in this educational activity, the participant will:1. Compare and contrast the responses of various types of cells to mechanical forces.2. Identify the mechanical devices and techniques that can help restore skin integrity.Skin provides a critical protective barrier for humans that is often lost following burns, trauma, or resection. Traditionally, skin loss is treated with transfer of tissue from other areas of the body such as a skin graft or flap. Mechanical forces can provide powerful alternatives and adjuncts for skin replacement and scar modulation. This article first provides an overview of the various mechanical forces that affect fibroblasts, keratinocytes, endothelial cells, and adipocytes at the cellular and molecular level. This is followed by a review of the mechanical devices currently in clinical use that can substantially augment the restoration of skin integrity and reduce scarring. Methods described include tissue expanders, external volume expansion, negative-pressure wound therapy, and skin taping.

Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disease characterized by the development of multiple jaw keratocysts and basal cell carcinomas (BCC) and accompanied by diverse phenotypes. The establishment of diagnosis lies on the identification of a heterozygous germline pathogenic variant in the patched homolog 1 gene (PTCH1). PTCH1 has alternative splicing and selective initial coding exon, leading to three types of encoding proteins (PTCHL, PTCHM and PTCHS). The expression of each protein in NBCCS remains ambiguous, especially the importance of the first two exons in translation. Here, we report a Chinese NBCCS family of a novel PTCH1 heterozygous mutation (IVS 2, c.394+1G>T, g.10652G>T) identified by genomic sequencing and reverse-transcription-PCR as aberrant splicing. To the best of our knowledge, this is the first report of NBCCS with a splicing site mutation in intron 2 resulting in exon 2 skipping. Our finding suggests that exon 2 plays an important role in the development of NBCCS and further speculates that the role of longer isoforms PTCHL and PTCHM is crucial in NBCCS, while that of short isoform PTCHS might be dispensable.

// Siqi Fu 1, * , Haijing Wu 1, * , Huiming Zhang 1 , Christine G. Lian 2 and Qianjin Lu 1 1 Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China 2 Program in Dermatopathology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA * These authors have contributed equally to this work Correspondence to: Lu Qianjin, email: qianlu5860@gmail.com Keywords: melanoma, 5-hmC, 5-mC, epigenetic therapy, TET Received: March 02, 2017 Accepted: May 03, 2017 Published: May 30, 2017 ABSTRACT Melanoma is a malignant tumor of melanocytes and is considered to be the most aggressive cancer among all skin diseases. The pathogenesis of melanoma has not been well documented, which may restrict the research and development of biomarkers and therapies. To date, several genetic and epigenetic factors have been identified as contributing to the development and progression of melanoma. Besides the findings on genetic susceptibilities, the recent progress in epigenetic studies has revealed that loss of the DNA hydroxymethylation mark, 5-hydroxymethylcytosine (5-hmC), along with high levels of DNA methylation at promoter regions of several tumor suppressor genes in melanoma, may serve as biomarkers for melanoma. Moreover, 5-Aza-2′-deoxycytidine, an epigenetic modifier causing DNA demethylation, and ten-eleven translocation family dioxygenase (TET), which catalyzes the generation of 5-hmC, demonstrate therapeutic potential in melanoma treatment. In this review, we will summarize the latest progress in research on DNA methylation/hydroxymethylation in melanoma, and we will discuss and provide insight for epigenetic biomarkers and therapies for melanoma. Particularly, we will discuss the role of DNA hydroxymethylation in melanoma infiltrating immune cells, which may also serve as a potential target for melanoma treatment.

// Heng Yin 1 , Haijing Wu 1 , Ming Zhao 1 , Qing Zhang 1 , Hai Long 1 , Siqi Fu 1 and Qianjin Lu 1 1 Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China Correspondence to: Qianjin Lu, email: qianlu5860@gmail.com Keywords: JMJD3, H3K27me3, CD11a, SLE, CD4 + T cells Received: February 13, 2017 Accepted: March 28, 2017 Published: April 06, 2017 ABSTRACT Aberrant CD11a overexpression in CD4 + T cells induces T cell auto-reactivity, which is an important factor for systemic lupus erythematosus (SLE) pathogenesis. Although many studies have focused on CD11a epigenetic regulation, little is known about histone methylation. JMJD3, as a histone demethylase, is capable of specifically removing the trimethyl group from the H3K27 lysine residue, triggering target gene activation. Here, we examined the expression and function of JMJD3 in CD4 + T cells from SLE patients. Significantly decreased H3K27me3 levels and increased JMJD3 binding were detected within the ITGAL (CD11a) promoter locus in SLE CD4 + T cells compared with those in healthy CD4 + T cells. Moreover, overexpressing JMJD3 through the transfection of pcDNA3.1-JMJD3 into healthy donor CD4 + T cells increased JMJD3 enrichment and decreased H3K27me3 enrichment within the ITGAL (CD11a) promoter and up-regulated CD11a expression, leading to T and B cell hyperactivity. Inhibition of JMJD3 via JMJD3-siRNA in SLE CD4 + T cells showed the opposite effects. These results demonstrated that histone demethylase JMJD3 regulates CD11a expression in lupus T cells by affecting the H3K27me3 levels in the ITGAL (CD11a) promoter region, and JMJD3 might thereby serve as a potential therapeutic target for SLE.

Background:. Plastic surgeons desire more efficient methods of processing lipoaspirate when performing fat grafting procedures. We compared, in a preclinical study, the quantity and quality of lipoaspirate processed by a novel Poloxamer Wash, Absorption, mesh filtration System (PWAS) to a frequently used Ringer’s Lactate wash, Decant, and mesh filtration System (RLDS). Methods:. Lipoaspirate from 10 patients was processed with the RLDS and PWAS systems. The processed lipoaspirate from each device was centrifuged to quantify the amount of fat, free oil, and aqueous components remaining in the fat graft. A trypan blue dye exclusion test assessed cell viability. The processing time for the lipoaspirate was also measured. Results:. The 10-patient average fat volume processed and available for grafting was similar using both systems. The adipose volume fraction of PWAS was greater (89% ± 3%) than RLDS (76% ± 10%, P = 0.02). The trypan blue exclusion values and processing time were similar for both systems. Oil was efficiently removed from the lipoaspirate, and both systems processed fat efficiently. Conclusion:. The PWAS effectively cleans lipoaspirate with increased fat concentration.

Background Wilms’ tumor 1-associating protein (WTAP) is a ubiquitously expressed nuclear protein, and involved in multiple pathophysiological processes, including cell cycle, RNA splicing and stabilization, N6-methyladenosine RNA modification, cell proliferation, and apoptosis as well as embryonic development. Here, we investigated the specific role of WTAP in the pathogenesis of psoriasis and its underlying mechanism. Methods Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analyses and multi-spectrum immunohistochemistry were applied to evaluate the level of WTAP expression in psoriatic skin and normal skin. HaCaT cells was stably transfected with WTAP small interfering (si)RNA and plasmid using Lipofectamine®2000 and proliferation was determined by CCK8. Apoptosis and cell cycle analysis were conducted by flow cytometry. Western blot assay was used to explore the expression levels of cell cycle-related proteins in HaCaT cells after WTAP overexpression or inhibition. Furthermore, HaCaT cells were stimulated with proinflammatory cytokines (ie, IL-17A, IL-22, IL-1a, oncostatin M, and TNF-a) to assess WTAP expression. Results We demonstrated that the mRNA and protein levels of WTAP were significantly increased in lesional skins of psoriasis patients and psoriatic cell model compared with normal controls. WTAP was highly expressed in epidermis rather than dermis. Overexpression of WTAP promoted keratinocytes proliferation, which might be related to the up-regulation of cyclinA2 and CDK2. Conclusions These results indicate that overexpression of WTAP may contribute to the pathogenesis of psoriasis by regulating cell cycle progression and highlight WTAP as a potential therapeutic target for psoriasis treatment.

Background Both in vivo and in vitro, cells are subjected to mechanical stress, which can affect their proliferation and differentiation. However, the detailed mechanisms of the accompanying morphologic and biochemical changes remain elusive. This is partially caused by the lack of suitable stretch model and method that mimic soft tissue expansion used in plastic surgery. In this study, we report the development of a novel model for uniaxial stretch cell mimicking tissue expansion. Materials and methods Fibroblasts, grown in plastic culture caskets, were stretched in a progressive and accumulative manner lasting from 1 to 4 days. Cell proliferation was measured using the methyl thiazolyl tetrazolium assay and the Western blot analysis of cell cycle proteins. Results Following the stretch protocol, fibroblasts elongated and aligned parallel to each other and to the applied strain vectors. Furthermore, stretch-stimulated cell proliferation was compared with the unstretched conditions. Conclusions These results demonstrate that this uniaxial cell stretcher device and the accumulative stretch method are a suitable system for mimicking the tissue expansion process used in clinical applications. Level of evidence Not gradable.

Cicatricial ectropion of the upper eyelid is a serious problem because of the association with exposure keratitis and ulceration. Traditional surgical treatment usually requires skin grafts or local flaps depending on the severity of the defect. However, outcomes have usually been discouraging, especially in terms of cosmetic appearance.From February 2000 to March 2012, a total of 12 upper eyelids with severe cicatricial ectropion were treated with a retrograde postauricular island flap and were included in this study. Based on the pedicle of the parietal branch of the superficial temporal artery and its choke anastomoses to the posterior auricular artery, the retrograde postauricular island flap was harvested with a supra-auricular incision down to the non-hair-bearing side skin of the postauricular region. The flap was then transferred to the upper-lid lesion by passing it through a subcutaneous tunnel between the pedicle base and the upper-lid lesion. The donor site was directly closed by advancing the postauricular scalp flap into the sulcus. The largest flap was 6.5 × 3.5 cm(2).After 6-12 months of follow-up, flaps survived with good color, texture, and contour. The eyelids moved freely without recurrence of ectropion. The donor site had an inconspicuous scar. No major complications occurred.The retrograde postauricular island flap can be a safe, simple, and effective procedure for aesthetic correction of severe cicatricial upper-eyelid ectropion with few complications and little donor-site morbidity.This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease involving multiple organs and tissues, which is characterized by the presence of excessive anti-nuclear autoantibodies. The pathogenesis of SLE has been intensively studied but remains far from clear. Increasing evidence has shown that the genetic susceptibilities and environmental factors-induced abnormalities in immune cells, dysregulation of apoptosis, and defects in the clearance of apoptotic materials contribute to the development of SLE. As the main source of auto-antigens, aberrant cell death may play a critical role in the pathogenesis of SLE. In this review, we summarize up-to-date research progress on different levels of cell death—including increasing rate of apoptosis, necrosis, autophagy and defects in clearance of dying cells—and discuss the possible underlying mechanisms, especially epigenetic modifications, which may provide new insight in the potential development of therapeutic strategies for SLE.

Summary Background The expanded forehead flap, using temporal pedicles, has been employed extensively in facial reconstruction. To overcome the disadvantages of the traditional dual temporal pedicles, such as the limited transfer range and the short length of the flap, the distal supercharging technique can be applied to lengthen the flap and extend the transfer range, especially in the cases with a past temporal burn injury. This article aims to present an application of the distal supercharged expanded forehead flap procedure for hemi-facial reconstruction and discuss the haemodynamics of the expanded forehead flap. Methods The tissue expander implantation and the following forehead tissue expansion were performed regularly. When the forehead skin expansion was completed, an expanded forehead flap was created and transferred to the damaged facial area with one distal temporal vessel pedicle that was anastomosed with facial vessels in a supercharged way. All patients were analysed retrospectively. Results From September 2009 to September 2011, eight male patients and one female patient were treated using this method. Their flaps size ranged from 20 cm × 8 cm to 30 cm × 11 cm and no flap loss occurred. Patients came in for follow-ups 9–16 months after the procedures. All the patients were satisfied with the results. Conclusions The supercharging expanded forehead flap procedure can provide reliable flap vascularity due to its elastic transferring abilities. By using a distal supercharging technique, we can lengthen and widen the flap to tailor it to the defect, while also minimising the donor defect in the patients with a past temporal injury.

Cleft palate is one of the most common congenital malformations in the maxillofacial region. After a cleft palate repair, surgeons must deal with the transverse growth restriction and palatal fistulas caused by scar tissue on the raw bone surface around the hard palate. This report describes the technique of the buccinator musculomucosal flap procedure performed together with repair of the cleft palate. The objective is to cover exposed bone areas of the hard palate to decrease scar contraction and subsequent transverse maxillary growth restriction, as well as tension at the closure.From August 2009 to February 2012, 15 patients underwent the buccinator musculomucosal flap procedure. First, the cleft palate was repaired by mucoperiosteal flaps, resulting in wide and raw bone surfaces around the hard palate. The outline of the flap was marked on the buccal mucosa. Grounding on the exposed bone areas around the hard palate, the authors designed widths of flaps ranging from 1.5 to 2.5 cm. These flaps were elevated from the buccopharyngeal fascia and turned 90° to cover the raw hard palate bone surfaces. The donor sites were closed by direct suture.The follow-up period was 1-26 months (average, 10 months). No complications were found in any patient who underwent the procedure, and no fistulas occurred in the midline of the palate. No patients experienced complications related to the donor sites. No trismus or other dysfunction related to mouth movement was observed.The buccinator musculomucosal flap is a convenient and safe flap procedure with fewer donor-site complications. This procedure also has significant potential for improving maxilla growth and reducing the secondary complications that often can result from cleft palate repair.This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Acne inverse (AI), also known as hidradenitis suppurativa, is characterized by inflammatory nodules, fistulating sinus tracts, and painful skin abscesses. The severe AI often produces disfiguring scars influenced in both the appearance and function, especially in the facial and cervical regions. There might be difficulties in the situation for surgical treatment. This report described a 26-year-old man with severe scarring contractures in the neck and mandible regions after a long-term AI treated successfully with a bilateral pedicled expanded forehead flap. With the achievement of mental cervical angle, the patient has been reconstructed well both aesthetically and functionally during the long-term follow-ups.