Impact of internal mammary artery perforator propeller flaps combined with radiotherapy in the treatment of large chest keloids: Our experience.

Background: Keloids are benign skin hyperplasias but have a tumor-like appearance. Clinical management of keloids remains challenging. Aims: We retrospectively evaluated the safety and efficacy of internal mammary artery perforator propeller flaps combined with timely radiotherapy in the treatment of large chest keloids. Methods: From June 2017 to May 2020, 25 patients with large chest keloids (average size 4.82 cm ± 2.53 cm × 9.04 cm ± 4.86 cm) who received both radiotherapy and internal mammary artery perforator flaps transplantation in our department were included. After surgical removal of the keloids, various propeller flaps based on the unilateral internal mammary artery were designed and applied to repair the defects. Timely and full-dose radiotherapy was performed for these patients after the operation. Results: After keloid resection, the dimensions of the defect area were 3 cm-15 cm × 4 cm-25 cm, and the sizes of the flaps were 3 cm-16 cm × 4 cm-27 cm. For all 25 patients, the flaps survived, and the incisions healed in one stage. During the follow-up (median 18 months), no local recurrence was observed, and the itching and pain symptoms in the scar area were significantly relieved. Both physicians and patients were satisfied with the results. Conclusions: The application of internal mammary artery perforator propeller flaps combined with radiotherapy in the treatment of chest keloids can effectively reduce the recurrence of keloids and relieve the related symptoms. It also has advantages including minimized donor site damage, short operation time and speedy postoperative recovery, suggesting its great clinical value.

Rhinoplasty with Simultaneous Autologous Full-Face Fat Transfer for Asian Facial Contouring Balance: A Retrospective Study.

BACKGROUND: The aesthetic facial contouring procedures have gained an increasing popularity in the Asian population. Nevertheless, currently, there are few specific literature assessments and studies on the outcomes of rhinoplasty combined with full-face fat graft contouring. To conduct an objective evaluation of the efficacy of Asian rhinoplasty combined with autologous facial fat transfer in terms of 3-dimensional measurement and patient-reported outcomes. METHODS: Patients who underwent rhinoplasty combined with full-face fat transfer for facial contouring between January 2016 and July 2019 were recruited in the study. The preoperative and postoperative clinical variables and 3-dimensional measurement of patients were also collected. The satisfaction outcome of surgeons and patients was assessed. RESULTS: Twenty patients completed rhinoplasty with full-face fat transfer. The average postoperative follow-up was 10.2 months (range 6-24 months). The nasal length, and the nasal protrusion rate were significantly increased (p < 0.05) after surgery, and the median number of nasolabial angles decreased from 106° to 101°, which was closer to the aesthetic standard of 90°-100°. The topographical projection images of whole face indicated that the volume of frontal, temporal, inner cheek and chin regions were increased obviously. All cases received satisfaction outcome based on surgeons' satisfaction scale, ROE scale, FACE-Q overall facial satisfaction scale, and FACE-Q Rhinoplasty scale. Additionally, no patients had intraoperative or postoperative complications. CONCLUSIONS: Rhinoplasty combined with full-face fat transfer is a reliable and effective method of augmenting and contouring the facial convexity in the Asian populations. LEVEL OF EVIDENCE IV: 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 .

Liposuction to improve the dorsocervical fat pad in esthetic need: Anatomical study and clinical case series.

BACKGROUND: Patients are undergoing surgery to relieve the prominent dorsocervical fat pad because of their esthetic needs. OBJECTIVE: To determine their clinical needs, it is necessary to research the clinic, radiography, and anatomy of dorsocervical fat pad. METHODS: The occipital fat thickness, dorsal fat thickness, and the length, width, and thickness of the dorsocervical fat were measured through MRI imaging. Body projection position were recorded. The correlation between the body mass index and dorsocervical hump was analyzed. Anatomical and histological studies of cadavers with a dorsocervical hump were performed. The liposuction for dorsocervical fat pad was introduced and patients were followed up. RESULTS: In measurement, the MRI imaging of 109 patients were evaluated. The average length, width, and thickness of the dorsocervical fat pad were 114.47, 89.24, and 23.46 mm, respectively, and it is commonly located from the 3rd cervical vertebra to the 3rd thoracic vertebra. The average dorsocervical ratio was 151%. 43.1% patients had a dorsocervical hump. Based on the protrusion degree, the dorsocervical fat pad was classified into three types. The dorsocervical hump severity had a low correlation with obesity. In anatomy, 4 cadavers were dissected. The histological staining indicated that two layers of fat pad constituted a dorsocervical fat pad. As for treatment, 34 patients underwent liposuction to improve the dorsocervical contour, all of them reported satisfactory outcome. CONCLUSIONS: The histological manifestations and morphological measurement of dorsocervical fat pad is researched. Besides, liposuction was applied in 34 patients with dorsocervical hump, and had received satisfied outcome.

A Retrospective Study of Double Eyelid Surgery for Sunken Upper Eyelid in Chinese.

OBJECTIVE: The aim of this study was to explore the effective technique of double eyelid surgery for mild, moderate, and severe sunken upper eyelid in Chinese. METHODS: According to the degree of the sunken upper eyelid, different procedures were performed. For mild sunken upper eyelid, the key technique was named eyelid volume redistribution (EVR)-1 technique, which was advancing or folding the pretarsal orbicularis oculi muscle flap toward up to the upper margin of the incision. For moderate sunken upper eyelid, the EVR-2 technique included EVR-1 technique and releasing orbital fat toward the upper margin of the tarsus. The other surgical steps were the same as conventional double eyelid surgery. For severe sunken upper eyelid, 2 steps were needed. The first step was eyelid volume augmentation (EVA). This technique injected fat into the retroorbicularis oculi fat layer. The second step was conventional double eyelid surgery which was performed 3 to 6 months later. RESULTS: One hundred sixty-seven patients with sunken upper eyelid underwent double eyelid surgery. In addition to the ameliorative recontouring of the sunken deformity, natural double eyelid was created. All patients had no complication, such as infection, skin irregularities, and lumps. The edema, bruising, and temporary ptosis recovered in 2 weeks. The edema resulted from double eyelid surgery, which last about 2 to 3 months. CONCLUSIONS: Our study showed that EVR-1, EVR-2, and EVA techniques have stable surgical results for mild, moderate, and severe sunken upper eyelids in Chinese. The procedures are simple, safe, and have less complications and preferable clinical reference value.

Diced costal cartilage graft combined with muscle repositioning improves Cleft-Side Alar asymmetry in Asian secondary unilateral cleft rhinoplasty: A three-dimensional evaluation.

OBJECTIVES: Asymmetry in a retrusive cleft-side ala situated posterior, lateral, and/or inferior to the non-cleft ala is aggravated by ipsilateral defect of the pyriform aperture. This study assessed diced costal cartilage graft combined with muscle repositioning in enhancing structural base and alar symmetry in secondary cleft rhinoplasty. METHODS: From 2016 to 2019, 20 consecutive patients who underwent pyriform aperture paranasal augmentation combined with muscle repair secondary unilateral cleft rhinoplasty were reviewed retrospectively. Clinical three-dimensional (3D) photos were analyzed pre- and postoperatively, and the augmentation method and muscle repositioning were described detailedly. RESULTS: Twenty cases aged 22.2 ±â€¯3.9 years were submitted to secondary cleft rhinoplasty with diced costal cartilage graft to the pyriform rim. They were followed up for 6.2-26.2 months, with postsurgical time averaging 10.3 ±â€¯3.4 months. After total lip takedown by anatomic muscle re-approximation, the cleft to non-cleft side showed enhanced alar symmetry (p < 0.001) and heightened vertical lip length (p < 0.001). Additionally, the alar base inclination was improved toward the horizontal plane (p < 0.001). CONCLUSIONS: The cleft-side ala was anatomically ameliorated after muscle repositioning combined with diced costal cartilage graft to the pyriform rim, improving alar symmetry. Complications were minimal, indicating the safety of this method.

Differences in Plastic Surgery Training Programs in China and the United States: Similarities, Pitfalls, and Opportunities.

ABSTRACT: As fueled by the booming of China's plastic surgery industry, the demand for prominent plastic surgeons has been growing. Accordingly, a better and more standard training system of plastic surgery specialists should be urgently implemented in China. To delve into and optimize the training system of this study, Peking University Health Science Center and Harvard Medical School are selected as the representatives of China and the United States, and the plastic surgery specialist training system between these 2 countries are compared based on literature research. As revealed from the results, the United States has gained sufficient experience in training of plastic surgery specialists. Moreover, the management agency of such training is more professional, as characterized by its longer development history, higher access requirement, more standard training program, higher training demands, as well as more quantitative training assessment. Thus, there is rich experience of the United States that can be referenced by China.

Morphological Classification of the Zygomatic Regions in Young Chinese Han Males and Females Based on a Simulated Moiré Pattern.

The complex curved contours of the zygomatic regions are difficult to analyze. Therefore, a better evaluation medium must be developed. We aimed to examine and summarize the morphological characteristics of the zygomatic region by using a moiré pattern map and computer algorithm. In this cross-sectional study, we collected three-dimensional images of the facial contours of 251 Han Chinese youth and established a morphological moiré map database. Clustering analysis using a computer algorithm was applied to obtain the zygomatic morphologies for classification. Aesthetic evaluation was performed to summarize the characteristics of the zygomatic types and provide reference for the preoperative morphological design of the midface. Zygomatic regions were morphologically classified into five types. Each type had its typical feature in the moiré pattern map. The moiré stripes in the left zygomatic region formed an "Ω" shape outward and downward in type 1, and they tended to be diagonal like "\\\" in type 2, smoothly curved like ")))" in type 3, vertical like "|||" in type 4, and diagonal like "///" in type 5. The aesthetic evaluation outcome indicated that the integrally flat zygoma (type 4) was more aesthetically pleasing among males, and the integrally prominent zygoma (type 3) was more aesthetically pleasing among females. Five morphological contour types of the zygoma were classified among the Chinese Han males and females based on the simulated moiré pattern. This morphological classification would aid in preparing a guide for clinical diagnosis and surgical planning.

Betacellulin enhances ovarian cancer cell migration by up-regulating Connexin43 via MEK-ERK signaling.

Epithelial ovarian cancer is the fifth common cause of cancer death in women and the most lethal gynecological malignancies. Our previous studies have shown that up-regulation of Connexin43, a gap-junction subunit crucial for cell-cell communication, enhances ovarian cancer cell migration. Betacellulin is a member of the epidermal growth factor (EGF) family which can bind to multiple EGF family receptors. Overexpression of betacellulin is found in a variety of cancers and is associated with reduced survival. However, the specific roles and molecular mechanisms of betacellulin in ovarian cancer progression are poorly understood. In the current study, we tested the hypothesis that betacellulin induces ovarian cancer cell migration by up-regulating Connexin43. Our results showed that treatment with betacellulin significantly increased Connexin43 expression and cell migration in both OVCAR4 and SKOV3 ovarian cancer cell lines. Moreover, betacellulin induced the activation of MEK-ERK signaling, and its effects on Connexin43 were inhibited by pre-treatment with U0126. Pre-treatment with AG1478 totally blocked the activation of MEK-ERK signaling but only partially inhibited betacellulin-induced Connexin43 expression and cell migration. Most importantly, betacellulin-induced cell migration was attenuated by knockdown of Connexin43, and co-treatment with gap junction inhibitor carbenoxolone did not alter this effect. Our results suggest a bilateral role of Connexin43 in ovarian cancer migration, and also demonstrate a gap junction-independent mechanism of betacellulin.

Direct micro-electric stimulation alters phenanthrene-degrading metabolic activities of Pseudomonas sp. strain DGYH-12 in modified bioelectrochemical system.

Bioelectrochemical systems (BESs) have great potential for treating wastewater containing polycyclic aromatic hydrocarbons (PAHs); however, detailed data on cell physiological activities in PAH biodegradation pathways stimulated by BESs are still lacking. In this paper, a novel BES device was assembled to promote the growth of Pseudomonas sp. DGYH-12 in phenanthrene (PHE) degradation. The results showed that in the micro-electric field (0.2 V), cell growth rate and PHE degradation efficiency were 22% and 27.2% higher than biological control without electric stimulation (BC), respectively. The extracellular polymeric substance (EPS) concentration in BES (39.38 mg L-1) was higher than control (33.36 mg L-1); moreover, the membrane permeability and ATPase activities were also enhanced and there existing phthalic acid and salicylic acid metabolic pathways in the strain. The degradation genes nahAc, pcaH, and xylE expression levels were upregulated by micro-electric stimulation. This is the first study to analyze the physiological and metabolic effect of micro-electric stimulation on a PHE-degrading strain in detail and systematically.

Exosomes from Adipose-Derived Stem Cells (ADSCs) Overexpressing miR-21 Promote Vascularization of Endothelial Cells.

In the past few years, exosomes released from adipose-derived stem cells (abbreviated as ADSCs) have shown promises to provide therapeutic benefits in the fields of regenerative medicine. miRNAs, existing in exosomes, are endogenous, small noncoding RNAs that play important roles in a variety of cellular functions and tumor development. Emerging evidences have indicated that miR-21 is one of the important miRNAs associated with tumor angiogenesis. In this study, we identified the role of exosomes from ADSCs overexpressing miR-21 in regulating/promoting vascularization of endothelial cells. Experimental data indicated an elevated miR-21 level in exosomes released by ADSCs overexpressing miR-21. In vitro matrigel angiogenesis assay showed that exosomes secreted by ADSCs overexpressing miR-21 significantly promoted the vascularization of HUVEC cells (an endothelial cell line). Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) revealed an upregulation of HIF-1α, VEGF, SDF-1, p-Akt, p-ERK1/2 and downregulation of PTEN in response to miR-21 overexpression, indicating that miR-21 enriched exosomes induced angiogenesis through Akt and ERK activation and also HIF-1α and SDF-1 expression. Our work suggests that exosomes from ADSCs that overexpressing miR-21 can potentially promote vascularization and therefore the transplantation of exosomes from their culture may be suitable for clinical effort in regenerative medicine.

Parathyroid hormone (PTH) promotes ADSC osteogenesis by regulating SIK2 and Wnt4.

Developing methods for regenerating bones and uncovering the molecular mechanism underlying bone formation have great significance to human health. In the last decade, people have been using adipose-derived stem cells (ADSCs), that are capable of multilineage differentiation, to reconstruct defected bones. Uncovering the molecular mechanisms of the osteoblast differentiation of ADSCs will provide more understanding of ADSCs in the application of bone regeneration and perhaps new methods for osteoporosis treatment. Here we studied how parathyroid hormone (PTH1-34) acts on osteoinduced ADSCs to orchestrate bone formation and how Wnt4 signaling is involved in PTH-promoted bone formation from ADSCs. We found that PTH1-34 can phosphorylate SIK2, upregulate RANKL and downregulate SOST, thereby upregulating Wnt4 to promote the osteogenesis process of ADSCs. Though the knockdown of Wnt4 with shRNA interference barely affects the expression of upstream proteins (i.e., RANKL, SOST), it affects the expression of other downstream osteogenic proteins (i.e., Runx2, Osterix, and Osteocalcin), and then inhibit the osteogenesis process of ADSCs. Overall, PTH can affect the osteogenesis process of ADSCs by regulating SIK2 and Wnt4. We anticipate that this work will provide researchers with new insights into the bone regeneration with ADSCs.

Facial aesthetic fat graft retention rates after filtration, centrifugation, or sedimentation processing techniques measured using three-dimensional surface imaging devices.

OBJECTIVE: How to increase the long-term retention rate of autologous fat grafting has been widely discussed. This study aimed to evaluate long-term fat graft retention rates for the most widely used fat processing methods in the area of facial esthetic surgery, including centrifugation, filtration, and sedimentation, using three-dimensional (3D) imaging. DATA SOURCES: PubMed, Embase, Wiley/Cochrane Library, and Web of Science databases were comprehensively searched from inception to July 2018 according to the guidelines of the American Society of Plastic Surgeons Fat Graft Task Force Assessment Methodology. STUDY SELECTION: Articles were screened using predetermined inclusion and exclusion criteria. Data collected included patient characteristics, follow-up devices, fat grafting techniques, and clinical outcomes. Patient cohorts were pooled, and fat graft retention rates were calculated. Complications were summarized according to different clinical characteristics. RESULTS: Of 77 articles, 10 clinical studies met the inclusion criteria and reported quantified measurement outcomes with 3D imaging which provide precise volumetric data with approximately 2% standard deviation compared to real volumes. Data of 515 patients were included. Fat grafting retention varied from 21% to 82%. We found filtration and centrifugation techniques could result in better retention outcomes. However, retention varied within each processing technique, with no significant difference among the 3 techniques. Twenty-two complications were reported among 515 patients, including donor-site hematoma (1 case), mild post-operative erythema (2 cases), mild volumetric asymmetries (2 cases), chronic edema (2 cases), overcorrection (2 cases), skin irregularity (6 cases), and headache or dysesthesia (7 cases). CONCLUSIONS: Filtration and centrifugation techniques may result in better fat grafting retention outcomes than gravity sedimentation; however, more accurate statistical evidence is needed. Controversies continue to exist with respect to the performance of the different fat-processing techniques in fat graft retention.

TGF-ß1 stimulates migration of type II endometrial cancer cells by down-regulating PTEN via activation of SMAD and ERK1/2 signaling pathways.

PTEN acts as a tumor suppressor primarily by antagonizing the PI3K/AKT signaling pathway. PTEN is frequently mutated in human cancers; however, in type II endometrial cancers its mutation rate is very low. Overexpression of TGF-ß1 and its receptors has been reported to correlate with metastasis of human cancers and reduced survival rates. Although TGF-ß1 has been shown to regulate PTEN expression through various mechanisms, it is not yet known if the same is true in type II endometrial cancer. In the present study, we show that treatment with TGF-ß1 stimulates the migration of two type II endometrial cancer cell lines, KLE and HEC-50. In addition, TGF-ß1 treatment down-regulates both mRNA and protein levels of PTEN. Overexpression of PTEN or inhibition of PI3K abolishes TGF-ß1-stimulated cell migration. TGF-ß1 induces SMAD2/3 phosphorylation and knockdown of common SMAD4 inhibits the suppressive effects of TGF-ß1 on PTEN mRNA and protein. Interestingly, TGF-ß1 induces ERK1/2 phosphorylation and pre-treatment with a MEK inhibitor attenuates the suppression of PTEN protein, but not mRNA, by TGF-ß1. This study provides important insights into the molecular mechanisms mediating TGF-ß1-induced down-regulation of PTEN and demonstrates an important role of PTEN in the regulation of type II endometrial cancer cell migration.

Growth differentiation factor 8 induces SKOV3 ovarian cancer cell migration and E-cadherin down-regulation.

Epithelial ovarian cancer is the most lethal gynecological malignancy because most women present with late stage disseminated disease. Epithelial-mesenchymal transition (EMT) is characterized by the down-regulation of E-cadherin and up-regulation of N-cadherin, and is a crucial event in the pathogenesis of ovarian cancer. Transforming growth factor-ß (TGF-ß) is a major regulator of EMT in many normal and neoplastic cell types. Growth differentiation factor 8 (GDF8), which also activates TGF-ß-like SMAD2/3 signaling, is best known for negatively regulating muscle growth. Though recent studies suggest that GDF8 enhances placental trophoblast cell migration, little is known about the role of GDF8 in EMT and cancer metastasis. We hypothesized that GDF8 could enhance ovarian cancer cell migration by inducing EMT. Here we demonstrate for the first time that GDF8 down-regulates E-cadherin but does not alter N-cadherin in SKOV3 ovarian cancer cells. This effect is abolished by the activin receptor-like kinase (ALK)4/5/7 inhibitor SB431542 or siRNA-mediated knockdown of ALK5, whereas knockdown of ALK4 is only partially inhibitory. GDF8 treatment increases the phosphorylation of SMAD2/3 and up-regulates the E-cadherin transcriptional repressors Snail and Slug; and these effects are abolished by pre-treatment with SB431542. Knockdown of common SMAD4 fully reverses the effects of GDF8 on E-cadherin and partially attenuates its effects on Snail and Slug. Importantly, GDF8 treatment increases SKOV3 cell migration and this effect is blocked by SB431542. Our study suggests that GDF8 promotes ovarian cancer cell migration via ALK4/5-SMAD2/3-E-cadherin signaling.

Betacellulin induces Slug-mediated down-regulation of E-cadherin and cell migration in ovarian cancer cells.

Epithelial ovarian cancer is the leading cause of death among gynaecological cancers. Previous studies have demonstrated that epidermal growth factor receptor (EGFR) ligands can induce ovarian cancer cell invasion by down-regulating E-cadherin. Betacellulin is a unique member of the EGF family. It is overexpressed in a variety of cancers and is associated with reduced survival. However, the biological functions and clinical significance of betacellulin in ovarian cancer remain unknown. In the current study, we tested the hypothesis that betacellulin induces ovarian cancer cell migration by suppressing E-cadherin expression. Treatment of SKOV3 and OVCAR5 ovarian cancer cell lines with betacellulin down-regulated E-cadherin, but not N-cadherin. In addition, betacellulin treatment increased the expression of Snail and Slug, and these effects were completely blocked by pre-treatment with EGFR inhibitor AG1478. Interestingly, only knockdown of Slug reversed the down-regulation of E-cadherin by betacellulin. Betacellulin treatment induced the activation of both the MEK-ERK and PI3K-Akt signaling pathways, and it also significantly increased ovarian cancer cell migration. Importantly, the effects of betacellulin on E-cadherin, Slug and cell migration were attenuated by pre-treatment with either U0126 or LY294002. Our results suggest that betacellulin induces ovarian cancer migration and Slug-dependent E-cadherin down-regulation via EGFR-mediated MEK-ERK and PI3K-Akt signaling.

Sprouty4 mediates amphiregulin-induced down-regulation of E-cadherin and cell invasion in human ovarian cancer cells.

Sprouty (SPRY) proteins are well-characterized factors that inhibit receptor tyrosine kinase (RTK)-mediated activation of cellular signaling pathways. The down-regulation of SPRY4 expression has been reported in human ovarian cancer. However, the specific roles and mechanisms by which SPRY4 affects ovarian cancer progression are completely unknown. Amphiregulin (AREG) binds exclusively to the epidermal growth factor receptor (EGFR) and has been considered to be a dominant autocrine/paracrine EGFR ligand in ovarian cancer. In the present study, we first examined the effects of AREG on SPRY4 expression and the possible underlying molecular mechanisms involved in this process in two human ovarian cancer cell lines. Our results demonstrated that treatment with AREG up-regulated SPRY4 expression by activating the ERK1/2 signaling pathway. In addition, we showed that small interfering RNA (siRNA)-mediated knockdown of SPRY4 attenuated the AREG-induced down-regulation of E-cadherin by inhibiting the expression of SNAIL but not SLUG. In contrast, overexpression of SPRY4 enhanced AREG-induced down-regulation of E-cadherin by increasing the expression of SNAIL. Moreover, SPRY4 knockdown attenuated AREG-induced cell migration and invasion. Overexpression of SPRY4 enhanced AREG-induced cell invasion. This study reveals that SPRY4 is involved in EGFR-mediated human ovarian cancer progression.

Transforming growth factor-ß stimulates human ovarian cancer cell migration by up-regulating connexin43 expression via Smad2/3 signaling.

Reduced connexin43 (Cx43) expression is frequently detected in different types of human cancer. Cx43 has been shown to regulate cancer cell migration in a cell-type dependent manner. In both primary and recurrent human ovarian cancer, overexpression of TGF-ß ligand and its receptors have been detected. TGF-ß can regulate Cx43 expression in other cell types and stimulate human ovarian cancer cell migration. However, whether Cx43 can be regulated by TGF-ß and is involved in TGF-ß-stimulated cell migration in human ovarian cancer cells remain unknown. In this study, we demonstrate that TGF-ß up-regulates Cx43 in two human ovarian cancer cell lines, SKOV3 and OVCAR4. The stimulatory effect of TGF-ß on Cx43 expression is blocked by inhibition of TGF-ß receptor. Treatment with TGF-ß activates Smad2 and Smad3 signaling pathways in both ovarian cancer cell lines. In addition, siRNA-mediated knockdown of Smad2 or Smd3 abolishes TGF-ß-induced up-regulation of Cx43 expression. Moreover, knockdown of Cx43 attenuates TGF-ß-stimulated cell migration. This study demonstrates an important role for Cx43 in mediating the effects of TGF-ß on human ovarian cancer cell migration.