Autologous Tissue Repair and Total Face Restoration.

Importance: Total face restoration remains a challenge in modern reconstructive surgery. After 17 years of experiments and preliminary clinical studies, a new concept of face prefabrication was developed for face restoration with autologous tissue. Objective: To evaluate the long-term results of face restoration with autologous tissue and report a finalized and standardized approach of face prefabrication. Design, Setting, and Participants: In this single-center long-term retrospective study, 32 patients who underwent total face restoration between 2005 and 2022 were reviewed. These patients underwent total facial reconstruction, which included flap prefabrication, 3-dimensional printing, tissue expansion, and flap transfer with aid of indocyanine green angiography (IGA). The flap first undergoes prefabrication by transferring vascularized fascia under the skin of the selected chest. A tissue expander is then placed under the fascia to create a large, thin, reliable skin flap after expansion. Once completed, the flap is transferred to the face during the second stage of the reconstruction. Intraoperative IGA is performed to guide the design of subsequent openings for facial fissures. Data were analyzed from July to September 2023. Main Outcomes and Measures: Flap healing, reconstructive outcome, and patient recovery were assessed during follow-up. Three questionnaires, including the 36-Item Short Form Health Survey (SF-36), Aesthetic and Functional Status Score of Facial Soft-Tissue Deformities/Defects, and the EuroQoL Health-Related Quality of Life (EQ-5D-5L), were used to evaluate the quality of life and satisfaction with facial aesthetic and functional status. Results: Of 24 included patients, 14 (58%) were male, and the mean (range) age was 32.9 (8-62) years. The mean (range) follow-up was 5.6 (2-12) years. All patients reported a significant improvement in quality of life (SF-36), especially in mean (SD) social functioning (preoperative score, 53.65 [34.51]; postoperative score, 80.73 [19.10]) and emotional stability (preoperative score, 56.67 [25.55]; postoperative score, 71.17 [18.51]). A total of 22 patients (92%) went back to work. Mean (SD) facial aesthetic status (preoperative score, 4.96 [3.26]; postoperative score, 11.52 [3.49]; P < .001) and functional status (preoperative score, 11.09 [3.51]; postoperative score, 15.78 [3.26]; P < .001) also improved. In addition, there was a significant increase in overall satisfaction and self-reported health status (preoperative score, 8.13 [1.52]; postoperative score, 3.58 [2.31]). Conclusions and Relevance: In this study, 5-year follow-up results suggested that this innovative approach to total face restoration offered a safe and valid option for indicated patients, with acceptable reconstructive and cosmetic outcomes.

Advances in GPCR-targeted drug development in dermatology.

Achieving the efficacy and specificity of G-protein-coupled receptor (GPCR) targeting-drugs in the skin remains challenging. Understanding the molecular mechanism underlying GPCR dysfunction is crucial for developing targeted therapies. Recent advances in genetic, signal transduction, and structural studies have significantly improved our understanding of cutaneous GPCR functions in both normal and pathological states. In this review, we summarize recent discoveries of pathogenic GPCRs in dermal injuries, chronic inflammatory dermatoses, cutaneous malignancies, as well as the development of potent potential drugs. We also discuss targeting of cutaneous GPCR complexes via the transient receptor potential (TRP) channel and structure elucidation, which provide new opportunities for therapeutic targeting of GPCRs involved in skin disorders. These insights are expected to lead to more effective and specific treatments for various skin conditions.

Total Face Reconstruction with Flap Prefabrication and Soft-Tissue Expansion Techniques.

SUMMARY: Total facial deformities always lead to psychological and functional consequences, making plastic and reconstructive surgery a great challenge. The skin of the anterior chest area is matched in thickness, texture, and color to the head and face. The purpose of this article was to discuss and evaluate reconstructive surgeons' experiences with obtaining a monoblock flap from the anterior thoracic area for entire face reconstruction using flap prefabrication, soft-tissue expansion, and facial plastic surgery following skin flap transplantation. Two patients underwent prefabricated expanded anterior thoracic flap reconstructions for total facial deformities; data collection included face defect size, flap type, the shape of the expander, expansion time, and complications. All the face flaps that were transplanted survived without major complications. It is concluded that using a prefabricated expanded flap to reconstruct an entire facial soft-tissue defect can provide a high degree of matching, a wide enough covering area, and a thin enough skin thickness to cover the face. Autologous flap grafting is easy to implement and has a high application value.

Corrigendum: Editorial: Recent innovations to inhibit scar formation for better skin regeneration.

[This corrects the article DOI: 10.3389/fsurg.2023.1325832.].

Midface Prelamination by using a Three-dimensional Cervicothoracic Prefabricated Flap.

SUMMARY: The midface is an important area in aesthetics and function and a complex area to manage after burn injuries, trauma, and tumor resection. Traditional treatment to reconstruct midface defects involving the nose, lips and cheeks requires multiple sequential flap surgeries but results in a patch-like appearance, which remains a major challenge for head and neck reconstructive surgeons. This article describes how the authors perform prelamination using the prefabricated cervicothoracic flap on the anterior chest for midface reconstruction. The key point of the authors' procedure is to three-dimensionalize the cervicothoracic prefabricated flap with flap folding, flap rotation, and cartilage grafts for coverage, lining, and support of the nose and lips. This technique may be indicated for extensive midface defects involving total nose and lip loss. It provides a uniform matched facial appearance and significant functional improvement. Donor-site morbidity and the need for multiple flap procedures could be reduced.

Intraoperative Indocyanine Green Angiography Facilitates Flap Fenestration and Facial Organ Fabrication in Total Facial Restoration.

BACKGROUND: As effective measures to visualize flap vasculature and perfusion were unavailable, flap fenestration and facial organ fabrication could not be performed safely, preventing the transition from 2-D coverage to the restoration of the 3-D structure of facial organs. This study aims to evaluate the efficacy of indocyanine green angiography (ICGA) in guiding flap fenestration and facial organ fabrication in total facial restoration. METHODS: Ten patients with total facial scarring following burn injury were enrolled in the study. They were treated with pre-expanded, prefabricated monoblock flaps for total face restoration. The opening of nostrils, oral and palpebral orifices, together with organ fabrication, were conducted under the guidance of intraoperative ICGA via hemodynamic evaluation of flap perfusion. Postoperative follow-up parameters include vascular crisis, infection, flap necrosis and patients' aesthetic and functional recovery. RESULTS: The opening of facial organ orifices was performed at the stage of flap transfer in nine patients. To avoid damaging the major nourishing vessels, the left palpebral orifice was opened eight days after the flap transfer in one patient, as observed by ICGA. Based on ICGA evaluation, the decision to perform additional vascular anastomosis before flap fenestration was made in six patients. Hemodynamic analysis of flap perfusion following fenestration revealed no significant change. Follow-up showed satisfactory aesthetic recovery and well-restored 3-D structures of facial organs. CONCLUSION: This pilot study demonstrates how intraoperative ICGA can enhance the safety of flap fenestration, thereby transforming full facial restoration from the 2-D to the 3-D realm by facilitating facial organ fabrication.

The application of augmented reality in plastic surgery training and education: A narrative review.

Continuing problems with fewer training opportunities and a greater awareness of patient safety have led to a constant search for an alternative technique to bridge the existing theory-practice gap in plastic surgery training and education. The current COVID-19 epidemic has aggravated the situation, making it urgent to implement breakthrough technological initiatives currently underway to improve surgical education. The cutting edge of technological development, augmented reality (AR), has already been applied in numerous facets of plastic surgery training, and it is capable of realizing the aims of education and training in this field. In this article, we will take a look at some of the most important ways that AR is now being used in plastic surgery education and training, as well as offer an exciting glimpse into the potential future of this field thanks to technological advancements.

Extracellular RNA in melanoma: Advances, challenges, and opportunities.

Melanoma, a malignant mass lesion that originates in melanocytes and has a high rate of malignancy, metastasis, and mortality, is defined by these characteristics. Malignant melanoma is a kind of highly malignant tumor that produces melanin and has a high mortality rate. Its incidence accounts for 1%-3% of all malignant tumors and shows an obvious upward trend. The discovery of biomolecules for the diagnosis and treatment of malignant melanoma has important application value. So far, the exact molecular mechanism of melanoma development relevant signal pathway still remains unclear. According to previous studies, extracellular RNAs (exRNAs) have been implicated in tumorigenesis and spread of melanoma. They can influence the proliferation, invasion and metastasis of melanoma by controlling the expression of target genes and can also influence tumor progression by participating in signal transduction mechanisms. Therefore, understanding the relationship between exRNA and malignant melanoma and targeting therapy is of positive significance for its prevention and treatment. In this review, we did an analysis of extracellular vesicles of melanoma which focused on the role of exRNAs (lncRNAs, miRNAs, and mRNAs) and identifies several potential therapeutic targets. In addition, we discuss the typical signaling pathways involved in exRNAs, advances in exRNA detection and how they affect the tumor immune microenvironment in melanoma.

Lean adipose tissue macrophage derived exosome confers immunoregulation to improve wound healing in diabetes.

Chronic non-healing wounds, a prevalent complication of diabetes, are associated with increased mortality in diabetic patients. Excessive accumulation of M1 macrophages in diabetic wounds promotes inflammation and results in dysregulated tissue repair. Adipose tissue macrophages (ATMs) derived from healthy lean donors have the ability to improve glucose tolerance and insulin sensitivity, as well as modulate inflammation. MicroRNAs (miRs), which can be packaged into exosomes (Exos) and secreted from cells, serve as essential regulators of macrophage polarization. Here, we revealed that ATMs isolated from lean mice secrete miRs-containing Exos, which modulate macrophage polarization and promote rapid diabetic wound healing when administered to diabetes-prone db/db mice. The miRs sequence of tissue samples from wounds treated with Exos secreted by lean ATMs (ExosLean) revealed that miR-222-3p was up-regulated. Further analyses showed that inhibiting miR-222-3p using a miR inhibitor impaired the macrophage-reprogramming effect of ExosLean. In the excisional skin wound mouse model, locally inhibiting miR-222-3p disrupted healing dynamics and failed to modulate macrophage polarization. Mechanistic studies revealed a connection between miR-222-3p, Bcl2l11/Bim, an inflammatory response effector, macrophage polarization, and diabetic wound healing. In summary, ExosLean act as positive regulators of macrophage polarization by regulating miR levels in wounds and accelerating wound healing, and thus have important implications for wound management in diabetes.

Clinical Application of Pre-Expanded Perforator Flaps.

Background: Challenging large soft tissue defects are typically treated with microvascular free tissue transfer; however, success has been noted with pre-expanded perforator flaps. Objective: To report outcomes and complications from pre-expanded perforator flaps. Methods: A retrospective chart review of patients undergoing tissue reconstruction with pre-expanded perforator flaps between 2014 and 2020. Data collection included flap type, defect characteristics, and complications. Results: All 29 patients had successful flap reconstruction without major complication. The median area of tissue defect was 17 × 13 cm2 (range 7 × 4 to 27 × 24 cm2). Mean tissue expansion period was 15.2 weeks (range 9-26 weeks). The most common flap was the pre-expanded internal mammary artery perforator flaps. Conclusion: The findings of this study suggest that combining tissue expansion with a perforator flap for large tissue reconstruction can be successful with limited complications. This technique may allow a larger pliable skin flap that deserves further investigation.

An Updated Definition of Plastic Surgery.

ABSTRACT: Modern medicine tends to provide comprehensive medical services based on disease or pathological features. As a result, the overlap between plastic surgery and other surgical departments greatly deepened. What was exclusively done by plastic surgeons are nowadays frequently practiced by other surgeons as well. Thus, generating confusion as to whether plastic surgery is an independent subject or a tool. Therefore, in this new era of modern medicine, it is necessary to reconsider the definition of plastic surgery.

Identification of MRAP protein family as broad-spectrum GPCR modulators.

BACKGROUND: The melanocortin receptor accessory proteins (MRAP1 and MRAP2) are well-known endocrine regulators for the trafficking and signalling of all five melanocortin receptors (MC1R-MC5R). The observation of MRAP2 on regulating several non-melanocortin G protein-coupled receptors (GPCRs) has been sporadically reported, whereas other endogenous GPCR partners of the MRAP protein family are largely unknown. METHODS: Here, we performed single-cell transcriptome analysis and drew a fine GPCR blueprint and MRAPs-associated network of two major endocrine organs, the hypothalamus and adrenal gland at single-cell resolution. We also integrated multiple bulk RNA-seq profiles and single-cell datasets of human and mouse tissues, and narrowed down a list of 48 GPCRs with strong endogenous co-expression correlation with MRAPs. RESULTS: 36 and 46 metabolic-related GPCRs were consequently identified as novel interacting partners of MRAP1 or MRAP2, respectively. MRAPs exhibited protein-protein interactions and varying pharmacological properties on the surface translocation, constitutive activities and ligand-stimulated downstream signalling of these GPCRs. Knockdown of MRAP2 expression by hypothalamic administration of adeno-associated virus (AAV) packed shRNA stimulated body weight gain in mouse model. Co-injection of corticotropinreleasing factor (CRF), the agonist of corticotropin releasing hormone receptor 1 (CRHR1), suppressed feeding behaviour in a MRAP2-dependent manner. CONCLUSIONS: Collectively, our study has comprehensively elucidated the complex GPCR networks in two major endocrine organs and redefined the MRAP protein family as broad-spectrum GPCR modulators. MRAP proteins not only serve as a vital endocrine pivot on the regulation of global GPCR activities in vivo that could explain the composite physiological phenotypes of the MRAP2 null murine model but also provide us with new insights of the phenotyping investigation of GPCR-MRAP functional complexes.

The Long Noncoding Transcript HNSCAT1 Activates KRT80 and Triggers Therapeutic Efficacy in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous carcinoma (HNSC) is the most prevalent malignancy of the head and neck regions. Long noncoding RNAs (lncRNAs) are vital in tumorigenesis regulation. However, the role of lncRNAs in HNSC requires further exploration. Herein, through bioinformatic assays using The Cancer Genome Atlas (TCGA) datasets, rapid amplification of cDNA ends (RACE) assays, and RNA-FISH, we revealed that a novel cytoplasmic transcript, HNSC-associated transcript 1 (HNSCAT1, previously recognized as linc01269), was downregulated in tumor samples and advanced tumor stages and was also associated with favorable outcomes in HNSC. Overexpression of HNSCAT1 triggered treatment efficacy in HNSCs both in vivo and in vitro. More importantly, through high-throughput transcriptome analysis (RNA-seq, in NODE database, OEZ007550), we identified KRT80, a tumor suppressor in HNSC, as the target of HNSCAT1. KRT80 expression was modulated by lncRNA HNSCAT1 and presented a positive correlation in tumor samples (R = 0.52, p < 0.001). Intriguingly, we identified that miR-1245 simultaneously interacts with KRT80 and HNSCAT1, which bridges the regulatory function between KRT80 and HNSCAT1. Conclusively, our study demonstrated that lncRNA HNSCAT1 functions as a necessary tumor inhibitor in HNSC, which provides a novel mechanism of lncRNA function and provides alternative targets for the diagnosis and treatment of HNSC.

Comparison between endoscopic submucosal tunnel dissection and endoscopic submucosal dissection for superficial neoplasia at esophagogastric junction: a case-matched controlled study of a single center from China.

BACKGROUND: So far, little evidence is available for the comprehensive comparison of endoscopic submucosal tunnel dissection (ESTD) with endoscopic submucosal dissection (ESD) for the treatment of superficial neoplasia at esophagogastric junction (EGJ). METHODS: EGJ superficial neoplasia patients with ESTD treatment between January, 2021 and August, 2020 were retrospectively reviewed and individually matched at 1:1 ratio with those with ESD treatment according to lesion size, specimen area and lesion location, forming ESTD and ESD group, respectively. A sample size of 17 patients was collected for each group. Treatment outcomes including resection time, specimen area, and resection speed as well as occurrence of complications were evaluated. RESULTS: Compared with ESD group, ESTD group got shorter resection time (111.00 ± 11.70 min for ESD group vs. 71.59 ± 6.18 min for ESTD group, p = 0.008) and faster section speed (0.23 ± 0.03 cm2/min for ESD group vs. 0.37 ± 0.06 cm2/min for ESTD group, p = 0.012). No complication was found to occur in ESTD group, while 1 patient with MP damage and 1 with delayed bleeding was found in ESD group. CONCLUSION: For the treatment of EGJ superficial neoplasia, ESTD is a safer and more effective and reliable endoscopic technique compared with ESD.

Reconstruction of Large Cervicofacial Defects With Expanded Island Superficial Temporal Artery Flaps and an 810-nm Diode Laser Hair Removal Technique.

BACKGROUND: Extensive cervicofacial reconstruction is challenging for plastic surgeons. Because of the location of the adjacent scalp flap nourished by the superficial temporal artery (STA), it can be a candidate for cervicofacial reconstruction. OBJECTIVES: This article aims to report a combined treatment of an expanded island STA flap and an 810-nm diode laser hair removal technique for extensive cervicofacial defects. METHODS: Between January 2015 and December 2018, 10 patients with lower face and neck scar contraction were reconstructed with a bilateral or unilateral expanded STA island flap and an 810-nm diode laser for hair removal in this retrospective study. Hair removal via the 810-nm laser was started when the injected volume reached the volume of the expander, with a fluence of 35 to 40 J/cm2 and a 1 to 2 Hz repetition rate. Before second-stage surgery, the hair reduction rate was assessed. Twelve months after surgery, the degree of epilation efficacy according to the satisfaction scale and Global Aesthetic Improvement Scale was evaluated. RESULTS: This study included 2 single-pedicle flaps and 8 double-pedicle flaps. The average size of the implanted expanders was 600 mL. The average injected volume was 1405 mL. Before second surgery, there was a 67.4% hair reduction rate. Twelve months after surgery, the results of Global Aesthetic Improvement Scale were very good (3), good (6), average (1), and poor (0). CONCLUSIONS: The expanded island STA flap and 810-nm diode laser technique may be a novel treatment option for severe face and neck aesthetic reconstruction.

MicroRNA therapy confers anti-senescent effects on doxorubicin-related cardiotoxicity by intracellular and paracrine signaling.

Doxorubicin (Dox), an important anthracycline, is a potent anticancer agent that is used for treating solid tumors and hematologic malignancies. However, its clinical use is hampered by cardiac cardiotoxicity. This study aimed to investigate the cardioprotective potential of miR-199a-3p. Continuous Dox treatment not only markedly induced cardiomyocyte senescence but also resulted in a growing number of senescence-associated secretory phenotype (SASP) cardiomyocytes, frequently leading to heart senescence. This study showed that miR-199a-3p was downregulated in cardiomyocytes when exposed to Dox. The cardiac-specific overexpression of miR-199a-3p promoted cell cycle re-entry and cell proliferation, resulting in relief from cardiac senescence. Also, the elevation of miR-199a-3p inhibited the generation of SASP, thus, hampering the spread of senescence. In cardiomyocytes, the modulation of miR-199a-3p changed the levels of senescence-related protein GATA4. The ectopic expression of GATA4 blunted the anti-senescence effect of miR-199a-3p. Together, the data supported a role for miR-199a-3p during Dox cardiotoxicity. The elevation of miR-199a-3p might provide a dual therapeutic advantage in Dox cardiotoxicity therapy by simultaneously preventing cardiac senescence and reducing the spread of senescence.

Identification and functional analysis of a three-miRNA ceRNA network in hypertrophic scars.

BACKGROUND: Hypertrophic scar (HTS) is a fibrotic disorder of skins and may have repercussions on the appearance as well as functions of patients. Recent studies related have shown that competitive endogenous RNA (ceRNA) networks centering around miRNAs may play an influential role in HTS formation. This study aimed to construct and validate a three-miRNA (miR-422a, miR-2116-3p, and miR-3187-3p) ceRNA network, and explore its potential functions. METHODS: Quantitative real­time PCR (qRT­PCR) was used to compare expression levels of miRNAs, lncRNAs, and genes between HTS and normal skin. Target lncRNAs and genes of each miRNA were predicted using starBase as well as TargetScan database to construct a distinct ceRNA network; overlapping target lncRNAs and genes of the three miRNAs were utilized to develop a three-miRNA ceRNA network. For every network, protein-protein interaction (PPI) network analysis was performed to identify its hub genes. For each network and its hub genes, Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to explore their possible functions. RESULTS: MiR-422a, miR-2116-3p, and miR-3187-3p were all downregulated in HTS tissues and fibroblasts. MiR-422a-based ceRNA network consisted of 101 lncRNAs with 133 genes; miR-2116-3p-centered ceRNA network comprised 85 lncRNAs and 978 genes; miR-3187-3p-derived ceRNA network encompassed 84 lncRNAs as well as 1128 genes. The three-miRNA ceRNA network included 2 lncRNAs with 9 genes, where MAPK1, FOSL2, ABI2, KPNA6, CBL, lncRNA-KCNQ1OT1, and lncRNA-EBLN3P were upregulated. According to GO and KEGG analysis, these networks were consistently related to ubiquitination. Three ubiquitination-related genes (CBL, SMURF2, and USP4) were upregulated and negatively correlated with the expression levels of the three miRNAs in HTS tissues. CONCLUSIONS: This study identified a three-miRNA ceRNA network, which might take part in HTS formation and correlate with ubiquitination.

LncRNA LUADT1 is Upregulated in Mantle Cell Lymphoma and Modulates TRIM11 by Sponging miR-24-3p to Inhibit Cell Apoptosis.

The microRNA MiR-24-3p suppresses cancer progression by targeting TRIM11. The long noncoding RNA LUADT1 has been reported to promote lung adenocarcinoma proliferation. We found LUADT1 may form base pairing with miR-24-3p. This study aimed to explore the interactions among LUADT1, miR-24-3p, and TRIM11 in mantle cell lymphoma (MCL). Our study recruited 40 MCL patients and 40 healthy volunteers. Tumor tissues were collected from 40 newly diagnosed MCL patients and embedded in paraffin wax. B lymphocytes were isolated from all tissue samples by using CD19+ magnetic beads and DETACHaBEAD CD19. Human MCL cell line Grante-519 and JeKo-1 were transfected with LUADT1 and TRIM11 expression vectors, microRNA mimics or inhibitors. Then, quantitative polymerase chain reaction and Western blot were used to detect the level of relative messenger RNA and protein expression, respectively. Flow cytometry was performed to detect the apoptosis rate. LUADT1 and miR-24-3p were upregulated while TRIM11 was downregulated in MCL both in tissues and cell lines compared with hyperplastic lymphadenitis and peripheral lymphocyte cells. Bioinformatics analysis showed that LUADT1 may bind miR-24-3p, which can target TRIM11. Correlation analysis showed that LUADT1 was not significantly correlated with miR-24-3p. However, it was positively and significantly correlated with TRIM11. In MCL cells, LUADT1 overexpression led to upregulated TRIM11, whereas miR-24-3p overexpression led to downregulated TRIM11. Cell apoptosis analysis showed that LU-ADT1, miR-24-3p inhibitor and TRIM11 overexpression led to decreased apoptotic rate of MCL cells, whereas miR-24-3p overexpression led to an increased apoptotic rate of MCL cells. In addition, miR-24-3p overexpression attenuated the effects of LUADT1 overexpression. Therefore, LUADT1 was upregulated in MCL and could modulate TRIM11 by sponging miR-24-3p to inhibit cancer cell apoptosis.